European Union pharmacovigilance capabilities : potential for the new legislation

European Directives and Regulations introduced between late 2010 and 2012 have substantially overhauled pharmacovigilance processes across the European Union (EU). In this review, the implementation of the pharmacovigilance legislative framework by EU regulators is examined with the aim of mapping Directive 2010/84/EU and Regulation EC No. 1235/2010 against their aspired objectives of strengthening and rationalizing pharmacovigilance in the EU. A comprehensive review of the current state of affairs of the progress made by EU regulators is presented in this paper. Our review shows that intense efforts by regulators and industry to fulfil legislative obligations have resulted in major positive shifts in pharmacovigilance. Harmonized decision making, transparency in decision processes with patient involvement, information accessibility to the public, patient adverse drug reaction reporting, efforts in communication and enhanced cooperation between member states to maximize resource utilization and minimize duplication of efforts are observed.peer-reviewe

Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma

In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.ERDF - Competitive Factors Thematic Operational ProgrammeFCT/PTDC/ QUI/68017/2006FCOMP-01-0124-FEDER-007439SFRH/BD/ 63430/2009National UNESCO Committee - L'Oréal Medals of Honor for Women in Science 200Portuguese National NMR Network - RNRM

Taxonomy and pathology of Togninia (Diaporthales) and its Phaeoacremonium anamorphs.

The genus Togninia (Diaporthales, Togniniaceae) is here monographed along with its Phaeoacremonium (Pm.) anamorphs. Ten species of Togninia and 22 species of Phaeoacremonium are treated. Several new species of Togninia (T.) are described, namely T. argentinensis (anamorph Pm. argentinense), T. austroafricana (anamorph Pm. austroafricanum), T. krajdenii, T. parasitica, T. rubrigena and T. viticola. New species of Phaeoacremonium include Pm. novae-zealandiae (teleomorph T. novae-zealandiae), Pm. iranianum, Pm. sphinctrophorum and Pm. theobromatis. Species can be identified based on their cultural and morphological characters, supported by DNA data derived from partial sequences of the actin and ß-tubulin genes. Phylogenies of the SSU and LSU rRNA genes were used to determine whether Togninia has more affinity with the Calosphaeriales or the Diaporthales. The results confirmed that Togninia had a higher affinity to the Diaporthales than the Calosphaeriales. Examination of type specimens revealed that T. cornicola, T. vasculosa, T. rhododendri, T. minima var. timidula and T. villosa, were not members of Togninia. The new combinations Calosphaeria cornicola, Calosphaeria rhododendri, Calosphaeria transversa, Calosphaeria tumidula, Calosphaeria vasculosa and Jattaea villosa are proposed. Species of Phaeoacremonium are known vascular plant pathogens causing wilting and dieback of woody plants. The most prominent diseases in which they are involved are Petri disease and esca, which occur on grapevines and are caused by a complex of fungi, often including multiple species of Phaeoacremonium. Various Phaeoacremonium species are opportunistic fungi on humans and cause phaeohyphomycosis. The correct and rapid identification of Phaeoacremonium species is important to facilitate the understanding of their involvement in plant as well as human disease. A rapid identification method was developed for the 22 species of Phaeacremonium. It involved the use of 23 species-specific primers, including 20 primers targeting the ß-tubulin gene and three targeting the actin gene. These primers can be used in 14 multiplex reactions. Additionally, a multiple-entry electronic key based on morphological, cultural and ß-tubulin sequence data was developed to facilitate phenotypic and sequence-based species identification of the different Phaeoacremonium species. Separate dichotomous keys are provided for the identification of the Togninia and Phaeoacremonium species. Keys for the identification of Phaeoacremonium-like fungi and the genera related to Togninia are also provided. The mating strategy of several Togninia species was investigated with ascospores obtained from fertile perithecia produced in vitro. Togninia argentinensis and T. novae-zealandiae have homothallic mating systems, whereas T. austroafricana, T. krajdenii, T. minima, T. parasitica, T. rubrigena and T. viticola were heterothallic.

The Relationship between the Presence of Chromosomal Instability and Prognosis of Squamous Cell Carcinoma of the Lung: Fluorescence in situ Hybridization Analysis of Paraffin-embedded Tissue from 47 Korean Patients

To evaluate the prognostic importance of chromosomal instability (CIN) in squamous cell carcinoma (SCC) of the lung, the relationship between CIN detected by fluorescence in situ hybridization (FISH) and survival in SCC patients was examined. Forty-seven surgical specimens of lung SCC were analyzed. To identify tumors with CIN, p16 and multi-target DNA FISH assays for c-myc, chromosome 6, EGFR, and chromosome 5 (LAVysion, Vysis) were performed on nuclei extracted from paraffin-embedded tumor tissues. Survival rates were compared in terms of age, T factor, N factor, CIN, and smoking status. A sample was defined as CIN-positive if at least four of the five chromosomes were positive. Among the 47 specimens, 9 (19%) were CIN-positive. The overall survival rate was 66%. Overall survival rates were estimated as 33.3% for CIN-positive patients and 76.7% for CIN-negative patients (Hazard ratio 3.47; 95% Confidence interval, 1.25-9.67; P=0.017). In multivariate analysis, the presence of CIN was a predictive factor for survival. CIN-positive based on FISH can be prognostic factor of lung SCC

Clinicopathological characteristics of resected adenosquamous cell carcinoma of the lung: Risk of coexistent double cancer

<p>Abstract</p> <p>Background</p> <p>adenosquamous carcinoma (ADSQ) of non-small cell lung cancer (NSCLC) is a rare disease and the biological behavior and clinicopathological characteristics have not yet been thoroughly described.</p> <p>Method</p> <p>This study reviewed the patient charts of 11 (1.6%) ADSQ cases among 779 patients with primary lung cancer who underwent a lung resection. The characteristics and clinicopathological factors were evaluated retrospectively.</p> <p>Results</p> <p>Six of the 11 patients with ADSQ were male and five were female. The mean age was 67.3 years' olds. Three patients had pathological stage IA, one patient each had stage IB and IIA, five patients had stage IIIA, and one patient stage IIIB. Five patients had coexistent double cancer including 2 gastric, 1 rectal, 1 prostate and 1 bladder cancer. ADSQ was found less frequently in males than squamous cell carcinoma (SQ). ADSQ was found more frequently in older patients, with advanced stage, advanced T status, and lymph node metastases than adenocarcinoma (AD). The proportion with coexistent double cancer of AD, SQ, and ADSQ were 21.1, 17.6, and 45.5%, respectively. ADSQ had a significantly correlation with double cancer (ADSQ vs. non- ADSQ p = 0.03). A multivariate analysis showed no significant prognostic difference between the patients with ADSQ and non- ADSQ.</p> <p>Conclusions</p> <p>In this study, cases with ADSQ showed no significantly prognostic difference in comparison to AD and SQ. However, surgeons must be cautious of any coexistent double cancer because approximately half of all patients with ADSQ of the lung have double cancer.</p

Las micorrizas: una relación planta-hongo que dura más de 400 millones de años

The concept of mycorrhiza is considered in a wide sense, as a not necessarily mutualistic symbiosis, covering the trophic relations of mycorrhizal fungi with “inferior” and achlorophyllics plants. A bibliographical review of the origin and diversification of mycorrhizae is made. The pioneering characteristics of the arbuscular mycorrhiza formed by &lt;i&gt;Glomeromycota&lt;/i&gt; are discussed, emphasizing its importance during the terrestrialization processes. The chronological appearance of the other types of mycorrhizas is discussed. The independent and recurrent evolution of the ectomycorrhizas formed by Basidiomycota and Ascomycota is discussed; their saprobiont or parasite origin points to the versatile nutritional strategy of these fungi, in adaptative response to environmental changes, as does the origin of the singular ericoid, arbutoid and helianthemoid mycorrhizas. The particular trophic relation between achlorophyllic plants, such as &lt;i&gt;Monotropa&lt;/i&gt; and orchids, in their heterotrophic phases, with their “mycorrhizal” fungi is also described. Finally, the recent evolution of the non mycotrophic root systems is commented on.&lt;br&gt;&lt;br&gt;Se define el concepto de micorriza en un sentido amplio, como una simbiosis no necesariamente mutualística, para incluir las relaciones tróficas de hongos micorrícicos con plantas “inferiores” y plantas aclorofílicas. Se realiza una revisión bibliográfica sobre el origen y diversificación de las micorrizas. Se evidencia el carácter pionero de la micorriza arbuscular formada por los &lt;i&gt;Glomeromycota&lt;/i&gt; y se resalta su importancia en el proceso de ‘terrestrialización’. Se comenta la formación cronológica de los restantes tipos de micorrizas. Se denota la evolución independiente y recurrente de las ectomicorrizas, formadas por &lt;i&gt;Basidiomycota&lt;/i&gt; y &lt;i&gt;Ascomycota&lt;/i&gt; inicialmente saprófitos, que sugiere una versatilidad en las estrategias nutricionales de estos hongos, como respuesta adaptativa a los cambios ambientales. Similares respuestas debieron ser la causa del origen de las singulares micorrizas ericoides, arbutoides y heliantemoides. Se expone la particular relación trófica entre plantas aclorofílicas como &lt;i&gt;Monotropa&lt;/i&gt; o de orquídeas en sus fases hetrotróficas con sus hongos simbiontes. Finalmente, se comenta la reciente evolución de sistemas radicales micotróficamente independientes

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

First evidence of mutualism between ancient plant lineages (Haplomitriopsida liverworts) and Mucoromycotina fungi and its response to simulated Palaeozoic changes in atmospheric CO2

© 2014 The Authors. New Phytologist © 2014 New Phytologist Trust. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The attached file is the published version of the article

Presence of three mycorrhizal genes in the common ancestor of land plants suggests a key role of mycorrhizas in the colonization of land by plants

• The colonization of land by plants fundamentally altered environmental conditions on earth. Plant–mycorrhizal fungus symbiosis likely played a key role in this process by assisting plants to absorb water and nutrients from soil. • Here, in a diverse set of land plants, we investigated the evolutionary histories and functional conservation of three genes required for mycorrhiza formation in legumes and rice ( Oryza sativa ), DMI1 , DMI3 and IPD3 . • The genes were isolated from nearly all major plant lineages. Phylogenetic analyses showed that they had been vertically inherited since the origin of land plants. Further, cross-species mutant rescue experiments demonstrated that DMI3 genes from liverworts and hornworts could rescue Medicago truncatula dmi3 mutants for mycorrhiza formation. Yeast two-hybrid assays also showed that bryophyte DMI3 proteins could bind to downstream-acting M. trunculata IPD3 protein. Finally, molecular evolutionary analyses revealed that these genes were under purifying selection for maintenance of their ancestral functions in all mycorrhizal plant lineages. • These results indicate that the mycorrhizal genes were present in the common ancestor of land plants, and that their functions were largely conserved during land plant evolution. The evidence presented here strongly suggests that plant–mycorrhizal fungus symbiosis was one of the key processes that contributed to the origin of land flora.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78704/1/j.1469-8137.2009.03137.x.pd