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.

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.

The Alps Vegetation Database - a geo-referenced community-level archive of all terrestrial plants occurring in the Alps.

Mountain ranges are biodiversity hotspots worldwide and provide refuge to many organisms under contemporary climate change. Gathering field information on mountain biodiversity over time is of primary importance to understand the response of biotic communities to climate changes. For plants, several long-term observation sites and networks of mountain biodiversity are emerging worldwide to gather field data and monitor altitudinal range shifts and community composition changes under contemporary climate change. Most of these monitoring sites, however, focus on alpine ecosystems and mountain summits, such as the global observation research initiative in alpine environments (GLORIA). Here we describe the Alps Vegetation Database, a comprehensive community level archive (GIVD ID EU-00-014) which aims at compiling all available geo-referenced vegetation plots from lowland forests to alpine grasslands across the greatest mountain range in Europe: the Alps. This research initiative was funded between 2008 and 2011 by the Danish Council for Independent Research and was part of a larger project to compare cross-scale plant community structure between the Alps and the Scandes. The Alps Vegetation Database currently harbours 35,731 geo-referenced vegetation plots and 5,023 valid taxa across Mediterranean, temperate and alpine environments. The data are mainly used by the main contributors of the Alps Vegetation Database in an ecoinformatics approach to test hypotheses related to plant macroecology and biogeography, but external proposals for joint collaborations are welcome.

Morphostructural analysis of an alpine debris flows catchment: implication for debris supply

Rock slope instabilities are implicitly linked to the supply of sediment and debris recharging channels prone to debris flow. Hence, the incorporation of bedrock structure and terrain morphology can be relevant in the analysis of sediment budget and debris flow hazard assessment. Here, the mode of debris production of the Manival catchment (northern French Alps) is documented by the study of its morphostructural aspects extracted from high resolution DEM. Terrain implication in the process of debris supply is evaluated by: a) A systematic classification of the major morphological units based on the slope gradient that enables a spatial analysis of zones of debris production and deposition. b) A detailed structural analysis performed on DEM in order to identify potential unstable slopes. c) An analysis of the gullies orientation that informs in term of structural control of the sources zones. d) Localisation of high density joints sets that document about whether sources of continuous debris production are controlled by the structural setting of the catchment. These DEM-based indicators can be used as proxies for assessing the influences of the current topography and enable to quantify a degree of susceptibility to mass wasting and hillslope erosion activity. This present contribution suggests some directions for characterizing sediment flux dynamic in small alpine catchment.

Development of appropriateness criteria for the surgical treatment of symptomatic lumbar degenerative spondylolisthesis (LDS).

PURPOSE: Spine surgery rates are increasing worldwide. Treatment failures are often attributed to poor patient selection and inappropriate treatment, but for many spinal disorders there is little consensus on the precise indications for surgery. With an aging population, more patients with lumbar degenerative spondylolisthesis (LDS) will present for surgery. The aim of this study was to develop criteria for the appropriateness of surgery in symptomatic LDS. METHODS: A systematic review was carried out to summarize the current level of evidence for the treatment of LDS. Clinical scenarios were generated comprising combinations of signs and symptoms in LDS and other relevant variables. Based on the systematic review and their own clinical experience, twelve multidisciplinary international experts rated each scenario on a 9-point scale (1 highly inappropriate, 9 highly appropriate) with respect to performing decompression only, fusion, and instrumented fusion. Surgery for each theoretical scenario was classified as appropriate, inappropriate, or uncertain based on the median ratings and disagreement in the ratings. RESULTS: 744 hypothetical scenarios were generated; overall, surgery (of some type) was rated appropriate in 27 %, uncertain in 41 % and inappropriate in 31 %. Frank panel disagreement was low (7 % scenarios). Face validity was shown by the logical relationship between each variable's subcategories and the appropriateness ratings, e.g., no/mild disability had a mean appropriateness rating of 2.3 ± 1.5, whereas the rating for moderate disability was 5.0 ± 1.6 and for severe disability, 6.6 ± 1.6. Similarly, the average rating for no/minimal neurological abnormality was 2.3 ± 1.5, increasing to 4.3 ± 2.4 for moderate and 5.9 ± 1.7 for severe abnormality. The three variables most likely (p < 0.0001) to be components of scenarios rated "appropriate" were: severe disability, no yellow flags, and severe neurological deficit. CONCLUSION: This is the first study to report criteria for determining candidacy for surgery in LDS developed by a multidisciplinary international panel using a validated method (RAM). The panel ratings followed logical clinical rationale, indicating good face validity. The work refines clinical classification and the phenotype of degenerative spondylolisthesis. The predictive validity of the criteria should be evaluated prospectively to examine whether patients treated "appropriately" have better clinical outcomes.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

A case of suicide by ingestion of caffeine.

Intentional or unintentional caffeine abuse due to excessive intake of beverages or energy drinks containing caffeine is relatively frequent. However, death due to caffeine intoxication is rare and case reports of fatalities from caffeine toxicity are relatively infrequent. In this report, we describe an autopsy case involving a 31 year-old man who intentionally took a large amount of caffeine tablets in the form of a weight loss supplement as part of a suicide plan. Caffeine femoral blood concentration (170 mg/l) was within the toxic and potentially lethal ranges reported in the literature in similar cases. Postmortem biochemistry results suggested depressed glomerular filtration rate and pre-renal failure at the time of death but failed to reveal myoglobinuria, glycosuria, ketonuria or ketonemia. Based on the absence of pathological findings at autopsy and the high blood caffeine level, death was attributed to acute caffeine toxicity. The case emphasizes the usefulness of performing exhaustive toxicology and searching for all potentially relevant information in order to formulate appropriate hypotheses concerning the cause and manner of death.

A novel bioinformatics pipeline to discover genes related to arbuscular mycorrhizal symbiosis based on their evolutionary conservation pattern among higher plants.

BACKGROUND: Genes involved in arbuscular mycorrhizal (AM) symbiosis have been identified primarily by mutant screens, followed by identification of the mutated genes (forward genetics). In addition, a number of AM-related genes has been identified by their AM-related expression patterns, and their function has subsequently been elucidated by knock-down or knock-out approaches (reverse genetics). However, genes that are members of functionally redundant gene families, or genes that have a vital function and therefore result in lethal mutant phenotypes, are difficult to identify. If such genes are constitutively expressed and therefore escape differential expression analyses, they remain elusive. The goal of this study was to systematically search for AM-related genes with a bioinformatics strategy that is insensitive to these problems. The central element of our approach is based on the fact that many AM-related genes are conserved only among AM-competent species. RESULTS: Our approach involves genome-wide comparisons at the proteome level of AM-competent host species with non-mycorrhizal species. Using a clustering method we first established orthologous/paralogous relationships and subsequently identified protein clusters that contain members only of the AM-competent species. Proteins of these clusters were then analyzed in an extended set of 16 plant species and ranked based on their relatedness among AM-competent monocot and dicot species, relative to non-mycorrhizal species. In addition, we combined the information on the protein-coding sequence with gene expression data and with promoter analysis. As a result we present a list of yet uncharacterized proteins that show a strongly AM-related pattern of sequence conservation, indicating that the respective genes may have been under selection for a function in AM. Among the top candidates are three genes that encode a small family of similar receptor-like kinases that are related to the S-locus receptor kinases involved in sporophytic self-incompatibility. CONCLUSIONS: We present a new systematic strategy of gene discovery based on conservation of the protein-coding sequence that complements classical forward and reverse genetics. This strategy can be applied to diverse other biological phenomena if species with established genome sequences fall into distinguished groups that differ in a defined functional trait of interest.

Measuring spiritual well-being in older rehabilitation patients using the facit-sp

Objectives: To determine psychometric properties of the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp) in a cohort of older patients admitted to rehabilitation. Method: Patients aged 65+, with MMSE score>19, admitted consecutively over 6 months in post-acute rehabilitation were enrolled (N=144, 81.27.2 years, 68.8% women). Data on medical, functional, and mental status were systematically collected upon admission. Spiritual well-being was assessed within 3 days after admission using the FACIT-Sp (12 items, score from 0 to 48, high spiritual well-being defined as a score ≥36) and the single question "Are you at peace?" (score from 0 to 10 on a visual analog scale). Results: FACIT-Sp scores ranged from 7 to 44(mean=29.87.7). Overall, 24.3% of the patients had high spiritual well-being. Internal consistency was optimal for total score (Cronbach's alpha =0.85). Itemto- total correlations were all significant, ranging from 0.28 to 0.73. A confirmatory factorial analysis yielded a 2-factor solution, consistent with Meaning and Faith proposed subscales and accounting for 52% of the variance . FACIT-Sp total score correlated positively with the question «Are you at peace ?» (Spearman's rho 0.49, P<.001) and negatively with depressive symptoms (Spearman's rho -0.37, P<.001), confirming FACIT-Sp validity. Compared to the others, patients with higher spiritual well-being had significantly better function at admission (Barthel's score 74.817.1 vs 68.514.1, P=.014). Conclusions: The FACIT-Sp remains a reliable and valid measure to assess spiritual well-being in older patients undergoing rehabilitation. The relatively low proportion of patients with high spiritual well-being deserves further investigation.

The evolution of personality in patients with mild cognitive impairment.

Aims: To describe personality traits and their changes in mild cognitive impairment (MCI) and control subjects. Methods: Sixty-three MCI and 90 control subjects were asked to describe their current personality traits by the Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close relative retrospectively assessed these descriptions both as to the previous and current personality traits, using the Revised NEO Personality Inventory, Form R (NEO-PI-R). Results: Self-assessed MCI subjects reported significantly lower scores in the openness dimension than control subjects [F(1, 150) = 9.84, p = 0.002, ηp(2) = 0.06]. In current observer ratings, MCI subjects had higher scores on neuroticism [F(1, 137) = 7.55, p = 0.007, ηp(2) = 0.05] and lower ones on extraversion [F(1, 137) = 6.40, p = 0.013, ηp(2) = 0.04], openness [F(1, 137) = 9.93, p = 0.002, ηp(2) = 0.07], agreeableness [F(1, 137) = 10.18, p = 0.002, ηp(2) = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001, ηp(2) = 0.16]. Previous personality traits discriminated the groups as previous openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p = 0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were negatively related to MCI group membership. In MCI subjects, conscientiousness [F(1, 137) = 19.20, p < 0.001, ηp(2) = 0.12] and extraversion [F(1, 137) = 22.27, p < 0.001, ηp(2) = 0.14] decreased between previous and current evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, ηp(2) = 0.14], whereas no significant change was found in control subjects. Conclusions: MCI subjects undergo significant personality changes. Thus, personality assessment may aid the early detection of dementia. © 2013 S. Karger AG, Basel.

Antiepileptika bei Frauen im gebärfähigen Alter und in der Schwangerschaft : Vergleich der Fachinformationen in Deutschland und der Schweiz mit dem aktuellen Wissensstand [Antiepileptics in women of childbearing age and during pregnancy : Comparison of specialized information with the current state of knowledge in Germany and Switzerland].

BACKGROUND: Healthcare professionals regularly read the summary of product characteristics (SmPC) as one of the various sources of information on the risks of drug use in women of childbearing age and during pregnancy. The aim of this article is to present an overview of the teratogenic potential of various antiepileptic drugs and to compare these data with the information provided by the SmPCs. METHODS: A literature search on the teratogenic risks of 19 antiepileptic agents was conducted and the results were compared with the information on the use in women of childbearing age and during pregnancy provided by the SmPCs of 38 commercial products available in Switzerland and Germany. RESULTS: The teratogenic risk is discussed in all available SmPCs. Quantification of the risk for birth defects and the numbers of documented pregnancies are mostly missing. Reproductive safety information in SmPCs showed poor concordance with risk levels reported in the literature. Recommendations concerning the need to monitor plasma levels and possibly perform dose adjustments during pregnancy to prevent treatment failure were missing in five Swiss and two German SmPCs. DISCUSSION: The information regarding use in women of childbearing age and during pregnancy provided by the SmPCs is heterogeneous and poorly reflects the current state of knowledge. Regular updates of SmPCs are warranted in order for these documents to be of reliable use for health care professionals.