Resezioni polmonari limitate “intenzionali” versus lobectomie nel trattamento dei tumori polmonari periferici non microcitomi allo stadio IA

Scopo del presente studio è valutare, attraverso l’analisi retrospettiva della nostra casistica e la revisione della letteratura, se le resezioni polmonari limitate siano equivalenti alla lobectomia nel trattamento dei tumori polmonari non microcitomi (NSCLC) periferici allo stadio IA (T1N0M0), in termini di radicalità oncologica, sopravvivenza e tasso di recidive locali, regionali e sistemiche.Viene inoltre preso in considerazione l’impatto delle resezioni limitate, rispetto alle resezioni lobari, sulla funzionalità polmonare postoperatoria. Pazienti e metodi. Abbiamo analizzato una serie consecutiva di 36 pazienti, 28 uomini e 8 donne, di età compresa fra 61 e 81 anni (media 73 anni), sottoposti ad intervento chirurgico, nel periodo compreso fra gennaio 2000 e dicembre 2003, per NSCLC periferici T1N0M0; sono state effettuate 11 resezioni limitate e 25 lobectomie. Sono state analizzate comparativamente sopravvivenza e recidive (follow-up 3-5 anni), nonché le prove di funzionalità respiratoria ad un anno dall’intervento. Risultati. La sopravvivenza a 3 e 5 anni è stata pari all’88% ed all’82% nel gruppo dei pazienti sottoposti a resezioni limitate, al 93% e all’88% nel gruppo dei pazienti sottoposti a lobectomia. Si è verificata una recidiva locale (9%) nel primo gruppo, una (4%) nel secondo. Ad un anno dall’intervento si sono osservati un moderato decremento del volume espiratorio forzato in 1 secondo (FEV1) e della capacità di diffusione per monossido di carbonio (DLCO) nei pazienti sottoposti a resezione lobare, e un sostanziale mantenimento dei parametri funzionali preoperatori, eccezion fatta per la DLCO, nei pazienti sottoposti a resezione limitata. Conclusioni. La nostra circoscritta esperienza, in accordo con le tendenze attuali della letteratura, indica che l’intervento di resezione polmonare limitata, in pazienti selezionati, con NSCLC periferici allo stadio IA, rappresenta una valida alternativa alla lobectomia in termini di sopravvivenza e tasso di recidiva, determinando altresì un minor decremento della funzionalità polmonare postoperatoria. La segmentectomia può essere dunque considerata, in tali casi, procedura chirurgica di scelta, anche in pazienti in grado di tollerare una resezione maggior

Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

<div><p>Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway <i>i</i>.<i>e</i>., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3–38 times <i>vs</i>. non-activated platelets) whereas ristocetin was ineffective. OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased only by thrombin. OxPhos was the main source of ATP in thrombin-activated platelets, whereas in platelets activated by any of the other agonists, glycolysis was the principal ATP supplier. In order to establish the biochemical mechanisms involved in the thrombin-induced OxPhos activation in platelets, several signaling pathways associated with mitochondrial activation were analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the thrombin-induced platelet activation. These results suggest that thrombin activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K and Akt activation, calcium mobilization and protein phosphorylation.</p></div

Herschel/PACS observations of young sources in Taurus: the far-infrared counterpart of optical jets

Observations of the atomic and molecular line emission associated with jets and outflows emitted by young stellar objects can be used to trace the various evolutionary stages they pass through as they evolve to become main sequence stars. To understand the relevance of atomic and molecular cooling in shocks, and how accretion and ejection efficiency evolves with the source evolutionary state, we will study the far-infrared counterparts of bright optical jets associated with Class I and II sources in Taurus (T Tau, DG Tau A, DG Tau B, FS Tau A+B, and RW Aur). We have analysed Herschel/PACS observations of a number of atomic ([OI]63um, 145um, [CII]158um) and molecular (high-J CO, H2O, OH) lines, collected within the OTKP GASPS. To constrain the origin of the detected lines we have compared the FIR emission maps with the emission from optical-jets and millimetre-outflows, and the line fluxes and ratios with predictions from shock and disk models. All of the targets are associated with extended emission in the atomic lines correlated with the direction of the optical jet/mm-outflow. The atomic lines can be excited in fast dissociative J-shocks. The molecular emission, on the contrary, originates from a compact region, that is spatially and spectrally unresolved. Slow C- or J- shocks with high pre-shock densities reproduce the observed H2O and high-J CO lines; however, the disk and/or UV-heated outflow cavities may contribute to the emission. While the cooling is dominated by CO and H2O lines in Class 0 sources, [OI] becomes an important coolant as the source evolves and the environment is cleared. The cooling and mass loss rates estimated for Class II and I sources are one to four orders of magnitude lower than for Class 0 sources. This provides strong evidence to indicate that the outflow activity decreases as the source evolves.Comment: 18 pages, 9 figures, accepted by A&

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Mitochondrial DNA Variant Discovery and Evaluation in Human Cardiomyopathies through Next-Generation Sequencing

Mutations in mitochondrial DNA (mtDNA) may cause maternally-inherited cardiomyopathy and heart failure. In homoplasmy all mtDNA copies contain the mutation. In heteroplasmy there is a mixture of normal and mutant copies of mtDNA. The clinical phenotype of an affected individual depends on the type of genetic defect and the ratios of mutant and normal mtDNA in affected tissues. We aimed at determining the sensitivity of next-generation sequencing compared to Sanger sequencing for mutation detection in patients with mitochondrial cardiomyopathy. We studied 18 patients with mitochondrial cardiomyopathy and two with suspected mitochondrial disease. We “shotgun” sequenced PCR-amplified mtDNA and multiplexed using a single run on Roche's 454 Genome Sequencer. By mapping to the reference sequence, we obtained 1,300× average coverage per case and identified high-confidence variants. By comparing these to >400 mtDNA substitution variants detected by Sanger, we found 98% concordance in variant detection. Simulation studies showed that >95% of the homoplasmic variants were detected at a minimum sequence coverage of 20× while heteroplasmic variants required >200× coverage. Several Sanger “misses” were detected by 454 sequencing. These included the novel heteroplasmic 7501T>C in tRNA serine 1 in a patient with sudden cardiac death. These results support a potential role of next-generation sequencing in the discovery of novel mtDNA variants with heteroplasmy below the level reliably detected with Sanger sequencing. We hope that this will assist in the identification of mtDNA mutations and key genetic determinants for cardiomyopathy and mitochondrial disease

The ALICE Silicon Pixel Detector: readiness for the first proton beam

The Silicon Pixel Detector (SPD) is the innermost element of the ALICE Inner Tracking System (ITS). The SPD consists of two barrel layers of hybrid silicon pixels surrounding the beam pipe with a total of 48 10^7 pixel cells. The SPD features a very low material budget, a 99.9% efficient bidimensional digital response, a 12 micron spatial precision in the bending plane (rf ) and a prompt signal as input to the L0 trigger. The SPD commissioning in the ALICE experimental area is well advanced and it includes calibration runs with internal pulse and cosmic ray runs. In this contribution the commissioning of the SPD is reviewed and the first results from runs with cosmic rays and circulating proton beams are presented

Anopheles gambiae Antiviral Immune Response to Systemic O'nyong-nyong Infection

Mosquito-borne viral diseases are found across the globe and are responsible for numerous severe human infections. In order to develop novel methods for prevention and treatment of these diseases, detailed understanding of the biology of viral infection and transmission is required. Little is known about invertebrate responses to infection in mosquito hosts. In this study we used a model system of Anopheles gambiae mosquitoes and O'nyong-nyong virus to study mosquito immune responses to infection. We examined the global transcriptional responses of A. gambiae to viral infection of the mosquito blood equivalent (the hemolymph) identifying a number of genes with immune functions that are switched on or off in response to infection, including complement-like proteins that circulate in the mosquito hemolymph. The switching on of these genes combined with co-infection experiments with malaria parasites suggests that viral infection inhibits the melanisation pathway. Through silencing the function of a selection of viral responsive genes, we identified four genes that have roles in A. gambiae anti-viral immunity; two putative recognition receptors (a galectin and an MD2-like receptor); two effector lysozymes. These molecules have previously non-described roles in antiviral immunity, and suggest uncharacterised mechanisms for targeting viral infection in A. gambiae mosquitoes

C-Type Lectin in Chlamys farreri (CfLec-1) Mediating Immune Recognition and Opsonization

Background: C-type lectins are a superfamily of Ca 2+ dependent carbohydrate-recognition proteins that play significant diverse roles in nonself-recognition and clearance of invaders. Though they are well characterized in vertebrates, the study of the potential function and mechanism of C-type lectins in invertebrate immunity is still in its infancy. Methodology: A C-type lectin (CfLec-1) from scallop Chlamys farreri, a dominant cultured mollusk species in China, was selected to investigate its mRNA expression, localization and the possible functions in innate immunity in the present study. After scallop was stimulated by three typical PAMPs, the mRNA expression of CfLec-1 in hemocytes was poles apart. It was significantly up-regulated (p,0.01) after scallops were stimulated by LPS or b-glucan, but significantly down-regulated (p,0.01) after PGN stimulation. The binding ability of recombinant CfLec-1 (designated as rCfLec-1) towards eight PAMPs was investigated subsequently by PAMPs microarray, which revealed rCfLec-1 could bind LPS, PGN and mannan in vitro, indicating CfLec-1 served as a PRR involved in the pathogen recognition. Immunofluorescence assay with polyclonal antibody specific for CfLec-1 revealed that CfLec-1 was mainly located in the mantle and gill of the scallop. CfLec-1 could bind to the surface of scallop hemocytes and recruited hemocytes to enhance their encapsulation in vitro, and this process could be specifically blocked by anti-rCfLec-1 antibody. Meanwhile, rCfLec-1 could also enhance the phagocytic activity of scallop hemocytes against Escherichia coli