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The theme of the study is the film in teaching undergraduate nursing: contributions of a learning strategy. The objective is the meaning produced by the use of film as a learning strategy for nursing students. The aim of this study is to describe the contributions of the use of film as a learning strategy and to analyze the significance of the contributions of film to student nurses' learning. This is a qualitative study developed at the Private University Center of Teresópolis / Rio de Janeiro. The subjects are eight students from the 4th and 5th periods of the nursing programme. We used semi-structured interviews, between May-August 2007, and followed ethical and legal procedures. Thematic analysis of the data was performed. The pre-analysis was done, according to the methods described by Thompson, by repeated reading; exploration of the material - coding; grouping by similarity; identification of theoretical units; interpretation of the findings; referencing the findings to the work of other authors. The unifying theme incorporated the contributions and implications of the use of film for student nurses' learning: the stimulus that leads the nursing student to think, the image of the theory and practice of nursing, and the intention of the use of film as a learning strategy. All subjects concluded that film that helps in training. [ABSTRACT FROM AUTHOR]

Objectives: Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus and small vessel vasculitis. We previously showed that neutrophil extracellular traps (NETs) were associated with the pathogenesis of pristane-induced DAH and demonstrated that neutrophil NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly participated in NET generation under sterile stimulation. We investigated whether NLRP3 inflammasome assembly in neutrophils may drive pulmonary NETosis in a mouse model of pristane-induced DAH., Methods: C57BL/6J mice received a single intraperitoneal injection of 0.5mL of pristane. Neutrophil NLRP3 inflammasome assembly and NETs were characterized by immunofluorescence staining of apoptosis-associated speck-like protein a CARD (ASC), co-staining of DNA, and citrullinated histones, respectively. Clinical status of mice was assessed 11 days after pristane injection by measurement of arterial oxygen saturation and of weight loss; severity of lung injury was determined using a quantification score from hematoxylin-eosin-stained slides., Results: Pristane induced ASC speck formation in neutrophils and we confirmed that NLRP3 inflammasome was involved in NET generation after pristane stimulation in vitro . NLRP3 deficiency reduced the severity of pristane-induced DAH in female, but not male mice. Interestingly, NLRP3 deficiency reduced the number of neutrophils and NETs in the lungs of females compared to males., Conclusions: Our results suggest a link between female sex-specific NLRP3 inflammasome activation and subsequent pulmonary NETosis in the development of pristane-induced DAH. Therefore, we identified NLRP3 inflammasome as a potential new therapeutic target in this severe complication of pro-female autoimmune disease for which specific inhibitors of NLRP3 are currently developed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jarrot, Kim, Chan, Heger, Schommer, Cunin, Silva, Robert, Nigrovic, Ewenstein and Wagner.)

Introduction: Worksite labor gymnastics programs are interventions that can positively affect industrial workers. Studies show that experienced and novice workers perceive their working conditions differently. Our premise is that labor gymnastics programs affect these two groups diversely., Objectives: This study aimed to evaluate the benefits of an labor gymnastics program for experienced and novice industrial workers., Methods: Novice (476) and experienced (489) workers working for a footwear factory located in Northeastern Brazil participated in an labor gymnastics program for 5 months (October 2019 to February 2020). The variables musculoskeletal pain relief improved interpersonal relationships, willingness to work, psychophysiological well-being, and perceived difficulties in performing occupational tasks were assessed. Data were analyzed using an ordinal logistic regression model. The odds ratio modeled the relationship between the labor gymnastics program and the variables . Results: Experienced workers were six times more likely to report psychophysiological well-being, and novice workers were twice as likely to report improved interpersonal relationships. The benefits of the labor gymnastics program were different for experienced and novice workers., Conclusions: Although both groups can experience musculoskeletal pain relief, novice workers reported more commonly the variable improved interpersonal relationships, while experienced workers reported psychophysiological well-being. These findings help us better understand the outcomes of labor gymnastics programs according to length of service of industrial workers., Competing Interests: Conflicts of interest: None

Major depressive disorder (MDD) affects over 300 million people globally and has a multifactorial etiology. The CYP2C19 enzyme, involved in metabolizing certain antidepressants, can influence treatment response. Following the PRISMA protocol and PECOS strategy, this systematic review assessed the variation in common CYP2C19 gene variants' frequencies across populations with MDD, evaluating their impact on clinical characteristics and treatment response. We comprehensively searched five databases, identifying 240 articles, of which only nine within the last decade met our inclusion criteria. Except for one study that achieved 74.28% of STROPS items, the rest met at least 75% of GRIPS and STROPS guidelines for quality and bias risk assessment. The CYP2C19 's *1 allele, the *1/*1 genotype, and the NM phenotype, considered as references, were generally more frequent. Other CYP2C19 polymorphism frequencies exhibit significant variability across different populations. Some studies associated variants with MDD development, a more extended history of depression, prolonged depressive episodes, and symptom severity, while others reported no such association. Some studies confirmed variants' effects on escitalopram and citalopram metabolism but not that of other drugs, such as sertraline, venlafaxine, and bupropion. Treatment tolerability and symptom improvement also varied between studies. Despite some common findings, inconsistencies highlight the need for further research to clarify the role of these polymorphisms in MDD and optimize treatment strategies.

(1) Context: Cancer triggers significant changes in family dynamics. It is noteworthy that coping and problem-solving skills, particularly in situations involving cancer in children and adolescents, have not been adequately explored in the context of family adaptation. This study aims to analyze the effectiveness of family interventions in coping to improve problem-solving skills in parents and/or caregivers of children and adolescents during and after oncological treatment. (2) Methods: This is a scoping review following the recommendations of the Joanna Briggs Institute and the Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR), from 2014 to 2024, in the databases LILACS, CINAHL, SCOPUS, Web of Science, and PUBMED. (3) Results: Forty-five studies were eligible. Coping strategies were categorized as follows: (1) positive attitudes (including a sense of courage and hope, family support to enhance resilience, and future planning), (2) caregiver empowerment (involving acceptance of diagnosis, emotional distancing, and coping through religiosity), and (3) communication skills (encompassing professional communication, horizontal dialogue with healthcare teams, and sincere communication with friends and family). (4) Conclusions: Over time, families develop coping and problem-solving strategies that influence changes in family functioning patterns, aiding them in accepting, reinterpreting, and reframing ideas and feelings associated with neoplasia.

Objectives: to map available evidence on telenursing use in the postoperative period and its impact on patient outcomes., Methods: a scoping review, conducted according to the JBI model and the PRISMA-ScR checklist. The search was carried out in the CINAHL, Embase, LILACS, PubMed, Web of Science, SciELO, Scopus and Cochrane Library databases., Results: twelve studies were included, published between 2011 and 2023, 66.6% of which were in developed countries. Of the positive outcomes, we highlight improved levels of disability, autonomy and quality of life, lower rates of post-operative complications, pain and reduced costs. Telephone monitoring was the most widely used modality, but there were few studies in the pediatric context and in Brazil., Conclusions: of the studies, 11 (91.6%) identified at least one positive outcome in telenursing use and none showed negative aspects in the postoperative period. The role of nurses in digital health needs further study.

Background: Inflammation in the lungs and other vital organs in COVID-19 is characterized by the presence of neutrophils and a high concentration of neutrophil extracellular traps (NETs), which seems to mediate host tissue damage. However, it is not known whether NETs could have virucidal activity against SARS-CoV-2., Methods: We investigated whether NETs could prevent SARS-CoV-2 replication in neutrophils and epithelial cells and what the consequence of NETs degradation would be in K18-humanized ACE2 transgenic mice infected with SARS-CoV-2., Results: Here, by immunofluorescence microscopy, we observed that viral particles colocalize with NETs in neutrophils isolated from patients with COVID-19 or healthy individuals and infected in vitro. The inhibition of NETs production increased virus replication in neutrophils. In parallel, we observed that NETs inhibited virus abilities to infect and replicate in epithelial cells after 24 hours of infection. Degradation of NETs with DNase I prevented their virucidal effect in vitro. Using K18-humanized ACE2 transgenic mice, we observed a higher viral load in animals treated with DNase I. However, the virucidal effect of NETs was not dependent on neutrophil elastase or myeloperoxidase activity., Conclusions: Our results provide evidence of the role of NETosis as a mechanism of SARS-CoV-2 viral capture and inhibition., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The best surgical exposure and fixation method for fractures affecting the posterolateral corner of the tibial plateau remain debatable. This study describes a surgical approach to treat lateral depressions of the posterolateral tibial plateau with or without rim involvement by osteotomy of the lateral femoral epicondyle associated with osteosynthesis with a one-third tubular horizontal belt plate to stabilize the fracture fragment., Method: We evaluated 13 patients with fractures of the tibial plateau affecting the posterolateral region. Assessments included the degree of the depression (in millimeters), quality of the reduction, complications, and function., Results: All fractures and osteotomies consolidated. The patients had a mean age of 48 years and were mostly men (n=8). Regarding the quality of the reduction, the mean reduction obtained was 15.8 mm, and 8 patients achieved anatomical reduction. The mean (± standard deviation) Knee Society Score was 92±13 (range 65-100), and the mean Function Score was 95±9.6 (range 70-100). The mean Lysholm Knee Score was 92±11.7 (range 66-100), and the mean International Knee Documentation Committee Score was 85±12.6 (range 63-100). All these scores reflect good results. None of the patients developed superficial or deep infection or presented healing disorders. Sensitive or motor complications of the fibular nerve were not observed., Conclusions: In this series of patients with depression fractures of the posterolateral tibial plateau, a surgical approach through osteotomy of the lateral femoral epicondyle allowed direct reduction and stable osteosynthesis of the fractures without functional impairment., Competing Interests: Declaration of Competing Interest This manuscript has not been published elsewhere and is not under consideration by another journal. We have approved the manuscript and agree with submission to Injury. There are no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Graphene-based materials have increasingly attracted attention in recent years. It is a material is recognized worldwide due to its numerous applications in several sectors. However, graphene production involves several challenges: scalability, high costs, and high-quality production. This study synthesized graphene-like porous carbon nanosheets (GPCNs) through a thermochemical process under a nitrogen atmosphere using grape bagasse as a precursor. Three temperatures (700, 800, and 900 ºC) of the pyrolysis process were studied. Chemical graphitization and activation were used to form high-specific surface area materials: FeCl 3 .6H 2 O (aq) and ZnCl 2(s) in a simultaneous activation-graphitization (SAG) method. The materials obtained (GPCN700, GPCN800, and GPCN900) were compared to previously produced chars (C700, C800, and C900). A high specific surface area and total pore volume were obtained for GPCN materials, and GPCN900 presented the highest values: 1062.7 m 2 g -1 and 0.635 cm 3  g -1 , respectively. The GPCN and char materials were classified as mesoporous and applied as adsorbents for CO 2(g) . The GPCN800 presented the best CO 2(g) adsorbent, with a CO 2(g) adsorption capacity of 168.71 mg g -1 ., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Research addressing the costs of Medication errors (MEs) is still scarce despite issues related to patient safety having significant economic and health impacts, making it imperative to analyze the costs and adverse events related to MEs for a better patient, professional, and institutional safety., Aim: To identify the number of medication errors and verify whether this number was associated with increased hospitalization costs for patients in an Intensive Care Unit (ICU)., Method: This retrospective cross-sectional cohort study evaluated secondary data from patients' electronic medical records to compile variables, create a model, and survey hospitalization costs. The statistical analysis included calculating medication error rates, descriptive analysis, and simple and multivariate regression., Results: The omission error rate showed the highest number of errors per drug dose (59.8%) and total errors observed in the sample (55.31%), followed by the time error rate (26.97%; 24.95%). The omission error had the highest average when analyzing the entire hospitalization (170.40) and day of hospitalization (13.79). Hospitalization costs were significantly and positively correlated with scheduling errors, with an increase of BRL 121.92 (about USD $25.00) (95% CI 43.09; 200.74), and to prescription errors, with an increase of BRL 63.51 (about USD $3.00) (95% CI 29.93; 97.09)., Conclusion: We observed an association between two types of medication errors and increased hospitalization costs in an adult ICU (scheduling and prescription errors).

The miRNA156 (miR156)/SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL/SBP) regulatory hub is highly conserved among phylogenetically distinct species, but how it interconnects multiple pathways to converge to common integrators controlling shoot architecture is still unclear. Here, we demonstrated that the miR156/SlSBP15 node modulates tomato shoot branching by connecting multiple phytohormones with classical genetic pathways regulating both axillary bud development and outgrowth. miR156-overexpressing plants (156-OE) displayed high shoot branching, whereas plants overexpressing a miR156-resistant SlSBP15 allele (rSBP15) showed arrested shoot branching. Importantly, the rSBP15 allele was able to partially restore the wild-type shoot branching phenotype in the 156-OE background. rSBP15 plants have tiny axillary buds, and their activation is dependent on shoot apex-derived auxin transport inhibition. Hormonal measurements revealed that indole-3-acetic acid (IAA) and abscisic acid (ABA) concentrations were lower in 156-OE and higher in rSBP15 axillary buds, respectively. Genetic and molecular data indicated that SlSBP15 regulates axillary bud development and outgrowth by inhibiting auxin transport and GOBLET (GOB) activity, and by interacting with tomato BRANCHED1b (SlBRC1b) to control ABA levels within axillary buds. Collectively, our data provide a new mechanism by which the miR156/SPL/SBP hub regulates shoot branching, and suggest that modulating SlSBP15 activity might have potential applications in shaping tomato shoot architecture., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Neutrophil recruitment to sites of infection and inflammation is an essential process in the early innate immune response. Upon activation, a subset of neutrophils rapidly assembles the multiprotein complex known as the NLRP3 inflammasome. The NLRP3 inflammasome forms at the microtubule organizing center, which promotes the formation of interleukin (IL)-1β and IL-18, essential cytokines in the immune response. We recently showed that mice deficient in NLRP3 (NLRP3 -/- ) have reduced neutrophil recruitment to the peritoneum in a model of thioglycolate-induced peritonitis. Here, we tested the hypothesis that this diminished recruitment could be, in part, the result of defects in neutrophil chemotaxis. We find that NLRP3 -/- neutrophils show loss of cell polarization, as well as reduced directionality and velocity of migration toward increasing concentrations of leukotriene B4 (LTB4) in a chemotaxis assay in vitro, which was confirmed through intravital microscopy of neutrophil migration toward a laser-induced burn injury of the liver. Furthermore, pharmacologically blocking NLRP3 inflammasome assembly with MCC950 in vitro reduced directionality but preserved nondirectional movement, indicating that inflammasome assembly is specifically required for polarization and directional chemotaxis, but not cell motility per se. In support of this, pharmacological breakdown of the microtubule cytoskeleton via nocodazole treatment induced cell polarization and restored nondirectional cell migration in NLRP3-deficient neutrophils in the LTB4 gradient. Therefore, NLRP3 inflammasome assembly is required for establishment of cell polarity to guide the directional chemotactic migration of neutrophils.

The TIGIT + FOXP3 + Treg subset (TIGIT + Tregs) exerts robust suppressive activity on cellular immunity and predisposes septic individuals to opportunistic infection. We hypothesized that TIGIT + Tregs could play an important role in intensifying the COVID-19 severity and hampering the defense against nosocomial infections during hospitalization. Herein we aimed to verify the association between the levels of the TIGIT + Tregs with the mechanical ventilation requirement, fatal outcome, and bacteremia during hospitalization. TIGIT + Tregs were immunophenotyped by flow cytometry from the peripheral blood of 72 unvaccinated hospitalized COVID-19 patients at admission from May 29th to August 6th, 2020. The patients were stratified during hospitalization according to their mechanical ventilation requirement and fatal outcome. COVID-19 resulted in a high prevalence of the TIGIT + Tregs at admission, which progressively increased in patients with mechanical ventilation needs and fatal outcomes. The prevalence of TIGIT + Tregs positively correlated with poor pulmonary function and higher plasma levels of LDH, HMGB1, FGL2, and TNF. The non-survivors presented higher plasma levels of IL-33, HMGB1, FGL2, IL-10, IL-6, and 5.54 times more bacteremia than survivors. Conclusions: The expansion of the TIGIT + Tregs in COVID-19 patients was associated with inflammation, lung dysfunction, bacteremia, and fatal outcome., (© 2023. Springer Nature Limited.)

Neutrophils rely predominantly on glycolytic metabolism for their biological functions, including reactive oxygen species (ROS) production. Although pyruvate kinase M2 (PKM2) is a glycolytic enzyme known to be involved in metabolic reprogramming and gene transcription in many immune cell types, its role in neutrophils remains poorly understood. Here, we report that PKM2 regulates ROS production and microbial killing by neutrophils. Zymosan-activated neutrophils showed increased cytoplasmic expression of PKM2. Pharmacological inhibition or genetic deficiency of PKM2 in neutrophils reduced ROS production and Staphylococcus aureus killing in vitro. In addition, this also resulted in phosphoenolpyruvate (PEP) accumulation and decreased dihydroxyacetone phosphate (DHAP) production, which is required for de novo synthesis of diacylglycerol (DAG) from glycolysis. In vivo, PKM2 deficiency in myeloid cells impaired the control of infection with Staphylococcus aureus. Our results fill the gap in the current knowledge of the importance of lower glycolysis for ROS production in neutrophils, highlighting the role of PKM2 in regulating the DHAP and DAG synthesis to promote ROS production in neutrophils., (© 2023. The Author(s).)

Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla-afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.

Background: COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment., Methods: Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. SARS-CoV-2-infected K18-hACE2 mice were performed for clinical sickness scores and lung pathology. Moreover, the levels of NETs were assessed and lung injuries were by histopathology and TUNEL assay. Finally, the injury in the heart and kidney was assessed by histopathology and biochemical-specific markers., Results: DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potentially deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I., Conclusions: Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes., (© 2023. The Author(s).)

(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. However, several complications were reported, such as 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 Taq I and Fok I 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 Taq I 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 Fok I allele f .

Objective: This study aimed to investigate the effects of FK506 on experimental sepsis immunopathology. It investigated the effect of FK506 on leukocyte recruitment to the site of infection, systemic cytokine production, and organ injury in mice with sepsis., Methods: Using a murine cecal ligation and puncture (CLP) peritonitis model, the experiments were performed with wild-type (WT) mice and mice deficient in the gene Nfat1 (Nfat1 -/- ) in the C57BL/6 background. Animals were treated with 2.0 mg/kg of FK506, subcutaneously, 1 h before the sepsis model, twice a day (12 h/12 h). The number of bacteria colony forming units (CFU) was manually counted. The number of neutrophils in the lungs was estimated by the myeloperoxidase (MPO) assay. The expression of CXCR2 in neutrophils was determined using flow cytometry analysis. The expression of inflammatory cytokines in macrophage was determined using ELISA. The direct effect of FK506 on CXCR2 internalization was evaluated using HEK-293T cells after CXCL2 stimulation by the BRET method., Results: FK506 treatment potentiated the failure of neutrophil migration into the peritoneal cavity, resulting in bacteremia and an exacerbated systemic inflammatory response, which led to higher organ damage and mortality rates. Failed neutrophil migration was associated with elevated CXCL2 chemokine plasma levels and lower expression of the CXCR2 receptor on circulating neutrophils compared with non-treated CLP-induced septic mice. FK506 did not directly affect CXCL2-induced CXCR2 internalization by transfected HEK-293 cells or mice neutrophils, despite increasing CXCL2 release by LPS-treated macrophages. Finally, the CLP-induced response of Nfat1 -/- mice was similar to those observed in the Nfat1 +/+ genotype, suggesting that the FK506 effect is not dependent on the NFAT1 pathway., Conclusion: Our data indicate that the increased susceptibility to infection of FK506-treated mice is associated with failed neutrophil migration due to the reduced membrane availability of CXCR2 receptors in response to exacerbated levels of circulating CXCL2., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cytotoxic agents synergize with immune checkpoint inhibitors and improve outcomes for patients with several cancer types. Nonetheless, a parallel increase in the incidence of dose-limiting side effects, such as peripheral neuropathy, is often observed. Here, we investigated the role of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in the modulation of paclitaxel-induced neuropathic pain. We found that human and mouse neural tissues, including the dorsal root ganglion (DRG), expressed basal levels of PD-1 and PD-L1. During the development of paclitaxel-induced neuropathy, an increase in PD-L1 expression was observed in macrophages from the DRG. This effect depended on Toll-like receptor 4 activation by paclitaxel. Furthermore, PD-L1 inhibited pain behavior triggered by paclitaxel or formalin in mice, suggesting that PD-1/PD-L1 signaling attenuates peripheral neuropathy development. Consistent with this, we observed that the combined use of anti-PD-L1 plus paclitaxel increased mechanical allodynia and chronic neuropathy development induced by single agents. This effect was associated with higher expression of inflammatory markers (Tnf, Il6, and Cx3cr1) in peripheral nervous tissue. Together, these results suggest that PD-1/PD-L1 inhibitors enhance paclitaxel-induced neuropathic pain by suppressing PD-1/PD-L1 antinociceptive signaling., (©2022 American Association for Cancer Research.)

This integrative review aims to identify the main flavonoids present in some species of the Myrtaceae family. Studies published between 2016 and 2022 were selected, specifically those which were fully available and written in Portuguese, English, or Spanish, and which were related to the fruits araçá ( Psidium cattleianum ), cambuí ( Myrciaria floribunda ), gabiroba ( Campomanesia xanthocarpa ), jabuticaba ( Plinia cauliflora ), and jambolan ( Syzygium cumini ). Scientific studies were gathered and selected in Google Scholar, Scielo, and Science Direct indexed databases, out of which 14 were about araçá, 7 concerned cambuí, 4 were about gabiroba, 29 were related to jabuticaba, and 33 concerned jambolan, when we observed the pre-established inclusion criteria. Results showed that the anthocyanins, such as cyanidin, petunidin, malvidin, and delphinidin, were the mostly identified class of flavonoids in plants of the Myrtaceae family, mainly relating to the purple/reddish color of the evaluated fruits. Other compounds, such as catechin, epicatechin, quercetin, and rutin were also identified in different constituent fractions, such as leaves, peel, pulp, seeds, and in developed products, such as jams, desserts, wines, teas, and other beverages. It is also worth noting the positive health effects verified in these studies, such as anti-inflammatory qualities for jambolan, antidiabetic qualities for gabiroba, antioxidant qualities for araçá, and cardioprotective actions for jabuticaba, which are related to the presence of these phytochemicals. Therefore, it is possible to point out that flavonoids are important compounds in the chemical constitution of the studied plants of the Myrtaceae family, with promising potential in the development of new products by the food, chemical, and pharmaceutical industries due to their bioactive properties.

This article aims to analyze the evidence available in the literature on the process of identifying adults and elderly people who can benefit from palliative care (PC) in primary health care (PHC). This is an integrative literature review carried out in PubMed, CINAHL, LILACS, Web of Science, and Embase. Eight studies were selected, in which different instruments and methods were distinguished with the purpose of identifying people who can benefit from PC in the context of PHC. The incorporation of these instruments into clinical practice is urgent in order to increase the reach and effectiveness of the services offered by health professionals, considering the current demographic and epidemiological profile that points to the increase of people with a potential need for PC. Different instruments have been successfully used to identify PC in the context of PHC. However, some have weaknesses, such as the fact that they only allow the identification of people with oncological diseases, leaving out other health conditions, which reinforces the need for further studies on this topic.

Background: The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear., Objectives: We aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19., Methods: We performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection., Results: We found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage., Conclusion: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy., (© 2022. The Author(s).)

Based on cleaner production and circular economy concepts, chars were produced through thermochemical conversion of grape bagasse and then used as adsorbents to uptake Cu(II) from aqueous media since Cu(II) is a common element found in fungicides to treat grapevines. The grape bagasse and char characteristics were investigated through several analytical techniques (TGA, SEM, XRD, FTIR, and BET). Three chars were obtained using different pyrolysis temperatures: 700, 800, and 900 °C. The materials had similar removal percentages and adsorption capacity. The char produced at 700 °C was chosen due to its lower production cost. Studies were conducted on the adsorbent dosage and pH effect, adsorption kinetics, isotherms, and thermodynamics. The most efficient dosage was 1.5 g L -1 , and the pH was 5.5. The kinetic study showed that the equilibrium was reached in 60 min and the pseudo-second-order model presents the best fit. After the temperature influence study (25, 35, 45, and 55 °C), it was possible to verify that Cu(II) adsorption through char was favored at 55 °C. The Freundlich model showed the best fit for the experimental data. The highest removal percentage was 96.56%, and the high maximum adsorption capacity was 42 mg g -1 . The thermodynamic study shows the adsorption as a spontaneous process, favorable, and endothermic., Supplementary Information: The online version contains supplementary material available at 10.1007/s13399-022-02792-8., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Background: The amount of visceral adipose tissue (VAT) tends to increase with age and is associated with several health problems, such as cardiometabolic diseases, increased infections, and overall mortality., Objectives: This review provides a general assessment of how visceral adiposity correlates with the development of health problems and changes in serum biochemical parameters in middle-aged and older adults., Methods: We searched specific terms in the Virtual Health Library (VHL) databases for VAT articles published in the English language between 2009 and 2019 related to older adults., Results: The search found twenty-three publications in this period, of which nine were excluded. The publications had a population aged between 42 and 83 years and correlated the VAT area ratio with several comorbidities (such as pancreatitis, depression, cancer, and coronary heart disease) and serum biochemical parameters., Conclusion: Further research on the association between visceral obesity and the emergence of health problems and the relationship between VAT and changes in serum biochemical parameters in older individuals should deepen the understanding of this connection and develop preventive actions., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study., (Copyright © 2022 Vanessa C. Moreira et al.)

Background: Although the literature shows that an increase in both the number and suppressive function of CD4+forkhead box P3 (FOXP3)+ T-regulatory cells (Tregs) during sepsis contributes to an immunosuppressed state, little is known about the identity of these cells., Methods: Using the sepsis mouse model of cecal ligation and puncture (CLP), we analyzed the frequency and molecular signature of the T-cell immunoglobulin and ITIM domain (TIGIT)+ and TIGIT- Treg subsets, using flow cytometry and quantitative polymerase chain reaction. In addition, ST2-/- and signal transducer and activator of transcription 6 (STAT6)-/- mice were submitted to CLP or recombinant interleukin 33 (IL-33) treatment to investigate the mechanism whereby TIGIT+ Tregs differentiate during sepsis., Results: Sepsis was marked by the sustained expansion of the highly suppressive TIGIT+ Treg subset, which expresses Helios, neuropilin 1, and high levels of Tnfrsf18 and Pdcd1 at 15 days after CLP. The increase in TIGIT+ Tregs was accompanied by higher susceptibility to nosocomial bacteria challenge, suggesting their association with post sepsis immunosuppression. Mechanistically, we found that the ST2 deletion abrogated the expansion of the TIGIT+ Treg subset during sepsis. Furthermore, treatment with recombinant IL-33 resulted in the expansion of TIGIT+ Tregs depending on the STAT6 and M2 macrophages., Conclusions: These findings demonstrated that only the TIGIT+ Tregs remain stably expanded at the late phase of sepsis. Moreover, the expansion of TIGIT+ Tregs is dependent on the IL-33/ST2/STAT6/M2 macrophage axis., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment., (© 2021 by The American Society of Hematology.)

This study aimed to assess Salmonella spp. prevalence in aquaculture Nile tilapia commercialized in the Federal District, Brazil, and determine the antimicrobial resistance profile of the isolates. Fifty-seven Salmonella spp. strains were isolated from 101 samples of fresh tilapia fillets collected in the Federal District, Brazil. These isolates were subjected to antimicrobial susceptibility testing by the Kirby-Bauer disk diffusion method and analyzed for the presence of blaCTX , tetB , sul2 , and floR resistance genes. The Salmonella spp. prevalence in fresh tilapia fillets was 45.5%; that is, 46 of 101 samples were positive for the InvA gene. The antimicrobial resistance profile showed high resistance rates for amoxicillin/clavulanic acid (87.7%), tetracycline (82.5%), sulfonamide (57.9%), and chloramphenicol (26.3%). Additionally, 56.1% of Salmonella spp. isolates were multidrug-resistant (MDR) isolates. The beta-lactam-resistant gene blaCTX was identified in 66.7% of isolates, the tetracycline resistance gene tetA in 54.4%, and the chloramphenicol resistance gene floR in 50.9%, while the sulfonamide resistance gene sul2 was present in 49.1%. The results revealed that tilapia fillets were highly contaminated with MDR Salmonella . These Salmonella spp. strains carried multiple antimicrobial resistance genes, which might facilitate their dissemination to consumers along the production chain. Hence, there is an evident need to control Salmonella in fish production systems to ensure public health.

Vigorous exercise can induce gastrointestinal disorders such decreased gastric emptying pace, while low-intensity exercise can accelerate gastric motility. However, the mechanisms of these effects are still unknown. We investigated the possible neurohumoral mechanisms involved in these phenomena. In sedentary (Sed) and acute exercise (Ex) groups of rats, we assessed the activation of c-Fos in NTS and DVMN and the plasma levels of CCK and OXT. Separate groups received pretreatment with the oxytocin antagonist atosiban (AT), the cholecystokinin antagonist devazepide (DVZ), or the TRPV 1 receptor inhibitor capsazepine (CAPZ). AT, DVZ and CAPZ treatments prevented (p<0.05) slower gastric emptying induced by acute exercise. The gene expression of OXT decreased (P<0.05) while that of CCK increased (P<0.05) in the gastric fundus and pylorus of the Ex group, while the plasma levels of OXT rose (p<0.05) and of CCK declined (p<5.05). We also observed activation (p<0.05) of c-Fos-sensitive neurons in the NTS and DVMN of exercised rats. In conclusion, acute exercise slowed gastric emptying by the vagal afferent pathway, which involved activation of CCK 1 /OXT/TRPV 1 sensitivity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects ( n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model's performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Rodrigues et al.)

Objective: To investigate the effect of different types of manual toothbrushes and brushing loads on the progression of erosive tooth wear (ETW) on enamel., Methods: Bovine enamel specimens (n = 10) were submitted to a 5-day erosive-abrasive cycling model (0.3 % citric acid for 5 min, artificial saliva for 60 min, 4x/day). Toothbrushing was carried out 2x/day for 15 s, according to the toothbrushes tested (ultra-soft (a): Curaprox 5460; ultra-soft (b): Sensodyne Repair & Protect; soft (a): Colgate Slim Soft; soft (b): Oral-B Indicator Plus; medium: Johnson's Professional; hard: Tek) and brushing loads (1.5 N, 3 N). Surface loss (SL, in μm) was assessed by optical profilometry on conclusion of the cycling. Some of the toothbrush characteristics were evaluated. Data were statistically analyzed (α = 0.05)., Results: For the 1.5 N load, the hard brush showed the highest SL value, with statistical significance. The other toothbrushes did not differ significantly, except that ultra-soft (a) caused significantly higher SL than ultra-soft (b). For the 3 N load, hard and soft (a) exhibited the highest SL. Soft (b) and medium had the lowest SL value, with statistical significance. Only soft (a) and ultra-soft (b) showed significant difference between loads, with lower SL for the load of 1.5 N. None of the toothbrush characteristics were significantly correlated with SL., Conclusions: Although different degrees of enamel surface loss were observed with use of the different toothbrushes, no association was found between the toothbrush characteristics and SL. Depending on the toothbrush, the force of brushing was capable of modulating the ETW of enamel. Based on the brushing loads usually applied by healthy individuals, hard brushes are not recommended for use by patients with ETW., Clinical Significance: The use of hard bristle brushes is not recommended for use by individuals who exert healthy forces when brushing their teeth. The toothbrush characteristics are of secondary importance in terms of causing enamel loss in ETW., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Systemic mycoses have become a major cause of morbidity and mortality, particularly among immunocompromised hosts and long-term hospitalized patients. Conventional antifungal agents are limited because of not only their costs and toxicity but also the rise of resistant strains. Lipopeptides from Paenibacillus species exhibit antimicrobial activity against a wide range of human and plant bacterial pathogens. However, the antifungal potential of these compounds against important human pathogens has not yet been fully evaluated, except for Candida albicans . Paenibacillus elgii produces a family of lipopeptides named pelgipeptins, which are synthesized by a non-ribosomal pathway, such as polymyxin. The present study aimed to evaluate the activity of pelgipeptins produced by P. elgii AC13 against Cryptococcus neoformans , Paracoccidioides brasiliensis , and Candida spp. Pelgipeptins were purified from P. elgii AC13 cultures and characterized by high-performance liquid chromatography (HPLC) and mass spectrometry (MALDI-TOF MS). The in vitro antifugal activity of pelgipeptins was evaluated against C. neoformans H99, P. brasiliensis PB18, C. albicans SC 5314, Candida glabrata ATCC 90030, and C. albicans biofilms. Furthermore, the minimal inhibitory concentration (MIC) was determined according to the CLSI microdilution method. Fluconazole and amphotericin B were also used as a positive control. Pelgipeptins A to D inhibited the formation and development of C. albicans biofilms and presented activity against all tested microorganisms. The minimum inhibitory concentration values ranged from 4 to 64 µg/mL, which are in the same range as fluconazole MICs. These results highlight the potential of pelgipeptins not only as antimicrobials against pathogenic fungi that cause systemic mycoses but also as coating agents to prevent biofilm formation on medical devices., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest., (© 2021 the Author(s), licensee AIMS Press.)

Thyroid cancer is the most common endocrine cancer in the world. Noting that the NOS3 gene polymorphism interferes with nitric oxide production, this study aims to identify and analyze the NOS3 gene polymorphism in the intron 4 region in patients with papillary thyroid cancer. A case-control study was conducted with 31 papillary thyroid cancer patients of both genders who underwent thyroidectomy and treatment with sodium iodide radiopharmaceutical (131I) compared with 81 control patients. Through papillary thyroid cancer, the results were observed, compiled, and analyzed using SPSS version 25.0. The significance level of 5% was adopted. Genotypic frequencies of healthy subjects were in the Hardy-Weinberg equilibrium ( P = 0.503). There was a significant genotypic difference between papillary thyroid cancer and healthy individuals ( P <0.001). The BB genotype conferred a protective factor for papillary thyroid cancer ( P <0.001, odds ratio (OR) 0.16; 95% confidence interval (CI) 0.06, 0.42), while the presence of the A allele appears to be a risk factor for papillary thyroid cancer ( P <0.001, OR 3.54; 95% CI 1.86, 6.73). The intron 4 polymorphism of the NOS3 gene was associated with susceptibility to papillary thyroid cancer. Thus, future research into the effects of this polymorphism is essential.

The inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogeneous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets boost the inflammasome capacity of human macrophages and neutrophils and are critical for IL-1 production by monocytes. Platelets license NLRP3 transcription, thereby enhancing ASC oligomerization, caspase-1 activity, and IL-1β secretion. Platelets influence IL-1β production in vivo, and blood platelet counts correlate with plasmatic IL-1β levels in malaria. Furthermore, we reveal an enriched platelet gene signature among the highest-expressed transcripts in IL-1β-driven autoinflammatory diseases. The platelet effect is independent of cell-to-cell contact, platelet-derived lipid mediators, purines, nucleic acids, and a host of platelet cytokines, and it involves the triggering of calcium-sensing receptors on macrophages. Hence, platelets provide an additional layer of regulation of inflammasomes and IL-1-driven inflammation., Competing Interests: Declaration of Interests E.L. is co-founder and consultant of IFM Therapeutics., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Previous data have reported that the growth of established tumors may be facilitated by postsepsis disorder through changes in the microenvironment and immune dysfunction. However, the influence of postsepsis disorder in initial carcinogenesis remains elusive., Methods: In the present work, the effect of postsepsis on inflammation-induced early carcinogenesis was evaluated in an experimental model of colitis-associated colorectal cancer (CAC). We also analyzed the frequency and role of intestinal T regulatory cells (Treg) in CAC carcinogenesis., Results: The colitis grade and the tumor development rate were evaluated postmortem or in vivo through serial colonoscopies. Sepsis-surviving mice (SSM) presented with a lower colonic DNA damage, polyp incidence, reduced tumor load, and milder colitis than their sham-operated counterparts. Ablating Treg led to restoration of the ability to develop colitis and tumor polyps in the SSM, in a similar fashion to that in the sham-operated mice. On the other hand, the growth of subcutaneously inoculated MC38luc colorectal cancer cells or previously established chemical CAC tumors was increased in SSM., Conclusion: Our results provide evidence that postsepsis disorder has a dual effect in cancer development, inhibiting inflammation-induced early carcinogenesis in a Treg-dependent manner, while increasing the growth of previously established tumors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Strenuous exercise triggers deleterious effects on the intestinal epithelium, but their mechanisms are still uncertain. Here, we investigated whether a prolonged training and an additional exhaustive training protocol alter intestinal permeability and the putative effect of alanyl-glutamine (AG) pretreatment in this condition. Rats were allocated into 5 different groups: 1) sedentary; 2 and 3) trained (50 min per day, 5 days per week for 12 weeks) with or without 6 weeks oral (1.5 g/kg) AG supplementation; 4 and 5) trained and subjected to an additional exhaustive test protocol with or without oral AG supplementation. Venous blood samples were collected to determine gasometrical indices at the end of the 12-week protocol or after exhaustive test. Lactate and glucose levels were determined before, during, and after the exhaustive test. Ileum tissue collected after all experimental procedures was used for gene expression analysis of Zonula occludens 1 (ZO-1), occludin, claudin-2, and oligopeptide transporter 1 (PepT-1). Intestinal permeability was assessed by urinary lactulose/mannitol test collected after the 12-week protocol or the exhaustive test. The exhaustive test decreased pH and base excess and increased pCO2. Training sessions delayed exhaustion time and reduced the changes in blood glucose and lactate levels. Trained rats exhibited upregulation of PEPT-1, ZO-1, and occludin mRNA, which were partially protected by AG. Exhaustive exercise induced intestinal paracellular leakage associated with the upregulation of claudin-2, a phenomenon protected by AG treatment. Thus, AG partially prevented intestinal training adaptations but also blocked paracellular leakage during exhaustive exercise involving claudin-2 and occludin gene expression.

In acidic soils, aluminium (Al) occurs as Al3+, which is phytotoxic. One of the most conspicuous symptoms of Al toxicity is the root growth inhibition, which can lead to low water uptake and consequent reduction in leaf hydration and gas exchange. However, fibrous xylem vessels have been observed in roots of 'Rangpur' lime plants (Citrus limonia L.) when exposed to Al, which could affect the functioning of aquaporins, ultimately reducing their expression. We confirmed a decrease of CO2 assimilation (A), stomatal conductance (gs), transpiration (E) and relative leaf water content (RWC) in 3-month-old C. limonia plants exposed to 1480 μM Al in nutrient solution for 90 days. The estimated hydraulic conductivity from soil to the leaf (KL) and leaf water potential (Ψw) also showed low values, although not consistently reduced over time of Al exposure. The relative expression of aquaporin genes belonging to PIP family (PIP1-1, PIP1-2 and PIP2) showed downregulation for ClPIP1-1 and ClPIP2 and upregulation for ClPIP1-2 in plants exposed to Al. Furthermore, ClPIP1-1 was positively correlated with A and gs in plants exposed to Al. Therefore, downregulation of ClPIP1-1 and ClPIP2 in roots of 'Rangpur' lime plants could be associated with the low leaf hydration of this species when exposed to Al.

Objective: Saliva is the most important biological factor to protect against erosive tooth wear (ETW). Gastroesophageal reflux disease (GERD) patients have an increased risk of ETW due to the frequent presence of intrinsic acids in the oral cavity. Remarkably, not all GERD patients suffer from ETW, which might be due to differences in the composition of the saliva., Methods: This study compared the proteomic profile of saliva in patients (1) with GERD and ETW (basic erosive wear examination, BEWE, score ≥9; GE group) and (2) with GERD without ETW (BEWE = 0; GNE group) using shotgun label-free quantitative proteomic analysis nLC-ESI-MS/MS. The ability of hemoglobin (Hb) to protect against initial enamel erosion caused by a daily 10-s immersion of enamel specimens in 0.01 M HCl (pH 2.3) for 3 days was evaluated in vitro for proof of concept. Surface hardness change was used as response variable., Results: The differential expression of Hb subunits was significantly increased in the GNE group versus the GE group, in particular the Hb α-subunit that showed a >22-fold increase. Expressions of serum albumin (4.5-fold) and isoforms of cytoskeletal keratin type II (>3-fold) were also increased in the GNE group. Proteinase inhibitors, such as α1-antitrypsin and α2-macroglobulin, were only identified in the GNE group. In vitro, Hb (1.0 and 4.0 mg/mL) significantly reduced initial enamel erosion compared to a negative control after 3 days., Conclusions: Our results indicate that many proteins, with special emphasis on Hb, may be involved in the resistance of GERD patients to the occurrence of ETW. These proteins may be candidates for inclusion in dental products to protect against ETW., (© 2020 S. Karger AG, Basel.)

This study aimed to evaluate the promising feasibility of the hydrothermal pre-processing of eucalyptus wood and eucalyptus bark under organosolv and organic acid conditions to produce a highly concentrated cellulose feedstock. For that, particulate samples of both biomasses were heated in water solutions containing from 0 to 50% vol/vol of ethanol and from 0 to 50 mmol.L -1 of oxalic acid at temperatures between 140 and 180 °C. Significant differences on the thermal degradation profiles were observed for both biomasses indicating the partial hydrolysis converted them into a more homogeneous solid fraction with higher contents of cellulose. It was also observed a significant variation of the glycan content from approximately 39 to 76% for wood particles, whereas the variation for bark was from 32 to 50%. In general, the proposed pre-processing route was considered potentially feasible to concentrate the cellulose/glycan contents of eucalyptus biomasses for subsequent industrial utilization., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: This in vivo study compared the protein profile of the acquired enamel pellicle (AEP) in volunteers 1) with gastroesophageal reflux disease (GERD) and erosive tooth wear (ETW) (BEWE ≥ 9; GE group); 2) with GERD without ETW (BEWE = 0; GNE group) and 3) control (without GERD and BEWE = 0; C group)., Materials and Methods: Twenty-four subjects (8/group) participated. AEP was formed during 120 min and collected. After protein extraction, the samples were submitted to reverse phase liquid chromatography coupled to mass spectrometry. Label-free proteomic quantification was performed using Protein Lynx Global Service software., Results: In total, 458 proteins were identified. Seventy-six proteins were common to all the groups. The proteomic profile of the AEP was quite different among the distinct groups. The numbers of proteins exclusively found in the C, GE and GNE groups were 113, 110 and 81, respectively. Most of the proteins exclusively identified in the C and GNE groups bind metals, while those in the GE group are mainly membrane proteins. Many proteins were found exclusively in the reflux groups. In the quantitative analyses, when the GNE group was compared with the GE group, the proteins with the highest decreases were Lysozyme C, Antileukoproteinase, Cathepsin G, Neutrophil defensins and Basic salivary proline-rich proteins, while those with the highest increases were subunits of Hemoglobin, Albumin and isoforms of Cystatin., Conclusion: Profound alterations in the proteomic profile of the AEP were seen in GNE compared with GE volunteers, which might play a role in the resistance to ETW seen in the first., Clinical Significance: This pioneer study compared the proteomic profile of the AEP of patients with GERD with or without ETW. Increased proteins in those without ETW might be protective and are good candidates to be added to dental products to protect against erosion caused by intrinsic acids., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To analyze the meanings assigned by people with systemic arterial hypertension to health education actions in the waiting room., Method: This is an analytical qualitative study, held in 2016 with 19 people with arterial hypertension from a health unit. The data were collected in households, through a semi-structured interview and field notes, recorded on audio, transcribed and organized by thematic analysis, being analyzed considering Vygostky's Cultural-Historical Learning Theory., Result: Meanings of attention, interest, pleasure and learning assigned to educational practice denote the importance of interaction and mediation to reconstruct knowledge about blood pressure control and to attribute a new meaning to self-care., Final Considerations: The waiting room became an environment that promoted interaction, favoring the construction of meanings and internalization of knowledge with potential for lifestyle changes.

Ifosfamide (IFO) is an antineoplastic drug that is commonly used to treat gynecological and breast cancers. Hemorrhagic cystitis (HC) is a common side effect associated with IFO injection, which courses with neutrophil accumulation and affects 6-50% of patients depending on dose intensity. Here, we investigated the role of neutrophils in this inflammatory process. Female Swiss mice (n = 8/group) were injected with saline, IFO (400 mg/kg, i.p.), fucoidan (a P- and L-selectins inhibitor, 100 mg/kg, i.v.) or IFO + fucoidan (1-100 mg/kg) alone or combined with mesna (80 mg/kg i.p.). Another group of mice received anti-Ly6G antibody (500 μg/mouse, once daily for 2 days) for neutrophil depletion before IFO injection. In another experimental setting, animals received granulocyte colony-stimulating factor (G-CSF, 400 μg/kg), IFO (200 mg/kg), G-CSF (25-400 μg/kg, for 5 days) + IFO (200 mg/kg, i.p.) or fucoidan + G-CSF + IFO. Bladder injury was evaluated 12 h after IFO injection. IFO 400 mg/kg significantly increased visceral hyperalgesia, bladder edema, hemorrhage, vascular permeability, MPO, IL-1β and IL-6 tissue levels, and COX-2 immunostaining and expression versus the saline group (P < 0.05). Conversely, fucoidan (100 mg/kg) significantly attenuated these parameters compared to IFO-injected mice (P < 0.05). Additionally, fucoidan potentiated mesna protective effect when compared with IFO + mesna group (P < 0.05). Accordingly, neutrophil depletion with anti-Ly6G reduced inflammatory parameters and bladder injury compared to IFO (P < 0.05). In contrast, G-CSF enhanced IFO (200 mg/kg)-induced HC, which was significantly attenuated by treatment with fucoidan (P < 0.05). Therefore, neutrophils contribute to the pathogenesis of HC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Intestinal mucositis (IM) is a common side effect of irinotecan-based chemotherapy. The involvement of inflammatory mediators, such as TNF-α, IL1-β, IL-18 and IL-33, has been demonstrated. However, the role of adaptive immune system cells, whose activation is partially regulated by these cytokines, is yet unknown. Thus, we investigated the role of regulatory T cells (Tregs) in irinotecan-induced IM. C57BL/6 mice were injected with saline or irinotecan (75mgkg -1 , i.p.), once a day for 4days, and euthanized at day 1, 3, 5 or 7 following the first dose of irinotecan. For Treg depletion, the mice were pretreated with a low single dose of cyclophosphamide (100mgkg -1 , i.p). Intestinal lamina propria lymphocytes were harvested and purified by Percoll gradient. Treg and Th17 cells were identified by flow cytometry. Blood leukocyte count was obtained and ileum samples were collected for histopathological analysis and myeloperoxidase assay. IM caused an accumulation of Tregs and Th17 cells over time. Treg depletion exacerbated intestinal damage, diarrhea, neutrophil infiltration and animal mortality, despite a reduction in Th17 cell number. The frequency of other Th cells increased and was positively correlated with neutrophil infiltration. Tregs showed a negative correlation with neutrophils and the frequency of non-regulatory Th cells. In conclusion, Tregs are important in the control of intestinal damage induced by irinotecan, and their depletion showed a deleterious effect on IM. Activation of these cells appears to be a compensatory mechanism for intestinal inflammation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

This study detected changes in the protein profile of the acquired enamel pellicle (AEP) formed in vivo after rinsing with whole milk, fat-free milk, or water. Nine subjects in good oral condition took part in the study. The acquired pellicle was formed in the morning, for 120 min, after prophylaxis with pumice. Following this, the volunteers rinsed with 10 mL of whole milk, fat-free milk, or deionized water for 30 s, following a blinded crossover protocol. After 60 min, the pellicle was collected with filter paper soaked in 3% citric acid and processed for analysis by liquid chromatography-electrospray ionization tandem mass spectrometry. The obtained tandem mass spectrometry spectra were searched against a human protein database (Swiss-Prot). The proteomic data related to protein quantification were analysed using the PLGS software. A total of 260 proteins were successfully identified in the AEP samples collected from all groups. Forty-nine were common to all 3 groups, while 72, 62, and 49 were specific to the groups rinsing with whole milk, fat-free milk, and water, respectively. Some were typical components of the AEP, such as cystatin-B, cystatin-SN, isoforms of α-amylase, IgA and IgG, lysozyme C, protein S100 A78, histatin-1, proline-rich protein 27, statherin, and lactotransferrin. Other proteins are not commonly described as part of the AEP but could act in defence of the organism against pathogens. Distinct proteomic profiles were found in the AEP after rinsing with whole or fat-free milk, which could have an impact on bacterial adhesion and tooth dissolution. The use of fat-free milk could favourably modulate the adhesion of bacteria to the AEP as well as biofilm formation when compared with whole milk., (© 2018 S. Karger AG, Basel.)

Objective: Changes in the protein profile of acquired enamel pellicles (AEP) formed in vivo over different time periods were evaluated after the application of hydrochloric acid (HCl)., Methods: Nine subjects were submitted to dental prophylaxis with pumice. After 3 or 120 min, the teeth were isolated with cotton rolls and 50 μL of 0.1 M HCl (pH 1.0), 0.01 M HCl (pH 2.0), or deionized water were applied on the buccal surface of the teeth for 10 s. The AEP was then collected using an electrode filter paper presoaked in 3% citric acid. After protein extraction, the samples were submitted to reverse-phase liquid chromatography coupled to mass spectrometry (nano LC-ESI-MS/MS). Label-free quantification was performed (Protein Lynx Global Service software)., Results: A total of 180 proteins were successfully identified in the AEP samples. The number of identified proteins increased with the time of pellicle formation. Only 4 proteins were present in all the groups (isoforms of IgA, serum albumin, and statherin). The greatest number of proteins identified uniquely in one of the groups was obtained for the groups treated with HCl after 2 h of pellicle formation (approx. 50 proteins)., Conclusion: Proteins resistant to removal by HCl, such as serum albumin and statherin, were identified even in the short-term AEP. In addition, 120-min pellicles present many proteins that are resistant to removal by HCl. This suggests an increase in protection against intrinsic acids with the time of pellicle formation, which should be evaluated in future studies., (© 2018 S. Karger AG, Basel.)