Effects of serial position of relevant cue in the rehearsal order and method of encoding on attention in a single cue concept identification task

Five groups of Ss were forced to encode briefly exposed stimuli in a prescribed order and to classify the stimulus as a negative or a positive instance of the concept. For the first four groups, trials to criterion were found to be a function of the ordinal position of the relevant cue in the encoding order. These groups were forced to encode in an ungrammatical order. The fifth group employed a grammatical order of encoding and the position of the relevant cue was randomly assigned to an S. The fifth group was found to be superior to the other four groups as measured by trials to criterion

Choosing the right databases and search techniques

This is the author accepted manuscript. The final version is available from Facet Publishing via the DOI in this recordIn this chapter we will explore how to choose resources and techniques to provide the best returns. Systematic searching is most often associated with systematic reviews in health care. However, systematic searching is also a key element of scoping reviews, systematic maps and realist reviews and the issues we describe here will certainly be useful when undertaking literature searching in any subject field including health, education and environment. By the end you will have confidence in how to plan for your search, how to select the best sources to search, and the best way to utilize those resources to maximize returns without increasing time pressures or workload. [...

Cost-effectiveness considerations in finding appropriate chemotherapy treatments for bacterial diseases in developing countries: The case of tuberculosis.

Infectious bacterial diseases in developing countries represent a major health threat. Living conditions and environment decrease health status such that those in developing countries are left vulnerable to many diseases that are seldom seen in industrialised countries. Many treatments for these diseases have proven very effective, making infectious bacterial disease one of the best targets for high yield, low cost health interventions. Antibiotics remain the primary approach in treating infectious bacterial disease, yet mismanagement in their use has led to unnecessary resistance making many major diseases difficult to treat. Additionally, poor antibiotic choices for treating diseases have further contributed to unnecessary resistance. The appropriate choice for treating diseases is not always made and many diseases continue to be treated with inappropriate drugs or combinations of drugs. Many treatments are chosen on the basis of their easy availability or their small cost, when in fact other treatments could be obtained that have a more substantial impact on decreasing the incidence of a given disease. This is especially true in the treatment of tuberculosis. Tuberculosis, once thought to have been almost eradicated, has been revived by the growth of HTV. TB still claims a substantial proportion of human lives and will be responsible for 30 million deaths in this decade alone. Of particular relevance is the rising incidence of drug resistant cases of TB, which is primarily due to inappropriate antibiotic use. Although some past research has acknowledged the influence of resistance on the cost of TB treatment in developing countries, few studies have thoroughly analysed this relationship. This thesis presents a comprehensive study of the impact of drug resistance on the cost of TB treatment within the context of a cost-effectiveness analysis comparing short-course chemotherapy and the standard drug regimen in Ethiopia. In addition, the impact of HIV on TB treatment is analysed together with other factors, such as case holding, in order to assess their respective influence on the cost of treatment. Criteria for better management of tuberculosis control efforts in order to eradicate this disease and control resistance are subsequently explored. Finally, a discussion of the broader applicability of the conclusions of these studies to many developing countries is presented

Effectiveness of pharmacist home visits for individuals at risk of medication-related problems: A systematic review and meta-analysis of randomised controlled trials

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: Not applicable, as this research article reviewed the published literature. The data published may be found in the original manuscripts cited in the references list.Background: Medication mismanagement is a major cause of both hospital admission and nursing home placement of frail older adults. Medication reviews by community pharmacists aim to maximise therapeutic benefit but also minimise harm. Pharmacist-led medication reviews have been the focus of several systematic reviews, but none have focussed on the home setting. Review methods: To determine the effectiveness of pharmacist home visits for individuals at risk of medication-related problems we undertook a systematic review and meta-analysis of randomised controlled trials (RCTs). Thirteen databases were searched from inception to December 2018. Forward and backward citation of included studies was also performed. Articles were screened for inclusion independently by two reviewers. Randomised controlled studies of home visits by pharmacists for individuals at risk of medication-related problems were eligible for inclusion. Data extraction and quality appraisal were performed by one reviewer and checked by a second. Random-effects meta-analyses were performed where sufficient data allowed and narrative synthesis summarised all remaining data. Results: Twelve RCTs (reported in 15 articles), involving 3410 participants, were included in the review. The frequency, content and purpose of the home visit varied considerably. The data from eight trials were suitable for meta-analysis of the effects on hospital admissions and mortality, and from three trials for the effects on quality of life. Overall there was no evidence of reduction in hospital admissions (risk ratio (RR) of 1.01 (95%CI 0.86 to 1.20, I2 = 69.0%, p = 0.89; 8 studies, 2314 participants)), or mortality (RR of 1.01 (95%CI 0.81 to 1.26, I2 = 0%, p = 0.94; 8 studies, 2314 participants)). There was no consistent evidence of an effect on quality of life, medication adherence or knowledge. Conclusion: A systematic review of twelve RCTs assessing the impact of pharmacist home visits for individuals at risk of medication related problems found no evidence of effect on hospital admission or mortality rates, and limited evidence of effect on quality of life. Future studies should focus on using more robust methods to assess relevant outcomes.National Institute for Health Research (NIHR

The reaction mechanism of metallo-beta-lactamases is tuned by the conformation of an active site mobile loop

Carbapenems are "last resort" β-lactam antibiotics used to treat serious and life-threatening health care-associated infections caused by multidrug-resistant Gram-negative bacteria. Unfortunately, the worldwide spread of genes coding for carbapenemases among these bacteria is threatening these life-saving drugs. Metallo-β-lactamases (MβLs) are the largest family of carbapenemases. These are Zn(II)-dependent hydrolases that are active against almost all β-lactam antibiotics. Their catalytic mechanism and the features driving substrate specificity have been matter of intense debate. The active sites of MβLs are flanked by two loops, one of which, loop L3, was shown to adopt different conformations upon substrate or inhibitor binding, and thus are expected to play a role in substrate recognition. However, the sequence heterogeneity observed in this loop in different MβLs has limited the generalizations about its role. Here, we report the engineering of different loops within the scaffold of the clinically relevant carbapenemase NDM-1. We found that the loop sequence dictates its conformation in the unbound form of the enzyme, eliciting different degrees of active-site exposure. However, these structural changes have a minor impact on the substrate profile. Instead, we report that the loop conformation determines the protonation rate of key reaction intermediates accumulated during the hydrolysis of different β-lactams in all MβLs. This study demonstrates the existence of a direct link between the conformation of this loop and the mechanistic features of the enzyme, bringing to light an unexplored function of active-site loops on MβLs.Fil: Palacios, Antonela Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Mojica, María F.. Case Western Reserve University; Estados UnidosFil: Giannini, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Taracila, Magdalena A.. Case Western Reserve University; Estados Unidos. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: Bethel, Christopher R.. Louis Stokes Veterans Affairs Medical Center; Estados UnidosFil: Alzari, Pedro M.. Institut Pasteur de Paris; FranciaFil: Otero, Lisandro Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Bonomo, Robert A.. Case Western Reserve University; Estados UnidosFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

The Chernobyl Tissue Bank - A Repository for Biomaterial and Data Used in Integrative and Systems Biology Modeling the Human Response to Radiation

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer post Chernobyl, the Chernobyl Tissue Bank (CTB: www.chernobyltissuebank.com) was established in 1998. Thus far it is has collected biological samples from 3,861 individuals, and provided 27 research projects with 11,254 samples. The CTB was designed from its outset as a resource to promote the integration of research and clinical data to facilitate a systems biology approach to radiation related thyroid cancer. The project has therefore developed as a multidisciplinary collaboration between clinicians, dosimetrists, molecular biologists and bioinformaticians and serves as a paradigm for tissue banking in the omics era

The Effects of Myelin on Macrophage Activation Are Phenotypic Specific via cPLA\u3csub\u3e2\u3c/sub\u3e in the Context of Spinal Cord Injury Inflammation

Spinal cord injury (SCI) produces chronic, pro-inflammatory macrophage activation that impairs recovery. The mechanisms driving this chronic inflammation are not well understood. Here, we detail the effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA2) in myelin-mediated potentiation of pro-inflammatory macrophage activation. We hypothesized that cPLA2 and myelin debris are key mediators of persistent pro-inflammatory macrophage responses after SCI. To test this, we examined spinal cord tissue 28-days after thoracic contusion SCI in 3-month-old female mice and observed both cPLA2 activation and intracellular accumulation of lipid-rich myelin debris in macrophages. In vitro, we utilized bone marrow-derived macrophages to determine myelin’s effects across a spectrum of activation states. We observed phenotype-specific responses with myelin potentiating only pro-inflammatory (LPS + INF-γ; M1) macrophage activation, whereas myelin did not induce pro-inflammatory responses in unstimulated or anti-inflammatory (IL-4; M2) macrophages. Specifically, myelin increased levels of pro-inflammatory cytokines, reactive oxygen species, and nitric oxide production in M1 macrophages as well as M1-mediated neurotoxicity. PACOCF3 (cPLA2 inhibitor) blocked myelin’s detrimental effects. Collectively, we provide novel spatiotemporal evidence that myelin and cPLA2 play an important role in the pathophysiology of SCI inflammation and the phenotype-specific response to myelin implicate diverse roles of myelin in neuroinflammatory conditions