Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Use and efficacy of bone morphogenetic proteins in fracture healing

Signal transduction in aging related disease

Different Domains of the RNA Polymerase of Infectious Bursal Disease Virus Contribute to Virulence

BACKGROUND: Infectious bursal disease virus (IBDV) is a pathogen of worldwide significance to the poultry industry. IBDV has a bi-segmented double-stranded RNA genome. Segments A and B encode the capsid, ribonucleoprotein and non-structural proteins, or the virus polymerase (RdRp), respectively. Since the late eighties, very virulent (vv) IBDV strains have emerged in Europe inducing up to 60% mortality. Although some progress has been made in understanding the molecular biology of IBDV, the molecular basis for the pathogenicity of vvIBDV is still not fully understood. METHODOLOGY, PRINCIPAL FINDINGS: Strain 88180 belongs to a lineage of pathogenic IBDV phylogenetically related to vvIBDV. By reverse genetics, we rescued a molecular clone (mc88180), as pathogenic as its parent strain. To study the molecular basis for 88180 pathogenicity, we constructed and characterized in vivo reassortant or mosaic recombinant viruses derived from the 88180 and the attenuated Cu-1 IBDV strains. The reassortant virus rescued from segments A of 88180 (A88) and B of Cu-1 (BCU1) was milder than mc88180 showing that segment B is involved in 88180 pathogenicity. Next, the exchange of different regions of BCU1 with their counterparts in B88 in association with A88 did not fully restore a virulence equivalent to mc88180. This demonstrated that several regions if not the whole B88 are essential for the in vivo pathogenicity of 88180. CONCLUSION, SIGNIFICANCE: The present results show that different domains of the RdRp, are essential for the in vivo pathogenicity of IBDV, independently of the replication efficiency of the mosaic viruses

A Longitudinal Area Classification of Migration in Great Britain –Testing the application of Group-Based Multi-Trajectory Modelling

The migration of people affects the geographical distribution of the population and the demographic composition of areas over the short, medium and long terms. To recognise and respond to the corresponding needs and challenges, including consequences for service provision, social cohesion and population health, there is a continuing need to understand migration patterns of the past and present. Area classifications are a useful tool to simplify the inherently complex data on migration flows and characteristics. Yet, existing classifications often lack direct migration measures or focus solely on cross-sectional data. This study addresses these limitations by employing Group-based Multi-Trajectory Modelling (GBMTM) to create a longitudinal, migration-specific classification of Great Britain's wards from 1981 to 2011, using six migration indicators. Using UK census data, we reveal six distinct migration clusters that highlight the rapid growth in studentifying neighbourhoods, the continuous influx of migrants into inner cities, and a noticeable North-South divide in terms of movers’ tenure enforced by persisting income selectivity. Additionally, the geographical distribution of clusters shows a common pattern in urban areas irrespective of size or location. The longitudinal perspective of our GBMTM classification highlights trends and changes in migration patterns that are not well reflected in either the general purpose or the cross-sectional migration classification that we used as comparators. We conclude that the method presented and the classification generated offer a novel lens on migration and provide new opportunities to explore the effects of migration on a variety of outcomes and at various scales