Rationale and study design of intravenous loop diuretic administration in acute heart failure. DIUR-AHF

Aims: Although loop diuretics are the most commonly used drugs in acute heart failure (AHF) treatment, their short-term and long-term effects are relatively unknown. The significance of worsening renal function occurrence during intravenous treatment is not clear enough. This trial aims to clarify all these features and contemplate whether continuous infusion is better than an intermittent strategy in terms of decongestion efficacy, diuretic efficiency, renal function, and long-term prognosis. Methods and results: This is a prospective, multicentre, randomized study that compares continuous infusion to intermittent infusion and a low vs. high diuretic dose of furosemide in patients with a diagnosis of acute heart failure, BNP ≥ 100 pg/mL, and specific chest X-ray signs. Randomization criteria have been established at a 1:1 ratio using a computer-generated scheme of either twice-daily bolus injection or continuous infusion for a time period ranging from 72 to 120 h. The initial dose will be 80 mg/day of intravenous furosemide and, in the case of poor response, will be doubled using an escalation algorithm. A high diuretic dose is defined as a furosemide daily amount >120 mg/day respectively. Conclusions: Continuous and high dose groups could reveal a more intensive diuresis and a greater decongestion with respect to intermittent and low dose groups; high dose and poor loop diuretic efficiency should be related to increased diuretic resistance, renal dysfunction occurrence, and greater congestion status. Poor diuretic response will be associated with less decongestion and an adverse prognosis

Transcriptome dynamics in the asexual cycle of the chordate Botryllus schlosseri

Background: We performed an analysis of the transcriptome during the blastogenesis of the chordate Botryllus schlosseri, focusing in particular on genes involved in cell death by apoptosis. The tunicate B. schlosseri is an ascidian forming colonies characterized by the coexistence of three blastogenetic generations: filter-feeding adults, buds on adults, and budlets on buds. Cyclically, adult tissues undergo apoptosis and are progressively resorbed and replaced by their buds originated by asexual reproduction. This is a feature of colonial tunicates, the only known chordates that can reproduce asexually. Results: Thanks to a newly developed web-based platform (http://botryllus.cribi.unipd.it), we compared the transcriptomes of the mid-cycle, the pre-take-over, and the take-over phases of the colonial blastogenetic cycle. The platform is equipped with programs for comparative analysis and allows to select the statistical stringency. We enriched the genome annotation with 11,337 new genes; 581 transcripts were resolved as complete open reading frames, translated in silico into amino acid sequences and then aligned onto the non-redundant sequence database. Significant differentially expressed genes were classified within the gene ontology categories. Among them, we recognized genes involved in apoptosis activation, de-activation, and regulation. Conclusions: With the current work, we contributed to the improvement of the first released B. schlosseri genome assembly and offer an overview of the transcriptome changes during the blastogenetic cycle, showing up- and down-regulated genes. These results are important for the comprehension of the events underlying colony growth and regression, cell proliferation, colony homeostasis, and competition among different generations

R-parity as a residual gauge symmetry : probing a theory of cosmological dark matter

We present a non-supersymmetric scenario in which the R-parity symmetry $R_P = (-1)^{3(B-L)+2s}$ arises as a result of spontaneous gauge symmetry breaking, leading to a viable Dirac fermion WIMP dark matter candidate. Direct detection in nuclear recoil experiments probes dark matter masses around $2-5$ TeV for $M_{Z^{\prime}} \sim 3-4$ TeV consistent with searches at the LHC, while lepton flavor violation rates and flavor changing neutral currents in neutral meson systems lie within reach of upcoming experiments.Comment: 7 pages, 3 figure

Grid-based estimates of stellar ages in binary systems: SCEPtER: Stellar CharactEristics Pisa Estimation gRid

Aims. We investigate the performance of grid-based techniques in estimating the age of stars in detached eclipsing binary systems. We evaluate the precision of the estimates due to the uncertainty in the observational constraints-masses, radii, effective temperatures, and [Fe/H]-and the systematic bias caused by the uncertainty in convective core overshooting, element diffusion, mixing-length value, and initial helium content. Methods. We adopted the SCEPtER grid, which includes stars with mass in the range [0.8; 1.6] M⊙ and evolutionary stages from the zero-age main sequence to the central hydrogen depletion. Age estimates have been obtained by a generalisation of the maximum likelihood technique described in our previous work. Results. We showed that the typical 1σ random error in age estimates-due only to the uncertainty affecting the observational constraints-is about ± 7%, which is nearly independent of the masses of the two stars. However, such an error strongly depends on the evolutionary phase and becomes larger and asymmetric for stars near the zero-age main sequence where it ranges from about + 90% to-25%. The systematic bias due to the including convective core overshooting-for mild and strong overshooting scenarios-is about 50% and 120% of the error due to observational uncertainties. A variation of ± 1 in the helium-to-metal enrichment ratio ΔY/ΔZ accounts for about ± 150% of the random error. The neglect of microscopic diffusion accounts for a bias of about 60% of the error due to observational uncertainties. We also introduced a statistical test of the expected difference in the recovered age of two coeval stars in a binary system. We find that random fluctuations within the current observational uncertainties can lead genuine coeval binary components to appear to be non-coeval with a difference in age as high as 60%

Completion total gastrectomy with intracorporeal robot-sewn esophago-jejunal anastomosis

Many technical reports concern minimally invasive surgery for stomach cancer; however, there is poor evidence about employing this approach for gastric stump cancer, which can arise at the anastomotic site in patients who have undergone previous partial gastrectomy for benign diseases such as gastric ulcer. Such surgery was quite common before the introduction of proton pump inhibitors (PPIs), and so today, according to different statistics, gastric stump cancer can be revealed in up to 8% of these patients. This report seeks to highlight the possibility of employing a minimally invasive approach in patients who already had an operation for gastric resection. The video shows technical notes about the hybrid laparoscopic-robotic approach performed in a patient who previously underwent open distal gastrectomy. Is the previous laparotomy an absolute or relative counterindication to reperform a surgery through a minimally invasive approach

A global gene evolution analysis on Vibrionaceae family using phylogenetic profile

<p>Abstract</p> <p>Background</p> <p><it>Vibrionaceae </it>represent a significant portion of the cultivable heterotrophic sea bacteria; they strongly affect nutrient cycling and some species are devastating pathogens.</p> <p>In this work we propose an improved phylogenetic profile analysis on 14 <it>Vibrionaceae </it>genomes, to study the evolution of this family on the basis of gene content.</p> <p>The phylogenetic profile is based on the observation that genes involved in the same process (e.g. metabolic pathway or structural complex) tend to be concurrently present or absent within different genomes. This allows the prediction of hypothetical functions on the basis of a shared phylogenetic profiles. Moreover this approach is useful to identify putative laterally transferred elements on the basis of their presence on distantly phylogenetically related bacteria.</p> <p>Results</p> <p><it>Vibrionaceae </it>ORFs were aligned against all the available bacterial proteomes. Phylogenetic profile is defined as an array of distances, based on aminoacid substitution matrixes, from single genes to all their orthologues. Final phylogenetic profiles, derived from non-redundant list of all ORFs, was defined as the median of all the profiles belonging to the cluster. The resulting phylogenetic profiles matrix contains gene clusters on the rows and organisms on the columns.</p> <p>Cluster analysis identified groups of "core genes" with a widespread high similarity across all the organisms and several clusters that contain genes homologous only to a limited set of organisms. On each of these clusters, COG class enrichment has been calculated. The analysis reveals that clusters of core genes have the highest number of enriched classes, while the others are enriched just for few of them like DNA replication, recombination and repair.</p> <p>Conclusion</p> <p>We found that mobile elements have heterogeneous profiles not only across the entire set of organisms, but also within <it>Vibrionaceae</it>; this confirms their great influence on bacteria evolution even inside the same family. Furthermore, several hypothetical proteins highly correlate with mobile elements profiles suggesting a possible horizontal transfer mechanism for the evolution of these genes. Finally, we suggested the putative role of some ORFs having an unknown function on the basis of their phylogenetic profile similarity to well characterized genes.</p

Combining ontologies and workflows to design formal protocols for biological laboratories

Background Laboratory protocols in life sciences tend to be written in natural language, with negative consequences on repeatability, distribution and automation of scientific experiments. Formalization of knowledge is becoming popular in science. In the case of laboratory protocols two levels of formalization are needed: one for the entities and individuals operations involved in protocols and another one for the procedures, which can be manually or automatically executed. This study aims to combine ontologies and workflows for protocol formalization. Results A laboratory domain specific ontology and the COW (Combining Ontologies with Workflows) software tool were developed to formalize workflows built on ontologies. A method was specifically set up to support the design of structured protocols for biological laboratory experiments. The workflows were enhanced with ontological concepts taken from the developed domain specific ontology. The experimental protocols represented as workflows are saved in two linked files using two standard interchange languages (i.e. XPDL for workflows and OWL for ontologies). A distribution package of COW including installation procedure, ontology and workflow examples, is freely available from http://www.bmr-genomics.it/farm/cow webcite. Conclusions Using COW, a laboratory protocol may be directly defined by wet-lab scientists without writing code, which will keep the resulting protocol's specifications clear and easy to read and maintain

PABS: An online platform to assist BAC-by-BAC sequencing projects

Genome sequencing projects are either based on whole genome shotgun (WGS) or on a BAC-by-BAC strategy. Although WGS is in most cases the preferred choice, sometimes the BAC-by-BAC approach may be better because it requires a much simpler assembly process. Furthermore, when the study is limited to specific regions of the genome, the WGS would require an unjustified effort, making the BAC-by-BAC the only feasible strategy. In this paper we describe an informatics pipeline called PABS (Platform Assisted BAC-by-BAC Sequencing) that we developed to provide a tool to optimize the BAC-by-BAC sequencing strategy. PABS has two main functions: (i) PABS-Select, to choose suitable overlapping clones; and (ii) PABS-Validate, to verify whether a BAC under analysis is actually overlapping the neighboring BAC