Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis.

BACKGROUND: Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia. METHODS: We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged <5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis. FINDINGS: We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26-0·89; specificity 0·59, 0·29-0·84) and lower chest wall indrawing (four studies; 0·48, 0·16-0·82; 0·72, 0·47-0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45-2·48), grunting (1·78, 1·10-2·88), chest indrawing (1·76, 0·86-3·58), and nasal flaring (1·75, 1·20-2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09-0·96), history of fever (0·53, 0·41-0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23-0·83). INTERPRETATION: Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy. FUNDING: Swiss National Science Foundation.

Sensitivity analysis, dominant factors, and robustness of the ECETOC TRA v3, Stoffenmanager 4.5, and ART 1.5 occupational exposure models

Occupational exposure modeling is widely used in the context of the E.U. regulation on the registration, evaluation, authorization, and restriction of chemicals (REACH). First tier tools, such as European Centre for Ecotoxicology and TOxicology of Chemicals (ECETOC) targeted risk assessment (TRA) or Stoffenmanager, are used to screen a wide range of substances. Those of concern are investigated further using second tier tools, e.g., Advanced REACH Tool (ART). Local sensitivity analysis (SA) methods are used here to determine dominant factors for three models commonly used within the REACH framework: ECETOC TRA v3, Stoffenmanager 4.5, and ART 1.5. Based on the results of the SA, the robustness of the models is assessed. For ECETOC, the process category (PROC) is the most important factor. A failure to identify the correct PROC has severe consequences for the exposure estimate. Stoffenmanager is the most balanced model and decision making uncertainties in one modifying factor are less severe in Stoffenmanager. ART requires a careful evaluation of the decisions in the source compartment since it constitutes ∼75% of the total exposure range, which corresponds to an exposure estimate of 20-22 orders of magnitude. Our results indicate that there is a trade off between accuracy and precision of the models. Previous studies suggested that ART may lead to more accurate results in well-documented exposure situations. However, the choice of the adequate model should ultimately be determined by the quality of the available exposure data: if the practitioner is uncertain concerning two or more decisions in the entry parameters, Stoffenmanager may be more robust than ART.

Primary root protophloem differentiation requires balanced phosphatidylinositol-4,5-biphosphate levels and systemically affects root branching.

Protophloem is a specialized vascular tissue in growing plant organs, such as root meristems. In Arabidopsis mutants with impaired primary root protophloem differentiation, brevis radix (brx) and octopus (ops), meristematic activity and consequently overall root growth are strongly reduced. Second site mutation in the protophloem-specific presumed phosphoinositide 5-phosphatase COTYLEDON VASCULAR PATTERN 2 (CVP2), but not in its homolog CVP2-LIKE 1 (CVL1), partially rescues brx defects. Consistent with this finding, CVP2 hyperactivity in a wild-type background recreates a brx phenotype. Paradoxically, however, while cvp2 or cvl1 single mutants display no apparent root defects, the root phenotype of cvp2 cvl1 double mutants is similar to brx or ops, although, as expected, cvp2 cvl1 seedlings contain more phosphatidylinositol-4,5-biphosphate. Thus, tightly balanced phosphatidylinositol-4,5-biphosphate levels appear essential for proper protophloem differentiation. Genetically, OPS acts downstream of phosphatidylinositol-4,5-biphosphate levels, as cvp2 mutation cannot rescue ops defects, whereas increased OPS dose rescues cvp2 cvl1 defects. Finally, all three mutants display higher density and accelerated emergence of lateral roots, which correlates with increased auxin response in the root differentiation zone. This phenotype is also created by application of peptides that suppress protophloem differentiation, CLAVATA3/EMBRYO SURROUNDING REGION 26 (CLE26) and CLE45. Thus, local changes in the primary root protophloem systemically shape overall root system architecture.

Relações filogenéticas e diversidade de isolados de Guignardia spp oriundos de diferentes hospedeiros nas regiões ITS1-5,8S-ITS2

Fungos do gênero Guignardia são frequentemente isolados em diferentes espécies de plantas, sendo muitas vezes caracterizados como fungos endofíticos. Entretanto, algumas espécies deste fungo, a exemplo de G. citricarpa e G. psidii, são causadores de importantes doenças que afetam culturas agrícolas, como a Mancha-Preta dos Citros (MPC) e a podridão dos frutos de goiabeira, respectivamente. Também são apontados como causadores de manchas foliares em diferentes espécies de frutíferas e também em outras culturas. Este trabalho teve o objetivo de isolar, identificar e caracterizar a diversidade genética existente entre isolados de Guignardia oriundos de citros, mangueira, goiabeira, eucaliptos, jabuticabeira e pitangueira através da análise da sequência de DNA do cístron ITS1-5,8-S-ITS2. Verificou-se que os isolados obtidos pertencem às espécies G. citricarpa e G. mangiferae. Entretanto, dois grupos encontrados em mangueira não puderam ser identificados em nível de espécie com base em sua sequência de DNA em função da baixa similaridade com as sequências de diferentes espécies de Guignardia já depositadas em banco de dados. Desta forma, goiabeira, eucaliptos, jabuticabeira e pitangueira são hospedeiras de G. mangiferae, enquanto os citros hospedam duas formas, G. citricarpa e G. mangiferae. Já a mangueira é hospedeira de G. mangiferae e de dois outros grupos ainda não identificados. Verificou-se ainda que isolados de Guignardia obtidos de sintomas de podridão de fruto de goiabeira foram identificados como G. mangiferae.

Early adversity and 5-HTT-BDNF genes: new evidences of gene-environment interactions on depressive symptoms in a general population

Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Likewise, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and the Brain-Derived Neurotrophic Factor (BDNF) seem to modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the GxE interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study is to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms.

DnaSP Version 5. DNA Sequence Polymorphism

DnaSP, DNA Sequence Polymorphism, is a software package for the analysis of nucleotide polymorphism from aligned DNA sequence data. DnaSP can estimate several measures of DNA sequence variation within and between populations (in noncoding, synonymous or nonsynonymous sites, or in various sorts of codon positions), as well as linkage disequilibrium, recombination, gene flow and gene conversion parameters. DnaSP can also carry out several tests of neutrality: Hudson, Kreitman and Aguadé (1987), Tajima (1989), McDonald and Kreitman (1991), Fu and Li (1993), and Fu (1997) tests. Additionally, DnaSP can estimate the confidence intervals of some test-statistics by the coalescent. The results of the analyses are displayed on tabular and graphic form.

Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse.

Myocardial ischaemia-reperfusion (MIR) triggers a sterile inflammatory response important for myocardial healing, but which may also contribute to adverse ventricular remodelling. Such inflammation is initiated by molecular danger signals released by damaged myocardium, which induce innate immune responses by activating toll-like receptors (TLRs). Detrimental roles have been recently reported for TLR2, TLR3 and TLR4. The role of other TLRs is unknown. We therefore evaluated the role of TLR5, expressed at high level in the heart, in the development of myocardial damage and inflammation acutely triggered by MIR. TLR5-/- and wild-type (WT) mice were exposed to MIR (30 min ischaemia, 2 h reperfusion). We measured infarct size, markers of cardiac oxidative stress, myocardial phosphorylation state of mitogen-activated protein (MAP) kinases and AKT, expression levels of chemokines and cytokines in the heart and plasma, as well as cardiac function by echography and conductance volumetry. TLR5-deficient mice had normal cardiac morphology and function under physiological conditions. After MIR, the absence of TLR5 promoted an increase in infarct size and myocardial oxidative stress. Lack of TLR5 fostered p38 phosphorylation, reduced AKT phosphorylation and markedly increased the expression of inflammatory cytokines, whereas it precipitated acute LV (left ventricle) dysfunction. Therefore, contrary to the detrimental roles of TLR2, TLR3 and TLR4 in the infarcted heart, TLR5 is important to limit myocardial damage, inflammation and functional compromise after MIR.

Factors associated with durable response to infliximab in Crohn's disease 5 years and beyond : a multicenter international cohort

BACKGROUND: Infliximab (IFX) has been used for over a decade worldwide. Less is known about the natural history of IFX use beyond a few years and which patients are more likely to sustain benefits. METHODS: Patients with Crohn's disease (CD) exposed to IFX from Massachusetts General Hospital, Boston, Saint-Antoine Hospital, Paris, and the Swiss IBD Cohort Study were identified through retrospective and prospective data collection, complemented by chart abstraction of electronic medical records. We compared long-term users of IFX (>5 yr of treatment, long-term users of infliximab [LTUI]), with non-LTUI patients to identify prognostic factors. RESULTS: We pooled data on 1014 patients with CD from 3 different databases, of whom 250 were defined as LTUI. The comparison group comprised 290 patients with CD who discontinued IFX: 48 primary nonresponses, 95 loss of responses, and 147 adverse events. Factors associated with LTUI were colonic involvements and an earlier age at the start of IFX. The prevalence of active smokers and obese patients differed markedly, but inversely, between American and European centers but did not impact outcome. The discontinuation rate was stable around 3% to 6%, each year from years 3 to 10. CONCLUSIONS: Young age at start of IFX and colonic CD are factors associated with a beneficial long-term use of IFX. After 5 years of IFX, there is still a 3% to 5% discontinuation rate annually. Several factors associated with a good initial response such as nonsmoker and shorter disease duration at IFX initiation do not seem associated with a longer term response.

AltitudeOmics : impaired pulmonary gas exchange efficiency and blunted ventilatory acclimatization in humans with patent foramen ovale after 16 days at 5,260 m.

A patent foramen ovale (PFO), present in ∼40% of the general population, is a potential source of right-to-left shunt that can impair pulmonary gas exchange efficiency [i.e., increase the alveolar-to-arterial Po2 difference (A-aDO2)]. Prior studies investigating human acclimatization to high-altitude with A-aDO2 as a key parameter have not investigated differences between subjects with (PFO+) or without a PFO (PFO-). We hypothesized that in PFO+ subjects A-aDO2 would not improve (i.e., decrease) after acclimatization to high altitude compared with PFO- subjects. Twenty-one (11 PFO+) healthy sea-level residents were studied at rest and during cycle ergometer exercise at the highest iso-workload achieved at sea level (SL), after acute transport to 5,260 m (ALT1), and again at 5,260 m after 16 days of high-altitude acclimatization (ALT16). In contrast to PFO- subjects, PFO+ subjects had 1) no improvement in A-aDO2 at rest and during exercise at ALT16 compared with ALT1, 2) no significant increase in resting alveolar ventilation, or alveolar Po2, at ALT16 compared with ALT1, and consequently had 3) an increased arterial Pco2 and decreased arterial Po2 and arterial O2 saturation at rest at ALT16. Furthermore, PFO+ subjects had an increased incidence of acute mountain sickness (AMS) at ALT1 concomitant with significantly lower peripheral O2 saturation (SpO2). These data suggest that PFO+ subjects have increased susceptibility to AMS when not taking prophylactic treatments, that right-to-left shunt through a PFO impairs pulmonary gas exchange efficiency even after acclimatization to high altitude, and that PFO+ subjects have blunted ventilatory acclimatization after 16 days at altitude compared with PFO- subjects.

The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity

The ascending midbrain 5-HT neurons to the forebrain may be dysregulated in depression and have a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by coimmunoprecipitation and colocation of the FGFR1 and 5-HT1A immunoreactivities in the midbrain raphe cells, evidence for the existence of FGFR1-5-HT1A receptor heterocomplexes in the dorsal and median raphe nuclei of the Sprague Dawley rat as well as in the rat medullary raphe RN33B cells has been obtained. Especially after combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA clusters was found in the RN33B cells. Similar results were reached with the FRET technique in HEK293T cells, where TM-V of the 5HT1A receptor was found to be part of the receptor interface. The combined treatment with FGF-2 and the 5-HT1A agonist also synergistically increased FGFR1 and ERK1/2 phosphorylation in the raphe midline area of the midbrain and the RN33B cells as well as their differentiation, as seen from development of the increased number and length of extensions per cell and their increased 5-HT immunoreactivity. These signaling and differentiation events were dependent on the receptor interface since they were blocked by incubation with TM-V but not by TM-II. Together, the results indicate that the 5-HT1A autoreceptors by being part of a FGFR1-5-HT1A receptor heterocomplex in the midbrain raphe 5-HT nerve cells appear to have a trophic role in the central 5-HT neuron systems in addition to playing a key role in reducing the firing of these neurons

Granuloma periférico de células gigantes. A propósito de 5 casos y revisión de la literatura

El granuloma periférico de células gigantes (GPCG) es una lesión reactiva benigna relativamente frecuente de la cavidad bucal. Se origina a partir del periostio o de la membrana periodontal tras una irritación o un traumatismo crónico que actúa localmente. Se manifiesta en forma de nódulo de color rojo-púrpura, situado en la encía o en el reborde alveolar edéntulo, preferentemente en la mandíbula. Aparece a cualquier edad, con una mayor incidencia entre la quinta y sexta décadas de la vida, con una ligera predilección por el sexo femenino. Es una lesión de las partes blandas que muy rara vez implica el hueso subyacente, aunque puede causarle una erosión superficial. Se han revisado cinco casos de GPCG que afectaban a 3 hombres y a 2 mujeres de edades comprendidas entre los 19 y 66 años, presentándose tres de ellos en el maxilar superior. En dos casos se observaba radiográficamente una reabsorción ósea en forma de"aplanamiento". El tratamiento consistió en realizar la exéresis-biopsia, efectuándose dos casos mediante láser de CO2 y tres con bisturí frío. No se ha observado ninguna recidiva en el seguimiento postoperatorio (rango de 10 meses a 4 años). En el diagnóstico diferencial se deben descartar lesiones de características clínicas e histológicas muy similares -como el granuloma central de células gigantes-, que asientan en el interior del propio maxilar y cuyo comportamiento es más agresivo; solamente el estudio radiológico permitirá esta distinción. El diagnóstico precoz y preciso de esta lesión permite efectuar un tratamiento conservador sin riesgo para los dientes vecinos ni para el hueso adyacente

Ácido 2,3,5-tri-iodobenzoico (TIBA) na micropropagação de abacaxizeiro 'IAC Gomo-de-Mel'

O abacaxi 'IAC Gomo-de-Mel' é uma espécie economicamente importante devido a diversas características sensoriais. Uma das técnicas para obter maior número de plantas é a micropropagação. Assim, o objetivo deste trabalho foi avaliar a ação do TIBA (ácido 2,3,5-tri-iodobenzoico) na formação de brotos e raízes do abacaxizeiro 'IAC Gomo-de-Mel', assim como possíveis alterações na morfologia de tecidos foliares. Foram utilizados segmentos das gemas da coroa de abacaxi, com aproximadamente 1 cm, oriundos de cultivo em meio líquido, suplementadas com 1,0 mg L-1 BAP+ 0,5 mg L-1 NAA , sendo posteriormente inoculados em meio MS líquido contendo diversas concentrações de TIBA, em condição de luz e temperatura controladas, implantando 3 diferentes experimentos para as análises biométrica, bioquímica e anatômica. Os experimentos foram implantados em delineamento experimental inteiramente ao acaso, com 8 tratamentos, com 4 repetições para as análises biométricas e 5 repetições para a bioquímica e anatômica. Ao final de 60 dias, foram avaliados o número e o comprimento das brotações, o comprimento da planta-mãe e o número de raízes. A análise da atividade de AIA-oxidase foi realizada no dia da instalação do experimento e aos 15; 30; 45 e 60 dias de cultivo. Conclui-se que o TIBA isoladamente não induz brotações. A redução na atividade da AIA-oxidase foi relacionada com a emissão de novas raízes, e o aumento na espessura dos tecidos foliares ocorreu após aplicação exógena de TIBA, em abacaxizeiro in vitro.

Vespignani, Giorgio, Iппoδρoμoς. Il circo di Costantinopoli nuova Roma dalla realtà alla storiografia, Fondazione Centro Italiano di Studi sull"Alto Medioevo, Spoleto, 2010, 303 páginas. ISBN: 978 88-7988-197-5

"El Circo Máximo es su templo, su hogar, su asamblea y la esperanza de todos sus deseos" (AmmiAnvs mArc., Res gest., XXVIII, 4, 29: eisque templum et habitaculum et contio et cupitorum spes omnis Circus est maximus). De este modo describió el historiador Amiano Marcelino, hacia el 382/397, la pasión que la plebe de Roma sentía hacia los espectáculos, especialmente hacia los ludi circenses. Se trata de una afición que se fue incrementando a lo largo de toda la historia del Imperio Romano, hasta el extremo que a mediados del siglo iv, según el calendario de Filócalo (CIL, I2, 1, p. 256-278), se alcanzaron los 177 días de juegos anuales. Y evidentemente tal apasionamiento no fue exclusivo de la ciudad de Roma, sino que se vivió de un modo común en todo el Imperio, sobre todo en las ciudades más grandes, entre las que destacó de una manera especial la capital de Oriente, Constantinopla, la nueva Roma fundada por Constantino I.