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There is no suitable vaccine against human visceral leishmaniasis (VL) and available drugs are toxic and/or present high cost. In this context, diagnostic tools should be improved for clinical management and epidemiological evaluation of disease. However, the variable sensitivity and/or specificity of the used antigens are limitations, showing the necessity to identify new molecules to be tested in a more sensitive and specific serology. In the present study, an immunoproteomics approach was performed in Leishmania infantum promastigotes and amastigotes employing sera samples from VL patients. Aiming to avoid undesired cross-reactivity in the serological assays, sera from Chagas disease patients and healthy subjects living in the endemic region of disease were also used in immunoblottings. The most reactive spots for VL samples were selected, and 29 and 21 proteins were identified in the promastigote and amastigote extracts, respectively. Two of them, endonuclease III and GTP-binding protein, were cloned, expressed, purified and tested in ELISA experiments against a large serological panel, and results showed high sensitivity and specificity values for the diagnosis of disease. In conclusion, the identified proteins could be considered in future studies as candidate antigens for the serodiagnosis of human VL.
Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD).
Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC – UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old).
The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79–0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71–0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower –0.57 (95% CI 0.54–0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73–0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/.
The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.
Forage cactus is an important dry-season feed source for livestock in semi-arid regions, but in north-eastern Brazil, its contribution is limited by susceptibility to the carmine cochineal [Dactylopius opuntiae (Cockerell)] insect. New cactus germplasm shows superior agronomic performance, but the nutritive value of this material has not been adequately described. The objective of the current study was to assess the divergence in chemical composition and rate and extent of in vitro degradation of these genotypes. The treatments were 13 spineless cactus genotypes, eight of which were insect resistant types, two semi-resistant and three susceptible to the carmine cochineal. Treatments were arranged in a randomized complete block design and were replicated three times. Nutritional divergence was assessed using canonical variate analysis and hierarchical agglomerative clustering, using the variables: crude protein, total and non-fibrous carbohydrates, degradation rate and potential dry matter degradation. Five distinct nutritional groups were identified: Group I (OO), Group II (F-13 and F-15), Group III (OEA, OEM, COP, IPA 20 and GG), Group IV (V-16 and F-08) and Group V (Miuda, IS and F-21). Group II (F-13 and F-15; resistant genotypes) showed a chemical composition degradability in vitro suggesting it may have the greatest nutritive value as ruminant feed, while Group I had the least. Spineless cactus genotypes resistant to the carmine cochineal showed nutritional characteristics similar to or better than traditionally used cactus genotypes, such as Gigante and IPA 20, which can expand the range of options for using this forage.
Although there is evidence of a relationship between religion/ spirituality and mental health, it remains unclear how Brazilian psychiatrists deal with the religion/spirituality of their patients.
To explore whether Brazilian psychiatrists enquire about religion/spirituality in their practice and whether their own beliefs influence their work.
Four hundred and eighty-four Brazilian psychiatrists completed a cross-sectional survey on religion/spirituality and clinical practice.
Most psychiatrists had a religious affiliation (67.4%) but more than half of the 484 participants (55.5%) did not usually enquire about patients' religion/spirituality. The most common reasons for not assessing patients' religion/spirituality were ‘being afraid of exceeding the role of a doctor’ (30.2%) and ‘lack of training’ (22.3%).
Very religious/spiritual psychiatrists were the most likely to ask about their patients' religion/spirituality. Training in how to deal with a patient's religiosity might help psychiatrists to develop better patient rapport and may contribute to the patient's quicker recovery.
The species Phytomonas serpens is known to express some molecules displaying similarity to those described in trypanosomatids pathogenic to humans, such as peptidases from Trypanosoma cruzi (cruzipain) and Leishmania spp. (gp63). In this work, a population of P. serpens resistant to the calpain inhibitor MDL28170 at 70 µm (MDLR population) was selected by culturing promastigotes in increasing concentrations of the drug. The only relevant ultrastructural difference between wild-type (WT) and MDLR promastigotes was the presence of microvesicles within the flagellar pocket of the latter. MDLR population also showed an increased reactivity to anti-cruzipain antibody as well as a higher papain-like proteolytic activity, while the expression of calpain-like molecules cross-reactive to anti-Dm-calpain (from Drosophila melanogaster) antibody and calcium-dependent cysteine peptidase activity were decreased. Gp63-like molecules also presented a diminished expression in MDLR population, which is probably correlated to the reduction in the parasite adhesion to the salivary glands of the insect vector Oncopeltus fasciatus. A lower accumulation of Rhodamine 123 was detected in MDLR cells when compared with the WT population, a phenotype that was reversed when MDLR cells were treated with cyclosporin A and verapamil. Collectively, our results may help in the understanding of the roles of calpain inhibitors in trypanosomatids.
Strongyloides venezuelensis is a parasitic nematode of rodents that is frequently used to obtain heterologous antigens for immunological diagnosis of human strongyloidiasis. The aim of this study was to identify antigens from filariform larvae of S. venezuelensis for immunodiagnosis of human strongyloidiasis. Soluble and membrane fractions from filariform larvae of S. venezuelensis were obtained in phosphate saline (SS and SM) and in Tris–HCl buffer (TS and TM), and were analysed by Western blotting. Different antigenic components were recognized by IgG antibodies from the sera of strongyloidiasis patients. Highest recognition was observed for a 30–40 kDa mass range present in all antigenic fractions. The band encompassing this mass range was then excised and subjected to mass spectrometry for protein identification. Immunoreactive proteins identified in the soluble fractions corresponded to metabolic enzymes, whereas cytoskeletal proteins and galectins were more abundant in the membrane fractions. These results represent the first approach towards identification of S. venezuelensis antigens for use in immunodiagnostic assays for human strongyloidiasis.
The aim of our article was to review the current literature on the effects of metabolic (re) programming on childhood obesity. PubMed/MEDLINE was the data source used to track the studies. Descriptors applied: children obesity, epigenetic, metabolic programming, exercise and nutrition. The focus was to analyze and discuss the international findings on the theme. The gathering of the papers was performed between June and August 2014. The search of articles with the descriptors used found 33.054 studies. In all, 5.709 studies were selected by crossing chosen keywords. Among these, after careful reading of the titles, 712 papers were considered potential as references. After applying inclusion/exclusion criteria, 50 studies were selected from 132 eligible abstracts. Most studies linked the development and treatment of obesity from epigenetically stimulated metabolic programming during the early stages of pregnancy and life. This review provides theoretical basis to the understanding that the programmed development of childhood obesity may be linked to early exposure to environmental factors, such as (nutrition and regular practice of exercise) and stimulus can epigenetically alter the modulation of the obesogenic metabolic behavior during pregnancy and the developmental stages of children and/or postpone the pathophysiologic disease stage to adulthood.
Pearl millet (Pennisetum glaucum (L.) R.) could play an important role as a feed source for ruminants in arid and semi-arid zones of the world owing to its high yield and drought tolerance. The current paper assessed the agronomic characteristics, ensilability, intake and digestibility of five Brazilian pearl millet cultivars (IPA Bulk1BF, BRS 1501, CMS-03, CMS-01 and BN-2) in a typical Brazilian northeastern semi-arid climate. Forage was harvested at the dough stage of grain maturity (growth stage 86 according to the BBCH scale) and ensiled under laboratory and farm conditions. Apparent digestibility of the silages was determined using 25 Santa Inês male lambs. The cultivars CMS-01, CMS-03 and BN-2 out-performed the others in terms of dry matter (DM) and digestible DM yield/ha. At DM partitioning among plant tissues, the cultivar IPA Bulk1BF had a greater DM associated with panicles and one of the greatest concentrations of organic matter, lactic acid and in vitro dry matter digestibility among the five cultivars. The cultivar BRS 1501 had greater butyric acid concentration as well as one of the highest pH values. Silage produced from BN-2 not only contained greater acetic acid concentration, but also showed one of the greatest total volatile fatty acid concentrations. There were no differences in feed intake and digestibility of nutrients and fibre fractions across all cultivars. Silage made from BN-2 resulted in greater urinary excretion of nitrogen than those produced from BRS 1501. Under the conditions of the present study, the results obtained for production of DM and digestible dry matter, and the ratio of plant fractions, indicates the possible use of these cultivars for silage production in the Brazilian semi-arid region.
Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood.
Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated.
Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers.
Maternal D&A is associated with persistent D&A during the daughter's transition to adulthood. Intervention strategies should consider the mother's mental health.
Previous studies have suggested an association between maternal smoking during pregnancy and asthma symptoms such as wheezing during childhood. However, few have evaluated this association in adolescence, especially in populations with high prevalence of wheezing as in Brazil. Using the 1993 Pelotas birth cohort, a longitudinal study set in southern Brazil of 5249 urban live births, we aimed to evaluate the association between maternal and the partner’s smoking during pregnancy and wheezing at 11 and 15 years of age. We evaluated smoking during pregnancy using number of cigarettes/day, and our main outcomes were as follows: wheezing in the last year and number of wheezing crises, at both 11 and 15 years of age, as well as persistent wheezing (having crises at 11 and 15 years of age) and medical asthma diagnosis at age 15. In addition, other socio-demographic variables were included as possible confounders and mediators of this association. We used Poisson regression models to evaluate crude and adjusted associations. Of the 5249 live births in 1993, 87.5% and 85.7% were followed-up to 11 and 15 years of age, respectively. Maternal smoking during pregnancy showed a dose-response association with number of wheezing crises at age 15 (P=0.023), presence of persistent wheezing (P=0.034) and asthma diagnosis (P=0.023). Partner’s smoking was not associated with any wheezing variables. Maternal smoking during pregnancy appears to exert an effect on respiratory morbidity of adolescents, evaluated by wheezing symptoms.
Malcolm Roy Clarke (1930–2013) was a British teuthologist who made an important contribution to marine science in the Azores archipelago (Portugal). Malcolm started doing research in the Azores from 1980s onward, settling for residency in 2000 after retirement (in 1987). He kept publishing on Azorean cephalopods collaborating in 20% of the peer reviewed works focusing on two main areas: dietary studies; and the ecology of cephalopods on seamounts. Since his first visit in 1981, he was involved in the description of the dietary ecology of several cetaceans, seabirds, and large pelagic and deep-water fish. Using his own data, Malcolm revised the association of cephalopods with seamounts, updating and enlarging the different cephalopod groups according to species behaviour and ecology. Malcolm taught several students working in the Azores on cephalopods and beak identification, lecturing the Third International Workshop in Faial (2007). He empowered the recently established research community, by providing important contacts with foreign institutes and informal advice. He collaborated in the regional cetacean stranding network (RACA) and was an active member of the advisory board of the journal Arquipelago—Life and Marine Sciences. But the scientific role of Malcolm Clarke in the Azores went beyond his academic activities. In the last 10 years Malcolm and Dot Clarke dedicated themselves to building and running a museum on Pico Island, showing the biology of the sperm whale and its interaction with squid; a cultural and touristic legacy for future generations to enjoy.
The efficiency of Ovaprim™ salmon gonadotropin-releasing hormone agonist (GnRHa) and dopamine antagonist on the induction of spawning and spermiation in Prochilodus lineatus in comparison with the commonly used method using pituitary extract (PE) was evaluated. Females received PE at 0.5 + 5.0 mg/kg and Ovaprim™ at 0.05 + 0.45 ml/kg or at 0.125 + 0.375 ml/kg. All males received a first dose of PE at 0.4 mg/kg and then PE at 4.0 mg/kg or Ovaprim™ at 0.25 ml/kg. Oocyte, egg, larvae and sperm quality were evaluated. All females spawned and oocyte, egg and larvae quality were similar between Ovaprim™-treated (both doses) and PE-treated females. Data from females were pooled and the mean values were: 242 g ova weight, 15% ova index, 1209 oocytes/g ova, 284,539 oocytes/female, 183 oocytes/g body weight, 1.18 mm oocyte diameter, 49% fertilization rate, 43% hatching rate and 89% normal larvae. Sperm quality was similar between Ovaprim™-treated and PE-treated males. Data from males were pooled and the mean values of semen were: volume of 3.0 ml, 14.9 × 109 sperm/ml, osmolality of 283 mOsm/kg, pH of 7.4, 71% motile sperm, 217 μm/s curvilinear velocity, 102 μm/s straight-line velocity and 189 μm/s average path velocity. Ovaprim™ treatment can be used for commercial reproduction of P. lineatus, without any loss of gamete quality in comparison with PE treatment.
The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.
The ASTEP project aims at detecting and characterizing transiting planets from Dome C, Antarctica, and qualifying this site for photometry in the visible. The first phase of the project, ASTEP South, is a fixed 10 cm diameter instrument pointing continuously towards the celestial South Pole. Observations were made almost continuously during 4 winters, from 2008 to 2011. The point-to-point RMS of 1-day photometric lightcurves can be explained by a combination of expected statistical noises, dominated by the photon noise up to magnitude 14. This RMS is large, from 2.5 mmag at R = 8 to 6% at R = 14, because of the small size of ASTEP South and the short exposure time (30 s). Statistical noises should be considerably reduced using the large amount of collected data. A 9.9-day period eclipsing binary is detected, with a magnitude R = 9.85. The 2-season lightcurve folded in phase and binned into 1,000 points has a RMS of 1.09 mmag, for an expected photon noise of 0.29 mmag. The use of the 4 seasons of data with a better detrending algorithm should yield a sub-millimagnitude precision for this folded lightcurve. Radial velocity follow-up observations reveal a F-M binary system. The detection of this 9.9-day period system with a small instrument such as ASTEP South and the precision of the folded lightcurve show the quality of Dome C for continuous photometric observations, and its potential for the detection of planets with orbital periods longer than those usually detected from the ground.
ASTEP (Antarctic Search for Transiting Exo Planets) is a research program funded mainly by French ANR grants and by the French Polar Institute (IPEV), dedicated to the photometric study of exoplanetary transits from Antarctica.
The preliminary “pathfinder” instrument ASTEP–South is described in another communication (Crouzet et al., these proceedings), and we focus in this presentation on the main instrument of the ASTEP program: “ASTEP–400”, a 40 cm robotized and thermally-controlled photometric telescope operated from the French-Italian Concordia station (Dome C, Antarctica).
ASTEP–400 has been installed at Concordia during the 2009-2010 summer campaign. Since, the telescope has been operated in nominal conditions during 2010 and 2011 winters, and the 2012 winterover is presently in progress. Data from the first two winter campaigns are available and processed. We give a description of the ASTEP–400 telescope from the mechanical, optical and thermal point of view. Control and software issues are also addressed. We end with a discussion of some astronomical results obtained with ASTEP–400.
Hepatitis C virus (HCV) infection is associated with oxidative stress and vitamin A possesses antioxidant activity. The objective of the present study was to investigate vitamin A nutritional status in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), according to biochemical, functional and dietetic indicators correlating these findings with liver function, liver damage and death. Vitamin A nutritional status was analysed by serum retinol levels, dietetic indicators and functional indicators. A total of 140 patients with HCV-related liver disease were enrolled. Vitamin A deficiency was detected in 54·3 % of all patients, and there was a progressive drop in serum retinol levels from chronic hepatitis C patients towards cirrhosis and HCC patients. Increased total bilirubin, liver transaminases and prothrombin time, presence of hepatic encephalopathy and ascites were related to reduced serum retinol levels, and values ≤ 0·78 μmol/l of serum retinol were associated with liver-related death. A high prevalence of inadequate intake of vitamin A was observed in all stages of chronic liver disease. The functional indicator was not an adequate parameter for evaluating the vitamin A nutritional status. Therefore, serum retinol concentration is related to severity of the disease, liver complications and mortality. The effectiveness of nutritional counselling and measures of intervention in this group in improving vitamin A nutritional status should be examined further in a controlled study.
Objective: Depressive disorders, including major depression, are serious and disabling for affected patients. Although the neurobiological understanding of major depressive disorder focuses mainly on the monoamine hypothesis, the exact pathophysiology of depression is not fully understood.
Methods: Animals received daily intra-peritoneal injections of paroxetine (10 mg/kg), nortriptyline (15 mg/kg) or venlafaxine (10 mg/kg) in 1.0 ml/kg volume for 15 days. Twelve hours after the last injection, the rats were killed by decapitation, where the brain was removed and homogenised. The activities of mitochondrial respiratory chain complexes in different brain structures were measured.
Results: We first verified that chronic administration of paroxetine increased complex I activity in prefrontal cortex, hippocampus, striatum and cerebral cortex. In addition, complex II activity was increased by the same drug in hippocampus, striatum and cerebral cortex and complex IV activity in prefrontal cortex. Furthermore, chronic administration of nortriptyline increased complex II activity in hippocampus and striatum and complex IV activity in prefrontal cortex, striatum and cerebral cortex. Finally, chronic administration of venlafaxine increased complex II activity in hippocampus, striatum and cerebral cortex and complex IV activity in prefrontal cortex.
Conclusion: On the basis of the present findings, it is tempting to speculate that an increase in brain energy metabolism by the antidepressant paroxetine, nortriptyline and venlafaxine could play a role in the mechanism of action of these drugs. These data corroborate with other studies suggesting that some antidepressants modulate brain energy metabolism.