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Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.
Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
The mechanisms involved in kidney disturbances during development, induced by vitamin D3 deficiency in female rats, that persist into adulthood were evaluated in this study. Female offspring from mothers fed normal (control group, n=8) or vitamin D-deficient (Vit.D-, n=10) diets were used. Three-month-old rats had their systolic blood pressure (SBP) measured and their blood and urine sampled to quantify vitamin D3 (Vit.D3), creatinine, Na+, Ca+2 and angiotensin II (ANGII) levels. The kidneys were then removed for nitric oxide (NO) quantification and immunohistochemical studies. Vit.D- pups showed higher SBP and plasma ANGII levels in adulthood (P<0.05) as well as decreased urine osmolality associated with increases in urinary volume (P<0.05). Decreased expression of JG12 (renal cortex and glomeruli) and synaptopodin (glomeruli) as well as reduced renal NO was also observed (P<0.05). These findings showed that renal disturbances in development in pups from Vit.D- mothers observed in adulthood may be related to the development of angiogenesis, NO and ANGII alterations.
Graded exercises tests are performed in adult populations; nonetheless, the use of this type of assessment is greatly understudied in overweight and obese adolescents.
To investigate heart rate autonomic responses to submaximal aerobic exercise in obese and overweight adolescents.
We recruited 40 adolescents divided into two groups: (1) overweight group comprising 10 boys and 10 girls between Z-score +1 and +2 and (2) obese group comprising 10 boys and 10 girls above Z-score >+2. Heart rate variability was analysed before (T1) and after exercise (T2–T4) on treadmill at a slope of 0%, with 70% of the maximal estimated heart rate (220 – age) for 20 minutes.
Heart rate in the overweight group was: 93.2±10.52 bpm versus 120.8±13.49 bpm versus 94.6±11.65 bpm versus 93.0±9.23 bpm, and in the obese group was: 92.0±15.41 bpm versus 117.6±16.31 bpm versus 92.1±12.9 bpm versus 91.8±14.33 bpm. High frequency in the overweight group was: 640±633.1 ms2 versus 84±174.66 ms2 versus 603.5±655.31 ms2 versus 762.6±807.21 ms2, and in the obese group was: 628.4±779.81 ms2 versus 65.4±119.34 ms2 versus 506.2±482.70 ms2 versus 677.9±939.05 ms2; and root mean square of successive differences in the overweight group was: 37.9±18.81 ms versus 10.9±8.41 ms versus 32.8±24.07 ms versus 36.7±21.86 ms, and in the obese group was: 38.7±23.17 ms versus 11.5±8.62 ms versus 32.3±16.74 ms versus 37.3±24.21 ms. These values significantly changed during exercise compared with resting values in overweight and obese groups. Moreover, we also reported no significant difference of resting parasympathetic control of heart rate between obese and overweight adolescents.
There was no significant difference of autonomic responses elicited by submaximal aerobic exercise between overweight and obese adolescents.
The increase of sheep meat competitiveness in international markets can be attributed to the rise of the quantity and the improvement of the quality of the edible portion of sheep carcasses. Usually, carcass yield is established after the slaughter of the animals. Yet, when carcass yield is determined in vivo, it can be both a costly and subjective method. This study proposes models for predicting the physical characteristics of lamb carcass using bioimpedance analysis (BIA) in live animals. Thirty-one Texel × Ile de France crossbreed ram lambs were slaughtered at 20, 26, 32 or 38 kg of BW. Before the slaughter, values of resistance (Rs) and reactance (Xc) were collected using a single-frequency BIA equipment (Model RJL Quantum II Bioelectrical Body Composition Analyzer). Then, BIA main variables such as body bioelectrical volume (V), phase angle (PA), resistive density (RsD) and reactive density (XcD) were calculated. After slaughter, cold carcass weight (CCW), cold carcass yield (CCY), subcutaneous fat thickness (SFT), soft tissue weight (STW) and soft tissue yield (STY) were also measured. Multiple regression analyses were carried out using the physical characteristics as dependent variables and the bioimpedance values as independent variables. Predictive performance of the models was assessed using leave-one-out cross-validation. The prediction model of CCW was obtained using the V, PA and RsD (R2 = 0.97), STW through the V, RsD and XcD (R2 = 0.97), CCY by Rs, Z and XcD (R2 = 0.69), STY by V and XcD (R2 = 0.67), and SFT only for XcD (R2 = 0.84). The results indicated that BIA has the potential to predict carcass characteristics of lambs at different body masses.
Keto analogues and amino acids (KAAA) supplementation can reduce blood ammonia concentrations in athletes undergoing high-intensity exercise under both ketogenic and thermoneutral conditions. This study evaluated the acute effects of KAAA supplementation on ammonia metabolism during extenuating endurance exercise in rats fed a ketogenic diet. In all, eighty male Fischer rats at 90 d of age were divided into eight groups, and some were trained using a swimming endurance protocol. A ketogenic diet supplemented with keto analogues was administered for 10 d. Administration of the ketogenic diet ended 3 d before the exhaustion test (extenuating endurance exercise). A ketogenic diet plus KAAA supplementation and extenuating endurance exercise (trained ketogenic diet supplemented with KAAA (TKKa)) increased blood ammonia concentrations by approximately 50 % compared with the control diet (trained control diet supplemented with KAAA (TCKa)) and similar training (effect size=1·33; statistical power=0·50). The KAAA supplementation reduced blood urea concentrations by 4 and 18 % in the control and ketogenic diet groups, respectively, compared with the groups fed the same diets without supplementation. The trained groups had 60 % lower blood urate concentrations after TCKa treatment than after TKKa treatment. Our results suggest that KAAA supplementation can reduce blood ammonia concentrations after extenuating endurance exercise in rats fed a balanced diet but not in rats fed a ketogenic diet.
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).
Phosphorus (P) is an essential nutrient in livestock production, involved in most metabolic processes in the body, and with an impact on bone development and growth. Diet supplementation with P can improve productivity, but at excess levels the P utilization can be low, and the high P excretion will lead to environmental pollution (Tamminga, 2003). P supplementation also adds substantially to the cost of feed. Using the isotopic dilution technique (Vitti et al., 2000), we have studied the effect of different P levels in diet on P absorption and excretion in Brazilian sheep, and identified the level at which true P absorption saturates.
The physical processes driving the chemical evolution of galaxies in the last ~ 11Gyr cannot be understood without directly probing the dust-obscured phase of star-forming galaxies and active galactic nuclei. This phase, hidden to optical tracers, represents the bulk of the star formation and black hole accretion activity in galaxies at 1 < z < 3. Spectroscopic observations with a cryogenic infrared observatory like SPICA, will be sensitive enough to peer through the dust-obscured regions of galaxies and access the rest-frame mid- to far-infrared range in galaxies at high-z. This wavelength range contains a unique suite of spectral lines and dust features that serve as proxies for the abundances of heavy elements and the dust composition, providing tracers with a feeble response to both extinction and temperature. In this work, we investigate how SPICA observations could be exploited to understand key aspects in the chemical evolution of galaxies: the assembly of nearby galaxies based on the spatial distribution of heavy element abundances, the global content of metals in galaxies reaching the knee of the luminosity function up to z ~ 3, and the dust composition of galaxies at high-z. Possible synergies with facilities available in the late 2020s are also discussed.
Urban slums provide suitable conditions for infestation by rats, which harbour and shed a wide diversity of zoonotic pathogens including helminths. We aimed to identify risk factors associated with the probability and intensity of infection of helminths of the digestive tract in an urban slum population of Rattus norvegicus. Among 299 rats, eleven species/groups of helminths were identified, of which Strongyloides sp., Nippostrongylus brasiliensis and, the human pathogen, Angiostrongylus cantonensis were the most frequent (97, 41 and 39%, respectively). Sex interactions highlighted behavioural differences between males and females, as eg males were more likely to be infected with N. brasiliensis where rat signs were present, and males presented more intense infections of Strongyloides sp. Moreover, rats in poor body condition had higher intensities of N. brasiliensis. We describe a high global richness of parasites in R. norvegicus, including five species known to cause disease in humans. Among these, A. cantonensis was found in high prevalence and it was ubiquitous in the study area – knowledge which is of public health importance. A variety of environmental, demographic and body condition variables were associated with helminth species infection of rats, suggesting a comparable variety of risk factors for humans.
Licuri (Syagrus coronate) cake is a biodiesel by-product used in ruminant feed as a beneficial energy source for supplementation in managed pastures. The objective was to evaluate the performance, digestibility, nitrogen balance, blood metabolites, ingestive behavior and diet profitability of eight crossbred Holstein (3/4)×Gyr (5/8) multiparous cows (480±25 kg BW and 100 days milking) grazing and supplemented with licuri cake partially replacing ground corn and soybean meal in concentrate (0, 200, 400 and 600 g/kg in dry matter (DM)), distributed in an experimental duplicated 4×4 Latin square design. Licuri cake partially replacing ground corn and soybean meal increased (P<0.01) the intake and digestibility of ether extract and decreased the non-fiber carbohydrates; however, there were no influences on the intakes of DM, CP, NDF and total digestible nutrients (TDN). The digestibilities of DM, CP and NDF were not influenced by licuri cake addition. There was a decrease trend on TDN digestibility (P=0.08). Licuri cake replacing ground corn and soybean meal in concentrate did not affect the intake; fecal, urinary and mammary excretions; N balance; and triglycerides concentrations. However, the blood urea nitrogen (P=0.04) concentration decreased with the licuri cakes inclusion in cow supplementation. There was an increasing trend for serum creatinine (P=0.07). Licuri cake inclusion did not affect body condition score, production, yield, protein, lactose, total solids and solid non-fat contents of milk and Minas frescal cheese. There was a linear decrease in average daily weight gain (g/day). The milk fat concentration and cheese fat production (P<0.1) presented a linear increase with partial replacement of ground corn and soybean meal with licuri cakes. The addition of licuri cake did not alter the time spent feeding, ruminating or idling. There was an increasing trend in NDF feeding efficiency (P=0.09). The replacing of ground corn and soybean meal with licuri cake up to 600 g/kg decreased the concentrate cost by US$0.45/cow per day. Licuri cake replacing corn and soybeans (400 g/kg) in concentrate promoted a profit of US$0.07/animal per day. Licuri cake is indicated to concentrate the supplementation of dairy cows with average productions of 10 kg/day at levels up to 400 g/kg in the concentrate supplement because it provides an additional profit of US$0.07/animal per day and increased milk and Minas frescal cheese fat without negative effects on productive parameters.
It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.
The present study investigated the impact of a western diet during gestation and lactation on the anthropometry, serum biochemical, blood pressure and cardiovascular autonomic control on the offspring. Male Wistar rats were divided into two groups according to their mother’s diet received: control group (C: 18% calories of lipids) and westernized group (W: 32% calories of lipids). After weaning both groups received standard diet. On the 60th day of life, blood samples were collected for the analysis of fasting glucose and lipidogram. Cardiovascular parameters were measured on the same period. Autonomic nervous system modulation was evaluated by spectrum analysis of heart rate (HR) and systolic arterial pressure (SAP). The W increased glycemia (123±2 v. 155±2 mg/dl), low-density lipoprotein (15±1 v. 31±2 mg/dl), triglycerides (49±1 v. 85±2 mg/dl), total cholesterol (75±2 v. 86±2 mg/dl), and decreased high-density lipoprotein (50±4 v. 38±3 mg/dl), as well as increased body mass (209±4 v. 229±6 g) than C. Furthermore, the W showed higher SAP (130±4 v. 157±2 mmHg), HR (357±10 v. 428±14 bpm), sympathetic modulation to vessels (2.3±0.56 v. 6±0.84 mmHg2) and LF/HF ratio (0.15±0.01 v. 0.7±0.2) than C. These findings suggest that a western diet during pregnancy and lactation leads to overweight associated with autonomic misbalance and hypertension in adulthood.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
First 405 GHz and 212 GHz solar flare observations were obtained during short campaigns while the new solar submillimeter-wave telescope (SST) was still undergoing adjustments at the CASLEO El Leoncito observatory in the Argentina Andes. We show here preliminary results for a large X1.1 class X-ray event occurred on 2000 March 22, which exhibited a small submm-w continuum response to the slow (minutes) bulk flare emission, and numerous subsecond spikes (100-300 ms), the brightest spikes reaching about 180 and 50 s.f.u. at 405 and 212 GHz, respectively.
A micro heteregenous reprocessed fuel spiked with thorium in a PWR fuel element considering (TRU-Th) cycle was simulated using three different configurations and different fissile materials that varied from 6.0% to 7.0%. The reprocessed fuels were obtained using the ORIGEN 2.1 code from a burned PWR standard fuel (33,000 MWd/tHM burned), with 3.1% of initial enrichment, which was remained in the cooling pool for five years and then reprocessed using UREX+ technique. The keff and plutonium generation during the burnup were evaluated and compared with the standard fuel. This study was performed using the SCALE 6.0.
Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL−1 concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0·05 mg mL−1. The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.
Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.
In the presented work, we have developed VLSI technology processes for new prototype sensors based on the synthesis of boron doped nanocrystalline diamond (B-NCD) and silicon based commercial detectors. The process is based on commercial passivated implanted planar silicon (PIPS) devices of PD450 and CAM450 types (CANBERRA). A layer of B-NCD of several hundred nanometers thickness and boron concentration up to 1021 atoms/cm3 is grown on the SiOx passivation layer in an ellipsoidal plasma enhanced chemical vapor deposition (PECVD) reactor at temperatures from 520-750°C, in hydrogen atmosphere. . The diamond electrode is dry chemically structured and aluminum electrodes are realized before mounting in a three-fold housing for measurements in aqueous solution. The prototype sensors show an alpha spectroscopy resolution of 100 keV for 241Am electroprecipitated from liquid solution.