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Margaritaria nobilis L.f. (Phyllanthaceae), a native Brazilian tree occurring mainly in the Amazon, is used in folk medicine for the treatment of abscesses (bark) and cancer-like symptoms (leaves). The present study evaluates the safety of its acute oral administration and its effects on nociception and plasma leakage. The chemical constitution of the leaf’s ethanolic extract is determined by ultra-performance liquid chromatography–high-resolution mass spectrometry (LC-MS. Its acute oral toxicity is evaluated in female rats at a dose of 2000 mg/kg, evaluating the occurrence of deaths and Hippocratic, behavioral, hematological, biochemical, and histopathological changes, as well as food and water consumption and weight gain. Antinociceptive activity is evaluated in male mice with acetic-acid-induced peritonitis (APT) and formalin (FT) tests. An open field (OF) test is performed to verify possible interferences in the animals’ consciousness or locomotion. LC-MS analysis shows the presence of 44 compounds classified as phenolic acid derivatives, flavonoids and O-glycosylated derivatives, and hydrolyzable tannins. No deaths or significant behavioral, histological, or biochemical changes are observed in the toxicity assessment. In nociception tests, M. nobilis extract significantly reduces abdominal contortions in APT, demonstrating selectivity for inflammatory components (FT second phase), not interfering in neuropathic components (FT first phase) or consciousness and locomotion levels in OF. Additionally, M. nobilis extract inhibits plasma acetic-acid-induced leakage. These data demonstrate the low toxicity of M. nobilis ethanolic extract, as well as its effectiveness in modulating inflammatory nociception and plasma leakage, possibly related to the flavonoids and tannins present in its composition.

Helicoverpa zea is a major target pest of Bt crops expressing Cry and/or Vip3Aa proteins in the U.S.A. Widespread practical resistance of H. zea to the Cry1 and Cry2 proteins makes Vip3Aa the only effective Bt protein against this pest. Understanding the frequency of resistance alleles against Vip3Aa in field populations of H. zea is crucial for resistance management and the sustainability of Vip3Aa technology. Using a modified F2 screen method by crossing susceptible laboratory female moth with feral male moth of H. zea, we successfully screened a total of 24,576 neonates from 192 F2 families of H. zea collected from Arkansas, Louisiana, Mississippi, and Tennessee during 2019–2020. We found five F2 families containing ≥3rd instar survivors on the diagnostic concentration of 3.0 µg/cm2 Vip3Aa39. Dose-response bioassays confirmed the high levels of Vip3Aa resistance in these F2 families, with an estimated resistance ratio of >909.1-fold relative to the susceptible strain. The estimated resistance allele frequency against Vip3Aa in H. zea for these four southern states is 0.0155 with a 95% CI of 0.0057–0.0297. These data should provide critical information for understanding the risks of Vip3Aa resistance in H. zea and help design appropriate resistance management strategies for the sustainability of the Vip3Aa technology.

Margaritaria nobilis is a shrubby species widely distributed in Brazil from the Amazon to the Atlantic Rainforest. Its bark and fruit are used in the Peruvian Amazon for disinfecting abscesses and as a tonic in pregnancy, respectively, and its leaves are used to treat cancer symptoms. From analyses via UHPLC-MS/MS, we sought to determine the chemical profile of the ethanolic extract of M. nobilis leaves by means of putative analyses supported by computational tools and spectral libraries. Thus, it was possible to annotate 44 compounds, of which 12 are phenolic acid derivatives, 16 are O-glycosylated flavonoids and 16 hydrolysable tannins. Among the flavonoids, although they are known, except for kaempferol, which has already been isolated from this species, the other flavonoids (10, 14, 15, 21, 24–26, 28–30, 33–35, 40 and 41) are being reported for the first time in the genus. Among the hydrolysable tannins, six ellagitannins present the HHDP group (6, 19, 22, 31, 38 and 43), one presents the DHHDP group (5), and four contain oxidatively modified congeners (12, 20, 37 and 39). Through the annotation of these compounds, we hope to contribute to the improved chemosystematics knowledge of the genus. Furthermore, supported by a metric review of the literature, we observed that many of the compounds reported here are congeners of authentically bioactive compounds. Thus, we believe that this work may help in understanding future pharmacological activities.

The Zika virus (ZIKV) was first isolated from a rhesus macaque in the Zika forest of Uganda in 1947. Isolated cases were reported until 2007, when the first major outbreaks of Zika infection were reported from the Island of Yap in Micronesia and from French Polynesia in 2013. In 2015, ZIKV started to circulate in Latin America, and in 2016, ZIKV was considered by WHO to be a Public Health Emergency of International Concern due to cases of Congenital Zika Syndrome (CZS), a ZIKV-associated complication never observed before. After a peak of cases in 2016, the infection incidence dropped dramatically but still causes concern because of the associated microcephaly cases, especially in regions where the dengue virus (DENV) is endemic and co-circulates with ZIKV. A vaccine could be an important tool to mitigate CZS in endemic countries. However, the immunological relationship between ZIKV and other flaviviruses, especially DENV, and the low numbers of ZIKV infections are potential challenges for developing and testing a vaccine against ZIKV. Here, we discuss ZIKV vaccine development with the perspective of the immunological concerns implicated by DENV-ZIKV cross-reactivity and the use of a controlled human infection model (CHIM) as a tool to accelerate vaccine development.

Evolution of resistance by pests can reduce the benefits of crops genetically engineered to produce insecticidal proteins from Bacillus thuringiensis (Bt). Because of the widespread resistance of Helicoverpa zea to crystalline (Cry) Bt toxins in the United States, the vegetative insecticidal protein Vip3Aa is the only Bt toxin produced by Bt corn and cotton that remains effective against some populations of this polyphagous lepidopteran pest. Here we evaluated H. zea resistance to Vip3Aa using diet bioassays to test 42,218 larvae from three lab strains and 71 strains derived from the field during 2016 to 2020 in Arkansas, Louisiana, Mississippi, Tennessee, and Texas. Relative to the least susceptible of the three lab strains tested (BZ), susceptibility to Vip3Aa of the field-derived strains decreased significantly from 2016 to 2020. Relative to another lab strain (TM), 7 of 16 strains derived from the field in 2019 were significantly resistant to Vip3Aa, with up to 13-fold resistance. Susceptibility to Vip3Aa was significantly lower for strains derived from Vip3Aa plants than non-Vip3Aa plants, providing direct evidence of resistance evolving in response to selection by Vip3Aa plants in the field. Together with previously reported data, the results here convey an early warning of field-evolved resistance to Vip3Aa in H. zea that supports calls for urgent action to preserve the efficacy of this toxin.

Doxorubicin (DOX), a chemotherapy drug successfully used in the therapy of various types of cancer, is currently associated with the mucositis development, an inflammation that can cause ulcerative lesions in the mucosa of the gastrointestinal tract, abdominal pain and secondary infections. To increase the safety of the chemotherapy, we loaded DOX into nanostructured lipid carriers (NLCs). The NLC–DOX was characterized by HPLC, DLS, NTA, Zeta potential, FTIR, DSC, TEM and cryogenic-TEM. The ability of NLC–DOX to control the DOX release was evaluated through in vitro release studies. Moreover, the effect of NLC–DOX on intestinal mucosa was compared to a free DOX solution in C57BL/6 mice. The NLC–DOX showed spherical shape, high drug encapsulation efficiency (84.8 ± 4.6%), high drug loading (55.2 ± 3.4 mg/g) and low average diameter (66.0–78.8 nm). The DSC and FTIR analyses showed high interaction between the NLC components, resulting in controlled drug release. Treatment with NLC–DOX attenuated DOX-induced mucositis in mice, improving shortening on villus height and crypt depth, decreased inflammatory parameters, preserved intestinal permeability and increased expression of tight junctions (ZO-1 and Ocludin). These results indicated that encapsulation of DOX in NLCs is viable and reduces the drug toxicity to mucosal structures.

The presence of denatured proteins within a therapeutic drug product can create a series of serious adverse effects, such as mild irritation, immunogenicity, anaphylaxis, or instant death to a patient. The detection of protein degradation is complicated and expensive due to current methods associated with expensive instrumentation, reagents, and processing time. We have demonstrated here a platform for visual biosensing of denatured proteins that is fast, low cost, sensitive, and user friendly by exploiting the plasmonic properties of noble metal nanoparticles. In this study we have exposed artificially heat stressed ferritin and gold nanoparticles to 3-aminopropyl triethoxysilane, which degrades the protein by showing a systematic blue shift in the absorbance spectra of the gold nanoparticle/ferritin and aminosilane solution. This blue shift in absorbance produces a detectable visual color transition from a blue color to a purple hue. By studying the Raman spectroscopy of the gold nanoparticle/ferritin and aminosilane solution, the extent of ferritin degradation was quantified. The degradation of ferritin was again confirmed using dynamic light scattering and was attributed to the aggregation of the ferritin due to accelerated heat stress. We have successfully demonstrated a proof of concept for visually detecting ferritin from horse spleen that has experienced various levels of degradation, including due to heat stress.

The corn earworm, Helicoverpa zea (Boddie), is a major pest of Bacillus thuringiensis (Bt) maize and cotton in the U.S. Reduced efficacy of Bt plants expressing Cry1 and Cry2 against H. zea has been reported in some areas of the U.S. In this study, we evaluated the occurrence and ear damage of H. zea on transgenic Bt maize expressing Cry proteins or a combination of Vip3A and Cry proteins in the field in Texas in 2018. We found that the occurrence of H. zea larvae and the viable kernel damage area on the ear were not different between non-Bt maize and Bt maize expressing Cry1A.105+Cry2Ab2 and Cry1Ab+Cry1F proteins. A total of 67.5% of the pyramided Bt maize expressing Cry1Ab+Cry1F+Vip3A was damaged by 2nd⁻4th instar larvae of H. zea. Diet bioassays showed that the resistance ratio against Vip3Aa51 for H. zea obtained from Cry1Ab+Cry1F+Vip3A maize was 20.4 compared to a field population collected from Cry1F+Cry1A.105+Cry2Ab2 maize. Leaf tissue bioassays showed that 7-day survivorship on WideStrike3 (Cry1F+Cry1Ac+Vip3A) cotton leaves was significantly higher for the H. zea population collected from Cry1Ab+Cry1F+Vip3A maize than for a Bt-susceptible laboratory population. The results generated from this study suggest that H. zea has evolved practical resistance to Cry1 and Cry2 proteins. Therefore, it is crucial to ensure the sustainable use of the Vip3A technology in Bt maize and cotton.

Carbon nanotube yarns are micron-scale fibers comprised by tens of thousands of carbon nanotubes in their cross section and exhibiting piezoresistive characteristics that can be tapped to sense strain. This paper presents the details of novel foil strain gauge sensor configurations comprising carbon nanotube yarn as the piezoresistive sensing element. The foil strain gauge sensors are designed using the results of parametric studies that maximize the sensitivity of the sensors to mechanical loading. The fabrication details of the strain gauge sensors that exhibit the highest sensitivity, based on the modeling results, are described including the materials and procedures used in the first prototypes. Details of the calibration of the foil strain gauge sensors are also provided and discussed in the context of their electromechanical characterization when bonded to metallic specimens. This characterization included studying their response under monotonic and cyclic mechanical loading. It was shown that these foil strain gauge sensors comprising carbon nanotube yarn are sensitive enough to capture strain and can replicate the loading and unloading cycles. It was also observed that the loading rate affects their piezoresistive response and that the gauge factors were all above one order of magnitude higher than those of typical metallic foil strain gauges. Based on these calibration results on the initial sensor configurations, new foil strain gauge configurations will be designed and fabricated, to increase the strain gauge factors even more.

The results regarding the relationship between creativity in virtual work environments and its influence on emotional exhaustion are inconclusive. Furthermore, autonomy, when it loses its original purpose of acting as a job resource, takes on an ambiguous role that needs further research., Objective: To analyze the relationship between creativity and emotional exhaustion, along with the role assumed by work autonomy in this link, in an online work context., Methodology: The sample was formed of 448 employees with university studies. The statistical analysis was conducted through a simple moderation process., Results: Creativity and work autonomy mitigate emotional exhaustion. In fact, work autonomy plays a moderating role regarding the relationship between creativity and emotional exhaustion. Control over work surely reduces the impact of work-related stressors, and this safety climate promotes adaptive and original responses that improve employees' emotional health. However, when creative demands coincide with an autonomy that extends working hours, instead of establishing limits, this supposed benefit becomes a demand that prevents employees from disconnecting, until emotionally exhausting them., Conclusion: A virtual work environment is an ideal habitat for creativity and self-management to improve employees' emotional health, as long as work autonomy acts as a resource.

Background and Aims : Colorectal cancer (CRC) represents 10% of all cancers worldwide with the highest incidence in developed countries; its incidence is also increasing in middle- and low-income countries. Population screening programs facilitate early diagnosis of the disease. When the diagnosis is carried out in advanced stages, approximately 80% of patients with liver metastases (LM) are considered unresectable at the time of diagnosis. In our study, variations in blood counts prior to CRC diagnosis were analyzed to assess whether they could be useful in identifying smaller, more manageable metastases at earlier stages for more effective treatment. Methods : A study was carried out using complete blood counts (CBCs) from CRC patients, obtained from primary health centers and the La Ribera University Hospital within La Ribera Health Department, Valencian Community, Spain, between July 2012 and September 2020. Data from CRC patients who presented synchronous liver metastasis (CRLM) were compared with those with CRC without LM at diagnosis (CRC patients). Results : Our analysis shows that at least 15 months before CRC diagnosis, a progressive alteration was observed in CBC parameters in both groups. A higher incidence of anemia ( p < 0.001) was observed among CRLM patients in the three months prior to CRC diagnosis than in CRC patients showing no LM. Conclusions : A statistically significant deterioration of CBC was observed in patients with advanced-stage CRC and synchronous or early LM (CRLM) in the three months prior to diagnosis. The primary goal of incorporating CBC variations into predictive models is to identify individuals who are at a greater risk of developing metastatic colon cancer, leading to early diagnosis. Our research improves these models by highlighting a more pronounced and rapid decline in hemoglobin levels among CRLM patients. Identification of metastases at an earlier stage when they are smaller, more manageable, and more amenable to treatment may be a valuable tool to prevent their further progression.

Introduction: Currently, there is little clinical evidence to support the medium- and long-term survival and clinical performance of ultraconservative approaches using adhesive restorations in full-mouth restorations. The aim of this case series study was to evaluate the medium-term clinical performance of anterior and posterior adhesive restorations applied with direct and indirect techniques using resin composites and glass-ceramic-based materials., Materials and Methods: The inclusion criteria were an esthetic problem as the main reason for consultation and severe generalized wear of grade 2 to 4 according to the Tooth Wear Evaluation System (TWES 2.0). In addition, at each follow-up appointment, patients were required to submit a clinical-parameter-monitoring record according to the modified United States Public Health Service (USPHS) criteria., Results: Eight patients with severe tooth wear were treated through full rehabilitation in a private dental clinic in Spain by a single operator (AFC). A total of 212 restorations were performed, which were distributed as follows: 66 occlusal veneers, 26 palatal veneers and 120 vestibular veneers. No signs of marginal microleakage or postoperative sensitivity were observed in any occlusal, vestibular and/or palatal restoration after the follow-up period. The estimated survival rate of the 212 restorations was 90.1% over 60 months of observation, with a survival time of 57.6 months. Only 21 restorations had complications, which were mostly resolved with a direct composite resin. The dichotomous variables of the restoration type (posterior veneer, anterior veneer) and the type of restored tooth (anterior, posterior) were the risk predictors with statistically significant influences ( p < 0.005) on the survival of the restorations., Conclusion: According to the results of this study, there is a significantly higher risk of restorative complications in posterior teeth compared to anterior teeth. Also, it can be concluded that the indication of adhesive anterior and posterior restorations is justified in the total oral rehabilitation of patients with severe multifactorial tooth wear, as they are associated with a low risk of failure.

The aim of this study was to develop an experimental composite resin with the addition of myristyltrimethylammonium bromide (MYTAB) and α -tricalcium phosphate (α-TCP) as an antibacterial and remineralizing material. Experimental composite resins composed of 75 wt% Bisphenol A-Glycidyl Methacrylate (BisGMA) and 25 wt% Triethylene Glycol Dimethacrylate (TEGDMA) were produced. Some 1 mol% Trimethyl benzoyl-diphenylphosphine oxide (TPO) was used as a photoinitiator, and butylated hydroxytoluene (BTH) was added as a polymerization inhibitor. Silica (1.5 wt%) and barium glass (65 wt%) particles were added as inorganic fillers. For remineralizing and antibacterial effect, α-TCP (10 wt%) and MYTAB (5 wt%) were incorporated into the resin matrix (α-TCP/MYTAB group). A group without the addition of α-TCP/MYTAB was used as a control. Resins were evaluated for their degree of conversion (n = 3) by Fourier Transform Infrared Spectroscopy (FTIR). The flexural strength (n = 5) was assessed based on ISO 4049:2019 requirements. Microhardness was assessed to calculate softening in solvent (n = 3) after ethanol immersion. The mineral deposition (n = 3) was evaluated after immersion in SBF, while cytotoxicity was tested with HaCaT cells (n = 5). Antimicrobial activity (n = 3) was analyzed against S. mutans. The degree of conversion was not influenced by the antibacterial and remineralizing compounds, and all groups reached values > 60%. The α-TCP/MYTAB addition promoted increased softening of polymers after immersion in ethanol and reduced their flexural strength and the viability of cells in vitro. A reduction in S. mutans viability was observed for the α-TCP/MYTAB group in biofilm formation and planktonic bacteria, with an antibacterial effect > 3log 10 for the developed materials. Higher intensity of phosphate compounds on the sample's surface was detected in the α-TCP/MYTAB group. The addition of α-TCP and MYTAB promoted remineralizing and antibacterial effects on the developed resins and may be a strategy for bioactive composites.

Different biomaterials, from synthetic products to autologous or heterologous grafts, have been suggested for the preservation and regeneration of bone. The aim of this study is to evaluate the effectiveness of autologous tooth as a grafting material and examine the properties of this material and its interactions with bone metabolism. PubMed, Scopus, Cochrane Library, and Web of Science were searched to find articles addressing our topic published from 1 January 2012 up to 22 November 2022, and a total of 1516 studies were identified. Eighteen papers in all were considered in this review for qualitative analysis. Demineralized dentin can be used as a graft material, since it shows high cell compatibility and promotes rapid bone regeneration by striking an ideal balance between bone resorption and production; it also has several benefits, such as quick recovery times, high-quality newly formed bone, low costs, no risk of disease transmission, the ability to be performed as an outpatient procedure, and no donor-related postoperative complications. Demineralization is a crucial step in the tooth treatment process, which includes cleaning, grinding, and demineralization. Since the presence of hydroxyapatite crystals prevents the release of growth factors, demineralization is essential for effective regenerative surgery. Even though the relationship between the bone system and dysbiosis has not yet been fully explored, this study highlights an association between bone and gut microbes. The creation of additional scientific studies to build upon and enhance the findings of this study should be a future objective of scientific research.

The aim of the present in vitro study was to evaluate specific mechanical and physicochemical properties of two calcium silicate based sealers, (AH Plus Bioceramic “AHPB”; Well-Root ST “WRST”), and a conventional resin sealer (AH Plus “AHP”). These aims were accomplished by assessing the porosity, pH, compression strength, roughness, wettability and cell attachment of the tested materials. The results were compared statistically using the one-way ANOVA test. Higher pH values were obtained in both AHPB and WRST compared to AHP at 3, 24 and 72 h (p < 0.05). A greater level of porosity and wettability was detected for both AHPB and WRST compared to the resin sealer AHP (p < 0.05). Evident cell growth characterized by elongated morphology was observed on the surface of AHPB and WRST, while only a thin layer of cells was seen on the surface of AHP. A significant lower compression strength and modulus were obtained in the specimens created using AHPB compared to those made with AHP and WRST (p < 0.05). The removal of calcium silicates may be quite tricky during endodontic retreatment. In conclusion, considering the limitations of the present in vitro study, both calcium silicate sealers demonstrated good physicochemical properties. However, the lower compression strength and modulus of AHPB may facilitate its removal and make the retreatment procedures considerably easier.

Low self-efficacy has been identified as one of the factors that could hinder the prescribing competence of nurses. No valid and reliable existing instruments assess Galician nurses' confidence to prescribe. The aim of this study was to determine the reliability and validity of the Galician version of the Nurse Prescribing Self-Efficacy Scale (G-NP-SES, 19 items). The study was conducted in two phases: the translation and adaptation to the Galician version of the NP-SES, and the assessment of its psychometric properties. G-NP-SES was sent to nurses working in primary healthcare centers in Galicia (Spain) between March and June of 2022. Its content, construct and discriminant validity, and internal consistency reliability were examined. A total of 193 people participated in the study. As the original scale, G-NP-SES also had three dimensions (% of cumulative variance = 80.82%). It showed good internal consistency (Cronbach's alpha coefficient (α) = 0.90, with each factor ranging from 0.86 to 0.89), high content validity (scale's content validity index = 0.92, with item-content validity index ranged from 0.87 to 1), and good discriminant validity. G-NP-SES is an instrument with good psychometric properties which could be used to accurately assess Galician nurses' self-efficacy to prescribe and consequently to improve their job performance.

The aim of this in vitro study was to investigate the compressive strength and the bulk porosity of a bidirectional (bFRC) and an experimental bidirectional spiral winding reinforced fiber composite (bswFRC). Cylindrical-shape specimens were prepared for each material group and processed for the evaluation of compressive strength after different storage conditions (dry, 1 and 3 months) in distilled water at 37 °C. The specimens were also assessed for the degree of bulk porosity through X-ray tomography. A scanning electron microscope (SEM) was used to determine the fracture mode after a compressive strength test. Data were statistically analyzed using Two-Way Analysis of Variance (ANOVA). A significantly lower compressive strength was obtained in dry conditions, and after 1 month of water immersion, with the specimens created with bFRC compared to those made with bswFRC (p < 0.05). No significant difference (p > 0.05) was found between the two groups after 3 months of water immersion. However, the presence of water jeopardized significantly the compressive strength of bswFRC after water storage. The type of fracture was clearly different between the two groups; bswFRC showed a brutal fracture, whilst bFRC demonstrated a shear fracture. The bswFRC demonstrated higher pore volume density than bFRC. In conclusion, bswFRC is characterized by greater compressive strength compared to bFRC in dry conditions, but water-aging can significantly decrease the mechanical properties of such an innovative FRC. Therefore, both the novel bidirectional spiral winding reinforced fiber composites (bswFRC) and the bidirectional fiber reinforced composites (bFRC) might represent suitable materials for the production of post-and-core systems via CAD/CAM technology. These findings suggest that both FRC materials have the potential to strengthen the endodontically treated teeth., Competing Interests: The authors declare no competing interest.

The potential role of cocoa supplementation in an exercise context remains unclear. We describe the effects of flavanol-rich cocoa supplementation during training on exercise performance and mitochondrial biogenesis. Forty-two male endurance athletes at the beginning of the training season received either 5 g of cocoa (425 mg of flavanols) or maltodextrin (control) daily for 10 weeks. Two different doses of cocoa (equivalent to 5 g and 15 g per day of cocoa for a 70 kg person) were tested in a mouse exercise training study. In the athletes, while both groups had improved exercise performance, the maximal aerobic speed increased only in the control group. A mitochondrial DNA analysis revealed that the control group responded to training by increasing the mitochondrial load whereas the cocoa group showed no increase. Oxidative stress was lower in the cocoa group than in the control group, together with lower interleukin-6 levels. In the muscle of mice receiving cocoa, we corroborated an inhibition of mitochondrial biogenesis, which might be mediated by the decrease in the expression of nuclear factor erythroid-2-related factor 2. Our study shows that supplementation with flavanol-rich cocoa during the training period inhibits mitochondrial biogenesis adaptation through the inhibition of reactive oxygen species generation without impacting exercise performance.

Background: Little is known about the relation between morbid obesity and duodenal transcriptomic changes. We aimed to identify intestinal genes that may be associated with the development of obesity regardless of the degree of insulin resistance (IR) of patients., Material and Methods: Duodenal samples were assessed by microarray in three groups of women: non-obese women and women with morbid obesity with low and high IR., Results: We identified differentially expressed genes (DEGs) associated with morbid obesity, regardless of IR degree, related to digestion and lipid metabolism, defense response and inflammatory processes, maintenance of the gastrointestinal epithelium, wound healing and homeostasis, and the development of gastrointestinal cancer. However, other DEGs depended on the IR degree. We mainly found an upregulation of genes involved in the response to external organisms, hypoxia, and wound healing functions in women with morbid obesity and low IR., Conclusions: Regardless of the degree of IR, morbid obesity is associated with an altered expression of genes related to intestinal defenses, antimicrobial and immune responses, and gastrointestinal cancer. Our data also suggest a deficient duodenal immune and antimicrobial response in women with high IR.

This study aimed at evaluating the physicochemical and biological properties of experimental epoxy-resin sealers containing polyphenols such as resveratrol and pyrogallol. A conventional epoxy resin (OB) was modified by adding different concentrations of resveratrol (RS) or pyrogallol (PY) to its composition. Antibacterial and antioxidant activities, mechanical properties, along with wettability and morphological changes were investigated. The results were statistically analyzed using ANOVA and multiple comparison tests (α = 0.05). The incorporation of the tested polyphenols into the epoxy resin enhanced its mechanical properties. PY demonstrated much better antioxidant and antibacterial activities than RS, which were associated with a higher release of PY. In contrast, PY showed a higher cytotoxicity than OB and OB doped with RS. OB containing PY presented a rougher surface and higher water absorption than OB doped with RS. Both tested polyphenols caused no notable changes to the overall porosity of OB. Resveratrol and pyrogallol may not only influence the morphology and mechanical properties of epoxy-resin sealers, but could also enhance antioxidant activity and antibacterial effects against Enterococcus faecalis . Most epoxy-resin sealers currently available in the market can be considered as "passive" materials. Thus, doping their composition with specific polyphenols may be a suitable strategy to confer some antibacterial properties, antioxidant potential, along with improvement of some mechanical properties.

The purpose of the present in vitro study was to investigate the bond strength of root canal dentin and the filling ability of a new multi-fiber-reinforced composite post (mFRC) compared to a conventional single fiber-reinforced-composite post (sFRC). Twenty-eight freshly maxillary first permanent single-rooted premolars were instrumented and divided into groups ( n = 14). Group 1: single-fiber-reinforced composite (sFRC), group 2: multi-fiber-reinforced composite (mFRC). Bonding procedures were performed using a dual-cure universal adhesive system and resin cement. All specimens were sectioned so that seven discs of 1 mm of thickness were obtained from each root. An optical microscope was used before the push-out test to measure the total area of the voids and to determine the length of the smaller/bigger circumferences. The push-out bond strength (PBS) test was performed using an Instron universal testing machine. Data were then compared by one-way ANOVA on ranks (α = 0.05). The dentin-cement-post interface was observed using scanning electron microscopy (SEM). At the coronal third, a significantly higher bond strength ( p < 0.05) was obtained in the sFRC group (44.7 ± 13.1 MPa) compared to the mFRC group (37.2 ± 9.2 MPa). No significant difference was detected between the groups at the middle third (sFRC group "33.7 ± 12.5 MPa" and mFRC group "32.6 ± 12.4 MPa") ( p > 0.05). Voids were significantly lower in the mFRC compared to those observed in the sFRC group ( p < 0.05) at the coronal third. Whereas, no significant difference was found at the middle third ( p > 0.05) between the tested groups. Filling ability was overall improved when employing mFRC, although such technique might have characteristic limitations concerning the bond strength to dentin.

Background: Little is known about the effects of hypoxia on scavenger receptors (SRs) levels in adipocytes. We analyzed the effect of morbid obesity and hypoxia on SRs and inflammation markers in human visceral adipocytes and whether ox-LDL modify the inflammatory profile produced by hypoxia., Methods: We studied in 17 non-obese and 20 subjects with morbid obesity (MO) the mRNA expression of HIF-1α, SRs (LOX-1, MSR1, CL-P1 and CXCL16), IL6 and TNFα in visceral adipocytes and the effect of hypoxia with or without ox-LDL on visceral in vitro-differentiated adipocytes (VDA)., Results: HIF-1α, TNFα, IL6, LOX-1, MSR1 and CXCL16 expression in adipocytes was increased in MO when compared with those in non-obese subjects ( p < 0.05). The expression of most of the inflammatory markers and SRs gene correlated with HIF-1α. In VDA, hypoxia increased TNFα, IL6, MSR1, CXCL16 and CL-P1 ( p < 0.05) in non-obese subjects, and TNFα, IL6, MSR1 and CXCL16 ( p < 0.05) in MO. Silencing HIF-1α prevented the increase of TNFα, IL6, LOX-1, MSR1, CL-P1 and CXCL16 expression ( p < 0.05). The combination of hypoxia and ox-LDL produced higher TNFα expression ( p = 0.041)., Conclusions: Morbid obesity and hypoxia increased SRs and inflammatory markers in visceral adipocytes. In a hypoxic state, ox-LDL increased the proinflammatory response of visceral adipocytes to hypoxia.

Vaccination against SARS-CoV-2 is postulated as the most effective measure to control the COVID-19 pandemic. However, the use of other protection measures is necessary to efficiently combat the spread of the virus. The aim of the present study was to determine the attitudes and intentions toward COVID-19 vaccination among non-regular social media users in Spain and to analyze how these factors could condition the acceptance of other personal protective measures once an individual has received the COVID-19 vaccine. A cross-sectional design was used in this work. In total, 719 subjects, ≥18 years old and of both sexes, were recruited from primary public healthcare centers to self-complete a questionnaire between March and April 2021. The majority of participants had a positive attitude toward vaccination and showed high levels of intention to be vaccinated. Likewise, except those participants who considered the vaccine to be the most effective measure to fight the COVID-19 pandemic, the rest of the participants highlighted the importance of continuing to limit social interactions and/or wearing masks even after being vaccinated. Since vaccination can create a perception of total immunity against SARS-CoV-2, it is necessary that healthcare staff organize effective awareness campaigns on the importance of maintaining personal protective measures until vaccination coverage is greater.

Saccharomyces cerevisiae is the most commonly used yeast in wine, beer, and bread fermentations. However, Torulaspora delbrueckii has attracted interest in recent years due to its properties, ranging from its ability to produce flavor- and aroma-enhanced wine to its ability to survive longer in frozen dough. In this work, publicly available genomes of T. delbrueckii were explored and their annotation was improved. A total of 32 proteins were additionally annotated for the first time in the type strain CBS1146, in comparison with the previous annotation available. In addition, the annotation of the remaining three T. delbrueckii strains was performed for the first time. eggNOG-mapper was used to perform the functional annotation of the deduced T. delbrueckii coding genes, offering insights into its biological significance, and revealing 24 clusters of orthologous groups (COGs), which were gathered in three main functional categories: information storage and processing (28% of the proteins), cellular processing and signaling (27%), and metabolism (23%). Small intraspecies variability was found when considering the functional annotation of the four available T. delbrueckii genomes. A comparative study was also conducted between the T. delbrueckii genome and those from 386 fungal species, revealing a high number of homologous genes with species from the Zygotorulaspora and Zygosaccharomyces genera, but also with Lachancea and S. cerevisiae . Lastly, the phylogenetic placement of T. delbrueckii was clarified using the core homologs that were found across 204 common protein sequences of 386 fungal species and strains.

Background: Many epidemiological and experimental studies have established that myopia is caused by a complex interaction between common genetic and environmental factors. The objective of this study was to describe and compare the allelic and genotypic frequencies of the rs524952 ( GJD2 ), rs8000973 ( ZIC2 ), rs1881492 ( CHRNG ), rs1656404 ( PRSS56 ), rs235770 ( BMP2 ), and rs7744813 ( KCNQ5 ) SNPs (single-nucleotide polymorphism) between responder and nonresponder patients who had undergone a two-year treatment with lenses for myopia control., Method: Twenty-eight participants from the MiSight Assessment Study Spain (MASS), who had received treatment for myopia control for two years with MiSight contact lenses, were examined. The criteria for better/worse treatment response was the change in the axial length (< / ≥ 0.22 mm two years after the treatment). The clinical procedure consisted of the extraction of a saliva sample, and the participants also underwent an optometric examination. Genetic data were analyzed using SNPStats software (Catalan Institute of Oncology, Barcelona, Spain), and statistical analysis was performed using SPSS v.25 (SPSS Inc., Chicago, IL, USA). Demographic variables were analyzed using the Student's t-test., Results: The T allele, the one with the lowest frequency, of the "rs235770" SNP was associated with a better treatment response [AL/CR (axial length/corneal radius): OR = 3.37; CI = 1.079-10.886; SE (spherical equivalent): OR = 1.26; CI: = 0.519-57.169; p = 0.019). By performing haplotype analysis, significant differences were found between the rs235770…rs1881492 and rs235770-rs1656404 polymorphisms. The latter presented a strong linkage disequilibrium with each other (r 2 ≥ 0.54)., Conclusion: The result of lens therapies for myopia control could vary depending on genetic variants. Studies with a larger sample are needed to confirm the results presented in this pilot study.

The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory diseases with common features in terms of clinical presentation and genetic predisposition. SpA is characterized by inflammation of the spine and peripheral joints, and is also be associated with extra-articular inflammatory manifestations such as psoriasis, uveitis, or inflammatory bowel disease (IBD). The etiology of SpA is not completely understood, but it is known to have a strong genetic component dominated by the human leukocyte antigen (HLA)-B27. In the last few years, our understanding of genetic susceptibility to SpA, particularly ankylosing spondylitis (AS), has greatly improved thanks to the findings derived from powered genome-wide association studies (GWAS) based on single nucleotide polymorphism (SNP) arrays. These studies have identified many candidate genes, therefore providing new potential directions in the exploration of disease mechanisms, especially with regard to the key role of the immune system in the pathogenesis of SpA. SpA is a complex disease where genetic variability, environmental factors, and random events interact to trigger pathological pathways. The aim of this review is to summarize current findings on the genetics of SpA, some of which might help to study new treatment approaches.

Background: The effects of different types of fatty acids on the gene expression of key players in the IRS1/PI3K signaling pathway have been poorly studied., Material and Methods: We analyzed IRS1, p85α, and p110β mRNA expression and the fatty acid composition of phospholipids in visceral adipose tissue from patients with morbid obesity and from non-obese patients. Moreover, we analyzed the expression of those genes in visceral adipocytes incubated with oleic, linoleic, palmitic and dosahexaenoic acids., Results: We found a reduced IRS1 expression in patients with morbid obesity, independent of insulin resistance, and a reduced p110β expression in those with lower insulin resistance. A positive correlation was found between p85α and stearic acid, and between IRS1 and p110β with palmitic and dosahexaenoic acid. In contrast, a negative correlation was found between p85α and oleic acid, and between IRS1 and p110β with linoleic, arachidonic and adrenic acid. Incubation with palmitic acid decreased IRS1 expression. p85α was down-regulated after incubation with oleic and dosahexaenoic acid and up-regulated with palmitic acid. p110β expression was increased and decreased after incubation with oleic and palmitic acid, respectively. The ratio p85α/p110β was decreased by oleic and dosahexaenoic acid and increased by palmitic acid., Conclusions: Our in vitro results suggest a detrimental role of palmitic acid on the expression of gene related to insulin signaling pathway, with oleic acid being the one with the higher and more beneficial effects. DHA had a slight beneficial effect. Fatty acid-induced regulation of genes related to the IRS1/PI3K pathway may be a novel mechanism by which fatty acids regulate insulin sensitivity in visceral adipocytes.

The study of mitogenomes allows the unraveling of some paths of yeast evolution that are often not exposed when analyzing the nuclear genome. Although both nuclear and mitochondrial genomes are known to determine phenotypic diversity and fitness, no concordance has yet established between the two, mainly regarding strains' technological uses and/or geographical distribution. In the current work, we proposed a new method to align and analyze yeast mitogenomes, overcoming current difficulties that make it impossible to obtain comparable mitogenomes for a large number of isolates. To this end, 12,016 mitogenomes were considered, and we developed a novel approach consisting of the design of a reference sequence intended to be comparable between all mitogenomes. Subsequently, the population structure of 6646 Saccharomyces cerevisiae mitogenomes was assessed. Results revealed the existence of particular clusters associated with the technological use of the strains, in particular regarding clinical isolates, laboratory strains, and yeasts used for wine-associated activities. As far as we know, this is the first time that a positive concordance between nuclear and mitogenomes has been reported for S. cerevisiae , in terms of strains' technological applications. The results obtained highlighted the importance of including the mtDNA genome in evolutionary analysis, in order to clarify the origin and history of yeast species.

Little is known about the jejunal insulin signalling pathways in insulin resistance/diabetes states and their possible regulation by insulin/leptin. We study in jejunum the relation between insulin signalling and insulin resistance in morbidly obese subjects with low (MO-low-IR) or with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM)), and the effect of insulin/leptin on intestinal epithelial cells (IEC). Insulin receptor substrate-1 (IRS1) and the catalytic p110β subunit (p110β) of phosphatidylinositol 3-kinase (PI3K) were higher in MO-high-IR than in MO-low-IR. The regulatory p85α subunit of PI3K (p85α)/p110β ratio was lower in MO-high-IR and MO-metf-T2DM than in MO-low-IR. Akt-phosphorylation in Ser473 was reduced in MO-high-IR compared with MO-low-IR. IRS1 and p110-β were associated with insulin and leptin levels. The improvement of body mass index (BMI) and HOMA-IR (homeostasis model assessment of insulin resistance index) after bariatric surgery was associated with a higher IRS1 and a lower p85α/p110β ratio. IEC (intestinal epithelial cells) incubation with a high glucose + insulin dose produced an increase of p85α and p110β. High dose of leptin produced an increase of IRS1, p85α and p110β. In conclusion, despite the existence of insulin resistance, the jejunal expression of genes involved in insulin signalling was increased in MO-high-IR. Their expressions were regulated mainly by leptin. IRS1 and p85α/p110β ratio was associated with the evolution of insulin resistance after bariatric surgery., Competing Interests: The authors declare that they have no conflict of interest.

Carbapenem-resistant Enterobacteriaceae (CRE) have become a public health threat worldwide. There are three major mechanisms by which Enterobacteriaceae become resistant to carbapenems: enzyme production, efflux pumps and porin mutations. Of these, enzyme production is the main resistance mechanism. There are three main groups of enzymes responsible for most of the carbapenem resistance: KPC ( Klebsiella pneumoniae carbapenemase) (Ambler class A), MBLs (Metallo-ß-Lactamases) (Ambler class B) and OXA-48-like (Ambler class D). KPC-producing Enterobacteriaceae are endemic in the United States, Colombia, Argentina, Greece and Italy. On the other hand, the MBL NDM-1 is the main carbapenemase-producing resistance in India, Pakistan and Sri Lanka, while OXA-48-like enzyme-producers are endemic in Turkey, Malta, the Middle-East and North Africa. All three groups of enzymes are plasmid-mediated, which implies an easier horizontal transfer and, thus, faster spread of carbapenem resistance worldwide. As a result, there is an urgent need to develop new therapeutic guidelines to treat CRE infections. Bearing in mind the different mechanisms by which Enterobacteriaceae can become resistant to carbapenems, there are different approaches to treat infections caused by these bacteria, which include the repurposing of already existing antibiotics, dual therapies with these antibiotics, and the development of new ß-lactamase inhibitors and antibiotics., Competing Interests: The authors declare no conflict of interest.

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a &ldquo;Priority 2&rdquo; microorganism in the World Health Organization (WHO) Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis, and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting of dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. The increase in the detection of resistant gonococci may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics; (2) development of new antibiotics; and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this superbug. This has led the scientific community to develop new antibiotics and alternative therapies in order to control this disease.