TEST OF PHYSIOLOGICAL PERFORMANCE: RATIONALE AND FEASIBILITY

Rigorous clinical evaluation of the physiological performance is currently performed with complex and long procedures which need expensive technology and skilled operators. In a wide range of situations (frail patients, daily clinical practice, etc.), these approaches are difficult to be applied and simpler tests, with a lack of scientific background, are mandatory. To avoid these problems, we propose a test (test of physiological performance (TOPP)) to evaluate the physiological behavior of a subject, in a really easy and safe clinical setting, measuring only the heart rate. The subject is submitted to an active standing-up test and then two submaximal exercises (with a low power load) on a cycle-ergometer. The heart rate modifications due to each submaximal step are analyzed by exponential interpolation to calculate the ascending and descending time constants and evaluate the way each subject adapts his heart rate to work. The standard deviation of the RR for each stationary phase (warm-up, load, recovery) was calculated as an index of short-term variability. Then a standard Fourier analysis of the stationary periods of the standing-up procedures allows to quickly and easily evaluate the autonomic nervous activation. We tested the protocol on five healthy subjects to verify the feasibility and the acceptance of the procedure. The five subjects demonstrated a good tolerance of the entire procedure. The standing-up showed a behavior of the autonomic system consistent with the physiology (with an increase in sympathetic activation in the passage to standing position). The analysis of the two submaximal steps highlights how younger and trained subjects present lower heart rates (both in the ascending phase and in the recovery) with a quicker adaptation ability (smaller time constants) consistent with what is expected. The short-term variability of heart rate is greater in young and trained subjects, thus confirming how the sympatho-vagal balance, in these subjects, is more dynamic. The proposed test is well tolerated by the subjects and the results, albeit in a small cohort of healthy volunteers, are consistent with what is expected from physiology and is already present in the literature. Our work aims to be a proposal with a feasibility check of a method for evaluating performance. The work to be done for the clinical validation of the TOPP is still long, but we are aware that it can give important results and that the TOPP can become an effective tool for the assessment of the physiological performance even of fragile subjects

Prefrontal Norepinephrine Determines Attribution of “High” Motivational Salience

Intense motivational salience attribution is considered to have a major role in the development of different psychopathologies. Numerous brain areas are involved in “normal” motivational salience attribution processes; however, it is not clear whether common or different neural mechanisms also underlie intense motivational salience attribution. To elucidate this a brain area and a neural system had to be envisaged that were involved only in motivational salience attribution to highly salient stimuli. Using intracerebral microdialysis, we found that natural stimuli induced an increase in norepinephrine release in the medial prefrontal cortex of mice proportional to their salience, and that selective prefrontal norepinephrine depletion abolished the increase of norepinephrine release in the medial prefrontal cortex induced by exposure to appetitive (palatable food) or aversive (light) stimuli independently of salience. However, selective norepinephrine depletion in the medial prefrontal cortex impaired the place conditioning induced exclusively by highly salient stimuli, thus indicating that prefrontal noradrenergic transmission determines approach or avoidance responses to both reward- and aversion-related natural stimuli only when the salience of the unconditioned natural stimulus is high enough to induce sustained norepinephrine outflow. This affirms that prefrontal noradrenergic transmission determines motivational salience attribution selectively when intense motivational salience is processed, as in conditions that characterize psychopathological outcomes

The skull of Epidolops ameghinoi from the early Eocene Itaboraí fauna, southeastern Brazil, and the affinities of the extinct marsupialiform order Polydolopimorphia

The skull of the polydolopimorphian marsupialiform Epidolops ameghinoi is described in detail for the first time, based on a single well-preserved cranium and associated left and right dentaries plus additional craniodental fragments, all from the early Eocene (53-50 million year old) Itaboraí fauna in southeastern Brazil. Notable craniodental features of E. ameghinoi include absence of a masseteric process, very small maxillopalatine fenestrae, a prominent pterygoid fossa enclosed laterally by a prominent ectopterygoid crest, an absent or tiny transverse canal foramen, a simple, planar glenoid fossa, and a postglenoid foramen that is immediately posterior to the postglenoid process. Most strikingly, the floor of the hypotympanic sinus was apparently unossified, a feature found in several stem marsupials but absent in all known crown marsupials. "Type II" marsupialiform petrosals previously described from Itaboraí plausibly belong to E. ameghinoi; in published phylogenetic analyses, these petrosals fell outside (crown-clade) Marsupialia. "IMG VII" tarsals previously referred to E. ameghinoi do not share obvious synapomorphies with any crown marsupial clade, nor do they resemble those of the only other putative polydolopimorphians represented by tarsal remains, namely the argyrolagids. Most studies have placed Polydolopimorphia within Marsupialia, related to either Paucituberculata, or to Microbiotheria and Diprotodontia. However, diprotodonty almost certainly evolved independently in polydolopimorphians, paucituberculatans and diprotodontians, and Epidolops does not share obvious synapomorphies with any marsupial order. Epidolops is dentally specialized, but several morphological features appear to be more plesiomorphic than any crown marsupial. It seems likely Epidolops that falls outside Marsupialia, as do morphologically similar forms such as Bonapartherium and polydolopids. Argyrolagids differ markedly in their known morphology from Epidolops but share some potential apomorphies with paucituberculatans. It is proposed that Polydolopimorphia as currently recognised is polyphyletic, and that argyrolagids (and possibly other taxa currently included in Argyrolagoidea, such as groeberiids and patagoniids) are members of Paucituberculata. This hypothesis is supported by Bayesian non-clock phylogenetic analyses of a total evidence matrix comprising DNA sequence data from five nuclear protein-coding genes, indels, retroposon insertions and morphological characters: Epidolops falls outside Marsupialia, whereas argyrolagids form a clade with the paucituberculatans Caenolestes and Palaeothentes, regardless of whether the Type II petrosals and IMG VII tarsals are used to score characters for Epidolops or not. There is no clear evidence for the presence of crown marsupials at Itaboraí, and it is possible that the origin and early evolution of Marsupialia was restricted to the "Austral Kingdom" (southern South America, Antarctica, and Australia)

Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia

The leishmaniases are a complex of diseases caused by Leishmania parasites. Currently, the diseases affect an estimated 12 million people in 88 countries, and approximately 350 million more people are at risk. The leishmaniases belong to the most neglected tropical diseases, affecting the poorest populations, for whom access to diagnosis and effective treatment are often not available. Leishmania parasites infect cells of the immune system called macrophages, which have the capacity to eliminate the intracellular parasites when they receive the appropriate signals from other cells of the immune system. In nonhealing persistent leishmaniasis, lymphocytes are unable to transmit the signals to macrophages required to kill the intracellular parasites. The local upregulation of the enzyme arginase has been shown to impair lymphocyte effector functions at the site of pathology. In this study, we tested the activity of this enzyme in skin lesions of patients presenting with localized cutaneous leishmaniasis. Our results show that arginase is highly upregulated in these lesions. This increase in arginase activity coincides with lower expression of a signalling molecule in lymphocytes, which is essential for efficient activation of these cells. These results suggest that increased arginase expression in the localized cutaneous lesions might contribute to persistent disease in patients presenting with cutaneous leishmaniasis

The flora and vegetation of rocky outcrops in three municipalities in the northern region of Ceará, Brazil: phytosociological characterization

Veja material suplementar em <https://doi.org/10.6084/m9.figshare.5915233.v2O presente estudo teve como objetivo identificar a flora e a vegetação dos afloramentos rochosos isolados e de baixa altitude (lajedos), na vegetação de Caatinga Arbustiva Aberta, que se encontram nos municípios de Sobral, Groaíras e Santa Quitéria, no estado do Ceará, Brasil e propor uma classificação fitossociológica para estas comunidades xerófilas. Foram definidas cinco áreas de coleta de dados com elevada proporção de rochas expostas (> 80%) onde as excursões de campo decorreram em março de 2014 e 2015 (3º56’S e 40º23’W, 4º01’S e 40º05’W, 4º07’S e 40º08’W, 4º09’S e 40º09’W e 4º03’S e 40º00’W). No estudo da vegetação aplicou-se os métodos TWINSPAN (two-way indicator species analysis) e o clássico sigmatista de Braun-Blanquet. As áreas mínimas dos inventários fitossociológicos variaram de 8 a 16 m2. Foram coletadas as espécies vegetais que crescem em fissuras, fendas e ilhas de vegetação que se encontram em afloramentos rochosos. Foram registradas 88 espécies, distribuídas em 59 gêneros e 30 famílias botânicas. Fabaceae foi a família que se destacou em riqueza específica (20 spp.), seguida por Poaceae (dez spp.), Euphorbiaceae (sete spp.) e Convolvulaceae (seis spp.). Quanto ao endemismo foram registradas, em vegetação rupestre, 19 espécies endêmicas para o Brasil. Na análise fitossociológica da vegetação propôs-se estudar a comunidade de Pilosocereus gounellei (FA.C.Weber) Byles & Rowley e Encholirium spectabile Mart. ex Schult. & Schult.f. e a de Crateva tapia L. e Combretum leprosum Martinfo:eu-repo/semantics/publishedVersio

Frequency of tiotropium bromide use and clinical features of patients with severe asthma in a real-life setting: Data from the severe asthma network in Italy (sani) registry

Purpose: Patients with uncontrolled asthma despite high doses of inhaled corticosteroid therapy plus another controller are defined as severe asthmatics. Tiotropium bromide respi-mat (TBR) is the only long-acting muscarinic antagonists (LAMA) approved for severe asthma. The aim of this study was to explore the frequency of severe asthmatics treated with TBR and characterize their clinical features in a real-life, registry-based setting. Materials and Methods: Baseline data from the Severe Asthma Network in Italy (SANI) registry have been analyzed to determine the use of TBR and other LAMA, and to compare clinical, functional and inflammatory features associated with the use of LAMA. Results: Among a total of 698 enrolled patients, 35.9% were treated with LAMA (23.3% TBR, 4.5% tiotropium bromide handihaler, 4.5% aclidinium, 3.4% glycopyrronium bromide 0.3% umeclidinium bromide). Age of asthma onset was higher in patients taking LAMA, whom, compared to others were more frequently former smokers. They also had a higher annual exacerbation rate, experienced worst asthma control, worst disease-related quality of life and poorer lung function. Bronchiectasis was more frequently found in LAMA users (25.9% vs 13.1%). Conclusion: TBR is still underused in severe asthma in a real-life setting, while a relevant proportion of patients are treated with other LAMA that are not approved for severe asthma treatment. Patients taking LAMA have features characteristic of even more severe asthma