Diagnostic performance of urinary metanephrines for the postmortem diagnosis of hypothermia.

The purpose of this study was to assess the diagnostic potential of urinary metanephrines and 3-methoxytyramine compared to urinary catecholamine determination in diagnosing antemortem cold exposure and fatal hypothermia. 83 cases of fatal hypothermia and 144 control cases were included in this study. Catecholamines (adrenaline, noradrenaline and dopamine), metanephrines (metanephrine, normetanephrine) and 3-methoxytyramine were measured in urine collected during autopsy. All tested analytes were significantly higher in hypothermia cases compared to control subjects and displayed a generally satisfying discriminative value, thus indicating urinary catecholamines and their metabolites as reliable markers of cold-related stress and hypothermia related-deaths. Metanephrine and adrenaline had the best discriminative value between hypothermia and control cases compared to other tested analytes, though with different sensitivity and specificity. These can therefore be considered the most suitable markers of cold-related stress.

Role of islet microRNAs in diabetes: which model for which question?

MicroRNAs are important regulators of gene expression. The vast majority of the cells in our body rely on hundreds of these tiny non-coding RNA molecules to precisely adjust their protein repertoire and faithfully accomplish their tasks. Indeed, alterations in the microRNA profile can lead to cellular dysfunction that favours the appearance of several diseases. A specific set of microRNAs plays a crucial role in pancreatic beta cell differentiation and is essential for the fine-tuning of insulin secretion and for compensatory beta cell mass expansion in response to insulin resistance. Recently, several independent studies reported alterations in microRNA levels in the islets of animal models of diabetes and in islets isolated from diabetic patients. Surprisingly, many of the changes in microRNA expression observed in animal models of diabetes were not detected in the islets of diabetic patients and vice versa. These findings are unlikely to merely reflect species differences because microRNAs are highly conserved in mammals. These puzzling results are most probably explained by fundamental differences in the experimental approaches which selectively highlight the microRNAs directly contributing to diabetes development, the microRNAs predisposing individuals to the disease or the microRNAs displaying expression changes subsequent to the development of diabetes. In this review we will highlight the suitability of the different models for addressing each of these questions and propose future strategies that should allow us to obtain a better understanding of the contribution of microRNAs to the development of diabetes mellitus in humans.

Cytochrome P450 1A2 activity and inducibility: impact of smoking, smoking cessation and genetic polymorphisms

Aims: Cytochrome P4501A2 (CYP1A2) is involved in the metabolism of severaldrugs (clozapine, olanzapine, theopylline, caffeine, etc) and is induced by smoking.This can result in decreased plasma levels of drugs metabolized by thisisoenzyme, causing a decrease in therapeutic response. After quitting smoking,increased plasma levels can lead to adverse effects of the concerned drugs, such asconfusion and seizures, described under clozapine treatment. The present studyaimed to examine the variation of CYP1A2 activity in a large group of smokersbefore and after smoking cessation. Moreover, we aimed to determine whethergenetic polymorphisms of CYP1A2 gene could influence the inducibility ofCYP1A2. Methods: CYP1A2 activity was determined by the paraxanthine/caffeineratio in 194 smokers and in 118 of them being abstinent during a 4-weekperiod. Participants were genotyped for CYP1A2*1F (rs762551), *1D(rs35694136) and *1C (rs2069514) polymorphisms. Results: Smokers had higherCYP1A2 activity (1.55-fold; p < 0.0001). Individual change of CYP1A2 activityafter smoking cessation ranged from 1.0-fold (no change) to 7.3-fold decreasedactivity. In five participants with low initial CYP1A2 activity, an increase wasobserved after smoking cessation. During smoking, CYP1A2*1F (p = 0.005), CYP1A2*1D (p = 0.014), the number of cigarettes/day (p = 0.012), contraceptives use(p < 0.001) and - 163A/- 2467T/- 3860G haplotype (p = 0.002) influencedCYP1A2 activity, while after quitting smoking, CYP1A2*1F (p = 0.017) and contraceptives(p = 0.05) did. No influence of CYP1A2 polymorphisms on the inducibilityof CYP1A2 was observed. Conclusion: Higher CYP1A2 activity wasmeasured in smokers, but with a large interindividual variability of its inductionby smoking. Careful clinical management with the help of therapeutic drug monitoringis therefore needed for patients receiving drugs which are metabolized byCYP1A2, who stop or start smoking. Unidentified genetic variations in theCYP1A2 gene and/or in other genes controlling CYP1A2 activity and other environmentalfactors could be responsible of the observed differences in CYP1A2enzymatic activity and inducibility.

Coordination pattern variability provides functional adaptations to constraints in swimming performance.

In a biophysical approach to the study of swimming performance (blending biomechanics and bioenergetics), inter-limb coordination is typically considered and analysed to improve propulsion and propelling efficiency. In this approach, 'opposition' or 'continuous' patterns of inter-limb coordination, where continuity between propulsive actions occurs, are promoted in the acquisition of expertise. Indeed a 'continuous' pattern theoretically minimizes intra-cyclic speed variations of the centre of mass. Consequently, it may also minimize the energy cost of locomotion. However, in skilled swimming performance there is a need to strike a delicate balance between inter-limb coordination pattern stability and variability, suggesting the absence of an 'ideal' pattern of coordination toward which all swimmers must converge or seek to imitate. Instead, an ecological dynamics framework advocates that there is an intertwined relationship between the specific intentions, perceptions and actions of individual swimmers, which constrains this relationship between coordination pattern stability and variability. This perspective explains how behaviours emerge from a set of interacting constraints, which each swimmer has to satisfy in order to achieve specific task performance goals and produce particular task outcomes. This overview updates understanding on inter-limb coordination in swimming to analyse the relationship between coordination variability and stability in relation to interacting constraints (related to task, environment and organism) that swimmers may encounter during training and performance.

Fatores associados à decisão para procura de serviço de saúde no infarto do miocárdio: diferenças entre gêneros

O objetivo deste estudo foi analisar, entre gêneros, a influência de variáveis cognitivas e emocionais no tempo de decisão (TD) para procura de atendimento face ao infarto do miocárdio. Cem adultos foram entrevistados em dois hospitais de Salvador-BA. Na análise empregaram-se médias percentuais, teste Q-quadrado e modelo de regressão linear robusto. Houve a predominância de homens, com idade média de 58,78 anos e baixa condição socioeconômica. A média geométrica da amostra foi 1,1h - 0,9h para homens; 1,4h para mulheres. Constatou-se menor tempo de decisão para quem considerou grave os sintomas, e maior para quem esperou melhora e tomou algo para recuperar-se, tais associações são estatisticamente significantes. Houve interação entre gênero e variáveis: esperar a melhora dos sintomas (p=0,014), ocultá-los (p=0,016) e pedir ajuda (p=0,050), quando verificou-se a associação das variáveis de interesse e TD. Os tempos de decisão foram elevados e sofreram influência de variáveis cognitivas, emocionais e de gênero. Cuidados de enfermagem podem promover o atendimento precoce.

Steroid use in Crohn's disease.

The incidence and prevalence of Crohn's disease are increasing, particularly in the Western world and Asia. Corticosteroids have been used for decades to treat active Crohn's disease and remain the mainstay in the management of moderate-to-severe relapses in Crohn's disease. The use of corticosteroids, despite their efficacy, may be associated with several drawbacks. This review article provides a comprehensive account of the role of corticosteroids in inducing remission in adult patients with Crohn's disease, including aspects such as approaches to corticosteroid sparing and to minimize the risk of corticosteroid dependency, as well as the role of newer corticosteroids such as budesonide in reducing systemic adverse effects.

Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth.

Brain natriuretic peptide (BNP) contributes to heart formation during embryogenesis. After birth, despite a high number of studies aimed at understanding by which mechanism(s) BNP reduces myocardial ischemic injury in animal models, the actual role of this peptide in the heart remains elusive. In this study, we asked whether BNP treatment could modulate the proliferation of endogenous cardiac progenitor cells (CPCs) and/or their differentiation into cardiomyocytes. CPCs expressed the NPR-A and NPR-B receptors in neonatal and adult hearts, suggesting their ability to respond to BNP stimulation. BNP injection into neonatal and adult unmanipulated mice increased the number of newly formed cardiomyocytes (neonatal: +23 %, p = 0.009 and adult: +68 %, p = 0.0005) and the number of proliferating CPCs (neonatal: +142 %, p = 0.002 and adult: +134 %, p = 0.04). In vitro, BNP stimulated CPC proliferation via NPR-A and CPC differentiation into cardiomyocytes via NPR-B. Finally, as BNP might be used as a therapeutic agent, we injected BNP into mice undergoing myocardial infarction. In pathological conditions, BNP treatment was cardioprotective by increasing heart contractility and reducing cardiac remodelling. At the cellular level, BNP stimulates CPC proliferation in the non-infarcted area of the infarcted hearts. In the infarcted area, BNP modulates the fate of the endogenous CPCs but also of the infiltrating CD45(+) cells. These results support for the first time a key role for BNP in controlling the progenitor cell proliferation and differentiation after birth. The administration of BNP might, therefore, be a useful component of therapeutic approaches aimed at inducing heart regeneration.

La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat [Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat].

AIM: The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues. METHODS: To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n=6 and 13; tissue n=4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n=8 and n=35, respectively) and for BK in various tissues less than 16% (n=5-8). RESULTS: In male Wistar rats (n=3), plasma BK was 8.2±6.6 fmol/mL (mean±SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14±3) and submaxillary gland (521±315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89±9) was not different from right renal BK (75±23). Similarly, KA was comparable in the two kidneys (left 18.0±1.5, right 15.8±1.4μkat/g). CONCLUSION: Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.

Clinical neurophysiological assessment of sepsis-associated brain dysfunction: a systematic review.

IntroductionSeveral studies have reported the presence of electroencephalography (EEG) abnormalities or altered evoked potentials (EPs) during sepsis. However, the role of these tests in the diagnosis and prognostic assessment of sepsis-associated encephalopathy remains unclear.MethodsWe performed a systematic search for studies evaluating EEG and/or EPs in adult (¿18 years) patients with sepsis-associated encephalopathy. The following outcomes were extracted: a) incidence of EEG/EP abnormalities; b) diagnosis of sepsis-associated delirium or encephalopathy with EEG/EP; c) outcome.ResultsAmong 1976 citations, 17 articles met the inclusion criteria. The incidence of EEG abnormalities during sepsis ranged from 12% to 100% for background abnormality and 6% to 12% for presence of triphasic waves. Two studies found that epileptiform discharges and electrographic seizures were more common in critically ill patients with than without sepsis. In one study, EEG background abnormalities were related to the presence and the severity of encephalopathy. Background slowing or suppression and the presence of triphasic waves were also associated with higher mortality. A few studies demonstrated that quantitative EEG analysis and EP could show significant differences in patients with sepsis compared to controls but their association with encephalopathy and outcome was not evaluated.ConclusionsAbnormalities in EEG and EPs are present in the majority of septic patients. There is some evidence to support EEG use in the detection and prognostication of sepsis-associated encephalopathy, but further clinical investigation is needed to confirm this suggestion.

Prediction of clinical response after renal angioplasty: respective value of renal Doppler sonography and scintigraphy.

OBJECTIVE: The goal of our study was to compare Doppler sonography and renal scintigraphy as tools for predicting the therapeutic response in patients after undergoing renal angioplasty. SUBJECTS AND METHODS. Seventy-four hypertensive patients underwent clinical examination, Doppler sonography, and renal scintigraphy before and after receiving captopril in preparation for renal revascularization. The patients were evaluated for the status of hypertension 3 months after the procedure. The predictive values of the findings of clinical examination, Doppler sonography, renal scintigraphy, and angiography were assessed. RESULTS: For prediction of a favorable therapeutic outcome, abnormal results from renal scintigraphy before and after captopril administration had a sensitivity of 58% and specificity of 57%. Findings of Doppler sonography had a sensitivity of 68% and specificity of 50% before captopril administration and a sensitivity of 81% and specificity of 32% after captopril administration. Significant predictors of a cure or reduction of hypertension after revascularization were low unilateral (p = 0.014) and bilateral resistive (p = 0.016) indexes on Doppler sonography before (p = 0.009) and after (p = 0.028) captopril administration. On multivariate analysis, the best predictors were a unilateral resistive index of less than 0.65 (odds ratio [OR] = 3.7) after captopril administration and a kidney longer than 93 mm (OR = 7.8). The two best combined criteria to predict the favorable therapeutic outcome were a bilateral resistive index of less than 0.75 before captopril administration combined with a unilateral resistive index of less than 0.70 after captopril administration (sensitivity, 76%; specificity, 58%) or a bilateral resistive index of less than 0.75 before captopril administration and a kidney measuring longer than 90 mm (sensitivity, 81%; specificity, 50%). CONCLUSION: Measurements of kidney length and unilateral and bilateral resistive indexes before and after captopril administration were useful in predicting the outcome after renal angioplasty. Renal scintigraphy had no significant predictive value.

Pheomelanin-based colouration is correlated with indices of flying strategies in the barn owl

Resource polymorphism refers to individuals from the same population foraging in alternative habitats or on alternative food. Food specialization can be associated with adaptations such as colour polymorphism, with pale and dark colours conferring differential camouflage in different habitats. Pale and dark-reddish pheomelanic Barn Owls (Tyto alba) forage on different prey species in closed and open habitats, respectively. We show here that darker-reddish owls have heavier stomach content when found dead, and their 5th secondary wing feather is more deeply anchored inside the integument. These correlations suggest that their feathers bend less when flying, and that darker-reddish Barn Owls are able sustain more intense flying than their paler conspecifics.

Aromatherapy with ylang ylang for anxiety and self-esteem: a pilot study

Objective: To verify if the use of ylang ylang essential oil by cutaneous application or inhalation alters the anxiety and self-esteem perception and physiological parameters as blood pressure and temperature. Method : A pilot study with 34 professionals from a nursing group randomized in three groups: one received the ylang ylang essential oil by cutaneous application, the second received through inhalation and the third (placebo) received the ylang ylang essence through cutaneous application. The assessment was done by an Anxiety Inventory (IDATE) and the Dela Coleta self-esteem scale, applied on baseline, after 30, 60 and 90 days and after 15 days post-intervention (follow up). Results : In the pre and post-intervention intergroup analysis, there was a significant difference in self-esteem for the three groups (p values: G1=0.014; G2=0.016; G3=0.038). There were no differences in the analysis between groups for anxiety or for physiological parameters. Conclusion : It was found significant alterations only to the intergroup perception of self-esteem for the three groups.


Late Early Triassic climate change: Insights from carbonate carbon isotopes, sedimentary evolution and ammonoid paleobiogeography

The late Early Triassic sedimentary-facies evolution and carbonate carbon-isotope marine record (delta(13)C(carb)) of ammonoid-rich, outer platform settings show striking similarities between the South ChinaBlock (SCB) and the widely distant Northern Indian Margin (NIM). The studied sections are located within the Triassic Tethys Himalayan belt (Losar section, Himachal Pradesh, India) and the Nanpanjiang Basin in the South China Block (Jinya section, Guangxi Province), respectively. Carbon isotopes from the studied sections confirm the previously observed carbon cycle perturbations at a time of major paleoceanographic changes in the wake of the end-Permian biotic crisis. This study documents the coincidence between a sharp increase in the carbon isotope composition and the worldwide ammonoid evolutionary turnover (extinction followed by a radiation) occurring around the Smithian-Spathian boundary. Based on recent modeling studies on ammonoid paleobiogeography and taxonomic diversity, we demonstrate that the late Early Triassic (Smithian and Spathian) was a time of a major climate change. More precisely, the end Smithian climate can be characterized by a warm and equable climate underlined by a flat, pole-to-equator, sea surface temperature (SST) gradient, while the steep Spathian SST gradient suggests latitudinally differentiated climatic conditions. Moreover, sedimentary evidence suggests a transition from a humid and hot climate during the Smithian to a dryer climate from the Spathian onwards. By analogy with comparable carbon isotope perturbations in the Late Devonian, Jurassic and Cretaceous we propose that high atmospheric CO(2) levels could have been responsible for the observed carbon cycle disturbance at the Smithian-Spathian boundary. We suggest that the end Smithian ammonoid extinction has been essentially caused by a warm and equable climate related to an increased CO(2) flux possibly originating from a short eruptive event of the Siberian igneous province. This increase in atmospheric CO(2) concentrations could have additionally reduced the marine calcium carbonate oversaturation and weakened the calcification potential of marine organisms, including ammonoids, in late Smithian oceans. (c) 2006 Elsevier B.V. All rights reserved.