Safety profile of L-arginine infusion in moderately severe falciparum malaria.

BACKGROUND: L-arginine infusion improves endothelial function in malaria but its safety profile has not been described in detail. We assessed clinical symptoms, hemodynamic status and biochemical parameters before and after a single L-arginine infusion in adults with moderately severe malaria. METHODOLOGY AND FINDINGS: In an ascending dose study, adjunctive intravenous L-arginine hydrochloride was infused over 30 minutes in doses of 3 g, 6 g and 12 g to three separate groups of 10 adults hospitalized with moderately severe Plasmodium falciparum malaria in addition to standard quinine therapy. Symptoms, vital signs and selected biochemical measurements were assessed before, during, and for 24 hours after infusion. No new or worsening symptoms developed apart from mild discomfort at the intravenous cannula site in two patients. There was a dose-response relationship between increasing mg/kg dose and the maximum decrease in systolic (rho = 0.463; Spearman's, p = 0.02) and diastolic blood pressure (r = 0.42; Pearson's, p = 0.02), and with the maximum increment in blood potassium (r = 0.70, p<0.001) and maximum decrement in bicarbonate concentrations (r = 0.53, p = 0.003) and pH (r = 0.48, p = 0.007). At the highest dose (12 g), changes in blood pressure and electrolytes were not clinically significant, with a mean maximum decrease in mean arterial blood pressure of 6 mmHg (range: 0-11; p<0.001), mean maximal increase in potassium of 0.5 mmol/L (range 0.2-0.7 mmol/L; p<0.001), and mean maximal decrease in bicarbonate of 3 mEq/L (range 1-7; p<0.01) without a significant change in pH. There was no significant dose-response relationship with blood phosphate, lactate, anion gap and glucose concentrations. All patients had an uncomplicated clinical recovery. CONCLUSIONS/SIGNIFICANCE: Infusion of up to 12 g of intravenous L-arginine hydrochloride over 30 minutes is well tolerated in adults with moderately severe malaria, with no clinically important changes in hemodynamic or biochemical status. Trials of adjunctive L-arginine can be extended to phase 2 studies in severe malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00147368.

Una revisión de la Cadena Datos-Información-Conocimiento desde el Pragmatismo de Peirce

La Cadena Datos-Información-Conocimiento (DIC), denominada “Jerarquía de la Información” o “Pirámide del Conocimiento”, es uno de los modelos más importantes en la Gestión de la Información y la Gestión del Conocimiento. Por lo general, la estructuración de la cadena se ha ido definiendo como una arquitectura en la que cada elemento se levanta sobre el elemento inmediatamente inferior; sin embargo no existe un consenso en la definición de los elementos, ni acerca de los procesos que transforman un elemento de un nivel a uno del siguiente nivel. En este artículo se realiza una revisión de la Cadena Datos-Información-Conocimiento examinando las definiciones más relevantes sobre sus elementos y sobre su articulación en la literatura, para sintetizar las acepciones más comunes. Se analizan los elementos de la Cadena DIC desde la semiótica de Peirce; enfoque que nos permite aclarar los significados e identificar las diferencias, las relaciones y los roles que desempeñan en la cadena desde el punto de vista del pragmatismo. Finalmente se propone una definición de la Cadena DIC apoyada en las categorías triádicas de signos y la semiosis ilimitada de Peirce, los niveles de sistemas de signos de Stamper y las metáforas de Zeleny.

Persistent measles virus infection of mouse neural cells lacking known human entry receptors

Aims: Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry.

Methods: To examine this hypothesis, virus antigen and caspase 3 expression (for apoptosis) was compared in primary mixed, neural cell cultures infected in vitro or prepared from mice infected intracerebrally with WT, vaccine or rodent neuroadapted viruses. Viral RNA levels were examined in mouse brain by nested and real-time reverse transcriptase polymerase chain reaction.

Results: WT and vaccine strains were demonstrated for the first time to infect murine oligodendrocytes in addition to neurones despite a lack of the known MV cell receptors. Unexpectedly, the percentage of cells positive for viral antigen was higher for WT MV than neuroadapted virus in both in vitro and ex vivo cultures. In the latter the percentage of positive cells increased with time after mouse infection. Viral RNA (total and mRNA) was detected in brain for up to 20 days, while cultures were negative for caspase 3 in WT and vaccine virus infections.

Conclusions: WT and vaccine MV strains can use an endogenous cell entry receptor(s) or alternative virus uptake mechanism in murine neural cells. However, viral replication occurs at a low level and is associated with limited apoptosis. WT MV mouse infection may provide a model for the initial stages of persistent MV human central nervous system infections.

Optimizing antibiotics in residents of nursing homes:protocol of a randomized trial.

BACKGROUND: Antibiotics are frequently prescribed for older adults who reside in long-term care facilities. A substantial proportion of antibiotic use in this setting is inappropriate. Antibiotics are often prescribed for asymptomatic bacteriuria, a condition for which randomized trials of antibiotic therapy indicate no benefit and in fact harm. This proposal describes a randomized trial of diagnostic and therapeutic algorithms to reduce the use of antibiotics in residents of long-term care facilities. METHODS: In this on-going study, 22 nursing homes have been randomized to either use of algorithms (11 nursing homes) or to usual practise (11 nursing homes). The algorithms describe signs and symptoms for which it would be appropriate to send urine cultures or to prescribe antibiotics. The algorithms are introduced by inservicing nursing staff and by conducting one-on-one sessions for physicians using case-scenarios. The primary outcome of the study is courses of antibiotics per 1000 resident days. Secondary outcomes include urine cultures sent and antibiotic courses for urinary indications. Focus groups and semi-structured interviews with key informants will be used to assess the process of implementation and to identify key factors for sustainability.

Effect of sublingual application of cannabinoids on intraocular pressure:A pilot study

PURPOSE: The purpose of this study was to assess the effect on intraocular pressure (IOP) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol (?-9-THC) and cannabidiol (CBD). PATIENTS AND METHODS: A randomized, double-masked, placebo-controlled, 4 way crossover study was conducted at a single center, using cannabis-based medicinal extract of ?-9-THC and CBD. Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg ?-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic effects. RESULTS: Two hours after sublingual administration of 5 mg ?-9-THC, the IOP was significantly lower than after placebo (23.5 mm Hg vs. 27.3 mm Hg, P=0.026). The IOP returned to baseline level after the 4-hour IOP measurement. CBD administration did not reduce the IOP at any time. However, the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours after administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual acuity were not significantly changed. One patient experienced a transient and mild paniclike reaction after ?-9-THC administration. CONCLUSIONS: A single 5 mg sublingual dose of ?-9-THC reduced the IOP temporarily and was well tolerated by most patients. Sublingual administration of 20 mg CBD did not reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise. Copyright © 2006 by Lippincott Williams & Wilkins.

Fabricated or Induced Illness in Children: A Narrative Review of the Literature

Although child maltreatment due to abuse or neglect is pervasive within our society, less
is known about fabricated or induced illness by carers (FII), which is considered to be a
rare form of child abuse. FII occurs when a caregiver (in 93% of cases, the mother)
misrepresents the child as ill either by fabricating, or much more rarely, producing
symptoms and then presenting the child for medical care, disclaiming knowledge of the
cause of the problem. The growing body of literature on FII reflects the lack of clarity
amongst professionals as to what constitutes FII, the difficulties involved in diagnosis,
and the lack of research into psychotherapeutic intervention with perpetrators. This lack
of clarity further complicates the identification, management and treatment of children
suffering from FII and may result in many cases going undetected, with potentially lifethreatening
consequences for children. It has been suggested that there is a national
under-reporting of fabricated or induced illness. In practice these cases are encountered
more frequently due to the chronic nature of the presentations, the large number of
professionals who may be involved and the broad spectrum including milder cases that
may not all require a formal child protection response. Diagnosis of fabricated disease
can be especially difficult, because the reported signs and symptoms cannot be confirmed
(when they are being exaggerated or imagined) or may be inconsistent (when they are
induced or fabricated). This paper highlights and discusses the controversies and
complexities of this condition, the risks to the child and how it affects children; the
paucity of systematic research regarding what motivates mothers to harm their children
by means of illness falsification; how the condition should be managed and treated for
both mother and child; and implications for policy and practice.

Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children: An observational cohort study

Background: Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department.

Methods: For this observational cohort study of diagnostic accuracy, children aged 0-13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid).

Findings: Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72-96], specificity 100% [97-100], positive predictive value 100% [85-100]; negative predictive value 98% [93-99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13-infinity] and negative likelihood ratio 0·11 [0·04-0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min-1 h 32 min).

Interpretation: Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful.

Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: time for an eosinophil guided clinical trial?

Childhood wheezing is common particularly in children under the age of six years and in this age-group is generally referred to as preschool wheezing. Particular diagnostic and treatment uncertainties exist in these young children due to the difficulty in obtaining objective evidence of reversible airways narrowing and inflammation. A diagnosis of asthma depends on the presence of relevant clinical signs and symptoms and the demonstration of reversible airways narrowing on lung function testing, which is difficult to perform in young children. Few treatments are available and inhaled corticosteroids are the recommended preventer treatment in most international asthma guidelines. There is however considerable controversy about its effectiveness in children with preschool wheeze and a corticosteroid responder phenotype has not been established. These diagnostic and treatment uncertainties in conjunction with the knowledge of corticosteroid side-effects, in particular the reduction of growth velocity, has resulted in a variable approach to inhaled corticosteroid prescribing by medical practitioners and a reluctance in carers to regularly administer the treatment. Identifying children who are likely responders to corticosteroid therapy would be a major benefit in the management of this condition. Eosinophils have emerged as a promising biomarker of corticosteroid responsive airways disease and evaluation of this biomarker in sputum has successfully been employed to direct management in adults with asthma. Obtaining sputum from young children is time-consuming and difficult and it is hard to justify more invasive procedures such as a bronchoscopy in young children routinely. Recently, in children, interest has shifted to assessing the value of less invasive biomarkers of likely corticosteroid response and the biomarker 'blood eosinophils' has emerged as an attractive candidate. The aim of this review is to summarise the evidence for blood eosinophils as a predictive biomarker for corticosteroid responsive disease with a particular focus on the difficult area of preschool wheeze. 

An evaluation of the effectiveness of an algorithm intervention in reducing inappropriate faecal samples sent for Clostridium difficile testing.

Background: Clostridium difficile (C. difficile) is a leading cause of infectious diarrhoea in hospitals. Sending faecal samples for testing expedites diagnosis and appropriate treatment. Clinical suspicion of C. difficile based on patient history, signs and symptoms is the basis for sampling. Sending faecal samples from patients with diarrhoea ‘just in case’ the patient has C. difficile may be an indication of poor clinical management.

Aim: To evaluate the effectiveness of an intervention by an Infection Prevention and Control Team (IPCT) in reducing inappropriate faecal samples sent for C. difficile testing.

Method: An audit of numbers of faecal samples sent before and after a decision-making algorithm was introduced. The number of samples received in the laboratory was retrospectively counted for 12-week periods before and after an algorithm was introduced.
Findings: There was a statistically significant reduction in the mean number of faecal samples sent post the algorithm. Results were compared to a similar intervention carried out in 2009 in which the same message was delivered by a memorandum. In 2009 the memorandum had no effect on the overall number of weekly samples being sent.

Conclusion: An algorithm intervention had an effect on the number of faecal samples being sent for C. difficile testing and thus contributed to the effective use of the laboratory service.

Neurology assessment by objective structured video examination (OSVE)

Summary
Background
The ability to carry out a neurological examination and make an appropriate differential diagnosis is one of the mainstays of our final Bachelor of Medicine (MB) exam; however, with the introduction of objective structured clinical examinations (OSCEs) it has become impossible to arrange for adequate numbers of suitable real patients to participate in the exam.

Context
It is vital that newly qualified doctors can perform a basic neurological examination, interpret the physical signs and formulate a differential diagnosis.

It is vital that newly qualified doctors can perform a basic neurological examination

Innovation
Since 2010 we have introduced an objective structured video examination (OSVE) of a neurological examination of a real patient as part of our final MB OSCE exam. The students view clips of parts of the examination process. They answer questions on the signs that are demonstrated and formulate a differential diagnosis.

Implications
This type of station is logistically a lot easier to organise than a large number of real patients at different examination sites. The featured patients have clearly demonstrated signs and, as every student sees the same patient, are perfectly standardised. It is highly acceptable to examiners and performed well as an assessment tool. There are, however, certain drawbacks in that we are not examining the student's examination technique or their interaction with the patient. Also, certain signs, in particular the assessment of muscle tone and power, are more difficult for a student to estimate in this situation

Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Language anxiety in English teachers during their teaching practice

Este estudo explora a influência da ansiedade linguística em futuros professores de Inglês em situação de prática pedagógica. Setting the Scene descreve o aumento de interesse pela ansiedade linguística por parte dos investigadores no contexto da aprendizagem e do ensino, e a relevância desta questão para professores estagiários fazendo a transição de aluno para professor. O autor também considera a sua própria experiência de ansiedade – enquanto estudante e investigador – de modo a gerar um maior entendimento desta emoção complexa. O Capítulo 1 da Parte 1 descreve como o afecto na aprendizagem e na investigação da língua tem vindo a ser um factor preponderante no interesse mais alargado sobre as emoções em contextos educacionais. A recente influência da teoria social na aquisição de uma segunda língua e como esta pode ajudar a repensar a investigação das emoções é discutida antes do final do capítulo, onde se examina ainda como as emoções são expressas na comunicação e interacção. O Capítulo 2 concentra-se na ansiedade na aprendizagem da língua e em como o peso da noção em contexto social alargado tem provavelmente influenciado uma abordagem dominantemente de cariz positivista na investigação sobre a ansiedade linguística. Controvérsias e variáveis da personalidade relacionadas com a ansiedade linguística são discutidas, considerando-se a possibilidade de novas direcções para a investigação. A prática pedagógica é vista como um campo fértil de investigação sobre a ansiedade linguística em estagiários, com estilos de supervisão e discursos – nomeadamente estratégias de delicadeza e de mitigação – sendo considerados influências importantes na experiência desta emoção. O Capítulo 3 da Parte 2 detalha a abordagem etnográfica e etnometodológica do estudo e o procedimento de investigação em si. Os dados foram recolhidos em três momentos distintos. Primeiro, através de inquéritos aplicados aos estagiários antes do começo do estágio. Numa segunda fase, durante o estágio, os dados principais foram recolhidos através das aulas e duma entrevista semi-estruturada com os estagiários, ambas vídeo gravadas, e dos encontros de pós-observação áudio-gravados. Os dados subsidiários recolhidos nesta mesma fase incluem reflexões escritas e dossiers dos estagiários, observações escritas das aulas do investigador e o relatório intercalar dos professores supervisor e cooperante. Na última fase, posterior às aulas, a recolha dos dados principais foi realizada através de uma vídeo gravação da reunião de avaliação final com todos os participantes e de stimulated recall protocols com cada professor estagiário. O Capítulo 4 é predominantemente uma análise qualitativa de discurso, utilizando categorias de análise para identificar sinais de ansiedade emergentes dos dados. Os resultados mostram que um dos estagiários pode ser caracterizado como tendo uma experiência de ansiedade mais debilitadora, outro uma ansiedade mais facilitadora, enquanto a experiência do terceiro é menos pronunciada e mais difícil de caracterizar. Sinais e fontes múltiplos e complexos de ansiedade foram identificados mas as próprias autoimagens dos sujeitos como professores de Inglês, construídas em interacção ao longo do estágio, estão no centro desta experiência emocional. O Capítulo 5 considera as implicações e as conclusões deste estudo. São dadas indicações para a relação estagiário-supervisor e quanto aos estilos do supervisor no quadro da prática pedagógica assim como sugestões para que a ansiedade linguística seja explicitamente abordada na formação em supervisão. Finalmente, é ponderada se a experiência da ansiedade linguística destas estagiárias e as suas fontes têm ou não implicações na formação dos alunos de línguas.

Local gist vision of man-made objects

Attention is usually modelled by sequential fixation of peaks in saliency maps. Those maps code local conspicuity: complexity, colour and texture. Such features have no relation to entire objects, unless also disparity and optical flow are considered, which often segregate entire objects from their background. Recently we developed a model of local gist vision: which types of objects are about where in a scene. This model addresses man-made objects which are dominated by a small shape repertoire: squares, rectangles, trapeziums, triangles, circles and ellipses. Only exploiting local colour contrast, the model can detect these shapes by a small hierarchy of cell layers devoted to low- and mid-level geometry. The model has been tested successfully on video sequences containing traffic signs and other scenes, and partial occlusions were not problematic.

Joaquim Rodrigo:a contínua reinvenção da pintura

Tese de doutoramento, História (História da Arte), Universidade de Lisboa, Faculdade de Letras, 2014

O efeito da técnica de inibição de Jones nos músculos Masseter e temporal nas disfunções temporomandibulares

Introdução: A disfunção temporomandibular (DTM), de causa muscular, caracteriza-se por uma dor músculo-esquelética crónica, com sinais e sintomas específicos como a presença de Trigger Points (TrPs). Objetivo: Avaliar o efeito da Técnica de Inibição de Jones (TIJ) nos músculos masseter e temporal em indivíduos com DTM, e a identificação dos sinais e sintomas, a relação entre a severidade da DTM, a ansiedade e a qualidade de sono. Métodos: Estudo quasi-experimental, constituído por 16 indivíduos no grupo experimental (GE) e 17 grupo controle (GC). O grau de severidade foi avaliado pelo Índice de Helkimo e as alterações do sono pelo questionário de Pittsburgh sobre a qualidade do sono. Apenas o GE foi sujeito a uma TIJ nos TrPs latentes dos músculos masseter e temporal. Os dois grupos foram avaliados pré-intervenção (M0), pós-intervenção (M1) e 3 semanas após (M2), as amplitudes de movimento ativas de abertura, lateralidade direita/esquerda e protusão da boca bem como a dor (EVA) em repouso e na abertura máxima. Resultados: Foi possível observar que quanto maior o grau de DTM, maior a frequência de ansiedade e pior a qualidade do sono. Observou-se um decréscimo de TrPs, no GE, após a aplicação da técnica, principalmente no masseter. Não foi possível verificar diferenças inter-grupos. Contudo, observou-se no GE uma melhoria em todas as amplitudes avaliadas entre o M0 e o M2. Em relação à EVA em repouso e na abertura máxima, o GE demonstrou diminuição da dor no M1 e manteve valores inferiores no M2. Conclusão: Verifica-se uma diminuição dos TrPs, uma melhoria das amplitudes ativas bem como uma diminuição da dor após a aplicação da TIJ no GE. Já ao longo do tempo, o efeito é menos expressivo contudo observam-se valores inferiores comparativamente a M0.