Current review of genetically modified lactic acid bacteria for the prevention and treatment of colitis using murine models

Inflammatory Bowel Diseases (IBD) are disorders of the gastrointestinal tract characterized by recurrent inflammation that requires lifelong treatments. Probiotic microorganisms appear as an alternative for these patients; however, probiotic characteristics are strain dependent and each probiotic needs to be tested to understand the underlining mechanisms involved in their beneficial properties. Genetic modification of lactic acid bacteria (LAB) was also described as a tool for new IBD treatments.The first part of this review shows different genetically modified LAB (GM-LAB) described for IBD treatment since 2000.Then, the two principally studied strategies are discussed (i) GM-LAB producing antioxidant enzymes and (ii) GM-LAB producing the anti-inflammatory cytokine IL-10. Different delivery systems, including protein delivery and DNA delivery, will also be discussed. Studies show the efficacy of GM-LAB (using different expression systems) for the prevention and treatment of IBD, highlighting the importance of the bacterial strain selection (with anti-inflammatory innate properties) as a promising alternative. These microorganisms could be used in the near future for the development of therapeutic products with anti-inflammatory properties that can improve the quality of life of IBD patients.Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Chatel, Jean Marc. Institut National de la Recherche Agronomique; FranciaFil: Miyoshi, Anderson. Universidade Federal do Minas Gerais; BrasilFil: Azevedo, Vasco. Universidade Federal do Minas Gerais; BrasilFil: Langella, Philippe. Institut National de la Recherche Agronomique; FranciaFil: Bermudez Humaran, Luis G.. Institut National de la Recherche Agronomique; FranciaFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

A Review of Lenalidomide in Combination with Dexamethasone for the Treatment of Multiple Myeloma

Lenalidomide (also known as Revlimid®, CC-5013) is an immunomodulatory derivative of thalidomide and has more potent anti-tumor and anti-inflammatory effects than thalidomide. The molecular mechanisms of anti-tumor activity of lenalidomide have been extensively studied in multiple myeloma (MM) both preclinical models and in clinical trials. Lenalidomide: directly triggers growth arrest and/or apoptosis of drug resistant MM cells; inhibits binding of MM cells to bone marrow (BM) extracellular matrix proteins and stromal cells; modulates cytokine secretion and inhibits angiogenesis in the BM milieu; and augments host anti-tumor immunity. Lenalidomide achieved responses in patients with relapsed refractory MM. Moreover, lenalidomide with dexamethasone (Dex) demonstrates more potent anti-MM activities than Dex both in vitro and in randomized phase III clinical trials. Specifically, the combination improved overall and extent of response, as well as prolonged time to progression and overall survival, resulting in FDA approval of lenalidomide with Dex for therapy MM relapsing after prior therapy

Synthesis and reactivity of olefin metathesis catalysts bearing cyclic (alkyl) (amino) carbenes

All it's CAACed up to be! Cyclic (alkyl)(amino)carbenes (CAACs) can be used as ligands for olefin metathesis catalysis. A dramatic steric effect of the N-aryl group of the CAAC on catalyst activity was observed and utilized to develop a new catalyst with activity comparable to standard commercially available catalysts

Parallel Batch-Dynamic Trees via Change Propagation

The dynamic trees problem is to maintain a forest subject to edge insertions and deletions while facilitating queries such as connectivity, path weights, and subtree weights. Dynamic trees are a fundamental building block of a large number of graph algorithms. Although traditionally studied in the single-update setting, dynamic algorithms capable of supporting batches of updates are increasingly relevant today due to the emergence of rapidly evolving dynamic datasets. Since processing updates on a single processor is often unrealistic for large batches of updates, designing parallel batch-dynamic algorithms that achieve provably low span is important for many applications. In this work, we design the first work-efficient parallel batch-dynamic algorithm for dynamic trees that is capable of supporting both path queries and subtree queries, as well as a variety of nonlocal queries. Previous work-efficient dynamic trees of Tseng et al. were only capable of handling subtree queries [ALENEX\u2719, (2019), pp. 92 - 106]. To achieve this, we propose a framework for algorithmically dynamizing static round-synchronous algorithms to obtain parallel batch-dynamic algorithms. In our framework, the algorithm designer can apply the technique to any suitably defined static algorithm. We then obtain theoretical guarantees for algorithms in our framework by defining the notion of a computation distance between two executions of the underlying algorithm. Our dynamic trees algorithm is obtained by applying our dynamization framework to the parallel tree contraction algorithm of Miller and Reif [FOCS\u2785, (1985), pp. 478 - 489], and then performing a novel analysis of the computation distance of this algorithm under batch updates. We show that k updates can be performed in O(klog(1+n/k)) work in expectation, which matches the algorithm of Tseng et al. while providing support for a substantially larger number of queries and applications

Integrating Incident Reporting into an Electronic Patient Record System

Developments in information technology offer new opportunities to design electronic patient record systems (EPR) which integrate a broad range of functions such as clinical decision support, order entry, or electronic alerts. It has been recently suggested that EPR could support new applications for disease surveillance and patient safety. We describe the integration of a voluntary incident reporting system into an EPR used in operating theatres, to allow the reporting of accidents and preventable complications. We assessed system's reliability and users' acceptance. During the 4-years observation period (2002-2006), 48,983 interventional procedures were performed. Clinicians documented 85.1% of procedures on the incident reporting form. Agreement between chart review and electronically reported incidents was 80.6%. The integration of an incident reporting system into an EPR is reliable and well supported by health care professional

WESTT (Workload, Error, Situational Awareness, Time and Teamwork): An analytical prototyping system for command and control

Modern developments in the use of information technology within command and control allow unprecedented scope for flexibility in the way teams deal with tasks. These developments, together with the increased recognition of the importance of knowledge management within teams present difficulties for the analyst in terms of evaluating the impacts of changes to task composition or team membership. In this paper an approach to this problem is presented that represents team behaviour in terms of three linked networks (representing task, social network structure and knowledge) within the integrative WESTT software tool. In addition, by automating analyses of workload and error based on the same data that generate the networks, WESTT allows the user to engage in the process of rapid and iterative “analytical prototyping”. For purposes of illustration an example of the use of this technique with regard to a simple tactical vignette is presented

Kinetic Selectivity of Olefin Metathesis Catalysts Bearing Cyclic (Alkyl)(Amino)Carbenes

The evaluation of ruthenium olefin metathesis catalysts 4–6 bearing cyclic (alkyl)(amino)carbenes (CAACs) in the cross-metathesis of cis-1,4-diacetoxy-2-butene (7) with allylbenzene (8) and the ethenolysis of methyl oleate (11) is reported. Relative to most NHC-substituted complexes, CAAC-substituted catalysts exhibit lower E/Z ratios (3:1 at 70% conversion) in the cross-metathesis of 7 and 8. Additionally, complexes 4–6 demonstrate good selectivity for the formation of terminal olefins versus internal olefins in the ethenolysis of 11. Indeed, complex 6 achieved 35 000 TONs, the highest recorded to date. CAAC-substituted complexes exhibit markedly different kinetic selectivity than most NHC-substituted complexes

Engineering and ethical perspectives in synthetic biology: Rigorous, robust and predictable designs, public engagement and a modern ethical framework are vital to the continued success of synthetic biology

The applications of synthetic biology will involve the release of artificial life forms into the environment. These organisms will present unique safety challenges that need to be addressed by researchers and regulators to win public engagement and support