Iron incorporation in red blood cells of pediatric sickle cell anemia: a stable isotope pilot investigation.

BACKGROUND/OBJECTIVES: Sickle cell anemia (SCA) is marked by hypoxia, inflammation, and secondary iron overload (IO), which potentially modulate hepcidin, the pivotal hormone governing iron homeostasis. The aim was to evaluate the iron incorporation in red blood cells (RBC) in SCA pediatric patients, considering the presence or absence of IO. SUBJECTS/METHODS: SCA children (n = 12; SCAtotal) ingested an oral stable iron isotope (57Fe) and iron incorporation in RBC was measured after 14 days. Patients with ≥1000 ng/mL serum ferritin were considered to present IO (SCAio+; n = 4) while the others were classified as being without IO (SCAio-; n = 8). Liver iron concentration (LIC) was determined by Magnetic Resonance Imaging (MRI) T2* method. RESULTS: The SCAio+ group had lower iron incorporation (mean ± SD: 0.166 ± 0.04 mg; 3.33 ± 0.757%) than SCAio- patients (0.746 ± 0.303 mg; 14.9 ± 6.05%) (p = 0.024). Hepcidin was not different between groups. Iron incorporation was inversely associated with serum ferritin level (SCAtotal group: r = -0.775, p = 0.041; SCAio- group: r = -0.982; p = 0.018) and sickle hemoglobin (HbS) presented positive correlation with iron incorporation (r = 0.991; p = 0.009) in SCAio- group. LIC was positively associated with ferritin (SCAtotal: r = 0.921; p = 0.026) and C reactive protein (SCAio+: r = 0.999; p = 0.020). CONCLUSION: SCAio+ group had lower iron incorporation in RBC than SCAio- group, suggesting that they may not need to reduce their intake of iron-rich food, as usually recommended. Conversely, a high percentage of HbS may indirectly exacerbate hypoxia and seems to increase iron incorporation in RBC. TRIAL REGISTRATION: This trial was registered at www.ensaiosclinicos.gov.br . Identifier RBR-4b7v8pt.

Unveiling the characteristics of D4 and R4 aptamers for their future use in prostate cancer clinical practice.

The DNA and RNA aptamers D4 and R4, respectively, emerged from the modification of PC-3 cell-binding aptamer A4. Our objective was to characterize the aptamers in silico and in vitro and begin to identify their target molecules. We represented their structures using computational algorithms; evaluated their binding to several prostate cell lines and their effects on the viability and migration of these cells; and determined their dissociation constant by flow cytometry. We analyzed circulating prostate tumor cells from patients using D4, R4, anti-CD133 and anti-CD44. Finally, the target proteins of both aptamers were precipitated and identified by mass spectrometry to simulate their in silico docking. The aptamers presented similar structures and bound to prostate tumor cells without modifying the cellular parameters studied, but with different affinities. The ligand cells for both aptamers were CD44+, indicating that they could identify cells in the mesenchymal stage of the metastatic process. The possible target proteins NXPE1, ADAM30, and MUC6 need to be further studied to better understand their interaction with the aptamers. These results support the development of new assays to determine the clinical applications of D4 and R4 aptamers in prostate cancer.

Iron absorption in adults with sickle cell anemia: a stable-isotope approach.

PURPOSE: Iron absorption in sickle cell anemia (SCA) remains unclear and studies in adults with SCA are scarce. The aim of this study was to evaluate the iron absorption SCA adults and its association with iron status and hepcidin concentration. METHODS: SCA patients (n = 13; SCAtotal) and control participants (n = 10) ingested an oral stable iron isotope (57Fe). Iron absorption was measured by inductively coupled plasma mass spectrometry (ICP-MS) 14 days after isotope administration. Patients with ≥ 1000 ng/mL serum ferritin were considered to present iron overload (IO) (SCAio+; n = 3) and others classified without IO (SCAio-; n = 10). RESULTS: Iron absorption in the control group ranged from 0.3 to 26.5% (median = 0.9%), while it varied from 0.3 to 5.4% in SCAio+ (median = 0.5%) and from 0.3 to 64.2% in the SCAio- (median = 6.9%). Hepcidin median values were 14.1 ng/mL (3.0-31.9 ng/mL) in SCAio-, 6.2 ng/mL (3.3-7.8 ng/mL) in SCAio + and 6.2 ng/mL (0.6-9.3 ng/mL) in control. Iron absorption was associated with ferritin level (r = - 0.641; p = 0.018) and liver iron concentration (LIC; r = - 0.786; p = 0.036) in the SCAtotal group. CONCLUSION: Our data suggest that SCAio- individuals may be at risk of developing primary IO. Simultaneously, secondary IO may induce physiological adaptation, resulting in reduced iron absorption. Further studies evaluating intestinal iron absorption using larger sample sizes should be conducted to help establish a safe nutrition approach to be adopted and to ensure the security of food-fortifying public policies for these patients. TRIAL REGISTRATION: This trial was registered at www.ensaiosclinicos.gov.br (Identifier RBR-4b7v8pt).

Antimicrobial efficiency of bromhexine hydrochloride against endometritis-causing Escherichia coli and Trueperella pyogenes in bovines.

In this study, the main agents associated with endometritis in cows in the state of Santa Catarina, Brazil, were identified and the resistance profile and virulence mechanisms of the bacterial isolates were evaluated. Isolates of Escherichia coli and Trueperella pyogenes were tested for their biofilm forming ability and the antimicrobial action of bromhexine hydrochloride in combination with other antimicrobials. A total of 37 uterine lavage samples were collected from cows with endometritis. Of the 55 bacteria isolated, 25.4% were identified as T. pyogenes and 16.3% as E. coli. The bacterial isolates showed greater resistance to sulfamethoxazole + trimethoprim (58.2%) and tetracycline (56.3%). Among the species, E. coli showed the highest resistance rates, with 100% of isolates showing resistance to amoxicillin, streptomycin, and gentamicin. The results of the minimum inhibitory concentration for the T. pyogenes isolates showed that 91.6% of the isolates were resistant to enrofloxacin and tetracycline, and 75% were resistant to ceftiofur and sulfamethoxazole + trimethoprim. All E. coli and T. pyogenes isolates showed biofilm forming ability. The plo, fimA, and nanH genes were identified in 100% of T. pyogenes isolates. In parallel, 100% of E. coli isolates had the fimH gene, and 11.1% had the csgD gene. Bromhexine hydrochloride showed antimicrobial activity against 100% of E. coli isolates and 66.6% of T. pyogenes isolates. Furthermore, when associated with antimicrobials, bromhexine hydrochloride has a synergistic and additive effect, proving to be an option in the treatment of endometritis in cows and an alternative for reducing the use of antimicrobials.

Development of collagenous scaffolds for wound healing: characterization and in vivo analysis.

The development of wound dressings from biomaterials has been the subject of research due to their unique structural and functional characteristics. Proteins from animal origin, such as collagen and chitosan, act as promising materials for applications in injuries and chronic wounds, functioning as a repairing agent. This study aims to evaluate in vitro effects of scaffolds with different formulations containing bioactive compounds such as collagen, chitosan, N-acetylcysteine (NAC) and ε-poly-lysine (ε-PL). We manufactured a scaffold made of a collagen hydrogel bioconjugated with chitosan by crosslinking and addition of NAC and ε-PL. Cell viability was verified by resazurin and live/dead assays and the ultrastructure of biomaterials was evaluated by SEM. Antimicrobial sensitivity was assessed by antibiogram. The healing potential of the biomaterial was evaluated in vivo, in a model of healing of excisional wounds in mice. On the 7th day after the injury, the wounds and surrounding skin were processed for evaluation of biochemical and histological parameters associated with the inflammatory process. The results showed great cell viability and increase in porosity after crosslinking while antimicrobial action was observed in scaffolds containing NAC and ε-PL. Chitosan scaffolds bioconjugated with NAC/ε-PL showed improvement in tissue healing, with reduced lesion size and reduced inflammation. It is concluded that scaffolds crosslinked with chitosan-NAC-ε-PL have the desirable characteristics for tissue repair at low cost and could be considered promising biomaterials in the practice of regenerative medicine.

Novel bioanalytical strategy using isotope pattern deconvolution and ICP-QMS for the study of iron incorporation in erythrocytes: An insight to better assessment.

Iron is an essential element for human life and its nutritional status in the human body is directly linked to human health. More than 1015 atoms of iron per second are necessary for the maintenance of haemoglobin formation. To predict iron bioavailability three approaches are normally employed: (a) faecal recovery; (b) plasma appearance; and (c) erythrocyte incorporation (the most used). Isotope Pattern Deconvolution (IPD) is a mathematical tool that allows the isolation of distinct isotope signatures from mixtures of natural abundance and enriched tracers. In this work we propose a novel strategy to assess erythrocyte iron incorporation, based on the use of an iron stable isotope (57Fe) and the IPD concept. This strategy allows direct calculation of the exogenous concentration of 57Fe incorporated into RBCs after supplementation. In this way, to determine the mass of iron incorporated into erythrocytes, the unique prediction that must be made is the blood volume, estimate to reproduce the natural dilution of the tracer (57Fe) in the blood. This novel bioanalytical approach was applied for the measurements of iron incorporation and further iron absorption studies in humans, using a group of twelve healthy participants, that should be further evaluated for the assessment of other chemical elements that could be of health concerns and directly impact society.

Protective role of CXCR7 activation in neonatal hyperoxia-induced systemic vascular remodeling and cardiovascular dysfunction in juvenile rats.

Neonatal hyperoxia induces long-term systemic vascular stiffness and cardiovascular remodeling, but the mechanisms are unclear. Chemokine receptor 7 (CXCR7) represents a key regulator of vascular homeostasis and repair by modulating TGF-ß1 signaling. This study investigated whether pharmacological CXCR7 agonism prevents neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction in juvenile rats. Newborn Sprague Dawley rat pups assigned to room air or hyperoxia (85% oxygen), received CXCR7 agonist, TC14012 or placebo for 3 weeks. These rat pups were maintained in room air until 6 weeks when aortic pulse wave velocity doppler, cardiac echocardiography, aortic and left ventricular (LV) fibrosis were assessed. Neonatal hyperoxia induced systemic vascular stiffness and cardiac dysfunction in 6-week-old rats. This was associated with decreased aortic and LV CXCR7 expression. Early treatment with TC14012, partially protected against neonatal hyperoxia-induced systemic vascular stiffness and improved LV dysfunction and fibrosis in juvenile rats by decreasing TGF-ß1 expression. In vitro, hyperoxia-exposed human umbilical arterial endothelial cells and coronary artery endothelial cells had increased TGF-ß1 levels. However, treatment with TC14012 significantly reduced the TGF-ß1 levels. These results suggest that dysregulation of endothelial CXCR7 signaling may contribute to neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction.

Comparative Evaluation of the Canal Shaping Ability, Pericervical Dentin Preservation, and Smear Layer Removal of TruNatomy, WaveOne Gold, and ProTaper Ultimate-An Ex Vivo Study in Human Teeth.

INTRODUCTION: Innovative file systems have been recently introduced, claiming improved effectiveness and superior ability to preserve the tooth structure, still allowing an efficient preparation and disinfection up to the apical region. Regardless, few data are available on the comparative effectiveness of the most recently developed systems. Thus, this ex vivo study aimed to comparatively evaluate, for the first time, the functionality of WaveOne Gold (WOG), TruNatomy (TN), and ProTaper Ultimate (PU) file systems regarding canal shaping, dentin preservation, and smear layer removal ability. METHODS: Human maxillary incisors were randomly divided for instrumentation with one of the assayed systems. Canal shaping ability and pericervical dentin preservation were characterized through microtomographic evaluation and morphometric assessment (n = 15). Smear layer removal ability was evaluated by scanning electron microscopy (SEM) (n = 6). RESULTS: TN and PU presented the lowest canal volume variation upon instrumentation, found to be significantly lower than that attained with WOG (P < .05). Pericervical dentin was reduced in all groups upon instrumentation, with TN evidencing the highest preservation, quantitatively similar to PU, and significantly higher than that attained with WOG (P < .05). SEM imaging revealed the presence of scattered remnants of the smear layer and partially opened dentinal tubules at the apical portion, with no significant differences between systems. CONCLUSIONS: TN and PU allowed for the highest tissue preservation, reporting the lowest volume variation and the highest preservation of the pericervical dentin. None of the assessed systems provided a complete removal of the smear layer in the apical region.

Use of the Maslach Burnout Inventory Among Public Health Care Professionals: Scoping Review.

BACKGROUND: Work can be considered a source of living, well-being, and socioeconomic development. When the work environment negatively influences individuals, it may trigger emotional disturbances, behavioral problems, chronic stress conditions, and illnesses such as burnout syndrome (BS). Recently, studies on BS have increased and placed a special focus on health care professionals. The prevalence of BS among health professionals is associated with their chronic exposure to human hardship and long working hours without proper rest. These factors have contributed to greater stress and high physical and emotional exhaustion levels. OBJECTIVE: This study aims to identify and map studies using the Maslach Burnout Inventory (MBI) scale to identify burnout syndrome in health professionals working in public health services. METHODS: This scoping review was developed based on the Joanna Briggs Institute (JBI) Reviewers Manual and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews). A total of 6 databases were searched to identify relevant studies: Embase, LILACS, MEDLINE or PubMed, PsycInfo, Scopus, and Web of Science. Gray literature was consulted on ProQuest Dissertations and Theses Global, Google Scholar, Brazilian Digital Library of Theses and Dissertations, and Open Access Theses and Dissertations. Additionally, the reference lists were searched to retrieve studies not previously selected. The steps followed in this study were proposed by Arskey and O'Malley and Levac, Colquhoun, and O'Brien: identification of research questions, identification of potential studies, study selection, data extraction and imputation, data analyses and interpretation, and consultation with stakeholders. The detailed methodology was published in a protocol. RESULTS: A total of 55 articles were identified after screening for eligibility criteria, published between 1999 and 2021 in 32 countries. Most reports were published in Brazil, Spain, and China. A total of 22 versions of the MBI were identified, presenting different items, scores, and cutoff points. The included studies had recommendations and implications for clinical practice. The consultation with stakeholders allowed knowledge translation for those interested in BS. CONCLUSIONS: Studies mostly included physicians (34/55, 61.8%) and nurses (24/55, 43.6%), and the original version of MBI was predominantly used. Divergences in BS classification were highlighted, which may be related to MBI cross-cultural adaptations and applications in other countries. This study contributes to the advancement of research regarding burnout syndrome as an occupational illness since it has harmful consequences for workers, health care services, and the quality of care provided to the population.

Changes in the Gut Microbiota after the Use of Herbal Medicines in Overweight and Obese Individuals: A Systematic Review.

BACKGROUND: Herbal medicine is a low-cost treatment and has been increasingly applied in obesity treatment. Gut microbiota (GM) is strongly associated with obesity pathogenesis. METHODS: We conducted a systematic review guided by the question: "Does the use of herbal medicine change the GM composition in obese individuals?" Randomized clinical trials with obese individuals assessing the effects of herbal medicine intervention in GM were retrieved from the Medline, Embase, Scopus, Web of Science, and Cochrane Library databases, including the Cochrane Controlled Trials Register. Two reviewers independently extracted data using standardized piloted data extraction forms and assessed the study-level risk of bias using an Excel template of the Cochrane "Risk of bias" tool 2-RoB 2. RESULTS: We identified 1094 articles in the databases. After removing duplicates and reading the title and abstract, 14 publications were fully evaluated, of which seven publications from six studies were considered eligible. The herbs analyzed were Moringa oleifera, Punica granatum, Scutellaria baicalensis, Schisandra chinensis, W-LHIT and WCBE. The analysis showed that Schisandra chinensis and Scutellaria baicalensis had significant effects on weight loss herbal intervention therapy composed by five Chinese herbal medicines Ganoderma lucidum, Coptis chinensis, Astragalus membranaceus, Nelumbo nucifera gaertn, and Fructus aurantii (W-LHIT) and white common bean extract (WCBE) on GM, but no significant changes in anthropometry and laboratory biomarkers. CONCLUSIONS: Herbal medicine modulates GM and is associated with increased genera in obese individuals.

Ex Vivo Osteogenesis Induced by Calcium Silicate-Based Cement Extracts.

Calcium silicate-based cements are used in a variety of clinical conditions affecting the pulp tissue, relying on their inductive effect on tissue mineralization. This work aimed to evaluate the biological response of calcium silicate-based cements with distinct properties-the fast-setting Biodentine™ and TotalFill® BC RRM™ Fast Putty, and the classical slow-setting ProRoot® MTA, in an ex vivo model of bone development. Briefly, eleven-day-old embryonic chick femurs were cultured for 10 days in organotypic conditions, being exposed to the set cements' eluates and, at the end of the culture period, evaluated for osteogenesis/bone formation by combining microtomographic analysis and histological histomorphometric assessment. ProRoot® MTA and TotalFill® extracts presented similar levels of calcium ions, although significantly lower than those released from BiodentineTM. All extracts increased the osteogenesis/tissue mineralization, assayed by microtomographic (BV/TV) and histomorphometric (% of mineralized area; % of total collagen area, and % of mature collagen area) indexes, although displaying distinct dose-dependent patterns and quantitative values. The fast-setting cements displayed better performance than that of ProRoot® MTA, with BiodentineTM presenting the best performance, within the assayed experimental model.

Personalized medicine: Function of CFTR variant p.Arg334Trp is rescued by currently available CFTR modulators.

Most of the 2,100 CFTR gene variants reported to date are still unknown in terms of their disease liability in Cystic Fibrosis (CF) and their molecular and cellular mechanism that leads to CFTR dysfunction. Since some rare variants may respond to currently approved modulators, characterizing their defect and response to these drugs is essential for effective treatment of people with CF (pwCF) not eligible for the current treatment. Here, we assessed how the rare variant, p.Arg334Trp, impacts on CFTR traffic and function and its response to existing CFTR modulators. To this end, we performed the forskolin-induced swelling (FIS) assay on intestinal organoids from 10 pwCF bearing the p.Arg334Trp variant in one or both alleles of the CFTR gene. In parallel, a novel p.Arg334Trp-CFTR expressing CFBE cell line was generated to characterize the variant individually. Results show that p.Arg334Trp-CFTR does not significantly affect the plasma membrane traffic of CFTR and evidences residual CFTR function. This CFTR variant is rescued by currently available CFTR modulators independently of the variant in the second allele. The study, predicting clinical benefit for CFTR modulators in pwCF with at least one p.Arg334Trp variant, demonstrates the high potential of personalized medicine through theranostics to extend the label of approved drugs for pwCF carrying rare CFTR variants. We recommend that this personalized approach should be considered for drug reimbursement policies by health insurance systems/national health services.

The impact of COPD on the private healthcare system in Brazil: an economic analysis / Impacto da DPOC no sistema de saúde privado no Brasil: uma análise econômica

Objective: To assess healthcare resource utilization and hospitalization costs of patients with chronic obstructive pulmonary disease (COPD) exacerbations in the Brazilian private healthcare system. Methods: A retrospective cohort study, considering data from an administrative database of a private company (Orizon). Patients aged ≥40 years old and with at least one COPD-related claim identified by the ICD-10 code (J40 to J44) at any time during the eligibility period (January/2010 to December/2013) were included in the analysis. Follow-up was performed until December/2014, death or inactivation of a health plan. Sociodemographic characteristics, number of emergency visits, hospital admissions (number and length of stay), length of hospital stay in an intensive care unit (ICU), number of severe COPD exacerbations, therapeutic approach, and hospitalization costs were assessed. Results: The analysis included 8,254 COPD patients. Emergency visits, hospital admission, and exacerbation rates were 0.4, 0.2, and 0.1 per person-year, respectively. The mean length of hospital stays and the length of stay of patients requiring or not ICU stay were 16.6 (SD = 77.0), 8.7 (SD = 36.9), and 27.6 (SD = 109.7), respectively. Mean costs associated to emergency department visits and hospitalizations were 258.2 BRL (SD = 383.1) and 38,165.4 BRL (SD = 124,683.5), respectively. Hospitalizations costs without ICU stay were 11,810.1 BRL (SD = 31,144.1) and 74,585.3 BRL (SD = 182,808.1) for those with ICU utilization. Conclusion: Costs for COPD management during disease exacerbation are very high and may reach almost 75 thousand BRL per hospitalization. The prevention of COPD exacerbations and better disease control may reduce the economic burden on the private healthcare system in Brazil.

Objetivo: Avaliar a utilização de recursos e custos de pacientes com exacerbação da doença pulmonar obstrutiva crônica (DPOC) no sistema de saúde suplementar (SSS) do Brasil. Métodos: Estudo de coorte retrospectiva, considerando banco de dados administrativo de uma empresa privada (Orizon). Pacientes com ≥40 anos e pelo menos um registro de admissão relacionado à DPOC identificado com CID-10 J40-J44, entre janeiro/2010 e dezembro/2013, foram incluídos e acompanhados até dezembro/2014, morte ou inativação no plano. Características sociodemográficas, número de visitas de emergência, admissões hospitalares (número e tempo de hospitalização), tempo de hospitalização em unidade de terapia intensiva (UTI), número de exacerbações graves, estratégias terapêuticas e custos hospitalares foram as variáveis analisadas. Resultados: A análise incluiu 8.254 pacientes com DPOC. As taxas de visita à emergência, internação hospitalar e exacerbação da doença foram de 0,4, 0,2 e 0,1 por pessoa-ano, respectivamente. Os tempos médios de hospitalização, hospitalização sem utilização de UTI e hospitalização com necessidade de UTI foram de 16,6 (DP = 77,0), 8,7 (DP = 36,9) e 27,6 (DP = 109,7) dias, respectivamente. Os custos médios relacionados à visita de emergência e por hospitalização foram de 258,2 BRL (DP = 383,1) e 38.165,4 BRL (DP = 124.683,5), respectivamente. Os custos para pacientes que não utilizaram UTI foram de 11.810,1 BRL (DP = 31.144,1) e de 74.585,3 BRL (DP = 182.808,1) para aqueles com necessidade desse serviço. Conclusão: Os custos para o manejo dos pacientes com exacerbação da DPOC são muito elevados, podendo chegar a 75.000 BRL por hospitalização. A prevenção de exacerbações e o melhor controle da doença podem reduzir esse impacto econômico no SSS.

Food Consumption of People with Sickle Cell Anemia in a Middle-Income Country.

Sickle cell anemia (SCA) is a genetic and hemolytic disease globally characterized by social vulnerability. Food consumption has been insufficiently analyzed in SCA. Secondary iron overload is often observed. This leads to unreliable recommendations for dietary iron restriction. We assessed food consumption and iron intake among adults with SCA. Considering the guidelines for healthy eating, foods were grouped according to the NOVA classification. This transversal study included 74.4% of eligible patients who were registered in the reference center for SCA treatment in Rio de Janeiro, Brazil, in 2019. Data on food consumption were collected through 24 h recall. The monthly household income of 82.3% of patients was less than $770. The consumption of fresh or minimally processed foods was directly associated with monthly household income (p < 0.0001; η2 = 0.87). Ultra-processed foods provided more than one-third of the total energy intake (35.2%). The prevalence of inadequate iron intake was about 40% among women, while that of iron intake above the tolerable upper limit was 0.8%. People from lower socioeconomic classes had the lowest iron intake. Strategies to encourage the consumption of fresh or minimally processed foods are needed considering the requirement of an antioxidant diet in SCA. These findings highlight the need for health equity to ensure food security and healthy eating in SCA.

The economic impact of asthma on private healthcare system in Brazil: Economic impact of asthma in Brazil.

To assess healthcare resource utilization and costs of patients with asthma in Brazilian Supplementary Healthcare System, focusing on hospitalization data. Retrospective cohort study, using data from an administrative database of a private company (Orizon). Patients aged ≥ 12 years with at least one record of emergency visit/hospitalization in the database with the ICD-10 J45 between January/2010 and June/2015 were included and followed until June/2016, death or inactivation of health plan. Sociodemographic characteristics, emergency visit and hospital admission per patient per year (exacerbation rate), physician visit with a procedure, exams, length of hospitalization (with/without intensive care unit (ICU)), and in-hospital treatments were assessed. A total of 54,568 patients were included in this analysis. Regarding resource utilization, emergency visit and hospital admission rates of 0.34 and 0.04 per person-year were observed, respectively. Mean length of hospital stay were 8.82 (SD = 36.48), 5.24 (SD = 19.06) and 19.53 (63.89) days for hospitalizations in general, without and with ICU, respectively. An exacerbation rate of 0.36 per person year was observed with a mean cost per episode of 3178 Brazilian Real (BRL) (SD = 31,667). Mean cost related to emergency department visits was estimated at 293 BRL (SD = 328). Hospitalization costs were stratified by the need of ICU and values observed were of 9307 BRL (SD = 18,979) without ICU, and 75,252 BRL (SD = 174,248) with ICU need. Asthma exacerbations may cost ~75,000 BRL for an ICU-dependent event in the Supplementary Healthcare System. To improve disease control may reduce disease burden for both healthcare system and patients.

Fast-Setting Calcium Silicate-Based Pulp Capping Cements-Integrated Antibacterial, Irritation and Cytocompatibility Assessment.

Calcium silicate-based cements (CSCs) are endodontic materials widely used in vital pulp-capping approaches. Concerning the clinical application, the reduced set time and pre-mixed formulations are relevant characteristics during the operative management of pulpal exposure, aiming to optimise the work time and improve cross-infection/asepsis control. Additionally, clinical success seems to be greatly dependent on the biological performance of the materials that directly contact the living pulp. As such, this work approaches an integrative biological characterisation (i.e., antibacterial, irritation, and cytocompatibility assays) of three fast-setting CSCs-BiodentineTM, TotalFill® BC RRM™ Fast Putty, and Theracal LC®. These cements, after setting for 24 h, presented the expected topography and elemental composition (assessed by scanning electron microscopy, coupled with EDS analysis), in accordance with the information of the manufacturer. The set cements displayed a significant and similar antibiofilm activity against S. mutans, in a direct contact assay. Twenty-four-hour eluates were not irritant in the standardised CAM assay, but elicited distinct dose- and time-dependent cytotoxicity profiles on fibroblastic cells-i.e., Biodentine was devoid of toxicity, TotalFill presented a slight dose-dependent initial toxicity that was easily overcome, and Theracal LC was deleterious at high concentrations. When compared to long-setting ProRoot MTA cement, which highlighted the pursued integrative approach, Biodentine presented a similar profile, but TotalFill and Theracal LC displayed a poorer performance regarding antibiofilm activity/cytocompatibility features, and Theracal LC suggested eventual safety concerns.

Glutamine Metabolism Supports the Functional Activity of Immune Cells against Aspergillus fumigatus.

The reprogramming of cellular metabolism of immune cells is an essential process in the regulation of antifungal immune responses. In particular, glucose metabolism has been shown to be required for protective immunity against infection with Aspergillus fumigatus. However, given the intricate cross talk between multiple metabolic networks and signals, it is likely that cellular metabolic pathways other than glycolysis are also relevant during fungal infection. In this study, we demonstrate that glutamine metabolism is required for the activation of macrophage effector functions against A. fumigatus. Glutamine metabolism was found to be upregulated early after fungal infection and glutamine depletion or the pharmacological inhibition of enzymes involved in its metabolism impaired phagocytosis and the production of both proinflammatory and T-cell-derived cytokines. In an in vivo model, inhibition of glutaminase increased susceptibility to experimental aspergillosis, as revealed by the increased fungal burden and inflammatory pathology, and the defective cytokine production in the lungs. Moreover, genetic variants in glutamine metabolism genes were found to regulate cytokine production in response to A. fumigatus stimulation. Taken together, our results demonstrate that glutamine metabolism represents an important component of the immunometabolic response of macrophages against A. fumigatus both in vitro and in vivo. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. The reprogramming of cellular metabolism is essential for innate immune cells to mount effective antifungal responses. In this study, we report the pivotal contribution of glutaminolysis to the host defense against A. fumigatus. Glutamine metabolism was essential both in vitro as well as in in vivo models of infection, and genetic variants in human glutamine metabolism genes regulated cytokine production in response to fungal stimulation. This work highlights the relevance of glutaminolysis to the pathogenesis of aspergillosis and supports a role for interindividual genetic variation influencing glutamine metabolism in susceptibility to infection.

The interaction between aging and protein malnutrition modulates peritoneal macrophage function: An experimental study in male mice.

Malnutrition is considered one of the most common problems in the elderly population worldwide and can significantly interfere in health evolution in these individuals, predisposing them to increased infection susceptibility. The immune response triggered by infections comprises several mechanisms, and macrophages play important roles in this response. This study aimed to evaluate mechanisms related to macrophage function in a model of protein malnutrition in the elderly. Two age groups (young: 3-5 months and elderly: 18-19 months) male C57BL/6NTac mice were subjected to protein malnutrition with a low-protein diet (2 %). The nutritional status, hemogram and number of peritoneal cells were affected by both age and nutritional status. Additionally, the spreading capacity as well as the phagocytic and fungicidal activity of peritoneal macrophages were affected by the nutritional status and age of the animal. Interestingly, the percentages of F4/80+/CD11b+ and CD86+ cells were reduced mostly in elderly animals, while the TLR-4+ population was more affected by nutritional status than by age. The production of pro-inflammatory cytokines such as TNF-α, IL-1α, and IL-6 was also influenced by nutritional status and/or by age, and malnourished animals of advanced age produced higher amounts of the anti-inflammatory cytokine IL-10. Furthermore, the phosphorylation ratio of the transcription factor NFκB (pNFκB/NFκB) was directly affected by the nutritional status, independently of age. Thus, these results allow us to conclude that aging and protein malnutrition compromise macrophage function, likely affecting their immune function, and in aged protein-malnourished animals, this impairment tends to be more pronounced.

Effect of Prepartum Maternal Supplementation with Diphenyl Diselenide on Biochemical, Immunological, and Oxidative Parameters of the Offspring.

This study aimed to assess the impact of prepartum maternal diphenyl diselenide (PhSe)2 supplementation on the development, biochemical, immune, and antioxidant parameters of calves. Eighteen Holstein breed calves were used, born to females who were or were not subjected to supplementation, at 42, 28, and 14 days prior to calving. The (PhSe)2 group (DDG) was administered 3 µmol/kg of (PhSe)2 in 4 mL of dimethyl sulfoxide (DMSO), while the DMSO and NaCl groups were administered 4 mL of DMSO and 0.9% NaCl, subcutaneously. The calves were evaluated based on their weight, withers height, body condition score 24 h post-birth (0), as well on days 14, 28, 42, 56, 70. Blood samples were also taken to determine serum variables. Calves on the DDG showed higher average levels of total protein, albumin, and globulins on day 0, and the immunoglobulin G level was significantly higher than the other groups on days 0, 14, 56, 70. Maternal supplementation showed immunomodulatory effect on calves, evidenced by the exceptional rates of passive immunity transfer, as well as the enhancement of humoral immunity. Our research offers fresh insights into the immunomodulatory potential of (PhSe)2, making it a viable alternative in facing this challenging phase, rearing dairy calves.

Eficácia e segurança do Felbamato comparado a medicamentos disponíveis no SUS para o tratamento da epilepsia refratária em crianças e adultos: revisão rápida de evidências / Effectiveness and safety of Felbamate compared to drugs available in SUS for the treatment of refractory epilepsy in children and adults: rapid evidence review

Tecnologia: Felbamato. Indicação: Tratamento de epilepsia refratária. Pergunta: O Felbamato é mais eficaz e seguro comparado a anticonvulsivantes disponíveis no Sistema Único de Saúde (SUS) em pacientes com epilepsia refratária? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas 2 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: O felbamato não demonstrou ser uma opção mais benéfica que os demais medicamentos disponíveis no SUS no tratamento de epilepsia refratária a medicamentos. Salienta-se que a maior parte das evidências eram de baixa certeza

Technology: Felbamate. Indication: Treatment of refractory epilepsy. Question: Is felbamate more effective and safer compared to anticonvulsants available in Brazilian Public Health System in patients with refractory epilepsy? Methods: A rapid review of evidence (overview) of systematic reviews, with bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Two systematic reviews that met the inclusion criteria were selected. Conclusion: Felbamate did not prove to be a more beneficial option than the other drugs available in the Brazilian Public Health System in the treatment of drug-refractory epilepsy. It should be noted that most of the evidence was of low certainty