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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.
Extracorporeal circulatory membrane oxygenation (ECMO) is a technology that allows recovery of adults in cardiorespiratory failure with encouraging results, but is not available in the Brazilian universal public health system (SUS) due to high implementation costs. Time-driven activity based costing (TDABC) is applied to measure processes in an economic perspective by identifying opportunities to make processes more efficient through the reduction of resources used in each activity. The literature has explored the use of TDABC to measure costs related with clinical procedures and technologies in microcosting studies, identifying opportunities to improve the process by making it more efficient. This research measures the real costs to implement ECMO in Brazil to compare with the current public reimbursement system.
This study applied TDABC using data from 6 patients to measure costs of ECMO intervention considering the public perspective in Brazil. In sequence, standard price payed by SUS was used to estimate the current reimbursement amount received by the hospital for ECMO procedure. Cost variable analysis was conducted to understand when and how patients receiving ECMO are using hospital resources. Cost data were collected from an academic public hospital using an average of 18 months (2016–2017) for the department costs.
The real average cost was USD 128,923. Most significant resource costs was medical staff, particularly for the three survivor patients, and the ECMO equipment presented the second highest cost. ECMO activities were separated into: before implantation of ECMO, period using ECMO, intensive care post-ECMO and rehabilitation, being the period where ECMO is the most expensive, particularly in nurse and physician costs. The SUS average was USD 31,437, which shows a difference of USD 97,485 between the real ECMO cost and the public reimbursement in Brazil.
A critical element of the propagation of ECMO in Brazil and its reimbursement by public health system is the high cost and out-of-date standard payments by the Ministry of Health. Effort to implement a trustworthy method to guide decisions of SUS for the adoption and financing new technologies is essential to contribute to the optimization of public health policies in a country with a universal health system and limited resources dedicated to health sectors.
We evaluated the effects of cattle manure and inoculation with arbuscular mycorrhizal fungi (AMF) in maize plants growing in a semiarid area of Brazilian north-east in 2012 and 2013. Three isolates of AMF (Acaulospora longula URM-FMA 07 and URM-FMA 03, Claroideoglomus etunicatum UNIVASF 06A) were used, with or without the application of cattle manure, during two growing cycles. In the first year, significant effects of inoculation were detected for straw yield only when the manure was applied. In the second year, there was an interaction between fertilisation and inoculation for plant height and grain yield, with the highest values in the fertilised treatments. Inoculation with A. longula demonstrated that mycorrhizal inoculation in field-grown plants could be an alternative management for improving plant growth and grain yield, reducing the use of cattle manure. The AMF sporulation and mycorrhizal colonisation were improved after inoculation, and A. longula URM-FMA 07 increased sporulation by more than 15 times while inoculation with C. etunicatum increased sporulation by more than 3 times. The mycorrhizal inoculation is a management practice that can be useful for recovering or maintaining AMF infective propagules in soil, showing potential to be used in large-scale field conditions in Brazilian semiarid. Although mycorrhisation presents high agricultural relevance due to benefits promoted to the soil and plants, the knowledge about the factors influencing the interactions among microorganisms, soil and plants need to be broadened aiming to achieve successful crop management in semiarid regions.
This study evaluated the effects of diet containing taro flour on hormone levels and the seminiferous tubules morphology of rats. After weaning, the male rats were divided into two groups (n=12 each): control group (CG) treated with control diet and taro group (TG), fed with 25% taro flour for 90 days. Food, caloric intake, mass and body length were evaluated at experiment end. Testis followed the standard histological processing. Immunostaining was performed using an anti-vimentin antibody to identify Sertoli cells. In histomorphometry, total diameter, total area, epithelial height, luminal height and luminal area were analyzed. The testosterone levels were performed using the radioimmunoassay method. Group TG presented (P<0.05): increase in mass, body length, testicular weight, histomorphometric parameters and hormonal levels. Food intake, calorie and Sertoli cells not presented statistical differences. The taro promoted increase in the testicles parameters and hormones.
Cepheids are excellent stellar tracers: they are bright enough to be observed even at large distances; their distances can be accurately determined via period-luminosity relations; their spectra contain numerous lines that enable us to derive abundances for many α, iron-peak or neutron-capture elements. Classical Cepheids are yellow supergiants that trace the young populations (⩽ 300 Myr); Type II Cepheids are post Horizontal Branch, low-mass, Population II stars (⩾ 10 Gyr). Both can be used for many purposes in Milky Way archaeology.
The stellar occultation technique is a powerful tool to study distant small solar system bodies. Currently, around 2 500 trans-neptunian objects (TNOs) and Centaurs are known. With the astrometry from Gaia and large surveys like the Large Synoptic Survey Telescope (LSST), accurate predictions of occultation events will be available to tens of thousands of TNOs and Centaurs and boost the knowledge of the outer solar system.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors.
Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC.
Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA.
UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.
The reporting period has shown that Space has become a firmly established domain in observational Astrophysics, also in the low energy astrophysics area. The launching of new spacecraft is always an important addition to the capabilities of the Astronomers, but the availability of space observatories is strongly affected by the fact that they disappear as their subsystems become damaged or, for other reasons, become inoperable. The relatively short life of astronomical space facilities has generated new dynamic in the life cycle of observational tools for the astronomer, rather different from that for ground facilities. Launch failures or the final in-orbit functionality verification can also very strongly affect the availability of observational capabilities in space astrophysics. The only spacecraft designed without this built-in life time restriction, is the Hubble Space Telescope, which can be serviced by the Space Shuttle.
Sorghum [Sorghum bicolor (L.) Moench] grown in India is of two adaptive types: rainy and post-rainy. The post-rainy sorghum is predominantly consumed by humans. While releasing new cultivars through multi-location testing, major emphasis is given to the superiority of new cultivars over existing cultivars, with very little emphasis on the genotype × environment interaction (GEI). To understand the complexity of GEI in post-rainy sorghum testing location trials, the multi-location evaluation data of two post-rainy seasons (2009/10 and 2010/11) under the All India Coordinated Sorghum Improvement Project were analysed. In both years, location explained the highest proportion of total sum of squares followed by the GEI effect and main effect of genotype. Additive main effects and multiplicative interaction (AMMI), stability values (ASV) and genotype + genotype × environment interaction (GGE) instability values recorded high correlation resulting in identification of the best performing cultivars. However, the rank correlations were lower, though still significant. A mixture of crossover and non-crossover GEI was a common occurrence in both years. ‘Which-won-where’ analysis suggested the existence of four possible mega-environments (ME) among post-rainy testing locations, with a few non-informative locations within ME. Mega-environments are characterized by soil type, rainfall pattern and moisture conservation practices. The present study indicated the possibility of reducing the number of test locations by eliminating non-representative highly correlated locations and suggested the need to breed for location-specific genotypes rather than genotypes with wider adaptability.
The objective of this study was to investigate relationships between ovulation rate (OR) and embryonic and placental development in sows. Topigs Norsvin® sows (n=91, parity 2 to 17) from three different genetic backgrounds were slaughtered at 35 days of pregnancy and the reproductive tract was collected. The corpora lutea (CL) were counted and the number of vital and non-vital embryos, embryonic spacing (distance between two embryos), implantation length, placental length, placental weight and embryonic weight were assessed. The difference between number of CL and total number of embryos was considered as early embryonic mortality. The number of non-vital embryos was considered as late mortality. Relationships between OR and all other variables were investigated using two models: the first considered parity as class effect (n=91) and the second used a subset of sows with parities 4 to 10 (n=47) to analyse the genetic background as class effect. OR was significantly affected by parity (P<0.0001), but was not affected by the genetic background of the sows. Parity and genetic background did not affect embryonic and placental characteristics at 35 days of pregnancy. OR (varying from 17 to 38 CL) was positively related with early embryonic mortality (β=0.49±0.1 n/ovulations, P<0.0001), with late embryonic mortality or number of non-vital embryos (β=0.24±0.1 n/ovulations, P=0.001) and with the number of vital embryos (β=0.26±0.1 n/ovulations, P=0.01). However, dividing OR in four classes, showed that the number of vital embryos was lowest in OR class 1 (17 to 21 CL), but not different for the other OR classes, suggesting a plateau for number of vital embryos for OR above 22. There was a negative linear relationship between OR and vital embryonic spacing (β=−0.45±0.1 cm/ovulation, P=0.001), implantation length (β=−0.35±0.1 cm/ovulation, P=0.003), placental length (β=−0.38±0.2 cm/ovulation, P=0.05) and empty space around embryonic-placental unit (β=−0.4±0.2 cm/ovulation, P=0.02), indicating uterine crowding. Further analyses showed that effects of OR on embryonic and uterine parameters were related with the increase in late mortality and not early embryonic mortality. Therefore, we conclude that a high OR results in an moderate increase in the number of vital embryos at day 35 of pregnancy, but compromises development in the surviving embryonic/placental units, suggesting that the future growth and survival of the embryos might be further compromised.
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.
The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0–∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.
The histone chaperone SET/TAF-Iβ is implicated in processes of chromatin remodelling and gene expression regulation. It has been associated with the control of developmental processes, but little is known about its function in helminth parasites. In Mesocestoides corti, a partial cDNA sequence related to SET/TAF-Iβ was isolated in a screening for genes differentially expressed in larvae (tetrathyridia) and adult worms. Here, the full-length coding sequence of the M. corti SET/TAF-Iβ gene was analysed and the encoded protein (McSET/TAF) was compared with orthologous sequences, showing that McSET/TAF can be regarded as a SET/TAF-Iβ family member, with a typical nucleosome-assembly protein (NAP) domain and an acidic tail. The expression patterns of the McSET/TAF gene and protein were investigated during the strobilation process by RT-qPCR, using a set of five reference genes, and by immunoblot and immunofluorescence, using monospecific polyclonal antibodies. A gradual increase in McSET/TAF transcripts and McSET/TAF protein was observed upon development induction by trypsin, demonstrating McSET/TAF differential expression during strobilation. These results provided the first evidence for the involvement of a protein from the NAP family of epigenetic effectors in the regulation of cestode development.
This study assessed the long-term effects of feeding diets containing either a gelling fibre (alginate (ALG)), or a fermentable fibre (resistant starch (RS)), or both, on feeding patterns, behaviour and growth performance of growing pigs fed ad libitum for 12 weeks. The experiment was set up as a 2×2 factorial arrangement: inclusion of ALG (yes or no) and inclusion of RS (yes or no) in the control diet, resulting in four dietary treatments, that is, ALG−RS− (control), ALG+RS−, ALG−RS+, and ALG+RS+. Both ALG and RS were exchanged for pregelatinized potato starch. A total of 240 pigs in 40 pens were used. From all visits to an electronic feeding station, feed intake and detailed feeding patterns were calculated. Apparent total tract digestibility of energy, dry matter (DM), and CP was determined in week 6. Pigs’ postures and behaviours were scored from live observations in weeks 7 and 12. Dietary treatments did not affect final BW and average daily gain (ADG). ALG reduced energy and DM digestibility (P<0.01). Moreover, ALG increased average daily DM intake, and reduced backfat thickness and carcass gain : digestible energy (DE) intake (P<0.05). RS increased feed intake per meal, meal duration (P<0.05) and inter-meal intervals (P=0.05), and reduced the number of meals per day (P<0.01), but did not affect daily DM intake. Moreover, RS reduced energy, DM and CP digestibility (P<0.01). Average daily DE intake was reduced (P<0.05), and gain : DE intake tended to be increased (P=0.07), whereas carcass gain : DE intake was not affected by RS. In week 12, ALG+RS− increased standing and walking, aggressive, feeder-directed, and drinking behaviours compared with ALG+RS+ (ALG×RS interaction, P<0.05), with ALG−RS− and ALG−RS+ in between. No other ALG×RS interactions were found. In conclusion, pigs fed ALG compensated for the reduced dietary DE content by increasing their feed intake, achieving similar DE intake and ADG as control pigs. Backfat thickness and carcass efficiency were reduced in pigs fed ALG, which also showed increased physical activity. Pigs fed RS changed feeding patterns, but did not increase their feed intake. Despite a lower DE intake, pigs fed RS achieved similar ADG as control pigs by increasing efficiency in DE use. This indicates that the energy utilization of RS in pigs with ad libitum access to feed is close to that of enzymatically digestible starch.
This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg−1, intraperitoneally [i.p.]) and C-LNCs (10 mg kg−1, i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0·05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.
Chagas’ disease is a neglected tropical disease caused by Trypanosoma cruzi and constitutes a serious public health problem for Latin America. Its unsatisfactory chemotherapy stimulates the search for novel antiparasitic compounds. Amidines and related compounds exhibit well-known activity towards different microbes including T. cruzi. In this vein, our present aim was to evaluate the biological effect of 10 novel structurally related amidines in vitro against bloodstream and intracellular forms of the parasite as well as their potential toxicity on cardiac cell cultures. Our results show that although active against the extracellular forms, with some of them like DB2247 being 6-fold more effective than benznidazole and displaying very low toxicity (>96 μm), none presented superior trypanocidal effect against intracellular forms as compared with the reference drug. These results may be due to differences in susceptibility profiles related to distinct uptake/extrusion mechanisms and cellular targets between bloodstream and amastigote forms. The present study adds to the knowledge base for the future design of novel amidines that may provide promising activity against T. cruzi.
During otologic surgical procedures, there is often a dilemma when ensuring that hair is kept out of the surgical field. For a surgeon, the simplest and commonest technique is to liberally shave the head, but this can cause aesthetic concerns for the patient. Failure to keep the area hair-free can lead to a range of adverse surgical outcomes including wound infection and poor scar cosmesis. We describe a technique used in our department to effectively control hair during otologic surgical procedures, with no post-operative aesthetic concerns.
The use of re-usable or disposable surgical drapes with disposable skin staples can effectively exclude hair from the operative field throughout the procedure, without fear of the drapes slipping or losing adhesiveness.
The authors have obtained good results both during and after surgery, using this quick and easily learnt method, with no cases of long-term skin damage or scarring.
We find this to be an effective method of hair and skin preparation for otologic surgical procedures, and suggest it to fellow otorhinolaryngologists as a helpful alternative technique.
Using high resolution powder neutron diffraction data, we show that there is a distinct anomaly in the structural noncentrosymmetry around the magnetic transition point TN for bulk and nanoscale BiFeO3. It appears that the structural noncentrosymmetry - which gives rise to the ferroelectric polarization - is suppressed anomalously by ~1% (of the average noncentrosymmetry at above the magnetic transition) in the bulk sample and by ~12% in the nanoscale sample as the magnetic transition is approached from higher temperature. This observation shows that the multiferroic coupling improves in the nanoscale sample which is expected to brighten the application prospects of nanoscale BiFeO3 in nanospintronics-based sensor devices.
The paper is concerned with the analytical study of nonlinear coupling of slow Alfvén wave (SW) with ion acoustic waves (IAWs) in high-β and low-β plasmas. Here the pump wave (SW) number density gets perturbed in the presence of IAW. The model equations of IAW and SW turn out to be the modified Zakharov system of equations when the ponderomotive nonlinearities are incorporated in the IAW and SW dynamics. Growth rate of modulational instability has been calculated. The relevance of these investigations for solar wind plasma and solar coronal plasma has also been discussed.