Anion transport inhibitor binding to band 3 in red blood cell membranes.

The inhibitor of anion exchange 4,4'-dibenzoamido-2,2'-disulfonic stilbene (DBDS) binds to band 3, the anion transport protein in human red cell ghost membranes, and undergoes a large increase in fluorescence intensity when bound to band 3. Equilibrium binding studies performed in the absence of transportable anions show that DBDS binds to both a class of high-affinity (65 nM) and low-affinity (820 nM) sites with stoichiometry equivalent to 1.6 nmol/mg ghost protein for each site, which is consistent with one DBDS site on each band 3 monomer. The kinetics of DBDS binding were studied both by stopped-flow and temperature-jump experiments. The stopped-flow data indicate that DBDS binding to the apparent high-affinity site involves association with a low-affinity site (3 microM) followed by a slow (4 s-1) conformational change that locks the DBDS molecule in place. A detailed, quantitative fit of the temperature-jump data to several binding mechanisms supports a sequential-binding model, in which a first DBDS molecule binds to one monomer and induces a conformational change. A second DBDS molecule then binds to the second monomer. If the two monomers are assumed to be initially identical, thermodynamic characterization of the binding sites shows that the conformational change induces an interaction between the two monomers that modifies the characteristics of the second DBDS binding site

Patologia Psiquiátrica nos Cuidados Primários de Saúde

É consensual a alta prevalência de patologia psiquiátrica ao nível dos Cuidados Primários Saúde. Consensual será também o papel fulcral que estes mesmos Cuidados desempenham enquanto primeiro filtro na abordagem dos problemas psiquiátricos, reconhecendo-se que, frequentemente, o Clínico Geral é o agente melhor posicionado para uma correcta abordagem diagnóstica e terapêutica deste tipo de problemas. Assume-se assim como necessidade objectiva que o Clínico Geral tome a seu cargo a maioria destes doentes e proceda à referenciação criteriosa duma minoria verdadeiramente necessitada de cuidados mais especializados. Em termos práticos, configura-se como prioritária uma progressiva melhoria da capacidade de actuação dos Clínicos Gerais, na área da Saúde Mental. É portanto neste contexto que surge a importância da articulação dos Serviços de Psiquiatria com os Centros de Saúde e a relevância do trabalho Consiliar e de Ligação do Psiquiatra junto dos Clínicos Gerais. No presente artigo os autores tecem algumas considerações e lançam diversas questões sobre o tema em apreço, procurando abordar determinados aspectos centrais, nomeadamente, as particularidades de apresentação da patologia psiquiátrica nos Cuidados de Saúde Primários, em particular da “depressão”, e decorrendo deste facto, as dificuldades na avaliação e abordagem das perturbações mentais neste setting particular

Evaluation of the Coverage of 3 Antibiotic Regimens for Neonatal Sepsis in the Hospital Setting Across Asian Countries.

Importance: High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens. Objective: To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries. Design, Setting, and Participants: A decision analytical model was used to estimate coverage of 3 prespecified antibiotic regimens according to a weighted-incidence syndromic combination antibiogram. Relevant data to parameterize the models were identified from a systematic search of Ovid MEDLINE and Embase. Data from Asian countries published from 2014 onward were of interest. Only data on blood culture isolates from neonates with sepsis, bloodstream infection, or bacteremia reported from the relevant setting were included. Data analysis was performed from April 2019 to July 2019. Exposures: The prespecified regimens of interest were aminopenicillin-gentamicin, third-generation cephalosporins (cefotaxime or ceftriaxone), and meropenem. The relative incidence of different bacteria and their antimicrobial susceptibility to antibiotics relevant for determining expected concordance with these regimens were extracted. Main Outcomes and Measures: Coverage was calculated on the basis of a decision-tree model incorporating relative bacterial incidence and antimicrobial susceptibility of relevant isolates. Data on 7 bacteria most commonly reported in the included studies were used for estimating coverage, which was reported at the country level. Results: Data from 48 studies reporting on 10 countries and 8376 isolates were used. Individual countries reported 51 (Vietnam) to 6284 (India) isolates. Coverage varied considerably between countries. Meropenem was generally estimated to provide the highest coverage, ranging from 64.0% (95% credible interval [CrI], 62.6%-65.4%) in India to 90.6% (95% CrI, 86.2%-94.4%) in Cambodia, followed by aminopenicillin-gentamicin (from 35.9% [95% CrI, 27.7%-44.0%] in Indonesia to 81.0% [95% CrI, 71.1%-89.7%] in Laos) and cefotaxime or ceftriaxone (from 17.9% [95% CrI, 11.7%-24.7%] in Indonesia to 75.0% [95% CrI, 64.8%-84.1%] in Laos). Aminopenicillin-gentamicin coverage was lower than that of meropenem in all countries except Laos (81.0%; 95% CrI, 71.1%-89.7%) and Nepal (74.3%; 95% CrI, 70.3%-78.2%), where 95% CrIs for aminopenicillin-gentamicin and meropenem were overlapping. Third-generation cephalosporin coverage was lowest of the 3 regimens in all countries. The coverage difference between aminopenicillin-gentamicin and meropenem for countries with nonoverlapping 95% CrIs ranged from -15.9% in China to -52.9% in Indonesia. Conclusions and Relevance: This study's findings suggest that noncarbapenem antibiotic regimens may provide limited coverage for empirical treatment of neonatal sepsis in many Asian countries. Alternative regimens must be studied to limit carbapenem consumption

Delivering manufacturing technology and workshop appreciation to engineering undergraduates using the flipped classroom approach

Delivery of manufacturing technology and practical workshop-based work, on undergraduate engineering courses that engage the learners, is challenging. The paper presents an experimental method of workshop delivery using the flipped learning approach, a pedagogical model in which the typical lecture and homework elements of a course are reversed. Video lectures are viewed by students prior to class. In-class time can be devoted to exercises, projects, or discussions as in this case. Learners were asked to observe three audiovisual clips in preparation for class. The objective was to determine whether the flipped classroom approach can enhance the learning experience, through better engagement with the students, compared to conventional classroom-based learning. The level of student participation and level of success have been established by means of feedback questionnaires from more than 100 participants and peer observation. The results are encouraging and demonstrate that this approach is favoured by the students

Vaccinations with live-attenuated Leishmania major promastigotes and challenge infection with L. major in balb/c mice

Background: Currently there is no vaccine available in use against any form of leishmaniases worldwide. Objective: To assess potential of a live-attenuated Leishmania major promastigates, for protection against a challenge infection with L. major in BALB/c mice. Design. A laboratory based study. Setting: Study was carried out at Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi. Results. The greatest protection against challenge with L. major was seen in mice immunised with live parasites (

Anatomy, morphology and evolution of the patella in squamate lizards and tuatara (Sphenodon punctatus)

The patella (kneecap) is the largest and best-known of the sesamoid bones, postulated to confer biomechanical advantages including increasing joint leverage and reinforcing the tendon against compression. It has evolved several times independently in amniotes, but despite apparently widespread occurrence in lizards, the patella remains poorly characterised in this group and is, as yet, completely undescribed in their nearest extant relative Sphenodon (Rhynchocephalia). Through radiography, osteological and fossil studies we examined patellar presence in diverse lizard and lepidosauromorph taxa, and using computed tomography, dissection and histology we investigated in greater depth the anatomy and morphology of the patella in 16 lizard species and 19 Sphenodon specimens. We have found the first unambiguous evidence of a mineralised patella in Sphenodon, which appears similar to the patella of lizards and shares several gross and microscopic anatomical features. Although there may be a common mature morphology, the squamate patella exhibits a great deal of variability in development (whether from a cartilage anlage or not, and in the number of mineralised centres) and composition (bone, mineralised cartilage or fibrotendinous tissue). Unlike in mammals and birds, the patella in certain lizards and Sphenodon appears to be a polymorphic trait. We have also explored the evolution of the patella through ancestral state reconstruction, finding that the patella is ancestral for lizards and possibly Lepidosauria as a whole. Clear evidence of the patella in rhynchocephalian or stem lepidosaurian fossil taxa would clarify the evolutionary origin(s) of the patella, but due to the small size of this bone and the opportunity for degradation or loss we could not definitively conclude presence or absence in the fossils examined. The pattern of evolution in lepidosaurs is unclear but our data suggest that the emergence of this sesamoid may be related to the evolution of secondary ossification centres and/or changes in knee joint conformation, where enhancement of extensor muscle leverage would be more beneficial.Sophie Regnault, Marc E. H. Jones, Andrew A. Pitsillides, John R. Hutchinso

Information Security as Strategic (In)effectivity

Security of information flow is commonly understood as preventing any information leakage, regardless of how grave or harmless consequences the leakage can have. In this work, we suggest that information security is not a goal in itself, but rather a means of preventing potential attackers from compromising the correct behavior of the system. To formalize this, we first show how two information flows can be compared by looking at the adversary's ability to harm the system. Then, we propose that the information flow in a system is effectively information-secure if it does not allow for more harm than its idealized variant based on the classical notion of noninterference

Evolution of magnetic fields through cosmological perturbation theory

The origin of galactic and extra-galactic magnetic fields is an unsolved problem in modern cosmology. A possible scenario comes from the idea of these fields emerged from a small field, a seed, which was produced in the early universe (phase transitions, inflation, ...) and it evolves in time. Cosmological perturbation theory offers a natural way to study the evolution of primordial magnetic fields. The dynamics for this field in the cosmological context is described by a cosmic dynamo like equation, through the dynamo term. In this paper we get the perturbed Maxwell's equations and compute the energy momentum tensor to second order in perturbation theory in terms of gauge invariant quantities. Two possible scenarios are discussed, first we consider a FLRW background without magnetic field and we study the perturbation theory introducing the magnetic field as a perturbation. The second scenario, we consider a magnetized FLRW and build up the perturbation theory from this background. We compare the cosmological dynamo like equation in both scenarios

The knowledge and skills required of advanced level practitioners for accreditation and safe practice

Change, for better or worse, seems to be endemic in western societies, and in the past two decades advanced practice has not been exempt. Healthcare leaders and lecturers in the UK have adapted education programmes that are preparing for increasing numbers of health professionals to take on advanced clinical practice roles that meet policy and practice developments emerging from population need and government-influenced changes. Such change has included advanced practice policy from Health Education England (HEE) regarding funding for advanced level students, and the introduction of the advanced clinical practitioner (ACP) title. This article focuses on advanced practice/ACP education