Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

“De-[Constructing] Growth” is offered as a deeper and more useful conceptualization that avoids the negative connotations of, and resistance to, “degrowth” by decoupling profit from unsustainable consumption, production, and inequality.

Nowadays, we can observe a worldwide trend towards the development of synthetic biomaterials. Numerous researches have been carried out in order to better understand the cellular behavior involved in the inflammation and bone healing processes related to living tissues. The aim of this study is to evaluate the tissue behavior of two different types of biomaterials: synthetic nano-hydroxyapatite / beta-tricalcium phosphate and hydroxyapatite in non-critical bone defects in rat calvaria. Twenty four rats underwent surgery in which two 3 mm defects in each cavity were performed. The rats were divided into 2 groups: Group 1, using xenogen hydroxyapatite (Bio oss ™); Group 2, using synthetic nano-hydroxyapatite / beta-tricalcium phosphate (Blue Bone ™). Sixty days after the surgery, the calvaria bone defect was filled with biomaterial, the animals were sacrificed and marked with Masson's trichrome and PAS staining, and immunohistochemistry (TNF-α, MMP-9) and electron microscopy analyzes were performed. Histomorphometric analysis indicates a greater presence in the protein matrix in Group 2, in addition to higher levels of TNF-α, MMP-9. The ultrastructural analysis shows an association of material with fibroblasts in the tissue regeneration stage. Paired statistical data indicates that Blue Bone ™ can improve bone formation / remodeling when compared to biomaterials of xenogenous origin.

The understanding of spatiotemporal variations in reference evapotranspiration (ETo) and its long-term trends is of paramount importance for water cycle studies, modeling, and water resource management, especially in the context of climate change. Therefore, the primary aim of this study is to critically evaluate the performance of various CMIP5 global climate models in simulating the Penman-Monteith reference evapotranspiration and its associated climate variables (maximum and minimum air temperature, incident solar radiation, relative humidity, and wind speed). This evaluation is based on data from nine climate models and 33 automatic meteorological stations (EMA) in the state of Mato Grosso, spanning the period 2007-2020. The statistical metrics used for evaluation include Bias, root mean square error, and Pearson and Spearman correlation coefficients. The projections of the most accurate model were then used to analyze the spatial and temporal changes and trends in ETo under the RCP 2.6, 4.5, and RCP 8.5 scenarios from 2007 to 2100. The HadGEM2-ES model projections indicate static averages similar to current conditions until the end of the century in the RCP 2.6 scenario. However, in the RCP 4.5 and 8.5 scenarios, there is a continuous increase in ETo, with the most significant increase occurring during the dry period (May to September). The areas of the Amazon biome in the north of Mato Grosso exhibit the largest increases in ETo when comparing the observed (2007-2020) and projected (2020-2100) averages. The trend analysis reveals significant changes in ETo and its variables across the state of Mato Grosso in the RCP 4.5 and 8.5 scenarios. In the RCP 2.6 scenario, significant trends in ETo are observed only in the northern Amazon areas. Despite not being observed in all AWSs, the trend analysis of the observed data demonstrates more intense changes in ETo and the existence of the evapotranspiration paradox with an increase in the Cerrado areas and reductions in the Pantanal and southern Amazon areas.

(1) Background: Obesity and its comorbidities can cause burdens and limitations. Bariatric surgery (BS) is indicated as a safe procedure to reduce body mass and improve present comorbidities. Yet, several complications were reported, like vitamin D [25(OH)D] deficiency. We evaluated if 25(OH)D serum levels relate to clinical characteristics, symptoms, or habits in women after their BS and whether the vitamin D receptor (VDR) gene's TaqI and FokI polymorphisms affected 25(OH)D levels and the total body bone mineral density (TBBMD). (2) Methods: This cohort cross-sectional comparative analytical prospective study consisted of 27 women, 61.6 ± 5.0 years, submitted to BS one year prior at a public reference hospital, DF-Brazil. All participants were asked to follow the physical and dietary activity recommendations and received vitamin D3 supplements. Their anthropometric, biochemical, and immunological measurements and blood samples were obtained. (3) Results: 73.3% of participants had low 25(OH)D levels, and their levels correlated positively with TBBMD and negatively with systolic pressure. VDR TaqI did not affect 25(OH)D levels, whereas VDR FokI's allele f presence correlated to a median rise in 25(OH)D levels. Neither polymorphism correlated to TBBMD. (4) Conclusions: 25(OH)D levels were positively correlated with TBBMD, negatively with systolic blood pressure, and were higher in those with the VDR FokI allele f.

Transforming growth factor beta (TGF-β) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of T. cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF) and L6E9 skeletal myoblasts to TGF-β. Cultures of CM, CF and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-β (1–10 ng/mL, 1h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-β, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 is less stimulated in CF than CM and L6E9. After T. cruzi infection, localized FN disorganization was observed in infected CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-β showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-β after T. cruzi infection.

Blackberry is a fruit that has high nutritional value, a factor that has expanded its consumption worldwide. However, due to the fragility of the fruits and the high incidence of postharvest diseases, the fruits have a short shelf life. Thus, the objective of this study was to evaluate whether the application of coatings based on microfibrillated cellulose (NC) and lemongrass essential oil (EO) nanoparticles can prolong the shelf life of blackberry fruits after harvest. EO-coated blackberry fruits at nanocellulose concentrations were analyzed as follows: 0; 0.2; 0.4; 0.6 and 0.8%, in addition to the control treatment of which neither essential oil nor nanocellulose was used, for each treatment five repetitions were used. The fruits were analyzed soon after the application of the cover and at three and six days after storage. Fruit quality was assessed by soluble solids (SS), titratable acidity (TA), pH, fresh weight loss (FWL) and colorimetric parameters such as luminosity, hue angle and fruit peel chroma. Coating on EO (1000 ppm) blackberries combined with NC at concentrations of 0.2, 0.4 and 0.6% is promising in preserving blackberry fruits and reducing the process color reversal, up to six days of storage. The 0.4% NC + 1000 ppm EO conjugated coating showed no SS changes in blackberry fruits during the six days of storage.

Verminosis causes great damage to the producer, with reduced milk production and decreased development of young animals. The use of bioproducts are an alternative to control worms. This study evaluated the effects of oral administration of one commercial formulations, based on the fungus Duddingtonia flagrans (Bioverm®) and experimental formulations D. flagrans associated with Pochonia chlamydosporia, on the control of worms in naturally infected cattle on February pasture to October 2021. Eighteen Holstein x Zebu cattle were divided into groups of six animals (group 1 Bioverm®, group 2 Association and control), separated into paddocks naturally infected with helminth larvae (L3). The parasite load was by means of fecal samples and pasture collection to determine L3 infestation. The study demonstrated low recovery of L3 in the pasture due to low rainfall during the experiment. The EPG was lower in groups 1 and 2 compared to the control in April, May and July, while in March the values were lower only in treatment 1 compared to the control. Individual or combined administration of fungal products reduced the presence of eggs and larvae in pastures at certain months of the year, indicating their effectiveness in the strategic control of gastrointestinal parasites in cattle.

An explanation of the origin of dark matter is suggested in this work. The argument is based on symmetry considerations about the concept of mass. In the Wigner's view, the rest mass and the spin of a free elementary particle in flat space-time are the two invariants that characterize the associated unitary irreducible representation of the Poincar\'e group. The Poincar\'e group has two and only two deformations with maximal symmetry. They describe respectively the de Sitter (dS) and Anti de Sitter (AdS) kinematic symmetries. Analogously to their shared flat space-time limit, two invariants, spin and energy scale for de Sitter and rest energy for Anti de Sitter, characterize the unitary irreducible representation associated with dS and AdS elementary systems. While the dS energy scale is a simple deformation of the Poincaré rest energy and so has a purely mass nature, AdS rest energy is the sum of a purely mass component and a kind of zero-point energy derived from the curvature. An analysis based on recent estimates on the chemical freeze-out temperature marking in Early Universe the phase transition quark-gluon plasma epoch to the hadron epoch supports the guess that dark matter energy might originate from an effective AdS curvature energy.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

Tabebuia aurea (Silva Manso) Benth. & Hook. f. The ex S.Moore (yellow ipe), belonging to the Bignoniaceae family, used in the popular for fever, inflammation and healing of skin wounds. The extract was prepared by maceration, using 70% ethanol. Through HPLC analysis, it was possible to identify substances, mainly phenolic, such as lapachol, present in Bignoniaceae. The phenolic content was 21.36 mg / Eag in the antioxidant activity, the effective concentration of 50% was 53.03 ± 1.14 µg / mL. The antimicrobial activity against S.aureus, E. coli and C. albicans was evaluated by microdilution in broth, which verified action against the tested microorganisms. Cell viability has been inhibited for tumor cells, although this has not been observed for normal cells. The LD50 against A.aegypti mosquito larvae was 3504.6 mg / L and there was no mortality in the concentration tested for the snail B.glabrata. Nontoxic or low toxicity for A. salina and T. molitor, respectively, and did not exhibit hemolytic action at concentrations of antibacterial effect. Given the above, it was concluded that the bark extract of the studied species has bioprospecting potential for the future development of antimicrobial products.

Plants exhibit the capacity for adaptation through their metabolic processes to various changes in environmental conditions. Investigating these adaptations in current and future climatic scenarios is of great importance for ensuring productive agricultural crops. This adaptative potential is commonly employed as an indicator of genotypes with higher potential in breeding programs. However, the complexity and interaction of plant metabolic parameters pose a challenge to selection strategies. In this context, the aim of this study was to explore phenotypic plasticity within the germplasm of Hybrid Timor coffee. Additionally, we assessed the utility of the Phenotypic Plasticity Index (MVPi) as a promising tool to predict genotype performance across diverse climatic conditions. To achieve this, we evaluated the performance of seven accessions from the Hybrid Timor germplasm in comparison to the Rubi and IPR 100 cultivars, known for their susceptibility and resistance to drought, respectively. The experiment was conducted at greenhouse conditions, with two treatments: a control scenario, maintaining soil moisture near its maximum water-holding capacity, and a water deficit scenario involving irrigation cessation followed by rehydration. Data encompassing physiological, biochemical, and growth aspects were collected during three distinct stages: pre-application of water deficit, its imposition, and subsequent rehydration. Furthermore, field evaluations of the productivity of the same genotypes were carried out over two consecutive seasons. Based on physiological and biochemical assessments, the MVPi was computed, employing Euclidean distance between principal component multivariate analysis scores. Subsequently, this index was correlated with growth and productivity data through linear regressions. Our findings reveal that the more plastic genotypes, capable of significantly altering physiological and biochemical parameters in response to environmental stimuli, exhibited reduced biomass loss in both aerial and root parts, consequently positively influencing their productivity. Enhanced plasticity was particularly prominent in accessions from the MG Germplasm Collection: MG 311 - Hybrid Timor UFV 428-02, MG 270 - Hybrid Timor UFV 377-21, and MG 279 - Hybrid Timor UFV 376-31, alongside the Rubi MG 1192 cultivar. The MVPi emerged as a valuable instrument to assess genotype adaptability and predict their performance under varying climatic scenarios.

As a form of protection, a nature park is often created to protect and valorise natural and cultural heritage in peripheral rural areas. However, in terms of multi-functionality, new nature parks are incorporated into traditional productive activities, such as recreational and tourist activities, which sometimes compromise sustainability. The research objective is to study the relationship between tourism and sustainability in the Nature Parks of “Sierra de Aracena y Picos de Aroche”, “Sierra Norte de Sevilla” and “Sierra de Hornachuelos” that makes up the Dehesas de Sierra Morena Biosphere Reserve in Andalusia, Spain. Therefore, selective interviews have been carried out with the stakeholders to establish their perception of sustainable tourism and the presence of dominant discourses. The main conclusions indicate (1) the presence of different dominant discourses on sustainability, namely the conservationist and mercantilist ones, with the prevalence of the economic dimension; (2) poor awareness and adaptation to the context of global change; and (3) the presence of competitive relationships that generate difficulties for the governance of sustainable tourism.

Breast cancer represents the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. The relationship between HPV and various types of cancer, such as breast and lung, still requires further studies. After infection with HPV, there is a remodeling of the tumor microenvironment, providing a post-infection alteration with immunosuppressive characteristics. This study evaluated the role of HPV in breast adenocarcinoma cell lineage (MDA-MB-231), transfected with the HPV16 E5, E6, and E7 oncogenes and co-cultured with PBMCs. Immunophenotyping was performed. There was an increase in CD4+ T cells number when compared with non-transfected and transfected MDA-MB-231, especially the Treg profile. Moreover, proinflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17 were impaired by transfected cells and a decrease in the cytolytic ac-tivity of the CD8+ and CD56+ lymphocytes was also observed in the presence of HPV oncogenes, mainly with E6 and E7 in NK and TCD8+ cells. In conclusion, MDA-MB-231 breast cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

A review on planar printed structures that are based on Matryoshka-like geometries is presented. These structures use the well-known principle of Matryoshka dolls that are successively nested inside each other. The well-known advantages of the planar printed technology and of the meandered nested Matryoshka geometries are combined to generate miniaturized, multi-resonance and/or wideband configurations. Both metal and complementary slot structures are considered. Closed and open configurations are analyzed. The working principles are explored do get physical insight of their behavior. Low cost and single layer applications as frequency selective surfaces, filters, antennas, and sensors, in the microwave frequency region, are reviewed. Potential future research perspectives and new applications are discussed.

We discuss the consequences of the unique symmetry of the de Sitter spacetime. This symmetry leads to the specific thermodynamic properties of the de Sitter vacuum, which produces the thermal bath for matter. The de Sitter spacetime is invariant under the modified translations, ${\bf r}\rightarrow {\bf r} -e^{Ht}{\bf a}$, where $H$ is the Hubble parameter. For $H\rightarrow 0$, this symmetry corresponds to the conventional invariance of Minkowski spacetime under translations ${\bf r}\rightarrow {\bf r} -{\bf a}$. Due to this symmetry, all the comoving observers at any point of the de Sitter space perceive the de Sitter environment as the thermal bath with temperature $T=H/\pi$, which is twice larger than the Gibbons-Hawking temperature of the cosmological horizon. This temperature does not violate the de Sitter symmetry, and thus does not require the preferred reference frame, as distinct from thermal state of matter, which violates the de Sitter symmetry. This leads to the heat exchange between gravity and matter, and to instability of de Sitter state towards the creation of matter, its further heating, and finally to the decay of the de Sitter state. The temperature $T=H/\pi$ determines different processes in the de Sitter environment, which are not possible in the Minkowski vacuum, such as the process of ionization of an atom in the de Sitter environment. This temperature also determines the local entropy of the de Sitter vacuum state, and this allows us to calculate the total entropy inside the cosmological horizon. The result reproduces the Gibbons-Hawking area law, which is related to the cosmological horizon, $S_{\rm hor}=4\pi KA$, where $K=1/16\pi G$. This supports the holographic properties of the cosmological event horizon. We extend the consideration of the local thermodynamics of the de Sitter state using the $f({\cal R})$ gravity. In this thermodynamics, the Ricci scalar curvature ${\cal R}$ and the effective gravitational coupling, $K$, are thermodynamically conjugate variables. The holographic connection between the bulk entropy of the Hubble volume, and the surface entropy of the cosmological horizon remains the same, but with the gravitational coupling $K=df/d{\cal R}$. Such connection takes place only in the $3+1$ spacetime, where there is the special symmetry due to which the variables $K$ and ${\cal R}$ have the same dimensionality. We also consider the lessons from the de Sitter symmetry for the thermodynamics of black and white holes.

The leaves and stems of Bauhinia guianensis Aubl. are used in traditional Amazonian phytotherapy for the treatment of pain and inflammation. This study investigates the anti-inflammatory and antinociceptive effects of hydroethanolic extracts from B. guianensis Aubl. leaves and stems (HELBg and HESBg, respectively) in in vivo models of inflammation and hyperalgesia. Danio rerio experimental animals were submitted to the acute inflammation test, induced by intraperitoneal (ip.) administration of carrageenan 20 μg / animal (abdominal edema), the groups were previously treated orally with saline solution 2 μl / animal (SS), Dimethyl sulfoxide 2 μl / animal (DMSO), Indomethacin 10 mg/kg, HELBg 100 mg/kg and HESBg 100 mg/kg, n = 12 per experimental group, to evaluate inhibition of edema and alterations histopathology of the liver, intestine and kidney of these animals. The antinociceptive effect was observed from the body curvature index and the behavioral responses of Danio rerio, after an experimental protocol for the induction of hyperalgesia, by ip. administration of 10 μl / animal of 2.5% acetic acid, the animals were previously orally treated with saline solution 2 μl/animal (SS), dimethyl sulfoxide 2 μl/animal (DMSO), morphine 2.5 mg/kg, HELBg 100 mg/kg and HESBg 100 mg/kg, n = 5 per experimental group. In carrageenan-induced edema, the group treated with HESBg inhibited edema formation over the 3 hours of the experiment. Maximum edema was inhibited by 54% (p < 0.05) when compared to the control group. Both HELBg and HESBg prevented body curvature index changes (t (df = 3 8) =, 6.96 and t (df = 3, 8) = 6.61, respectively, both p < 0.0001). In the behavioral parameters sensitive to antinociceptive pharmacological modulation, due to the abdominal constriction induced by acetic acid, the administration of HELBg and HESBg resulted in an improvement in swimming activity, by increasing the distance covered (F (df = 3, 16) = 6.50 and F (df = 3, 16)  = 7.72, respectively, both p < 0.0001), decrease in freezing time (F (df = 3, 16)  = 2.04 and F (df = 3, 16)  = 1.28, respectively, both p < 0.0059), increase in the number of ascents to the upper area of the tank (F (df = 3, 16)  = 33.02 and F (df = 3, 16)  = 35.62, respectively, both p < 0.0009 ) and decreased time spent in that area (F (df = 3, 16)  = 101.19 and F (df = 3, 16)  = 103.59, respectively, both p < 0.0038). It is reasonable to suppose that both extracts modulated the variations induced by carrageenan and acetic acid through the inhibition of prostaglandin biosynthesis, decreasing the release of inflammatory mediators and the sensitization of peripheral nociceptors and, consequently, the perception of pain. These results suggest that HELBg and HESBg have anti-inflammatory and antinociceptive activities, probably of peripheral origin and linked to the inhibition of prostaglandin biosynthesis.

Dyslipidemia presents high levels of serum cholesterol, being characterized as a risk factor for cardiovascular diseases, especially for the development of atherosclerosis. E. oleracea (OFEO), A. esculentus (OFAE), B. orellana (OFBO) and granulated (CHR) oils are rich in bioactive compounds with potential to treat changes in lipid metabolism. This study investigated the effects of treatments with oils from A. esculentus, E. oleracea, B. orellana and granules (Chronic SM®) on saturated fat-induced dyslipidemia Cocos nucifera L. The chromatographic profile showed the majority of unsaturated fatty acids in the tested oils. The quantification of tocotrienols and geranylgeraniol was obtained in OFBO and CHR. Treatments with OFEO, OFAE, OFBO and CHR were able to significantly reduce glycemia with p>0.001, as well as hypertriglyceridemia, total cholesterol and LDL-cholesterol, in addition to increasing HDL-cholesterol. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats. The obtained results suggest that the OFEO, OFAE, OFBO and CHR groups have antidyslipidemic effects and antiatherogenic activity.

As recommended in the ICH Guidelines (S5-R2 and S6-R1), and based on bioethical concerns, we chose bovine embryos (BE) to check the in vitro embryo development considering the use of different amounts of rHGAL-1 as supplementations of in vitro embryo culture (IVP) mediums. Based on procedures for commercial BE in vitro production, using oocytes aspirated from slaughterhouse ovaries, the rHGAL-1 supplementation performed in two experiments (#01 on the oocyte maturation - IVM medium supplemented and experiment #2 on culture step IVC, supplemented SOF medium). There were IVP commercial procedures done, with 3 IVP batches per experiment and distributed the oocytes in four groups of treatment (one control group and three different dosages of rHGAL-1 to supplement both IVM and SOF mediums, using (2, 20 and 40µg.mL-1 respectively). A total of 962 (experiment 1) and 1,213 (experiment 2) oocytes were aspirated and submitted to IVP procedure. There was no damage to in vitro bovine embryos growth, considering cleavage percentage (%CLE), blastocysts development on day 7 (BlD7, BxD7, BhD7), or hatching blastocysts maturation on day 8 (BhD8%), regardless of rHGAL-1 supplementation. The immunohistochemistry assay with D8 embryos cultivated with rHGAL-1 supplementation on the culture medium (SOF medium) could demonstrate the presence of exogenous GAL-1, distributed in mass cell and trophoblastic cells, and the profile observed is dependent of exogenous supplementation and it was more evident in hatched embryos. The findings reassure the use of a reasonable amount of rHGAL-1 for in vitro embryonic development and make using rHGAL-1 in assisted reproduction in humans more reliable and safer.

The leaves and stems of Bauhinia guianensis Aubl. are used in traditional Amazonian phytotherapy for the treatment of pain and inflammation. This study investigates the anti-inflammatory and antinociceptive effects of hydroethanolic extracts from B. guianensis Aubl. leaves and stems (HELBg and HESBg, respectively) in in vivo models of inflammation and hyperalgesia. Danio rerio experimental animals were submitted to the acute inflammation test, induced by intraperitoneal (ip.) administration of carrageenan 20 μg / animal (abdominal edema), the groups were previously treated orally with saline solution 2 μl / animal (SS), Dimethyl sulfoxide 2 μl / animal (DMSO), Indomethacin 10 mg/Kg, HELBg 100 mg/Kg and HESBg 100 mg/Kg, n = 12 per experimental group, to evaluate inhibition of edema and alterations histopathology of the liver, intestine and kidney of these animals. The antinociceptive effect was observed from the body curvature index and the behavioral responses of Danio rerio, after an experimental protocol for the induction of hyperalgesia, by ip administration. of 10 μl / animal of 2.5% acetic acid, the animals were previously orally treated with saline solution 2 μl/animal (SS), dimethyl sulfoxide 2 μl/animal (DMSO), morphine 2.5 mg/Kg, HELBg 100 mg/Kg and HESBg 100 mg/Kg, n = 5 per experimental group. In carrageenan-induced edema, the group treated with HESBg inhibited edema formation over the 3 hours of the experiment. Maximum edema was inhibited by 54% (p < 0.05) when compared to the control group. Both HELBg and HESBg prevented body curvature index changes (t (df = 3 8) =, 6.96 and t (df = 3, 8) = 6.61, respectively, both p < 0.0001). In the behavioral parameters sensitive to antinociceptive pharmacological modulation, due to the abdominal constriction induced by acetic acid, the administration of HELBg and HESBg resulted in an improvement in swimming activity, by increasing the distance covered (F (df = 3, 16) = 6.50 and F (df = 3, 16)  = 7.72, respectively, both p < 0.0001), decrease in freezing time (F (df = 3, 16)  = 2.04 and F (df = 3, 16)  = 1.28, respectively, both p < 0.0059), increase in the number of ascents to the upper area of the tank (F (df = 3, 16)  = 33.02 and F (df = 3, 16)  = 35.62, respectively, both p < 0.0009 ) and decreased time spent in that area (F (df = 3, 16)  = 101.19 and F (df = 3, 16)  = 103.59, respectively, both p < 0.0038). It is reasonable to suppose that both extracts modulated the variations induced by carrageenan and acetic acid through the inhibition of prostaglandin biosynthesis, decreasing the release of inflammatory mediators and the sensitization of peripheral nociceptors and, consequently, the perception of pain. These results suggest that HELBg and HESBg have anti-inflammatory and antinociceptive activities, probably of peripheral origin and linked to the inhibition of prosta-glandin biosynthesis

In voice analysis, the electroglottographic (EGG) signal has long been recognized as a useful complement to the acoustic signal, if only when the vocal folds are actually contacting, such that this signal has an appreciable amplitude. However, phonation can occur also without vocal fold contacting, as in breathy voice, in which case the EGG amplitude is low, but not zero. It is of great interest to identify the transition from non-contacting to contacting, because this will substantially change the nature of the vocal fold oscillations; yet that transition is not in itself audible. The magnitude of the normalized peak derivative of the EGG signal is a convenient indicator of contacting, but no current EGG hardware has a sufficient signal-to-noise ratio of the derivative. The textbook techniques of spectral thresholding and static notch filtering are straightforward to implement, can run in real time, and can mitigate several noise problems in EGG hardware.

Recently quantum cosmology in tomographic representation was considered. as an important tool to analyze the quantum states of the early universe in relation with the subsequent classical evolution. Given a wave function the correspondent tomogram is defined proportional to the square modulus of its fractional Fourier transform. The classical limit obtained by taking the limit ℏ→0 can be compared with the classical tomogram obtained from the classical hamiltonian formalism. In this paper we show that a set of tomograms can be derived as exact solutions of a third order equation when a de Sitter quantum universe is considered. We finally discuss the limits of this approach to quantum cosmology because the extension to equations with arbitrary potentials can become extremely complicated for potentials given by algebraic polynomials of degree greater than two and therefore also for potentials expressible by arbitrary functions.

Despite advances in algorithms and computational platforms, de-novo genome assembly remains a challenging process. Due to the constant innovation in sequencing technologies (Sanger, SOLiD, Illumina, 454, PacBio and Oxford Nanopore), genome assembly has evolved to respond to the changes in input data type. This paper includes a broad and comparative review of the most recent short-read, long-read and hybrid assembly techniques. In this review, we provide (1) an algorithmic description of the important processes in the workflow that introduces fundamental concepts and improvements; (2) a review of existing software that explains possible options for genome assembly; and (3) a comparison of the accuracy and the performance of existing methods executed on the same computer using the same processing capabilities and using the same set of real and synthetic datasets. Such evaluation allows a fair and precise comparison of accuracy in all aspects. As a result, this paper identifies both the strengths and weaknesses of each method. This comparative review is unique in providing a detailed comparison of a broad spectrum of cutting-edge algorithms and methods.

Wound healing is rarely seen as a problem in healthy individuals; however, under certain pathophysiological conditions, this process can be impaired, leading to the emergence of chronic wounds, which are themselves a serious public health problem. This work aimed to review the most important and recent literature on the use of metallic nanoparticles, in this case those produced from plant extracts, and their application as healing agents. For this, we firstly provided an insight into the pathophysiology of the wound healing process and then the main routes for obtaining metallic nanoparticles. The methodology of synthesis, which is part of the so-called green synthesis, has been the subject of several studies reporting the use of medicinal plants as subtracts for the production of different nanoparticles (of silver, gold, and zinc). Additionally, their use as wound healing agents is close related with biological properties such as antimicrobial, anti-inflammatory, and healing. Finally, we addressed in vitro and in vivo studies reporting the efficiency of metallic nanoparticles synthesized with plant extracts and applied in different pharmaceutical forms on the wound healing process. Based on these satisfactory results, we verified that metallic nanoparticles are potential therapeutic alternatives when compared to the traditional synthetic healing agents, thus foreseeing the production of new drugs in the pharmaceutical market.

This paper describes the preparation and description of four new complexes [Bu₂Sn(AA)Cl] (AA = glycine, DL-valine and L-leucine) and [Bu₂SnPhen₂] (Phen = DL-phenylalanine) They were characterized by elemental analyses of carbon, hydrogen, nitrogen, chlorine and tin; and by infrared, ^119mSn-Mössbauer and ^119mSn-RMN spectroscopies, and by the applications of TG and DSC techniques in dynamic helium atmosphere. For the [Bu₂Sn(AA)Cl], trigonal bipyramidal tin species, AA were coordinated bidentatedly by the carboxylic oxygen and by the NH₂ group. The [Bu₂SnPhen₂)], with tin atoms in trans-octahedral sites, had the Phen-coordinated by both carboxylic oxygen atoms.

The aim of this study was synthesize and evaluate the effects of Poly (D, L-Lactide-co-glycolide) (PLGA) Nanoparticles (NPs) of metformin (PLGA+ Met) on inflammation, and bone loss in a ligature-induced periodontitis rat model. The prepared NPs were characterized by mean diameter, size particle, polydispensity index and encapsulation efficiency by Atomic force microscopy (AFM). Male albino Wistar rats were randomly divided into four groups of 20 rats in each group, and given the following treatments for 10 days to evaluate in vivo activity: (1) Sham: no ligature + water; (2) Positive control: ligature + water (with Periodontal disease and Diabetes); (3) ligature + PLGA+ 10 mg/kg Met (With Periodontal disease and Diabetes); and (4) ligature + PLGA+ 100 mg/kg Met (with Periodontal disease and Diabetes). Water or PLGA + Met was administered orally by gavage. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantify linear of bone loss. Histopathological characteristics were assessed through immunohistochemical staining for Osteocalcin, Cathepsyn K, RANKL/RANK/OPG pathway. IL-1β and TNF-α from gingival tissues were analysed by Elisa immunoassay. Quantitative RT-PCR reaction was used to evaluate gene expression of AMPK, NF-κB p-65, Hmgb1 and TAK-1 from gingival tissues. Statistical analysis was performed using one-way ANOVA at 5% significance. The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm with a polydispersity index of 0.285, zeta potential: 8.16 ± 1.1 mV and entrapment efficiency (EE) was 70%. The results suggest that the addition of MET in the core slightly affected the particle sizes. Treatment with PLGA+ 10 mg/kg Met showed low inflammatory cells, decreased bone loss and integrity cement and levels of IL-1β, and TNF-α (p < 0.05) were significantly reduced. Additionally, weak staining was shown by RANKL, Cathepsyn K, OPG, and osteocalcin. Radiographically, linear measurements showed a statistically significant reduction in bone loss after treatment with PLGA+ 10 mg/kg Met compared to the positive control (p < 0.05). RT-PCR showed increased AMPK expression (p < 0.05) and decreased expression of NF-κB P65, HMGB1 and TAK-1 after PLGA+ 10 mg/kg Met (p < 0.05). The PLGA nanoparticle + 10 mg/kg Met decreased glucose levels and also decreased the inflammatory response, and bone loss in ligature-induced periodontitis in rats.

Objective: to analyze the relationships between sociodemographic variables, intolerance to uncertainty (INT), social support and psychological distress (i.e., indicators of Common Mental Disorders [CMDs] and perceived stress [PS]) in Brazilian men during the COVID-19 pandemic. Methods: a cross-sectional study with national coverage, of the web survey type, and conducted with 1,006 Brazilian men during the period of social circulation restriction imposed by the health authorities in Brazil, for suppression of the coronavirus and control of the pandemic. Structural equation modeling analysis was performed. Results: Statistically significant direct effects of race/skin color (λ=0.268; p-value<0.001), socioeconomic status (SES) (λ=0.306; p-value<0.001), household composition (λ=0.281; p-value<0.001), PS (λ=0.513; p-value<0.001) and INT (λ=0.421; p-value<0.001) were evidenced in the occurrence of CMDs. Black-skinned men, with higher SES, living alone and with higher PS and INT levels presented higher prevalence values of CMDs. Conclusions: high levels of PS and INT were the factors that presented the strongest associations with the occurrence of CMDs among the men. It is necessary to implement actions to reduce the stress-generating sources, as well as to promote an increase in resilience and the development of intrinsic reinforcements to deal with uncertain threats.

Cryptococcus neoformans is a fungus that mainly affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, part of the first line of defense, important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse" taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal or capsule total did not present toxic effects for the DH82 macrophage cell line. However, it was possible to demonstrate that phagocytic activity was decreased after treatment with polysaccharides. In addition, yeasts recovered from macrophages treated with the polysaccharides, after phagocytosis, could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR- expression. Furthermore, our data suggests that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.

While there are software tools available for assisting to conduct the Life Cycle Assessment (LCA), such as OpenLCA, these tools lack integration with process design, simulation and optimization software. As LCA has critical role in sustainable product design, it is presented in this work a platform called EMSO_OLCA, which integrates the LCA provided by OpenLCA into the Environment for Modeling, Simulation, and Optimization (EMSO). EMSO_OLCA incorporates a database of environmental impact assessment methodologies from OpenLCA and aligns to the principles of LCA outlined in ISO 14040 and ISO 14044. Validation tests were conducted to compare the results obtained by the LCA of sugarcane ethanol using OpenLCA and EMSO_OLCA, revealing a high level of agreement. The average relative error was 0.045%, indicating a negligible discrepancy between the tools. Besides, it took only 0.3 seconds for calculation, which is desirable for using with process systems engineering tools. A second case study was applied to a steam and bioelectricity production from the combustion of sugarcane bagasse and straw in a combined heat and power system. The results show the integration of LCA with simulation and sensitivity analysis tools, thus contributing for supporting sustainable decision-making processes. EMSO_OLCA bridges the gap between LCA and process engineering, enabling a holistic approach to sustainability, design and implementation of environmentally friendly solutions.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relation exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms." Bibliographic references from relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

Changes in food quality can dramatically impair zooplankton fitness, especially in eutrophic water bodies where cyanobacteria are usually predominant. Cyanobacteria are considered a food with low nutritional value, besides some species can produce bioactive secondary metabolites reported as toxic to zooplankton. Considering that cyanobacteria can limit survival, growth and reproduction of zooplankton, we hypothesized that the adverse effects of the dietary exposure of Daphnia species to saxitoxin-producing cyanobacteria depend on the relative abundance of nutitious food source in the diet. Life table experiments were conducted with different diets: 1) without nutritional restriction, where neonates were fed with diets at a constant green algae (Monoraphidium capricornutum) biomass as a nutritious food source, and increasing cyanobacterial concentration (STX-producing Raphidiopsis raciborskii), and 2) with diets consisting of different proportions of M. capricornutum (nutritious) and R. raciborskii (poor food) at a total biomass 1.0 mg C L 1. In general, the presence of high proportions of cyanobacteria promoted a decrease in Daphnia somatic growth, reproduction and intrinsic rate of population increase (r) in both diets with more pronounced effects in the nutritionally restricted diet (90% R. raciborskii). Two-way ANOVA revealed significant effects of species/clone and treatments in both assays, with significant interaction between those factors only in the second assay. Regarding the grazing assay, only D. laevis was negatively affected by increased cyanobacterial proportions in the diet. In the life table assay with constant edible food, a reduction in the reproduction parameters and the intrinsic rate of population increase (r) of all species was observed, In conclusion, we found adverse effects of the toxic cyanobacterial strain R. raciborskii on Daphnia fitness, regardless of the constant amount of nutritious food available, proving the toxic effect of R. raciborskii and the nutritional quality of the food has a greater influence on the fitness of these animals.

The wave energy converter (WEC) technology constantly develops new designs and models. To encourage its development within the energy sector, research is required to improve current designs and create durable and effective devices. However, it is also crucial to investigate the suitability of a WEC to a site-specific sea condition as this can impact its optimal power absorption and constructability. This study evaluates and compares the efficiency of a heaving buoy with varied geometries in one of the most energetic places along the Mexican coast. A statistical analysis of the wave climate on the coast of Ensenada during the last 42 years is performed to define the conditions to which the device is subjected. The location of the WEC in shallow waters is chosen using a computational model which solves the modified mild slope equation in its elliptic shape. The heaving buoy floater is studied using three distinct geometries: a semi-sphere, a cylinder, and a proposed rounded semi-rectangle. The hydrodynamic response of the three geometries is then analysed in the frequency and time domain using ANSYS AQWA. The hydrodynamic study involves the assessment of the floating body dynamics, exerted forces, the power absorbed as well as the suitability of the proposed power take-off (PTO) system. Findings reveal that the proposed geometry absorbs the most energy, with an annual power of 135.11 MW, and that the transmission PTO design is appropriate for this type of technology.

Antarctica is one of the most inhospitable continents on the planet, with lichens and mosses being the most common terrestrial organisms in ice-free areas. Antarctica is represented by only two species of Angiosperms, Deschampsia antarctica Desv. (Poaceae) and Colobanthus quitensis (Kunth) Bartl. (Caryophyllaceae). In this study, we characterized fungi isolated from the leaves of this grass species. The fungi were isolated from 4 individual plants from Half Moon Island (246 leave fragments investigated), and 7 from King George Island - Keller Peninsula (with 111 leave fragments investigated) Antarctica. Neoascochyta paspali, Phaeosphaeria elongata, Pyrenophora cf. chaetomioides and Alternaria sp. were associated with the plant and identified through analysis of the sequences of the internal transcribed spacer region (ITS) of the rDNA and nuclear ribosomal large subunit rRNA gene (LSU) as well as macro and micro-morphological characteristics. The isolates showed a better growth rate ranging from 10–20°C. An interesting result was that the fungi are already recognize as both plant pathogens and endophytic fungi. The results demonstrate that D. antarctica is an interesting fungal source. Those species might provide important information about the relationship on the endemic Antarctic biota.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p&lt; 0.0001) and NAC+Pb groups (p&lt;0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was done by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins and DNA. The cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile shows obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with IC50 of 4.86 ± 0.51 µg/mL and 8.33 ± 0.90 µg/mL in the ABTS assay for ELSR and ERSR, respectively. And in the DPPH• assay, the IC50 was 19.98 ± 1.96 µg/mL for ELSR and 13.37 ± 1.05 µg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 µg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 hours of treatment. After 48 h, results against the K562 cell line demonstrate IC50 of 242.54 ± 2.38 µg/mL and 223.00 ± 2.34 µg/mL for ELSR and ERSR , respectively. While against the Jurkat cell line, these extracts showed IC50 of 171.45 ± 2.25 µg/mL and 189.30 ± 2.27 µg/mL, respectively Results on PBMC viability, demonstrate that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions. This study expands the repertoire of identified chemical compounds and underscores their significant pharmacological potential in conditions related to oxidative stress and leukemia.

Drought stress has been considered a major problem in coffee crops, and the higher occurrence of unpredictable environmental events has highlighted the vulnerability of agricultural systems. Several reports have indicated selenium (Se) as a plant biostimulant against environmental stress, including drought. The effects of Se in plants are related to the modulation of enzymatic activity, energetics and osmoprotectants plant content, and nutrient balance in plants. However, investi-gating the effective time of Se application is crucial for better understanding its effects on coffee plants, a drought-sensitive crop. This study aimed to investigate the role of Se supply in improving drought tolerance in coffee seedlings while also evaluating the best timing for Se application. Five times of Se foliar application were assessed during induced drought stress by PEG-6000 using the day of imposing stress as a default, plus two control treatments: i) with osmotic stress and without Se; ii) without osmotic stress and Se. The treatments were compared with both control treatments. Results demonstrated that the osmotic stress (OS) promoted mild stress in the coffee plants, as ex-pected. Plants under stress showed reduced GR and SOD activity compared with the non-stressed ones, and the OS induces starch degradation, which is potentialized by Se foliar supply, mainly when Se is applied before inducing the stress. The decline in the starch content might be considered a strategy to provide energy to coffee seedlings. The seedlings that received foliar Se application 8 days before the stress exhibited higher CAT, APX, and SOD than those that did not receive OS nor Se application. The results obtained in this study suggest that the previous Se foliar spray is more effective than the Se supply after OS to overcome the adverse condition. On the other hand, the post-stress application seems to impose extra stress on the plants, leading them to reduce the water potential.

The covid-19 pandemic has generated substantial changes in the lives of the population, such as increased physical inactivity, which can lead to overweight and, consequently, repercussions on glucose homeostasis. A population-based household epidemiological survey was conducted by stratified, multistage probability cluster sampling (October and December 2020) in Brazil. Participants were classified as physically active or inactive during leisure time according to the recommendations of the World Health Organization. HbA1c levels were categorized as normal (≤6.4%) or with glycemic changes (≥ 6.5%). The mediating variable was excess weight (overweight and obese). Multivariate logistic regression analyzes were performed to examine the association between physical inactivity and glycemic changes. Mediation was analyzed using the Karlson–Holm–Breen method to verify the influence of excess weight on the association. We interviewed 1,685 individuals, mostly women (52.4%), 35–59 years old (45.8%), race/ethnicity brown (48.1%), and excess weight (56.5%). The mean HbA1c was 5.68% (95% CI: 5.58-5.77). Individuals physically inactive were 2.62 times more likely to have glycemic alterations (OR:2.62.95% CI:1.29-5.33), and 26.87% of this association was mediated by excess weight (OR:1.30:95% CI:1.06-1.57). Physical inactivity in leisure time increases the chances of glycemic alterations, and part of this association can be explained by excess weight.

Computer systems that operate in remote locations such as satellites, remote weather stations and autonomous robots are highly limited in the availability of energy for their operation. This work aims to employ artificial intelligence algorithms in energy management in order to obtain the maximum energy yield and the prediction of energy availability to the system. The work presents the main types of algorithms used in artificial intelligence and presents the creation of a prototype that will operate as a low power system powered by batteries and a small solar plate, the prototype will perform inferences on the LSTM neural network algorithm in order to predict the future availability of energy, consequently the management system will carry out the energy distribution in order to obtain the maximum operation of the prototype without total discharge of the batteries. So that the artificial intelligence system could be embedded in the prototype, the TensorFlow Lite framework was used, which allows the inference to be carried out in devices with low consumption and limited processing power.

The catalytic parameters describing enzyme catalysis are discussed in the context of the design of de novo enzymes. It is shown that high values of the catalytic efficiency may in some cases reflect tight substrate binding and lead to an immediate levelling-off of rates to reach a low plateau, an undesirable scenario for many industrial applications. It is argued that increasing the catalytic rate constant should be a main target in de novo enzyme engineering.

The Human Herpesviruses persist in the form of a latent infection in specialized cell types. During latency, the herpesvirus genomes associate with cellular histone proteins and the viral lytic genes assemble into transcriptionally repressive heterochromatin. Although there is divergence in the nature of heterochromatin on latent herpesvirus genomes, in general the genomes assemble into forms of heterochromatin that can convert to euchromatin to permit gene expression and therefore reactivation. This reversible form of heterochromatin is known as facultative heterochromatin and is most commonly characterized by polycomb silencing. Polycomb silencing is prevalent on the cellular genome and plays a role in developmentally regulated and imprinted genes, as well as X chromosome inactivation. As herpesviruses initially enter the cell in an un-chromatinized state, they provide an optimal system to study how de novo facultative heterochromatin is targeted to regions of DNA and how it contributes to silencing. Here, we describe how polycomb-mediated silencing potentially assembles onto herpesvirus genomes, synergizing what is known about herpesvirus latency with facultative heterochromatin targeting to the cellular genome. A greater understanding of polycomb silencing of herpesviruses will inform on the mechanism of persistence and reactivation of these pathogenic human viruses and provide clues regarding how de novo facultative heterochromatin forms on the cellular genome.

Evaluating the economic impact of airports is crucial for understanding the benefits they bring to a region. However, when an area has more than one airport, it becomes essential to analyze each airport's contribution to the local economy to make informed investment and policy decisions. Thus, studying economic models that can distinguish each airport's impact on the region's economy becomes essential. In this context, this paper aims to compare three different approaches to determine the economic contribution of airports in a given region and identify their social and economic benefits. The International Civil Aviation Organization recommends using Input-Output analysis in this context. The study considered three weight factors for the Input-Output basic model: circular buffer, displacement time, and Huff's gravitational model. The analysis was performed using the three largest airports in São Paulo's state, Brazil, due to their proximity and influence on the surrounding area. The models were compared based on their efficiency and accuracy in reflecting the reality of the case study context. The study identified the most suitable model for establishing correlations between investments made in airport infrastructure and the generation of gross domestic product, employment, and added value. This study fills a gap in the existing literature by proposing improvements to the methods for evaluating airports' economic and social benefits. In recent times, airport investors, both in the government and private sectors, have become increasingly demanding in their need for accurate analyses before making investments. Therefore, the results of this paper will provide valuable insights into the benefits of investing in airport infrastructure and help policymakers and investors make informed decisions.

Background: This work presents Com@Rehab, a technological patient-centred activity for individuals needing a physical rehabilitation approach and with a specific loss of functionality. Within this scope, this paper focuses on the description of the activity in virtual reality (VR), its components, design and user profile, and its versatility and future adaptability regarding different ages, pathologies and rehabilitation contexts. Methods: The VR activity has been customised according to the patient's clinical needs while replicating an activity of daily living, namely showering. In addition, to validate and get feedback on the developed system, a validation questionnaire was applied to a group of healthy individuals to test the efficiency of the technology that supports the VR activity. Results: Preliminary results show that 94% of the participants recommended the experience, the performance of the various components of the system was successfully implemented, participants quickly adhered to the VR technology, and the UI assistant’s functionality should be improved. Conclusion: This solution creates a more effective, interactive, humanised rehabilitation approach based on a Virtual Reality (VR) activity. The Com@Rehab Communication Module improves human-human and human-machine communication while contributing to health literacy.

Endophytic fungi are those that present part of their life cycle in healthy tissues of different plant hosts in symbiosis without causing harm. At the same time, fungus-plant symbiosis makes it possible for microorganisms to synthesize their own bioactive secondary metabolites while in stationary stage. Such microorganism-derived secondary metabolites contribute. Therefore, this work aimed to. To accomplish this, the endophytic fungus Trichoderma asperellum was isolated from Bertholletia excelsa (Brazil nut) almonds. The fungus was cultivated and extracted with ethyl acetate, obtaining AM07Ac. Then, using HPTLC (High-performance thin-layer chromatography) and Nuclear Magnetic Resonance (1H NMR), β-amyrin, kaempferol, and brucine were identified as major compounds. Further in vivo assays in Zebrafish demonstrated the activity of AM07Ac on melanogenesis by producing a concentration-response inhibitory effect, which, through an in silico study, proved to be related to the noted major compounds known to inhibit tyrosinase activity. The inhibition of tyrosinase prevents melanin accumulation in skin. Therefore, these results imply the importance of investigating microorganisms and their pharmacological activities, in particular the endophytic fungus Trichoderma asperellum as a generator of active metabolites for melanogenesis modulation.

Alzheimer's disease is characterized by a progressive decline of cognitive functions. The class of drugs used for the treatment are acetylcholinesterase inhibitors. Essential oils have contributed to folk medicine and discovery of new drugs for a long time. The purpose of the study was to investigate the in vitro and in silico the anti-acetylcholinesterase activity, as well as acute toxicity of the essential oil of Lippia origanoides. EOLO was obtained by hydrostelting and analyzed by gas chromatography-mass spectrometry. The inhibition assay of acetylcholinesterase enzyme activity was evaluated in vitro, as well as in silico by docking. The effects of EOLO on hematological, biochemical and behavioral parameters were analyzed in mices. We expose that EOLO shows good anti-acetylcholinesterase activity and low toxicity, possibly resulting from the action of the majority compounds thymol, carvacrol and p-cymene. The anti-acetylcholinesterase potential in vitro demonstrating a 70% inhibition. The docking results elucidated the participation of the major phenolics in AChE inhibition by interacting with the catalytic cavity of AchE. The acute oral toxicity test classified as low toxicity. These results contribute to expand the knowledge about essential oil of Lippia origanoides. Therefore, appears to be promising for herbal medicine production with anti-acetylcholinesterase and antioxidant activity.

Objectives Bone fractures are very common diseases, which can be caused by impact injuries or physiological disorders. Thus, the present review aimed to study the use of medicinal plants in the healing mechanism of bone fractures. Evidence acquisition Through research in the PubMed, Google Academic, and Scielo databases, this article reviews 11 ethnopharmacological studies and 34 preclinical studies on the biological actions of different plants in bone fracture healing mechanism. Results Indian tribes have highlighted in the plants ethnopharmacological study for various diseases, including bone fractures. However, despite the large citations of traditional use, technical-scientific studies are still scarce in the literature. Chenopodium ambrosioides, Piper sarmentosum, quadrangular Cissus, Ricinus communis and Radix salvia miltiorrhiza plants were the most studied in the literature regarding their osteogenic, angiogenic, anti-inflammatory and remodeling effects, acting on bone receptors, stimulating bone metabolism, increasing minerals uptake, and assisting in free radicals breakdown. Conclusion Thus, the medicinal plants use is promising in the field of bone regeneration, as well as being alternative when conventional therapies are unfeasible, increasing herbal medicines demand and popularity.

Pesticide exposure is a growing concern for public health. Although Brazil is the world's largest consumer of pesticides, few studies addressed the health effects among farmers. This study aimed to evaluate whether pesticide exposure is associated with respiratory outcomes among rural workers and relatives in Brazil during the crop and off-seasons. 82 family farmers were interviewed about occupational history and respiratory symptoms, and cholinesterase tests were conducted in the crop-season. Spirometry was performed during the crop and off-season. Respiratory outcomes were compared between seasons and multiple regressions were conducted to search for associations with exposure indicators. Participants were occupationally and environmentally exposed to multiple pesticides from an early age. During the crop and off-season, respectively, they presented a prevalence of 40% and 30.7% for cough, 30.7% and 24% for nasal allergies, and 24% and 17.3% for chest tightness. Significant relations between spirometry impairments and exposure indicators were found both during the crop and off-season. These findings provide complementary evidence about the association of pesticide exposure with adverse respiratory effects among family farmers in Brazil. This situation requires special attention as it may increase the risk of pulmonary dysfunctions, and the morbidity and mortality burden associated with these diseases.

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state of the art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states which interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological sates, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented adding an exponential cutoff to the interaction term of PPP model. In this way, an adjusted cutoff distance λ = 2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond Hubbard model but not completely unscreened as is the case for the PPP model.

Aging is a complex process associated with tissue degeneration and an increased risk of age-related diseases. This study aimed to evaluate the impact of Terasen®, a nutraceutical containing standardized extracts of Euterpe oleracea, Myrciaria dubia, and purified oil of Bixa orellana and Astrocaryum aculeatum on the lifespan of Caenorhabditis elegans, a widely used model organism for aging research. The findings demonstrated that Terasen® exhibited significant antioxidant activity and influenced the feeding behavior of C. elegans, leading to a reduced pharyngeal pumping rate and a decreased number of offspring produced by treated individuals. Notably, Terasen® also displayed a remarkable ability to extend the lifespan of C. elegans. These findings suggest that Terasen® may possess promising anti-aging effects in vivo, warranting further investigation.

It is already known that a simple nonlocal de Sitter gravity model, which we denote as dS gravity, contains an exact vacuum cosmological solution which mimics dark energy and dark matter and is in very good agreement with the standard model of cosmology. This success of dS gravity motivated us to investigate how it works at lower than cosmic scale – galactic and the solar system. This paper contains our investigation of the corresponding Schwarzschild-de Sitter metric of the dS gravity model. To get exact solution, it is necessary to solve the corresponding nonlinear differential equation, what is a very complicated and difficult problem. What we obtained is a solution of linearized equation, which is related to space metric far from the massive body, where gravitational field is weak. The obtained approximate solution is of particular interest for examining the possible role of non-local de Sitter gravity dS in describing the effects in galactic dynamics that are usually attributed to dark matter. The solution has been tested on the Milky Way and the spiral galaxy M33 and is in good agreement with observational measurements.

In this paper we propose the generation of synthetic small and more sophisticated molecule structures that optimize the binding affinity to a target (ASYNT-GAN). To achieve this we leverage on three important achievements in A.I.: Attention, Deep Learning on Graphs and Generative Adversarial Networks. Similar to text generation based on parts of text we are able to generate a molecule architecture based on an existing target. By adopting this approach, we propose a novel way of searching for existing compounds that are suitable candidates. Similar to question and answer Natural Language solutions we are able to find drugs with highest relevance to a target. We are able to identify substructures of the molecular structure that are the most suitable for binding. In addition, we are proposing a novel way of generating the molecule in 3D space in such a way that the binding is optimized. We show that we are able to generate compound structures and protein structures that are optimised for binding to a target.

Long-read single-molecule sequencing has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. It also has been widely used to study structural variants, phase haplotypes and more. Here, we introduce the assembler— SMARTdenovo, which is an SMS assembler that follows the overlap-layout-consensus (OLC) paradigm. SMARTdenovo (RRID: SCR_017622) was designed to be a fast assembler that did not require highly accurate raw reads for error correction, unlike other, contemporaneous SMS assemblers. It has performed well for evaluating congeneric assemblers and has been successful for a variety of assembly projects. It is compatible with Canu for assembling high-quality genomes, and several of the assembly strategies in this program have been incorporated into subsequent popular assemblers. The assembler has been in use since 2015, and here we provide information on the development of SMARTdenovo and how to implement its algorithms into current projects.

A thin-shell wormhole is crafted by the cut-and-paste method of two Bardeen de-Sitter black holes using Darmois-Israel formalism. Energy conditions are considered for different values of magnetic charge while both mass and cosmological constant are fixed. The attractive and repulsive characteristics of the throat of the thin-shell wormhole are also examined through the radial acceleration. Dynamics and stability of the wormhole are studied around the static solutions of the linearized radial perturbations at the throat of the wormhole. The regions of stability are determined by checking out the condition of concavity of the potential as a function in the throat radius for different values of magnetic charges.

Abstract: Objective: analyze the effectiveness of the implementation of the Lean Healthcare sys-tem at the emergency room of the Clinical Hospital of the Federal University of Uberlândia (HC-UFU), based on a comparison of hospital indicators obtained over the three phases corre-sponding to the period of one year before the implementation (T1), the year during the imple-mentation (T2) and one year after implementation (T3). Material and Methods: this is applied research, classified as a case study, exploratory, descriptive that is developed in stages. Based herein on the search for hospital indicators, as occurred in the implementation process of Lean in Emergencies at the HC-UFU and a description of the implemented Lean system. Results and Discussions: during the period where it was possible to collect data relevant to the NEDOCS and LOS indicators, the motivation of the teams grew, but with a notable tension between municipal management and hospital management. It was found that, despite the fluctuations, the patient length of stay in the Emergency Room remained high. Noteworthy here is that with the excep-tion of the variable of female deaths before 24 hours of hospitalization, all other variables showed percentage increases before and after the intervention. Conclusion: the methodology followed for the implementation of Lean in Emergencies in the emergency sector of the hospital did not produce an improvement in hospital indicators.

The term “medical error” is quite often used to refer to any mistake committed in the provision of healthcare services which has caused harm to a patient. Objective: To analyze civil lawsuits involving medical errors in pediatrics by evaluating: 1) causal link; 2) type of medical error; 3) conviction of the court and its legal basis; 4) correlation between medical expert understanding and legal understanding. Materials and Method: Retrospective analysis of 60 pediatric forensic medical examinations carried out by a pediatric expert between April 2009 and February 2014 at the Institute of Medicine and Criminology of the State of São Paulo (IMESC). The expert’s reports were analyzed according to age, gender, type of forensic medical report (direct or indirect), conclusion of the expert’s report (causal link between the medical conduct and complaint or not), type of medical error (negligence, recklessness, malpractice), judgment in the first instance (if in accordance with the expert’s report or not), and basis of judgment as objective or subjective (type of law). Results: Most expert’s examinations (65%) were indirect (death). In 27 reports (45%), the expert’s conclusion determined that there was a causal link between medical care and the damage inflicted to a patient. Of the 27 reports with causal link, the judge was not in accordance with the expert’s report in one case, thus not considering medical error. The vast majority of sentences (55) were in accordance with the expert’s conclusion (91.6%). Subjective law was mostly used to support the judge’s ruling (61.70%), followed by objective law (23.30%). All lawsuits claimed moral damages (100%). In the statistical analysis of distribution of nominal variables (frequency), an excellent agreement (kappa= 0.86), with statistical significance, was verified between the expert’s report and the court ruling. Conclusion: Expert evidence supported 91.6% of the sentences and was considered to be highly valuable evidence. Expert evidence had a major impact on the legal proceedings and has proven statistically significant (p<0.005). Subjective law was used to assess medical error in all cases in which healthcare professionals were involved. Claims for moral damages was requested in all lawsuits, and was fully or partially granted in 100% of the cases.

The first treatments with dental implants had low success rates (75%). Nowadays, oral rehabilitation with titanium dental implants has a high success rate (95-98%). The success rate significantly increases due to increased scientific knowledge about osseointegration, changes in surgical techniques, and the development of implant surface treatments. Despite the high success rate of implants, no protocol defines the time for the prosthesis to be installed and loaded after surgery. This work compares a new dental implant's primary (mechanical) and secondary (osseointegration) stability. Dental implant with micro- and nano-roughness surface was placed in 24 patients with a minimum of 35 N.cm and a maximum of 60 N.cm. Primary stability was quantified with a torque wrench and Ostell Mentor. The secondary stability 45 and 60 days after surgery was measured with Ostell. The results showed no statistical difference in secondary stability at 45 and 60 days postoperatively among implants. The success rate of dental implants can be associated with the surface morphology with micro and nano-roughness and the shape of the fillets of the implant threads. When the manufacturer's guidelines are followed, it is possible to prosthetically rehabilitate the patient with an implant 45 days after surgery.

In the course of SARS-CoV-2 infection, the 3CL or nsp5 protease plays a pivotal role as the most important viral protease required for the maturation of viral proteins during host infection. Herein, we simulated for 500 ns 3CLproWT, 3CLproH41A, , 3CLproBeta, and 3CLproOmicron, in complex with the substrates nsp 4|5 and nsp 5|6. Our results show that mutations in the 3CLpro present in the SARS-CoV-2 variant of concerns (VOCs) did not lead to significant conformational changes or changes in substrate binding affinities. However, significantly high cleavage rates for the boundary between nsp4 and nsp5 were obtained for 3CLproBeta and 3CLproOmicron and may play a key role in the viral replication and virus fitness gain. Our molecular dynamics data suggest that the cleavage rate of nsp4|5 may be related to the increased amount of viral load observed for these VOCs, releasing more nsp4 than other non-structural proteins. Based on our hydrogen bonding analyses, we also discovered that Gly143 and Glu166 are key residues in substrate recognition, suggesting that these residues may be incorporated as pharmacophoric centers for Beta and Omicron variants in drug design. Our results suggest that Gly143 and Glu166 are essential residues to interact with Gln6 of the different substrates and, therefore, are potential broad-spectrum pharmacophoric centers of SARS-CoV-2 3CLpro.

We validated a new noninvasive tool (B4C) to assess intracranial pressure waveform (ICPW) morphology in a set of neurocritical patients, correlating the data with ICPW obtained from invasive catheter monitoring. Materials and Methods: Patients undergoing invasive intracranial pressure (ICP) monitoring were consecutively evaluated using the B4C sensor. Ultrasound-guided manual internal jugular vein (IJV) compression was performed to elevate ICP from the baseline. ICP values, amplitudes, and time intervals (P2/P1 ratio and time-to-peak [TTP]) between the ICP and B4C waveform peaks were analyzed. Results: Among 41 patients, the main causes for ICP monitoring included traumatic brain injury, subarachnoid hemorrhage, and stroke. Bland-Altman’s plot indicated agreement between the ICPW parameters obtained using both techniques. The strongest Pearson’s correlation for P2/P1 and TTP was observed among patients with no cranial damage (r = 0.72 and 0.85, respectively) in detriment of those who have undergone craniotomies or craniectomies. P2/P1 values of 1 were equivalent between the two techniques (area under the receiver operator curve [AUROC], 0.9) whereas B4C cut-off 1.2 was predictive of intracranial hypertension (AUROC 0.9, p < 000.1 for ICP > 20 mmHg). Conclusion: B4C provided biometric amplitude ratios correlated with ICPW variation morphology and is useful for noninvasive critical care monitoring.

For the KdV-Burgers equations on cylindrical and spherical waves the development of a regular profile starting from an equilibrium under a periodic perturbation at the boundary is studied. The equations describe a medium which is both dissipative and dispersive. Symmetries, invariant solutions and conservation laws are investigated. For an appropriate combination of dispersion and dissipation the asymptotic profile looks like a periodical chain of shock fronts with a decreasing amplitude (sawtooth waves). The development of such a profile is preceded by a head shock of a constant height and equal velocity which depends on spatial dimension as well as on integral characteristics of boundary condition; an explicit asymptotic for this head shock and a median of the oscillating part is found.

Recently, the properties of bouncing oil droplets, also known as `walkers', have attracted much attention because they are thought to offer a gateway to a better understanding of quantum behaviour. They indeed constitute a macroscopic realization of wave-particle duality, in the sense that their trajectories are guided by a self-generated surrounding wave. The aim of this paper is to try to describe walker phenomenology in terms of de Broglie-Bohm dynamics and of a stochastic version thereof. In particular, we first study how a stochastic modification of the de Broglie pilot-wave theory, à la Nelson, affects the process of relaxation to quantum equilibrium, and we prove an H-theorem for the relaxation to quantum equilibrium under Nelson-type dynamics. We then compare the onset of equilibrium in the stochastic and the de Broglie-Bohm approaches and we propose some simple experiments by which one can test the applicability of our theory to the context of bouncing oil droplets. Finally, we compare our theory to actual observations of walker behavior in a 2D harmonic potential well.

Soil water infiltration is an important component of the hydrological cycle and it is best evaluated when the raindrop is impacted on the ground surface. For this reason, it is affected by changes in land use and occupation, and by the characteristics and physical-hydric properties of the soil. This study aimed to evaluate soil water infiltration in areas occupied with annual crops (soybean and corn) and pastures, in two watersheds of the Teles Pires River-MT, using simulated rainfall, physical models and principal component analysis. Infiltration rates were evaluated from simulated rainfall with an average intensity of 75 mm h-1, with 4 repetitions per region (upper, middle and lower) of the hydrographic sub-basins of the Caiabi and Renato rivers, and soil use with cover, without cover and disturbed. Soil tillage provided higher water infiltration rates into the soil, especially in pasture areas in the two hydrographic sub-basins. There were significant adjustments of the mathematical models to the infiltration rate data for all land use and land cover conditions. The soil attributes that most interfered with the infiltration rate were microporosity, soil density and total porosity in the crop areas of the middle Caiabi, and microporosity, clay content, total porosity and silt content in the areas farming at the source of the Renato River. The Horton and Philip models presented the best adjustments in the hydrographic sub-basins of the Renato and Caiabi and Renato rivers, being recommended for estimating the rate of water infiltration into the soil in different uses, coverages, and regions.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for the delivery of vaccine antigens, besides present adjuvants properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. These prophylactic strategies are fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the Envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, besides activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct, using yeast as a vehicle, reinforcing the applicability of P. pastoris as a whole yeast cell vaccine.

(1) Background: Older people hospitalized with Covid-19 can reduced the capacity to walk. However, the prevalence of impairment of ambulation capacity still need to be established. Objective: To estimate the prevalence and identify the risk factors associated with the impairment of ambulation capacity at hospital discharge of older people with Covid-19. (2) Methods: A retrospective cohort study. Included age &gt; 60 years, both sexes, hospitalized due to Covid-19. Clinical data was collected from the medical records. Ambulation capacity prior to Covid-19 infection was assessed through the patient report from his relatives. Multiple logistic regressions were performed to identify the risk factors associated with the impairment of ambulation at hospital discharge. (3) Results: Data from 429 older people were randomly. Among the 56.4% who were discharged, 57.9% had reduced ambulation capacity. Factors associated with reduced ambulation capacity at discharge were hospital stay higher than 20 days (OR: 3.5) and dependent ambulation capacity prior to Covid-19 (OR: 11.3). (4) Conclusion: More than half of the older people who survived hospitalized due to Covid-19 had reduced ambulation capacity at hospital discharge. Impaired ambulation prior to the infection, and a longer hospital stay were risks factors for reduced ambulation capacity.

During the last years there has been a high interest in the development of new purely-organic single-component conductors. Very recently, we have reported a new neutral radical conductor based on the perchlorotriphenylmethyl (PTM) radical moiety linked to a monopyrrolo-tetrathiafulvalene (MPTTF) unit by a -conjugated bridge (1). Interestingly, this system behaves as a semiconductor with high conductivity and small energy gap under high pressure. With the aim of developing a new material with improved conducting properties, we have designed and synthesized the radical dyad 2 which was functionalized with an ethylenedithio (EDT) group in order to improve the intermolecular interactions of the TTF subunits. The physical properties of the new radical dyad 2 were studied in detail in solution to further analyze its electronic structure as well as its potential use as radical conductor in the solid state.

The violence against women is a theme that extrapolates health issues, since after a victim seek for a health care, there is the notification of the act [1]. In Brazil, many times, these women are first assisted by mobile urgency services (SAMU/SIATE) and, as far as we have concern, there are no other studies with specific data about these assistance. The present paper aimed to analyze SAMU/SIATE assistance to abused women. Qualitative and retrospective epidemiological study of assistance to assaulted women carried out by SIATE and SAMU Maringá/Norte Novo between 2011 and 2020. Women between 20 and 39 years old, non-pregnant, were the main victims, and 19,52% of them have used some kind of drug. The (ex)partner figured as the perpetrator in 17,35%, but there were no information about this variable in 73,75% of the records. The Qui-square test shows a mortality rate superior to 70% among the severe traumatized victims. This is one of the first studies to analyze this kind of care provided by SAMU/SIATE, and reveals some gaps in its “modus-operandi” that can limitate an extrapolation of the results to bigger spheres. More researches in mobile urgency care services, in other provinces also, are needed to propose strategies to fight against this epidemic.

Over the last decades, the increased incidence of metabolic disorders such as type 2 diabetes and obesity has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes was assessed by in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated by Lineweaver–Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 1.67–10.23 x 10-1 mmol/L). The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 1.62–5.19 x 10-1 mmol/L). Finally, PPC84, PPC89, and PPC101 also showed a potent inhibitory effect on α-glucosidase (IC50 of 0.51–3.53 x 10-1 mmol/L). PPC80 and PPC82 followed a non-competitive inhibition mechanism against pancreatic lipase, while PPC84 acted through competitive inhibition. The inhibition of pancreatic α-amylase by the derivatives was non-competitive, as well as for PPC84, PPC89 and PPC101 against α-glucosidase. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

The plague caused by the Yersinia pestis bacterium is primarily a flea-transmitted zoonosis of rodents that can also be conveyed to humans and other mammals. In this work, we analyzed the spatial and temporal distribution of rodents’ populations during active and quiescent periods of the plague in the municipality of Exu, northeastern Brazil. The geospatial analyses had shown that all rodent species occurred through the whole territory of the municipality with different hotspots for the risk of occurrence of the different species. Important fluctuation in the rodent populations was observed with a reduction in the wild rodent fauna following the end of a plague epidemic period, mostly represented by Necromys lasiurus and increase of the commensally species Rattus rattus. A higher abundance of rats might lead to an increased exposure of humans populations, favoring spillovers of plague and other rodent-borne diseases. Our analysis contributed to further highlight the role of the wild rodent species as the amplifier hosts and of the commensally rats (Rattus rattus) as the preserver hosts on the quiescent period on that transmission infection area.

Introduction: Studies conducted in real-life scenarios on vaccine protection against COVID-19 constitute an important global priority, but one that is currently mostly neglected in low- and middle-income countries such as Angola. Here, we analyze for the first-time vaccine protection against COVID-19 in a real-life scenario after 6 months of implementing a multi-vaccination plan in Angola, providing estimation of odds ratios in vaccinated individuals and vaccine efficacy against infection by SARS-CoV-2 in a period that coincided with the identification of the Omicron variant in the country. Methods: We used a negative test case-control design to assess the effectiveness of vaccination against confirmed SARS-CoV-2 infection. A total of 4.232 vaccinated and unvaccinated individuals with the result of a rapid antigen diagnostic test against SARS-CoV-2 performed from December 27 to 28, 2021 were included in the study. Data were extracted from the Digital Vaccination Record Platform (Rediv) of the Ministry of Health of Angola. All ethical procedures related to the authorization necessary to carry out the study were followed. Statistical analyzes were performed using version 7.5.2.0 of CDC's Epi Info. Frequency distributions and measures of central tendency were used to characterize the study universe. The general and sex-adjusted and age-adjusted odds ratios, were evaluated by comparing the chances of vaccination between cases and controls, and their associated 95% CI, which were calculated using the Mantel-Haenszel stratification method. The risk classification of Axel Kroeger, Piscoya and Alarcon was used to interpret the odds ratio. The Breslow-Day statistic was used to assess the homogeneity of the odds ratios. Vaccine efficacy was calculated using the odds ratio applying the accepted statistical vaccine efficacy formula:(1 − odds ratio) × 100. For all estimates, a P value < 0.05 was considered statistically significant. Results: The population consisted of 63.63% male and 36.37% female. The mean age was 36 years with a standard deviation of 13. 83. Regarding vaccination status, 83.27% of individuals were vaccinated and 16.73% were unvaccinated, with 21.81% positive and 78.19% negative for SARS -CoV-2. The odds of SARS-CoV-2 infection were 0.85 (95% CI 0.70 – 1.03) times lower in vaccinated compared to unvaccinated individuals, with P=0.09. The overall vaccine efficacy (VE) was 15% (95% CI -3 – 30). Conclusion: There was no statistically significant decrease in the chances of SARS-CoV-2 infection in vaccinated versus unvaccinated individuals. However, the overall vaccine efficacy was 15%.

De-escalation is currently taking place both in surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor over 20 years ago was a milestone in the treatment of HER2 positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in case of small, node-negative, HER2 positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2 targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2 positive early breast cancer. Despite promising early results from these studies, combination of anti-HER2 treatment with chemotherapy backbone remains standard of care.

The recent covid crisis has proven important lessons for academia and industry regarding digital reorganization. Among fascinating lessons from these times is the huge potential of data analytics and artificial intelligence. The crisis exponentially accelerated the adoption of analytics and artificial intelligence, and this momentum is predicted to continue into the 2020s and over. Moreover, drug development is a costly and time-consuming business, and only a minority of approved drugs return the revenue that exceeds the research and development costs. As a result, there is a huge drive to make drug discovery cheaper and faster. With modern algorithms and hardware, it is not too surprising that the new technologies of artificial intelligence and other computational simulation tools can help drug developers. In only two years of covid research, many novel molecules have been designed/identified using artificial intelligence methods with astonishing results in terms of time and effectiveness. This paper will review the most significant research on artificial intelligence in the de novo drug design for COVID-19 pharmaceutical research.

It is shown that, for a de Sitter Universe, the Hartle-Hawking (HH) wave function can be obtained in a simple way starting from the Friedmann- Lemaitre-Robertson-Walker (FLRW) line element of cosmological equations. An oscillator having imaginary time is indeed derived starting from the Hamiltonian obtaining the HH condition. This proposes again some crucial matter on the meaning of complex time in cosmology. In order to overcome such difficulties, we propose an interpretation of the HH framework based on de Sitter Projective Holography.

Speckle noise corrupt the major part of ultrasound image, because of which the quality deteriorate and loss of valuable information leads to false diagnosis. A large community of images like synthetic aperture radar (SAR) image, Synthetic image, and simulated ultrasound image, require despeckling at pre-processing stage for better processing. Cleaning the speckle from image and preserving the edge details is a vital task. Nowadays not only despeckling is considered as an important process but also preserving information at boundary and edges of image is also important. As most of the algorithms able to remove speckle noise but fails to preserve the details of edges. This paper covers several recent methods for removal of speckle noise along with various metrics opted for comparisons. The distinctive part of this paper is, a mathematical and parametric review has been done. Also a table is also included which summarizes the entire paper.

Primary stability is an important factor for dental implant success. In the past years, a new method for bone site preparation was introduced, named osseodensification (OD). OD produces a condensation of the trabecular portion of the bone, increasing bone-to-implant contact and primary stability. This study aims to compare the effect of OD in cylindrical and conical implants to conventional instrumentation. A total of 40 implants, divided in 4 groups, were placed in porcine tibia: cylindrical conventional (1a); cylindrical OD (1b); conical conventional (2a); and conical OD (2b). Each implant was measured for implant stability quotient (ISQ), insertion torque (IT) and removal torque (RT). Group 2b showed the higher values for each of the evaluated parameters; groups 1b and 2b showed better results than 1a and 2a, respectively. Regarding IT and RT, group 1b achieved higher values than group 2a, but not for ISQ. The inter-groups comparison showed significant difference between groups 1a vs 2a, 1a vs 2b and 1b vs 2b for ISQ, and 1a vs 1b and 1a vs 2b for RT analysis. OD resulted in improved ISQ, IT and RT of both cylindrical and conical implants. Conical implants groups showed higher ISQ, but cylindrical OD resulted in higher IT and RT, compared to conical conventional ones.

Autonomous weapons systems (AWS), sometimes referred to as “killer robots”, are receiving evermore attention, both in public discourse as well as by scholars and policymakers. Much of this interest is connected with emerging ethical and legal problems linked to increasing autonomy in weapons systems, but there is a general underappreciation for the ways in which existing law might impact on these new technologies. In this paper, we argue that as AWS become more sophisticated and increasingly more capable than flesh-and-blood soldiers, it will increasingly be the case that such soldiers are “in the power” of those AWS which fight against them. This implies that such soldiers ought to be considered hors de combat, and not targeted. In arguing for this point, we draw out a broader conclusion regarding hors de combat status, namely that it must be viewed contextually, with close reference to the capabilities of combatants on both sides of any discreet engagement. Given this point, and the fact that AWS may come in many shapes and sizes, and can be made for many different missions, we argue that each particular AWS will likely need its own standard for when enemy soldiers are deemed hors de combat. We conclude by examining how these nuanced views of hors de combat status might impact on meaningful human control of AWS.

The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the improvements in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa in latest years. The USA SEER Research Data (2000-2017) were analyzed using the SEER*Stat software. The Kaplan-Meier method and Cox regression were used. Patients with de novo mPCa were allocated to 3 cohorts based on year of diagnosis: A (2000-2003), B (2004-2010), C (2011-2014). Maximum follow-up was fixed to 5 years. Overall, 26434 patients were included. Age, race and metastatic stage significantly affected OS and CSS. After adjustment for age and race, patients in cohort C showed 9% reduced risk of death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) and 8% reduced risk of cancer-specific death (HR:0.91 [95% CI, 0.87-0.95], p&lt;0.001) compared to those in cohort A. After adjustment for age, race and metastatic stage, patients in cohort C showed an improvement in OS and CSS compared to cohort B (HR:0.94 [95% CI, 0.91-0.97], p=0.001 and HR:0.89 [95% CI, 0.85-0.92], p&lt;0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between cohort B and C. In conclusion, the prognosis of de novo mPCa remains poor with a median OS of 30 months and a median CSS of 35 months. Limited OS and CSS improvements were observed in latest years.

This article studies examines the relationship of literature, ideology, and reading through a study of language, or la langue, as explored by De Man, Derrida, and Lacan. It attempts to show that structure, assumed to be the given of language, even within deconstruction, is, as structure, that which undoes structure. Literature explores this possibility of language, which is that it be and not be at the same time. The article finishes by studying the connection between this idea of literature as the possibility of language and the possibility of man, an important theme of the above three thinkers.

The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

Knowing the spatial variability of factors that influence crop yield is essential to carry out a localized treatment. The present study aimed to map the spatial variability of apparent soil electrical conductivity (ECa) in two cultivation areas, delimit management zones (MZ), characterize the soil density (Sd) at two depths, in each MZ, and assess whether the delimitation of MZ, based on the spatial variability of ECa, was able to identify regions of the productive field with different Sd. Spatial variability of ECa was detected. MZ with the highest mean value of ECa also presented the highest mean values of Sd. The highest Sd values were observed for the 0.1 – 0.2 m layer, regardless of the studied area. Regardless of granulometry, the proposed method was able to detect density differences from ECa. The delimitation of MZ, based on the spatial variability of ECa mapping, was able to differentiate the mean values of Sd between MZ 1 (1.53 g cm-3) and MZ 2 (1.67 g cm-3) in the Area A, in the 0.1 – 0.2 m layer. A statistical difference was observed for the mean values of Sd, in MZ 1, layer 0.1 - 0.2 m, when comparing the two study areas: A (1.53 g cm-3) and B (1.64 g cm-3). We suggest that further studies should be carried out, as the mapping of the spatial variability of the apparent soil electrical conductivity showed potential in the differentiation of soil bulk density at different depths.

The phytonutraceutical Ormona® is a product composed of: purified oil of Bixa orellana Linné; dry extract of Myrciaria dubia McVaugh; dry extract of Trifolium pratense L. and dry extract of Euterpe oleracea Mart. obtained using Evolve® technology. This study evaluated the effects of Ormona® on Wistar rats affected by ovariectomy-induced osteoporosis. Pre-treatment was conducted for 15 days before surgery and continued for a further 45 days after the surgical procedure. The experimental design consisted of 5 groups (n=5): OVW: treated with distilled water (1 mL/ kg, p.o); ADS: alendronate sodium (4 mg/ kg p.o); EST: conjugated estrogen (2 ug/ kg, p.o); ORM: Ormona® (20 mg/kg, p.o); ORM + EST: Ormona® (20 mg/kg + conjugated estrogen 2 ug/ kg, p.o. Biochemical and hormonal parameters, along with bone histopathology and trabecular and femoral diaphysis size, were evaluated through Scanning Electron Microscopy (SEM) and bone calcium quantification by atomic absorption spectrophotometry. The results show that ovariectomy caused bone alterations such as loss of femoral microarchitecture, decreased bone homeostasis parameters, and changes in the lipid profile. Estrogen supplementation reduced parameters such as cholesterol, LDL, and Ca2+ concentration. However, Ormona® showed higher serum estradiol levels (p&lt; 0.01), effects on the lipid profile, including parameters that estrogen replacement and alendronate sodium did not affect, with an increase in HDL, and positive modulation of bone metabolism, increasing osteocytes and the presence of osteoblasts. Ormona®, therefore, produced better results than the groups treated with estrogen and alendronate sodium.

The accumulation of brown algae from the genus Sargassum has been increasing over the years in coastal regions of the Caribbean, Africa, Brazil, and Mexico. This causes harmful effects to the ecosystem, health, economy, and climate due to gas emissions from its decomposition process. There is the possibility of this biomass being reused in civil construction, and few studies have been carried out on its application to common Portland cement mortar. As such, the objective of this study is to evaluate the potential of sargassum ash as a mineral addition to partial replacement of fine aggregates in Portland cement mortar. Characterizations of the raw materials were carried out through X-ray fluorescence spectroscopy, loss on ignition, particle size distribution, Brunauer–Emmett–Teller (BET), real density, X-ray diffraction, scanning electron microscopy, and dispersion spectroscopy of electrons. The mortars were prepared by partially replacing the fine aggregate (sand) with sargassum ash, at 0%, 5%, 10% and 20%. Mortar performance was evaluated through water absorption, apparent porosity, apparent specific mass, compressive strength after 7, 28, and 63 days after curing. Lastly, a life cycle assessment in accordance with ISO standards 14040:2006 and 14044:2006. The results showed that replacing sand with sargassum ash increases water absorption, apparent porosity, and decreases the apparent specific mass and compressive strength as replacement increases. Nevertheless, the compressive strength results after 63 days, for 5 and 10% replacement did not differ statistically from reference values. The life cycle assessment indicates that mortars with partial replacement of sand by sargassum ash showed positive environmental impacts when compared to reference values for most categories regardless of the scenario analyzed, especially for mortar with 10% replacement. As such, the use of sargassum ash at 10% does not alter compressive strength values after 63 days while reducing its environmental impact. The application of this biomass in civil construction materials provides a destination for this algae that has been causing several social, environmental, and economic problems.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

The anti-Covid19 vaccination campaign has been fortified on the positive effects that immunization is bringing the nations, since infection rates, hospitalizations, and deaths have been falling according to the data in constant disclosure by official government organs and the channels of communication. In Brazil, the effective and free National Vaccination Program haven’t prioritized patients with rare diseases, who have extreme comorbidities, and who had to follow the calendar prepared by the government. The problematic question is why these “rare people” weren´t considered priorities. The understanding of the reasons and the resumption of the debate about the rights of patients with rare diseases justify this study, which sought to be based on regular descriptors issued by official government agencies and by critics of rare disease issues in debates made in scientific articles. We sought to respond to the following objectives: analyze dispensed care of rare disease patients in the vaccination campaign anti-Covid-19; identify the procedures implemented by the National Vaccination Plan for the Brazilian population over 18 years of age; describe the panorama of the pandemic disease since its discovery to the mutations already disseminated; and evaluate the effectiveness of the plan implemented from the perspective of “rare person”.

In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width - Coefficient of Variation)—in 117 glioblastoma patients. Data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan-Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in NLR, PLR, and RDW-CV across different treatment stages. NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p=0.007, η2p=0.06; PLR: p=0.001, η2p=0.23), while RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p &lt; 0.001, η2p=0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR=1.03, p=0.029; RDW-CV at progression: HR=1.14, p=0.004). We proposed specific marker cutoffs that demonstrated significant associations with survival outcomes when applied to Kaplan-Meier survival curves (NLR at 2nd line &lt; 5: p&lt;0.017; RDW-CV at progression &lt; 15: p=0.007). Elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

Taking into account the growing interest in microalgae to be used as raw material for biodiesel production, this research is aimed at analyzing the rheological behaviour of microalgae suspensions (Chlorella sp) at different culture times under eight different conditions (temperature, salinity and CO₂, NO₃ and PO₄ levels) in order to estimate the energy demands of each step, with the purpose of optimizing a continuous feed tubular bioreactor construction. For each condition, it was calculated the biomass and oil yields, so as to correlate these results with rheological parameters. The suspension results indicated that the microalgae Chlorella sp is a non-Newtonian material with dilatant characteristics; the processing time hardly exerted an influence on the rheograms of the suspension of the microalgae Chlorella sp, except for the simultaneous conditions of low salinity and low CO₂ content; NO₃ and PO₄ contents and the amount of supplements influenced the rheological parameters of the suspension of the microalgae Chlorella sp, when in low concentration of CO₂ and low salinity levels.

Background: Bibliometric analysis provides insight into knowledge gaps of a specific field. We want to know what part of medical care has been the subject of research in a group of Mexican physicians. The Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) cares for a wide spectrum of disease and it provides a unique vision of what specialists has investigated about health. Methods: Papers belonging to “ISSSTE” affiliation were harvested and downloaded to .csv Excel files from the Scopus database including most bibliometric variables. VOSviewer, biblioshiny and bibliometric were used to conduct the bibliometric. Results: 2,063 papers were found and re-trieved; internal medicine had the greatest number of papers with 831; nine institutions were listed claiming “ISSSTE” as their mother affiliation; original papers represent 82% of the total and 52% of them were written in Spanish. Research production in Mexico City and the most productive center is Centro Médico Nacional 20 de Noviembre. Discussion: We identified main institutions, prolific authors, top-cited researchers and their affiliations, however, our paper is a call to action for the medical community in Latin America to join our efforts in building a solid group of researchers for the future of science.

Dengue virus (DENV) and chikungunya virus (CHIKV) are reemergent arboviruses that are transmitted by mosquitoes of the Aedes genus. During the last several decades, these viruses have been responsible for millions of cases of infection and thousands of deaths worldwide. Therefore, several investigations were conducted over the past few years to find antiviral compounds for the treatment of DENV and CHIKV infections. One attractive strategy is the screening of compounds that target enzymes involved in the replication of both DENV and CHIKV. In this review, we describe advances in the evaluation of natural products targeting the enzymes involved in the replication of these viruses.

Object recognition is an essential element of machine intelligence tasks. However, one model cannot practically be trained to identify all the possible objects it encounters. An ensemble of models may be needed to cater to a broader range of objects. Building a mathematical understanding of the relationship between various objects that share comparable outlined features is envisaged as an effective method of improving the model ensemble through a pre-processing stage, where these objects' features are grouped under a broader classification umbrella. This paper proposes a mechanism to train an ensemble of recognition models coupled with a model selection scheme to scale-up object recognition in a multi-model system. An algorithmic relationship between the learnt parameters of a trained classification model and the features of input images is presented in the paper for the system to learn the model selection scheme. The multiple models are built with a CNN structure, whereas the image features are extracted using a CNN/VGG16 architecture. Based on the models' excitation weights, a neural network model selection algorithm, which links a new object with the models and decides how close the features of the object are to the trained models for selecting a particular model for object recognition is developed and tested on a five-model neural network platform. The experiment results show the proposed model selection scheme is highly effective and accurate in selecting an appropriate model for a network of multiple models.

In recent decades, the requirements for implantable medical devices increased, but the risks of implant rejection still exist. These issues are primarily associated with poor osseointegration, leading to biofilm formation on the implant surface. This study focuses on addressing these issues by developing a biomaterial for implant coatings. 45S5 Bioglass has been widely used in tissue engineering due to its ability to form a hydroxyapatite layer, ensuring a strong bond between the hard tissue and the bioglass. In this context, 45S5 bioglasses, modified by the incorporation of different amounts of copper oxide, from 0 to 8 mol%, were synthesized by the melt-quenching technique. The incorporation of Cu ions does not show a significant change in the glass structure. Since the bioglass exhibited the capacity of being polarized, and therefore promoting the osseointegration effectiveness, the electrical properties of the prepared samples were studied using the impedance spectroscopy method, in the frequency range of 102-106 Hz and temperature range of 200-400 K. The effects of CuO on charge transport mobility were investigated. Additionally, the bioactivity of the modified bioglasses was evaluated through immersion tests in simulated body fluid. The results revealed the initiation of a Ca-P-rich layer formation on the surface within 24 h, indicating the potential of the bioglasses to enhance the bone regeneration process.

O26 enteropathogenic Escherichia coli (EPEC), possesses a unique pseudocapsule composed of polysaccharides identical to the O antigen in their lipopolysaccharide (LPS) membrane. Therefore, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC was investigated. Our findings reveal that the concentration of GlcNAc, an immunodominant unit of O26 polysaccharides capable of activating the MBL (Mannose Biding Lecting) pathway of the complement system, was found to be lower in capsulated EPEC O26 compared to naked shiga toxin-producing E. coli (STEC) O26 strain. It was noted that, unlike the naked STEC strain, the capsulated EPEC O26 strain was protected against lysis by the alternative pathway of the com-plement system by inhibiting C3b adhesion to its bacterial surface. Capsulated EPEC O26 strains were also able to avoid phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies. Additionally, these antibodies were able to recognize O26 EPEC in the presence of biofilm and inhibit their adhesion to human epithelial cells. Overall, the results indicate that the O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the de-velopment of a vaccine against capsulated O26 E. coli

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, while using Karen Freeze’s criteria as to the breakup of primordial black holes to give radiation era contributions to GW generation. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes of the order of Planck mass (10^15 grams) which isabout when the mass of relic black holes is created, 10^-27 or so seconds after expansion starts. Need to state a key result will be in the initial potential V calculated, in terms of other input variables

Immediate load of full-arch rehabilitations over implants, specially over 4 implants are very well documented in the literature. More recently, the use of computed surgical guides to help the planning and the execution of these treatments, in many situations without the need of raising a flap, and diminishing the appearance of hematomas, bleeding and with less trauma to the patient has gained preference among implantologists. The objective of this case report is to show a clinical case of an immediate load full-arch fixed rehabilitation over 4 implants produced by 3D printing manufacturing technology, and placed with a computed surgical guide, in the same appointment, and the 24 months follow-up. The patient returned after 3 months to replace the immediate temporary fixed prosthesis for a new one, with metallic bar, better teeth and more delicate. Soft and hard tissue around the implants seemed to be stable, without signs of inflammation, either on the 3 or the 24 months follow-up. 3D printing of implants by direct metal laser sintering is a technology that seems to be promising for oral implantology, with solid studies showing reliable results, as seen in this single case. More clinical studies are necessary to testify its efficacy.

Despite the global richness of food plants, only a small portion is used as food for humans. Although most wild food plants (WFPs) are underutilized as food, they can contribute to food security and biocultural conservation through sustainable management. The goal of this research was to identify the best terminological presentation of a novel food product and to understand the influences of the expectations on products with WFP. This research was conducted using an online questionnaire with a final national sample of 724 people. The participants answered questions about their socioeconomic profile, food neophobia, prior knowledge, and expectations regarding the taste and appropriateness of native fruit juices. The questions were randomized so that a person would not receive the same picture or product name more than once. The results show that taste expectancy decreases in relation to products associated with WFP names and forest environments. Food neophobia is the variable that influences expectations the most. To ensure biocultural conservation and cultural valuation, WFP popularization programs should maintain the original (popular) name of the species. However, to help more distant consumers develop familiarity, the flavor, shape, color, or texture of these products can be associated with those of conventional plants.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.

Abstract: Obstructive sleep apnea (OSA) is well known to often improve with non-supine positioning as opposed to su¬pine positioning. Emerging research supports a role for sleep position management in patients with central sleep apnea (CSA) as well. We report a case of de novo Complex Sleep apnea Syndrome (CompSAS) in a 78-year-old female, who presented after a car accident due to unclear syncope. Diagnostic polysomnography (PSG) showed a moderate OSA. A CompSAS developed under Automatic positive airway pressure (APAP), while download data of 4 years showed a good adherence. No significant benefit was reported under Adaptive Servo Ventilation (ASV) and BiPAP-ST, while a reduction of CSA in non-supine position was noticed. Oxygen and sleep positional therapy (SPT) were considered resulting in a significant improvement of CSA and sleep quality. Further research on the prevalence of positional CSA is needed.

Alphaviruses are positive-sense RNA arboviruses that are capable of causing severe disease in otherwise healthy individuals. There are many aspects of viral infection that determine pathogenesis and major efforts regarding the identification and characterization of virulence determinants have largely focused on the roles of the nonstructural and structural proteins. Nonetheless, the viral RNAs of the alphaviruses themselves play important roles in regard to virulence and pathogenesis. In particular, many sequences and secondary structures within the viral RNAs play an important part in the development of disease and may be considered important determinants of virulence. In this review article, we summarize the known RNA-based virulence traits and host:RNA interactions that influence alphaviral pathogenesis for each of the viral RNA species produced during infection. Overall, the viral RNAs produced during infection are important contributors to alphaviral pathogenesis and more research is needed to fully understand how each RNA species impacts the host response to infection as well as the development of disease.

This paper describes a proposed fractional filter-based multi-scale underwater and hazy image enhancement algorithm. The proposed system combines a modified global contrast operator with fractional order-based multi-scale filters used to generate several images, which are fused based on entropy and standard deviation. The multi-scale-global enhancement technique enables fully adaptive and controlled colour correction and contrast enhancement without over exposure of highlights when processing hazy and underwater images. This in addition to illumination/reflectance estimation coupled with global and local contrast enhancement. The proposed algorithm is also compared with the most recent available state-of-the-art multi-scale fusion de-hazing algorithm. Experimental comparisons indicate that the proposed approach yields better edge and contrast enhancement results without halo effect, colour degradation and is faster and more adaptive than all other algorithms from the literature.

Multidrug Artemisin-resistant (ART-R) Plasmodium falciparum (Pf) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region (pfk13) gene allows tracking mutations in parasite resistance to artemisinin. The increase of illegal miners in Roraima Yanomami indigenous land (IYL) could favor ART-R parasites. Thus, the study aimed to investigate ART-R in patients from illegal gold mining in the YIL of Roraima, Brazil. A questionnaire was applied and blood was collected from 48 patients diagnosed with P. falciparum or mixed malaria (Pf +P. vivax). The DNA was extracted and the pfk13 gene was amplified by PCR. The amplicons were subjected to DNA Sangers sequenced; the entire amplified fragment was analyzed. Among patients, 96% (46) were from illegal mining areas of the YIL. All parasite samples carried the wild-type genotypes / ART-sensitive phenotypes. These data reinforce the continued use of ACTs in Roraima as well as the maintenance of systematic monitoring for early detection of parasite populations resistant to ART, mainly in areas exposed to the individual’s influx from mining areas, such as the YIL. This is especially true when the achievement of falciparum malaria elimination in Brazil is planned and expected by 2030.

The production of fuels and other industrial products from renewable sources has intensified the search for new substrates or for the expansion of the use of substrates already in use, as well as the search for microorganisms with different metabolic capacities. In the present work, we isolated and tested a yeast from the soil of sugarcane irrigated with vinasse, that is, with high mineral content and acidic pH. The strain of Meyerozyma caribbica URM 8365 was able to ferment glucose, but the use of xylose occurred when some oxygenation was provided. However, some fermentation of xylose to ethanol in oxygen limitation also occurs if glucose is present. This strain was able to produce ethanol from molasses substrate with 76% efficiency, showing its tolerance to possible inhibitors. High ethanol production efficiencies were also observed in acidic hydrolysates of each bagasse, sorghum, and cactus pear biomass. Mixtures of these substrates were tested and the best composition was found for the use of excess plant biomass in supplementation of primary substrates. It was also possible to verify the production of xylitol from xylose when the acetic acid concentration is reduced. Finally, the proposed metabolic model allowed calculating how much of the xylose carbon can be directed to the production of ethanol and/or xylitol in the presence of glucose. With this, it is possible to design an industrial plant that combines the production of ethanol and/or xylitol using combinations of primary substrates with hydrolysates of their biomass.