Four cases of progressive multifocal leukoencephalopathy in iatrogenic immunocompromised patients

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by John Cunningham Virus (JCV). We report four PML cases in immunocompromised patients, respectively treated with (1) Natalizumab, (2) Rituximab, (3) autologous stem-cell transplantation, and (4) Tacrolimus. All patients underwent neurological examination, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), JCV-DNA research on biological samples, and lymphocytes subpopulation study. All cases presented with motor, behavioural, and cognitive disorders. Visual, sensitive, and cerebellar deficits developed in three cases. MRI revealed widespread progressive demyelinating areas with active borders; three patients presented contrast enhancement. One patient developed inflammatory reconstitution syndrome (IRIS). At MRS, all cases presented decreased N-acetyl-aspartate (NAA) and three cases showed increased choline (Cho). In one patient, plasma and urine tested positive for JCV-DNA, while cerebrospinal fluid (CSF) analysis confirmed JCV in two patients. The fourth patient had a low JCV-DNA blood titer and brain biopsy showed subacute necrosis. Two patients had abnormal lymphocyte subpopulations. Three patients underwent therapy with Mirtazapine, one of whom received Mefloquine in add-on. No clinical response was registered. Clinical onset, MRI and MRS were highly suggestive of PML in all patients, despite three cases presented contrast enhancement. In three cases JCV-DNA detection in biological samples confirmed the diagnosis. The fourth patient fulfilled diagnosis of “presumptive PML”. Our data confirm the importance to complete the diagnostic workup despite the presence of findings not completely consistent with classical PML. We hypothesize that atypical characteristics could due to the clinical conditions leading to PML

Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure

The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate the role of ERFE as a physiological erythroid regulator in humans, we conducted two studies: first, 24 males received six injections of saline (placebo), recombinant Epo (rhEpo) 20 UI kg-1 (micro-dose) or 50 UI kg-1 (low-dose). Second, we quantified ERFE in 22 subjects exposed to high altitude (3800 m) for 15 hours. In the first study, total hemoglobin mass (Hbmass) increased after low- but not after micro-dose injections, when compared to placebo. Serum ERFE levels were enhanced by rhEpo, remaining higher than after placebo for 48 (micro-dose) or 72 hours (low-dose) post-injections. Conversely, hepcidin levels decreased when Epo and ERFE arose, before any changes in serum iron parameters occurred. In the second study, serum Epo and ERFE increased at high altitude. The present results demonstrate that in healthy humans ERFE responds to slightly increased Epo levels not associated with Hbmass expansion and down-regulates hepcidin in an apparently iron-independent way. Notably, ERFE flags micro-dose Epo, thus holding promise as novel anti-doping biomarker

Importance of the logistics performance index in international trade

This is an author's accepted manuscript of an article published in: “Applied Economics"; Volume 46, Issue 24, 2014; copyright Taylor & Francis; available online at: http://dx.doi.org/10.1080/00036846.2014.916394Logistics and transport increasingly play a pivotal role in international trade relations. The Logistics Performance Index (LPI) analyses differences between countries in terms of customs procedures, logistics costs and the quality of the infrastructure for overland and maritime transport. The aim of this article is to analyse the impact that each of these components has on trade in emerging economies using a gravity model. Furthermore, the study also attempts to detect possible advances in logistics in developing countries, which are grouped into five regions (Africa, South America, Far East, Middle East and Eastern Europe) by comparing the first LPI data published in 2007 with the most recent data, released in 2012. The results obtained reveal that improvements in any of the components of the LPI can lead to significant growth in a country’s trade flows. Specifically, LPI components are becoming increasingly important for international trade in many countries in Africa, South America and Eastern Europe.Martí Selva, ML.; Puertas Medina, RM.; García, L. (2014). Importance of the logistics performance index in international trade. Applied Economics. 46(24):2982-2992. doi:10.1080/00036846.2014.916394S298229924624Anderson, J. E., & van Wincoop, E. (2003). Gravity with Gravitas: A Solution to the Border Puzzle. American Economic Review, 93(1), 170-192. doi:10.1257/000282803321455214Bergstrand, J. H. (1985). The Gravity Equation in International Trade: Some Microeconomic Foundations and Empirical Evidence. The Review of Economics and Statistics, 67(3), 474. doi:10.2307/1925976Bergstrand, J. H. (1989). The Generalized Gravity Equation, Monopolistic Competition, and the Factor-Proportions Theory in International Trade. The Review of Economics and Statistics, 71(1), 143. doi:10.2307/1928061De Souza, R., Goh, M., Gupta, S.et al.(2007) An investigation into the measures affecting the integration of ASEAN’s priority sectors: phase 2: the case of logistics.REPSF ProjectNo. 06/001d Regional Economic Policy Support Facility, Association of Southeast Asian Nations, Manila.Heckman, J. J. (1979). Sample Selection Bias as a Specification Error. Econometrica, 47(1), 153. doi:10.2307/1912352Hoekman, B., & Nicita, A. (2010). Assessing the Doha Round: Market access, transactions costs and aid for trade facilitation. The Journal of International Trade & Economic Development, 19(1), 65-79. doi:10.1080/09638190903327476Iwanow, T., & Kirkpatrick, C. (2009). Trade Facilitation and Manufactured Exports: Is Africa Different? World Development, 37(6), 1039-1050. doi:10.1016/j.worlddev.2008.09.014Marti, L., Puertas, R., & García, L. (2012). Relevance of trade facilitation in emerging countries’ exports. The Journal of International Trade & Economic Development, 23(2), 202-222. doi:10.1080/09638199.2012.698639Martínez-Zarzoso, I., & Suárez-Burguet, C. (2000). The determinants of trade performance: influence of R&D on export flows. Applied Economics, 32(15), 1939-1946. doi:10.1080/00036840050155869Mustra, M. A. (2011) Logistic Performance Index, connecting to compete 2010, inUNESCAP Regional Forum and Chief Executives Meeting, The World Bank, Cairo

DrugBank 3.0: a comprehensive resource for ‘Omics’ research on drugs

DrugBank (http://www.drugbank.ca) is a richly annotated database of drug and drug target information. It contains extensive data on the nomenclature, ontology, chemistry, structure, function, action, pharmacology, pharmacokinetics, metabolism and pharmaceutical properties of both small molecule and large molecule (biotech) drugs. It also contains comprehensive information on the target diseases, proteins, genes and organisms on which these drugs act. First released in 2006, DrugBank has become widely used by pharmacists, medicinal chemists, pharmaceutical researchers, clinicians, educators and the general public. Since its last update in 2008, DrugBank has been greatly expanded through the addition of new drugs, new targets and the inclusion of more than 40 new data fields per drug entry (a 40% increase in data ‘depth’). These data field additions include illustrated drug-action pathways, drug transporter data, drug metabolite data, pharmacogenomic data, adverse drug response data, ADMET data, pharmacokinetic data, computed property data and chemical classification data. DrugBank 3.0 also offers expanded database links, improved search tools for drug–drug and food–drug interaction, new resources for querying and viewing drug pathways and hundreds of new drug entries with detailed patent, pricing and manufacturer data. These additions have been complemented by enhancements to the quality and quantity of existing data, particularly with regard to drug target, drug description and drug action data. DrugBank 3.0 represents the result of 2 years of manual annotation work aimed at making the database much more useful for a wide range of ‘omics’ (i.e. pharmacogenomic, pharmacoproteomic, pharmacometabolomic and even pharmacoeconomic) applications

Divergence via Europeanisation: rethinking the origins of the Portuguese debt crisis

A founding myth of the euro was that profound economic convergence could be achieved across the core and periphery of Europe. Scholarship from within Comparative Political Economy (CPE) has compellingly pointed to this myth of convergence as the fundamental mistake of the euro project (Regan, “Imbalance of Capitalisms”). Economic and Monetary Union was applied across a range of incompatible varieties of capitalism with little appreciation for how difficult it would be for peripheral economies to overcome long-standing institutional stickiness. Yet, while institutional stickiness tells us much about the causes of declining competitiveness, it tells us much less about the origins of brand new patterns of debt-led growth. This article modifies this CPE account by drawing attention to the much overlooked case of Portugal. In contrast to CPE’s emphasis on institutional stickiness, this paper explores the ways in which negotiation of European integration has been generative of institutional transformation leading to debt-led growth in Portugal. By combining Europeanisation with CPE, this article shows that, far from an inability to do so, in the case of Portugal, it has been the attempt to ‘follow the rules’ of European Integration that explains its damaging patterns of debt-led growth

Relict periglacial soils on Quaternary terraces in the central Ebro Basin (NE Spain)

Pedofeatures associated with ancient cold climatic conditions have been recognized in soils on terraces in the Monegros area (central Ebro Basin, Spain), at a latitude of 41°49′N and an altitude of 300 m a.s.l. Eleven soil profiles were described on fluvial deposits corresponding to the most extensive terrace (T5) of the Alcanadre River, Middle Pleistocene in age (MIS8–MIS7). Each soil horizon was sampled for physical, chemical, mineralogical and micromorphological analyses. Macromorphological features related to pedocryogenic processes were described: involutions, jacked stones, shattered stones, detached and vertically oriented carbonatic pendents, fragmented carbonatic crusts, laminar microstructures, succitic fabric, silt cappings on rock fragments and aggregates, and irregular, broken, discontinuous and deformed gravel and sandy pockets. Accumulations of Fe–Mn oxides, dissolution features on the surface of carbonatic stones, and calcitic accumulations were identified related to vadose–phreatic conditions. The observed periglacial features developed under cold environmental conditions in exceptional geomorphic and hydrological conditions. This soil information may have potential implications in studies of paleoclimate in the Ebro Valley as well as in other Mediterranean areas

On the potential economic costs of cutting carbon dioxide emissions in Portugal

The objective of this paper is to estimate the impact of reducing carbon dioxide emissions from fossil fuel combustion activities on economic activity in Portugal. We find that energy consumption has a significant impact on macroeconomic activity. In fact, a 1 ton of oil equivalent permanent reduction in aggregate energy consumption reduces output in the long term by €6,340. More importantly, and since carbon dioxide emissions are linearly related to the amounts of fuel consumed, our results allow us to estimate the costs of reductions in carbon dioxide emissions. We estimate that a uniform standard for reducing carbon dioxide emissions from fossil fuel combustion activities would lead to a marginal abatement cost of €95.74 per ton of carbon dioxide. This is a first rough estimate of the potential economic costs of policies designed to reduce carbon dioxide emissions. At this level one may conclude that uniform, across the board reductions in carbon emissions would have a clear negative effect on economic activity. Hence, at the aggregate level there is clear evidence for a trade-off between economic performance and a reduction in carbon emissions. This opens the door to the investigation of the scope for policy to minimize the costs of environmental policy and regulation.info:eu-repo/semantics/publishedVersio

Angiostrongylus vasorum infection in dogs from a cardiopulmonary dirofilariosis endemic area of Northwestern Italy : A case study and a retrospective data analysis

BACKGROUND: In Italy, Angiostrongylus vasorum, an emergent parasite, is being diagnosed in dogs from areas considered free of infection so far. As clinical signs are multiple and common to other diseases, its diagnosis can be challenging. In particular, in areas where angiostrongylosis and dirofilariosis overlap, a misleading diagnosis of cardiopulmonary dirofilariosis might occur even on the basis of possible misleading outcomes from diagnostic kits. CASE PRESENTATION: Two Cavalier King Charles spaniel dogs from an Italian breeding in the Northwest were referred to a private veterinary hospital with respiratory signs. A cardiopulmonary dirofilariosis was diagnosed and the dogs treated with ivermectin, but one of them died. At necropsy, pulmonary oedema, enlargement of tracheo-bronchial lymphnodes and of cardiac right side were detected. Within the right ventricle lumen, adults of A. vasorum were found. All dogs from the same kennel were subjected to faecal examination by FLOTAC and Baermann's techniques to detect A. vasorum first stage larvae; blood analysis by Knott's for Dirofilaria immitis microfilariae, and antigenic tests for both A. vasorum (Angio Detect\u2122) and D.immitis (DiroCHEK\uae Heartworm, Witness\uaeDirofilaria). The surviving dog with respiratory signs resulted positive for A. vasorum both at serum antigens and larval detection. Its Witness\uae test was low positive similarly to other four dogs from the same kennel, but false positive results due to cross reactions with A. vasorum were also considered. No dogs were found infected by A. vasorum. Eventually, the investigation was deepened by browsing the pathological database of Veterinary Pathology Laboratories at Veterinary School of Milan University through 1998-2016, where 11 cases of angiostrongylosis were described. Two out of 11 dogs had a mixed infection with Crenosoma vulpis. CONCLUSION: The study demonstrates the need for accurate surveys to acquire proper epidemiological data on A. vasorum infection in Northwestern Italy and for appropriate diagnostic methods. Veterinary clinicians should be warned about the occurrence of this canine parasite and the connected risk of a misleading diagnosis, particularly in areas endemic for cardiopulmonary dirofilariosis