Antimicrobial prophylaxis in colorectal surgery: focus on ertapenem

Despite improvement in infection control measures and surgical practice, surgical site infections (SSIs) remain a major cause of morbidity and mortality. In colorectal surgery, perioperative administration of a suitable antimicrobial regimen that covers both anaerobic and aerobic bacteria is universally accepted. In a prospective, double-blind, randomized study ertapenem was recently found to be more effective than cefotetan, a parenteral cephalosporin so broadly used as to be considered as gold standard in the prevention of SSIs following colorectal surgery. In this adequate and well controlled study, the superiority of ertapenem over cefotetan was clearly demonstrated from the clinical and bacteriological points of view. However, data that directly compares ertapenem with other antimicrobial regimen effective in preventing SSIs following colorectal surgery are lacking; furthermore, the possible risk of promotion of carbapenem resistance associated with widespread use of ertapenem prophylaxis as well as the ertapenem effects on the intestinal gut flora are of concern. Further comparative studies of ertapenem versus other widely used prophylactic regimens for colorectal surgery in patients submitted to mechanical bowel preparation versus no preparation as well as further research on adverse events of antibiotic prophylaxis, including emergence of resistance and Clostridium difficile infection, seem warranted

Invariant natural killer T cells reconstitution and the control of leukemia relapse in pediatric haploidentical hematopoietic stem cell transplantation

CD1d-restricted invariant (i)NKT cells are innate-like, lipid-reactive T lymphocytes implicated in the control of infections, cancer and autoimmunity. Our study suggests that the reconstitution of the peripheral iNKT cell compartment, following HLA-haploidentical hematopoietic stem cell transplantation, associates with leukemia control in children affected by different hematological malignancies

Similarity in metaheuristics:a gentle step towards a comparison methodology

Metaheuristics are found to be efficient in different applications where the use of exact algorithms becomes short-handed. In the last decade, many of these algorithms have been introduced and used in a wide range of applications. Nevertheless, most of those approaches share similar components leading to a concern related to their novelty or contribution. Thus, in this paper, a pool template is proposed and used to categorize algorithm components permitting to analyze them in a structured way. We exemplify its use by means of continuous optimization metaheuristics, and provide some measures and methodology to identify their similarities and novelties. Finally, a discussion at a component level is provided in order to point out possible design differences and commonalities

Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells

The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor（GM-CSF）, monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway

Optimising discrete dynamic berth allocations in seaports using a Levy Flight based meta-heuristic

Seaports play a vital role in our everyday life: they handle 90% of our world trade goods. Improving seaports' efficiency means improving the efficiency of sending and receiving our goods. In seaports, one of the most important and most expensive operations is how to allocate vessels to berths. In this paper, we solve this problem by proposing a new meta-heuristic, which combines the nature-inspired Levy Flight random walk with local search, while taking into account tidal windows. With our algorithm, we meet the following goals: (i) to minimise the cost of all vessels while staying in the port, and (ii) to schedule available berths for the arriving vessels taking into account a multi-tidal planning horizon. In comparison with the state-of-the-art exact method using commercial solver and a competitive heuristic, the computational results prove our approach guarantees feasibility of solutions for all the problem instances and is able to find good solutions in a short amount of time, especially for large-scale instances. We also compare our results to an existing state-of-the-art Particle Swarm Optimisation and our work produces significantly better performances on all the test instances

A hybrid GRASP-VNS for Ship Routing and Scheduling Problem with Discretized Time Windows

This paper addresses the Ship Routing and Scheduling Problem with Discretized Time Windows. Being one of the most relevant and challenging problems faced by decision makers from shipping companies, this tramp shipping problem lies in determining the set of contracts that should be served by each ship and the time windows that ships should use to serve each contract, with the aim of minimizing total costs. The use of discretized time windows allows for the consideration of a broad variety of features and practical constraints in a simple way. In order to solve this problem we propose a hybridazation of a Greedy Randomized Adaptive Search Procedure and a Variable Neighborhood Search, which improves previous heuristics results found in literature and requires very short computational time. Moreover, this algorithm is able to achieve the optimal results for many instances, demonstrating its good performance

Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis

Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignant CD5(+) B lymphocytes in blood, bone marrow and lymphoid organs. CD1d-restricted invariant Natural Killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance. We investigated the impact of iNKT cells in the natural history of the disease both in Eμ;-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients. We found that Tcl1-CLL cells express CD1d and iNKT cells critically delay the disease onset, but become functionally impaired upon disease progression. In patients, disease progression correlates also with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative/low CD1d expression on CLL cells and normal iNKT cells, suggesting an indirect leukemia control. iNKT cells indeed hinder CLL survival in vitro by restraining CD1d-expressing Nurse Like Cells, a relevant pro-leukemia macrophage population. Finally, multivariate analysis identifies iNKT cell frequency as independent predictor of disease progression. Together, these results support iNKT cell contribution to CLL immune-surveillance and highlight iNKT cell frequency as prognostic marker for disease progression

Neonatal invariant Va24+ NKT lymphocytes are activated memory cells.

NKT cells are a small subset of T lymphocytes which express an invariant V(alpha24JalphaQ TCR and recognize glycolipids presented by CD1d. In adults, NKT cells have a memory phenotype, frequently associated with oligoclonal expansion, express NK cell markers, and produce TO cytokines upon primary stimulation. Because of these features, NKT cells are regarded as lymphocytes of innate immunity. We investigated NKT cells from cord blood to see how these cells appear in the absence of exogenous stimuli. We found that NKT cells are present at comparable frequencies in cord blood and adult peripheral blood mononuclear cells and in both cases display a memory (CD45RO+CD62L-) phenotype. However, neonatal NKT cells differ from their adult counterparts by the following characteristics: (1) they express markers of activation, such as CD25; (2) they are polyclonal; (3) they do not produce cytokines in response to primary stimulation. Together, our data show that human NKT cells arise in the newborn with an activated memory phenotype, probably due to recognition of an endogenous ligand(s). The absence of oligoclonal expansion and primary effector functions also suggest that neonatal NKT cells, despite their activated memory phenotype, require a further priming/differentiation event to behave as fully functional cells of innate immunity

Efficacy of a Solution Composed by Verbascoside, Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate in the Treatment of Chemotherapy-induced Oral Mucositis in Children With Acute Lymphoblastic Leukemia

Summary: The aim of this study was to assess the efficacy of a solution composed by verbascoside, polyvinylpyrrolidone, and sodium hyaluronate (Mucosyte) in the treatment of chemotherapy- induced oral mucositi (OM). Patients between 5 and 18 years receiving chemotherapy for acute lymphoblastic leukemia and with OM grade 1 or 2 were randomized in group A (treated with Mucosyte, 3 mouthwashes/d per 8d) and group B (treated with placebo, ie, an inert water-based solution, 3 mouthwashes/d per 8 d). The OM scoring was performed at day 1 (diagnosis of OM- T0), after 3 days of treatment (T1), and at day 8 (T2). Pain was evaluated through the visual analog scale with the same timing of OM measurement. A total of 56 patients were included (28 patients per group). Group A experienced a statistically significant decline of OM at T2 (P=0.0038); a statistically significant difference in pain reduction between 2 groups both at T1 and at T2 (P < 0.005) was observed. The use of Mucosyte mouthwashes in children with chemotherapy-induced OM may be recommended as supportive therapy