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Maneuvering a spacecraft in the cislunar space is a complex problem, since it is highly perturbed by the gravitational influence of both the Earth and the Moon, and possibly also the Sun. Trajectories minimizing the needed fuel are generally preferred in order to decrease the mass of the payload. A classical method to constrain maneuvers is mathematically modeling them using the Two Point Boundary Value Problem (TPBVP), defining spacecraft positions at the start and end of the trajectory. Solutions to this problem can then be obtained with optimization techniques like the nonlinear least squares conjugated with the Theory of Functional Connections (TFC) to embed the constraints, which recently became an effective method for deducing orbit transfers. In this paper, we propose a tangential velocity (TV) type of constraints to design orbital maneuvers. We show that the technique presented in this paper can be used to transfer a spacecraft (e.g. from the Earth to the Moon) and perform gravity assist maneuvers (e.g. a swing-by with the Moon). In comparison with the TPBVP, solving the TV constraints via TFC offers several advantages, leading to a significant reduction in computational time. Hence, it proves to be an efficient technique to design these maneuvers.

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INTRODUCTION: The application of occlusal concepts in prosthodontics is still under debate.This study assessed the impact of compensating curves on the comminution of complete denture wearers. METHODS: Seven edentulous subjects, aged 64.6 ± 2.0 years, were rehabilitated with new muco-supported complete dentures and tested in two occlusal plane settings: with and without compensating curves. A randomised triple-blind clinical trial was conducted, considering one-week and one-month as adaptation periods for dentures. After each trial, the subjects were crossed over to their respective groups. One-week was also chosen as the washout period, and after that, the subjects were re-examined. The masticatory performance and swallowing threshold were determined while chewing Optocal test food. The multiple sieve method was used for fractionation and granulometry. RESULTS: During the masticatory performance and swallowing threshold estimates, no differences were found between the median particle sizes obtained with the both occlusal plane conditions (P ⟩ 0.05). However, the swallowing threshold improved after one month, resulting in smaller particle sizes. Moreover, the chewing rates for the both test foods were also increased (P ⟨ 0.05). CONCLUSIONS: These findings suggest that the compensating curves did not have an impact on the masticatory function of subjects wearing complete dentures.

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OBJECTIVE: The aim of the study was to investigate sleep characteristics, use of supplements, and training volume of recreational triathletes, and to verify possible associations with perceived performance drops and occurrence of injuries. MATERIALS AND METHODS: Recreational triathletes (n=942) answered a questionnaire inquiring about their demographic characteristics, performance, injuries and training volume. RESULTS: When comparing athletes who slept more (9-10 hours) with those who slept less, less sleep was associated with a higher prevalence of perceived performance drops. Regarding difficulties in initiating sleep, the absence of initiating difficulties (p<0.001) was a protective factor against perceived performance drops. Regarding weekly training volume, compared to those who trained more than 20 hours, training less than 3 hours (p<0.001), 3-5 hours (p<0.001), or 12-14 hours (p<0.001) were protective factors against perceived performance drops. Concerning training volume and injuries, we found that compared to those who trained more than 20 hours, training 18-20 hours (p<0.001), 15-17 hours (p<0.001), 12-14 hours (p<0.001), 6-8 hours (p<0.001), or 3-5 hours (p<0.001) were protective factors against injuries. CONCLUSIONS: Triathletes with a lower sleep quantity and those who have difficulties initiating sleep frequently experience drops in performance. Training volumes can influence both performance and the likelihood of injuries.

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Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14th day, brain 18FDG-microPET scans were performed. Hypothalamic pAMPKT172/AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18FDG uptake. We found that ND increased the pAMPKT172/AMPK ratio in both adult and aged mice but increased 18FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.

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It is important to consider the use of the epigenome as source of complementary data for genome knowledge, which is suitable for the diagnosis of schistosomiasis. Usually, a laboratory diagnosis of schistosomiasis is performed by means of 1. Egg detection in the stool or urine by microscopy remains with limited sensitivity; 2. Immunological screening, in which positivity persists after treatment, and 3. Molecular appraisals prevail over the disadvantages of the currently used methods. In this sense, molecular methodologies are being developed based on epigenetic biomarkers, aiming to improve the diagnosis of the disease and clinical treatment as early as possible to prevent the occurrence of serious liver damage.

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Anaerobic systems for domestic sewage treatment, like septic tanks and anaerobic filters, are used in developing countries due to favorable economic and functional features. The anaerobic filter is used for the treatment of the septic tank effluent, to improve the COD removal efficiency of the system. The microbial composition and diversity of the microbiome from two wastewater treatment systems (factory and rural school) were compared through 16S rRNA gene sequencing using MiSeq 2 × 250 bp Illumina sequencing platform. Additionally, 16S rRNA data were used to predict the functional profile of the microbial communities using PICRUSt2. Results indicated that hydrogenotrophic methanogens, like Methanobacterium, were found in higher abundance in both systems compared to acetotrophic methanogens belonging to Methanosaeta genus. Also, important syntrophic microorganisms (Smithella, Syntrophus, Syntrophobacter) were found in the factory and rural school wastewater treatment systems. Microbial communities were also compared between stages (septic tank and anaerobic filter) of each wastewater treatment stage, revealing that, in the case of the rural school, both microbial communities were quite similar most likely due to hydraulic short-circuit issues. Meanwhile, in the factory, microbial communities from the septic tank and anaerobic filter were different. The school system showed lower COD removal rates (2-30%), which were probably related to a higher abundance of Firmicutes members in addition to the hydraulic short-circuit and low abundance of Chloroflexi members. On the other hand, the fiberglass factory presented higher COD removal rates (60-83%), harboring phyla reported as the core microbiome of anaerobic digesters (Bacteroidetes, Chloroflexi, and Proteobacteria phyla). The knowledge of the structure and composition of wastewater treatment systems may provide support for the improvement of the pollutant removal in anaerobic process.

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BACKGROUND: Exergaming is a fun, engaging, and interactive form of exercising that may help overcome some of the traditional exercise barriers and help improve adherence on the part of older adults, providing therapeutic applications for balance recovery and functional mobility. The purpose of this systematic review is to summarize the effects of exergames on mobility and balance in older adults. METHODS: The PRISMA guidelines for systematic reviews were followed. The following databases were searched from inception to August 2019: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PEDro, CINAHL, and INSPEC. We selected randomized controlled trials that assessed the effects of exergames on balance or mobility of older adults without neurological conditions, in comparison to no intervention or health education. Two review authors independently screened the trials' titles and abstracts and identified trials for inclusion according to the eligibility criteria. An almost perfect agreement between the authors was observed with respect to interrater reliability of trial selection (kappa = 0.84; P < 0.001). We performed descriptive analysis of the quantitative data to summarize the evidence. Meta-analysis was carried out using RevMan. A random effects model was used to compute the pooled prevalence with 95% confidence intervals. RESULTS: After screening 822 records, 12 trials comparing exergames with no intervention were included. A total of 1520 older adults participated in the studies, with a mean age of 76 ± 6 years for the experimental group and 76 ± 5 years for the control group. Quantitative synthesis showed significant improvements in balance and mobility based on the center of pressure sway (SMD = - 0.89; 95%CI = - 1.26 to - 0.51; P = 0.0001; I2 = 58%), Berg Balance Scale (MD = 2.15; 95%CI = 1.77 to 2.56; P = 0.0001; I2 = 96%), and on Timed Up and Go test (MD = - 2.48; 95%CI = - 3.83 to - 1.12; P = 0.0003; I2 = 0). CONCLUSIONS: Exergames improved balance and mobility in older adults without neurological disorders and motivate patients to keep performing balance exercises. High quality studies with standardized assessment protocols are necessary to improve the strength of the evidence.

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BACKGROUND: Recent clinical trials using regulatory T cells (Treg) support the therapeutic potential of Treg-based therapy in transplantation and autoinflammatory diseases. Despite these clinical successes, the effect of Treg on inflamed tissues, as well as their impact on immune effector function in vivo, is poorly understood. Therefore, we here evaluated the effect of human Treg injection on cutaneous inflammatory processes in vivo using a humanized mouse model of human skin inflammation (huPBL-SCID-huSkin). METHODS: SCID beige mice were transplanted with human skin followed by intraperitoneal (IP) injection of 20-40 × 106 allogeneic human PBMCs. This typically results in human skin inflammation as indicated by epidermal thickening (hyperkeratosis) and changes in dermal inflammatory markers such as the antimicrobial peptide hBD2 and epidermal barrier cytokeratins K10 and K16, as well as T cell infiltration in the dermis. Ex vivo-expanded human Treg were infused intraperitoneally. Human cutaneous inflammation and systemic immune responses were analysed by immunohistochemistry and flow cytometry. RESULTS: We confirmed that human Treg injection inhibits skin inflammation and the influx of effector T cells. As a novel finding, we demonstrate that human Treg injection led to a reduction of IL-17-secreting cells while promoting a relative increase in immunosuppressive FOXP3+ Treg in the human skin, indicating active immune regulation in controlling the local proinflammatory response. Consistent with the local control (skin), systemically (splenocytes), we observed that Treg injection led to lower frequencies of IFNγ and IL-17A-expressing human T cells, while a trend towards enrichment of FOXP3+ Treg was observed. CONCLUSION: Taken together, we demonstrate that inhibition of skin inflammation by Treg infusion, next to a reduction of infiltrating effector T cells, is mediated by restoring both the local and systemic balance between cytokine-producing effector T cells and immunoregulatory T cells. This work furthers our understanding of Treg-based immunotherapy.

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The biosafety of innovative procedures that utilize stem cells in regenerative medicine has been addressed in several studies. Previous work has showed no tumour formation following the use of feline and human amniotic membrane-derived stem cells (AMSCs). In contrast, tumour formation was observed when canine AMSCs were utilized. These findings suggested that feline and human, but not canine, AMSCs are suitable for cell transplantation trials. This study aimed to further evaluate the feasibility of utilizing canine AMSCs for transplantation purposes as well as for felines. We tested teratoma formation following cell injection into BALB/c nude mice and then assessed expression of haematopoietic, mesenchymal, tumorigenic, pluripotency and cellular regulation markers using flow cytometry and qPCR. The use of canine AMSCs did not result in macroscopic tumour formation as determined 60 days after transplantation. The immunophenotypic characterization by flow cytometry revealed expression of mesenchymal markers (CD73 and CD90) and expression of the pluripotent marker OCT4 and SOX2. Quantitative PCR analysis revealed that there were no differences in the patterns of gene expression (CD34, CD73, OCT4, CD30 and P53) between canine and feline AMSCs, with the exception of the expression of SOX2 and CD90.

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Genomic imprinting is an important epigenetic phenomenon, wherein genes or gene clusters are marked by DNA methylation during gametogenesis. This plays a major role in several functions of normal cells, including cell differentiation, X chromosome inactivation, and the maintenance of chromatin structure, in mammalian development. The aim of this study was to investigate the possible differences in SNRPN gene methylation profiles in non-obese and obese individuals, and in children and adults. Our results did not reveal any statistical correlations between the DNA methylation profiles of the SNRPN gene in children or adult obese and non-obese groups. However, a comparison of the methylation levels with the chronological age revealed statistically significant differences between the means of methylation in adults and children (46.20 ± 5.88 and 39.40 ± 2.87, respectively; P < 0.001). Pearson's correlation analysis indicated a positive association between the level of DNA methylation and the chronological age (R2 = 0.326; P < 0.001). Therefore, we concluded that the methylation profile of the SNRPN promoter (in blood) is not a useful biomarker for determining the predisposition of an individual to obesity. Additionally, we have confirmed that SNRPN methylation increases with age, which raises further questions regarding the role of SNRPN expression during the aging process.

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High-resolution melting (HRM) is considered an inexpensive, rapid, and attractive methodology for methylation analysis. In the application of the polymerase chain reaction (PCR) to methylation analysis, amplification efficiencies are biased towards unmethylated, rather than methylated, templates: a phenomenon known as PCR bias. To overcome PCR bias, primers that include CpG site(s) and are fully complementary to the methylated sequence have been proposed. However, genes mapped within imprinted regions usually present higher methylation levels, and an unusual PCR bias towards the methylated template can therefore arise. The manipulation of primer affinity attempts to overcome this problem. We attempted to show that mismatches at the primer's methylated binding sites increase the area between the 50 and 100% methylation plots on the melting curves, and may increase HRM accuracy for samples that have high methylation levels. Sets of primers for imprinted genes that included CpG sites at their binding sequences were designed, and were complementary to methylated or unmethylated templates. Primers fully complementary to methylated templates produced a very small area between the 50 and 100% methylation plots. When using primers that were fully complementary to the unmethylated sequence, we were able to increase the area between the 50 and 100% methylation plots. Therefore, when samples are highly methylated, such as targets in genes mapped in imprinted regions, we propose that primers should favor amplification of the rarest, unmethylated sequence. Primers may be designed to include one CpG at its binding site and be fully complementary to the unmethylated template.

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The adsorption of pH-responsive polyelectrolyte chains onto oppositely charged spherical macroions is investigated through Metropolis Monte Carlo simulations and the Weighted Histogram Analysis Method. In this case, the polymer charge density is susceptible to the solution conditions, such as salt concentration and pH, as well as the presence of other charged species. Thus, the pH and ionic strength variations leads to abrupt variations of the conformational and electric properties of the chain, as a result of first-order-like transition between the adsorbed and desorbed states. The diagram of states as a function of ionic strenght and p H is provided. Despite the inhomogeneities in the polyelectrolyte charge distribution induced by the macroion presence and its dependence on ionic strength, the scaling relation between the macromolecular charge densities and the critical Debye length is obtained in agreement with experimental investigations.

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To better understand the role of the M2 protein of the murine herpes virus strain 68 (MHV-68) in vivo, B-lymphocyte-restricted, M2-transgenic mice were constructed. The transgenic mice contained normal B-cell subpopulations in bone marrow, lymph nodes and spleen. After immunization with sheep red blood cells, spleens from M2-transgenic mice had increased germinal centres. Transgenic mice responded to the T-cell-dependent antigen keyhole limpet haemocyanin (KLH) with higher levels of secondary IgM and IgG2a antibodies than WT mice. Normal and M2-transgenic mice were infected with WT and M2 frame-shift mutant (M2FS) MHV-68 viruses. The pathogenesis of M2-transgenic mice infected with the M2-deficient mutant virus did not revert to that observed upon infection of normal mice with WT virus. However, the higher reactivation levels late after M2-transgenic mice were infected with WT virus reflected the importance of M2 as a target for the immune response, and thus with an impact on the establishment of latency. Finally, there was markedly less apoptosis in B-cells from M2-transgenic mice infected with either WT or M2FS mutant than from similarly infected WT mice, consistent with the published inhibitory influence of M2 on apoptosis in vitro. Thus, M2 provides a strategy to increase the pool of germinal centre B-cells through inhibition of apoptosis in the infected cell.

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The present cross-sectional study was designed to assess the frequency of 36 possible triggering factors precipitating a migraine crisis (hormonal, environmental, and dietary) in adult outpatients suffering from migraine attacks. A group of 123 migraine sufferers, aged 43.2 ± 13.9 (mean ± SD) years, including 114 (92.7%) women, 68.3% having migraine without aura, 68.3% reporting pain severe enough to require drug prophylaxis, and 29.3% presenting with hypertension, were evaluated. The most common triggers were stress and fasting, and environmental and hormonal factors were frequently found to precipitate a crisis. More than 90% of the patients reported susceptibility to 5 or more factors, and only 2.4% did not complain about any dietary factor. The large number of triggers detected in the present study emphasises the importance of awareness and avoidance of these factors in the management of patients with migraine.

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The present cross-sectional study was designed to assess the frequency of 36 possible triggering factors precipitating a migraine crisis (hormonal, environmental, and dietary) in adult outpatients suffering from migraine attacks. A group of 123 migraine sufferers, aged 43.2 ± 13.9 (mean ± SD) years, including 114 (92.7%) women, 68.3% having migraine without aura, 68.3% reporting pain severe enough to require drug prophylaxis, and 29.3% presenting with hypertension, were evaluated. The most common triggers were stress and fasting, and environmental and hormonal factors were frequently found to precipitate a crisis. More than 90% of the patients reported susceptibility to 5 or more factors, and only 2.4% did not complain about any dietary factor. The large number of triggers detected in the present study emphasises the importance of awareness and avoidance of these factors in the management of patients with migraine (AU)

El presente es un estudio transversal que fue diseñado para estimar la frecuencia de 36 posibles factores desencadenantes de iniciar una crisis de migraña (hormonales, ambientales y dietéticos) en pacientes adultos ambulatoriales que sufren ataques de migraña. Fue evaluado un grupo de 123 adultos que sufre de migraña, con edades entre 43,2 ± 13,9 (media ± DE), incluyendo 114 (92,7%) mujeres con migraña sin aura, 68,3% de las cuales informaron sentir dolor suficiente como para requerir profilaxis con fármacos y 29,3% con hipertensión. Los factores desencadenantes más comunes fueron el estrés y el ayuno; factores ambientales y hormonales fueron también desencadenantes frecuentes. Más del 90% de los pacientes informaron susceptibilidad a 5 o más factores, y sólo el 2,4% no informó de ningún factor dietético. El gran número de factores desencadenantes detectados en el presente estudio enfatiza la importancia del cuidado y la prevención de estos factores en el manejo de pacientes con migraña (AU)

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African swine fever virus (ASFV) encodes proteins that manipulate important host antiviral mechanisms. Bioinformatic analysis of the ASFV genome revealed ORF I329L, a gene without any previous functional characterization as a possible inhibitor of TLR signaling. We demonstrate that ORF I329L encodes a highly glycosylated protein expressed in the cell membrane and on its surface. I329L also inhibited dsRNA-stimulated activation of NFκB and IRF3, two key players in innate immunity. Consistent with this, expression of I329L protein also inhibited the activation of interferon-ß and CCL5. Finally, overexpression of TRIF reversed I329L-mediated inhibition of both NFκB and IRF3 activation. Our results suggest that TRIF, a key MyD88-independent adaptor molecule, is a possible target of this viral host modulation gene. The demonstration of an ASFV host evasion molecule inhibiting TLR responses is consistent with the ability of this virus to infect vertebrate and invertebrate hosts, both of which deploy innate immunity controlled by conserved TLR systems.

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Physical exercise induces biochemical changes in the body that modify analytes in blood and saliva among other body fluids. This study analyzed the effect of an incremental effort test on the salivary protein profile to determine whether any specific protein is altered in response to such stress. We also measured thresholds of salivary alpha amylase, total salivary protein and blood lactate and searched for correlations among them. Twelve male cyclists underwent a progressive test in which blood and saliva samples were collected simultaneously at each stage. The salivary total protein profile revealed that physical exercise primarily affects the polypeptide corresponding to salivary alpha-amylase, the concentration of which increased markedly during the test. We observed thresholds of salivary alpha-amylase (sAAT), total salivary protein (PAT) and blood lactate (BLT) in 58%, 83% and 100% of our sample, respectively. Pearson's correlation indicates a strong and significant association between sAAT and BLT (r= 0.84, P<0.05), sAAT and PAT (r= 0.83, P<0.05) and BLT and PAT (r= 0.90, P<0.05). The increased expression of the salivary alpha-amylase (sAA) polypeptide suggests that sAA is the main protein responsible for the increase in total protein concentration of whole saliva. Therefore, monitoring total protein concentration is an efficient tool and an alternative noninvasive biochemical method for determining exercise intensity.

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Aminophylline is a complex of theophylline-ethylenediamine, where theophylline is the main component. Theophylline is a methyxanthine and besides inhibiting phosphodiesterase enzymes, it is also a nonselective adenosine antagonist. Several reports suggested the involvement of the brain adenosinergic system in the ethanol-induced motor incoordination. Thus, the objective of this work was to study the effects of the interaction of ethanol with aminophylline as assessed by behavioral tests in mice. Eight groups of male Swiss mice were used. The animals were treated with either distilled water (control) or ethanol (E; 2, 4, and 6 g/kg, orally) for 5 days, or with distilled water for 4 days, and on the fifth day with aminophylline (A; 5 and 10 mg/kg, intraperitoneally). In the association groups (association protocols), the animals were treated with ethanol (E; 6 g/kg, orally) for 4 days, and on the fifth day received aminophylline (A; 10 mg/kg, intraperitoneally), 30 min after the last ethanol administration (first protocol, E/A). In the second association protocol (A/E), ethanol was administered for 4 days, and on the fifth day the animals received aminophylline (A; 10 mg/kg, intraperitoneally), followed again by ethanol (E; 6 g/kg, orally) administration, 30 min later. E (6 g/kg) evoked a central nervous system depressor effect, by decreasing both the locomotor activity and rearing in the open field test, and A (5 and 10 mg/kg) showed opposite effects. However, the E/A or A/E associations blocked the ethanol effect. In the rota rod test, ethanol presented a muscular relaxant effect, which was decreased in both association protocols. In the tail suspension test, while the E/A association decreased immobility, A/E association increased it, as compared with controls. In conclusion, the effects of ethanol were inhibited by its association with aminophylline, suggesting that ethanol acts on the adenosine neurotransmission.

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