The respiratory oxygenation index for identifying the risk of orotracheal intubation in COVID-19 patients receiving high-flow nasal cannula oxygen.

OBJECTIVE: To assess whether the respiratory oxygenation index (ROX index) measured after the start of high-flow nasal cannula oxygen therapy can help identify the need for intubation in patients with acute respiratory failure due to coronavirus disease 2019. METHODS: This retrospective, observational, multicenter study was conducted at the intensive care units of six Brazilian hospitals from March to December 2020. The primary outcome was the need for intubation up to 7 days after starting the high-flow nasal cannula. RESULTS: A total of 444 patients were included in the study, and 261 (58.7%) were subjected to intubation. An analysis of the area under the receiver operating characteristic curve (AUROC) showed that the ability to discriminate between successful and failed high-flow nasal cannula oxygen therapy within 7 days was greater for the ROX index measured at 24 hours (AUROC 0.80; 95%CI 0.76 - 0.84). The median interval between high-flow nasal cannula initiation and intubation was 24 hours (24 - 72), and the most accurate predictor of intubation obtained before 24 hours was the ROX index measured at 12 hours (AUROC 0.75; 95%CI 0.70 - 0.79). Kaplan-Meier curves revealed a greater probability of intubation within 7 days in patients with a ROX index ≤ 5.54 at 12 hours (hazard ratio 3.07; 95%CI 2.24 - 4.20) and ≤ 5.96 at 24 hours (hazard ratio 5.15; 95%CI 3.65 - 7.27). CONCLUSION: The ROX index can aid in the early identification of patients with acute respiratory failure due to COVID-19 who will progress to the failure of high-flow nasal cannula supportive therapy and the need for intubation.

Effect of Reintubation Within 48 Hours on Mortality in Critically Ill Patients After Planned Extubation.

BACKGROUND: Re-intubation is necessary in 2% to 30% of cases of patients receiving a planned extubation. This procedure is associated with prolonged mechanical ventilation, a greater need for tracheostomy, a higher incidence of ventilator-associated pneumonia, and higher mortality. The aim of this study was to evaluate the effect of re-intubation within 48 h on mortality after planned extubation by using a randomized controlled trial database. METHODS: Secondary analysis of a multi-center randomized trial, which evaluated the effect of reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial, followed by extubation. The study included adult subjects who received invasive mechanical ventilation for > 12 h. The subjects were divided into an extubation failure group and an extubation success group. The outcome was in-hospital mortality. Two multivariate logistic regression models were constructed to identify independent factors associated with mortality. RESULTS: Among the 336 subjects studied, extubation failed in 52 (15.4%) and they were re-intubated within 48 h. Most re-intubations occurred between 12 and 24 h after planned extubation (median [interquartile range] 16 [6-36] h). Mortality of the extubation failure group was higher both in the ICU (32.6% vs 6.6%; odds ratio [OR] 6.77, 95% CI 3.22-14.24; P < .001) and in-hospital (42.3% vs 14.0%; OR 4.47, 95% CI 2.34-8.51; P < .001) versus the extubation success group. Multivariate logistic regression analyses showed that re-intubation within 48 h was independently associated with both ICU mortality (OR 6.10, 95% CI 2.84-13.07; P < .001) and in-hospital mortality (OR 3.36, 95% CI 1.67-6.73; P = .001). In-hospital mortality was also associated with rescue noninvasive ventilation after extubation (OR 2.44, 95% CI 1.25-4.75; P = .009). CONCLUSIONS: Re-intubation within 48 h after planned extubation was associated with mortality in subjects who were critically ill.

Anti-inflammatory actions of aspirin-triggered resolvin D1 (AT-RvD1) in bronchial epithelial cells stimulated by cigarette smoke extract.

Smoking causes several diseases such as chronic obstructive pulmonary disease (COPD). Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. Here we evaluated the role of AT-RvD1 (100 nM) in bronchial epithelial cells (BEAS-2B) stimulated by cigarette smoke extract (CSE; 1%; 1 cigarette) for 24 h. CSE induced the productions of IL-1ß, TNF-α, IL-10, IL-4 and IFN-γ as well as the activations of NF-κB and STAT3 and the expression of ALX/FPR2 receptor. AT-RvD1 reduced the IL-1ß and TNF-α production and increased the production of IFN-γ. These effects were reversed BOC2, an antagonist of ALX/FPR2 receptor for AT-RvD1. The production of IL-4 and IL-10 were not altered by AT-RvD1. In addition, AT-RvD1 reduced the phosphorylation of NF-κB and STAT3 when compared to CSE-stimulated BEAS-2B cells. No alteration of ALX/FPR2 expression was observed by AT-RvD1 when compared to CSE group. In the human monocytic leukemia cell line, the relative number of copies of IL-1ß and IL-4 was significantly higher in CSE + AT-RvD1 group compared CSE group, however, the expression of M1 cytokine was more pronounced than M2 profile. AT-RvD1 could be an important target for the reduction of inflammation in the airways associated with smoking.

Serum uric acid concentration is associated with lower glomerular filtration rate in children undergoing kidney transplantation.

BACKGROUND: The relationship between serum concentration of uric acid (UA) and chronic kidney disease is complex due to many confounding variables. There is currently debate over whether hyperuricemia acts as a marker of kidney disease or as an independent risk factor. OBJECTIVES: To test the impact of serum UA concentration on the estimated glomerular filtration rate (GFR) of children undergoing kidney transplantation. PATIENTS AND METHODS: Prospective longitudinal study of children and adolescents after kidney transplantation. We analyzed clinical, anthropometric, and laboratory data at pre-transplant and 1, 3, and 6 months after transplant. We developed models of repeated measures analysis, using the generalized estimating equations technique for the outcome evolution of the estimated GFR at 1, 3 and 6 months. High serum UA concentration at 1 and 3 months was modeled as the main exposure variable. RESULTS: We included 103 transplant patients. In a model adjusted for time, recipient sex and age, the occurrence of acute rejection episodes, and the estimated glomerular filtration at baseline, the trajectory of GFR exhibited an inverse relationship with UA (ß = -7.1, 95% CI: -11.5 to -2.6, p < .01). CONCLUSION: Serum UA increase was associated with lower graft function over time.

Is Trimethylamine N-oxide (TMAO) Associated with NF-κB mRNA Expression in Patients with Coronary Artery Disease?

Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is associated with cardiovascular disease (CVD) development. TMAO can trigger an inflammatory response by inducing the nuclear factor-kappa B (NF-κB) signaling cascade and increasing the expression of pro-inflammatory cytokines, contributing to the worsening of CVD. This study aimed to evaluate the association between TMAO plasma levels and inflammation in patients with coronary artery disease (CAD). Methods: A cross-sectional study was carried out including 29 patients with CAD. Peripheral blood mononuclear cells (PBMC) were isolated from fasting blood samples, and NF-κB and vascular cell adhesion protein 1 (VCAM1) mRNA expression were estimated using real-time quantitative PCR. We determined TMAO plasma levels by LC-MS/MS and TNF-α by ELISA. Routine biochemical parameters were evaluated using an automatic biochemical analyzer. Correlations were estimated by Spearman or Pearson test. Statistical significance was set at the level of p < 0.05. Results: All patients presented TMAO levels within the normal range according to EUTox (normal range: 2.83 ± 1.53 mg/L; CAD patients: 0.2 [0.1 to 0.2] ng/μL). TMAO plasma levels were positively correlated with NF-κB mRNA expression (0.555; p = 0.002). Conclusion: TMAO plasma levels may be associated with NF-κB mRNA expression in patients with CAD and may contribute to the pathogenesis of this disease.

Effects of Supplementation of Murici (Byrsonima crassifolia) and Taperebá (Spondias mombin) Pulp Extracts on Food Intake, Body Parameters, and Oxidative Stress Markers in Healthy Rats.

This study evaluates the effects of supplementation of murici (Byrsonima crassifolia) and taperebá (Spondias mombin) pulp extracts on dietary intake, body composition, biochemical parameters, and markers of oxidative stress. Two experiments were conducted with a total of 80 healthy male Wistar rats and a 30-day supplementation. In the first experiment, animals were divided into control (C) group, murici group 50 mg/(kg⸱day) (50Mu), murici group 100 mg/(kg⸱day) (100Mu), and murici group 200 mg/(kg⸱day) (200Mu). In the second experiment, animals were divided into C group, taperebá group 50 mg/(kg⸱day) (50Tap), taperebá group 100 mg/(kg⸱day) (100Tap), and taperebá group 200 mg/(kg⸱day) (200Tap). Results showed lower feed intake in 50Mu, 100Mu, and 100Tap groups (13%, 12%, and 10%, respectively, P < .05) and lower body fat in 200Mu, 100Tap, and 200Tap groups (16.0%, 29.1%, and 27.1%, respectively, P < .05). Only the 100Tap group showed reduced adipose tissue content (30.4%; P < .05). Increased plasma antioxidant capacity was observed at all doses for both fruits. Taperebá supplementation reduced ferrous oxidation-xylenol orange levels (50Tap: 8.4%, 100Tap: 16.1%, 200Tap: 24.3%; P < .05) and increased thiol levels (50Tap: 39%, 100Tap: 31%; P < .05). Serum thiobarbituric acid reactive substances levels were reduced in all groups receiving taperebá (50Tap: 77.7%, 100Tap: 73.1%, 200Tap: 73.8%; P < .05) and murici (50Mu: 44.5%, 100Mu: 34%, 200Mu: 43%; P < .05). Therefore, it is suggested that the inclusion of these fruits in the diet can contribute to health maintenance and disease prevention, through their effects on controlling food intake, improving body composition, and in combating oxidative stress.

Prevalence of Critical Congenital Heart Disease Detected in the Pulse Oximetry Test in Asymptomatic Newborns, ≥35 Gestational Weeks, in a Maternity in Southern Brazil

Abstract Background Congenital heart diseases (CHD) are one of the most prevalent malformations, and the screening tests to identify critical congenital heart disease (CCHD) is the pulse oximetry test, with subsequent investigation and treatment. Objective To quantify positive pulse oximetry tests and verify the prevalence of CCHD detected by it in asymptomatic newborns, ≥35 gestational weeks, in a Brazilian maternity hospital. Methodology This is an observational, retrospective, quantitative, analytical and cross-sectional study, conducted from October 2020 to May 2022, in a maternity hospital in southern Brazil, through the collection of records of positive oximetry pulse tests, following the norms of screening CCHD test of the Brazilian Society of Pediatrics (SBP), after they were evaluated with echocardiography for confirmation or exclusion of CHD. Results A total of 5,667 newborns were evaluated in this study, according to the inclusion criteria; 0.17% (n = 10) had a positive pulse oximetry test. Regarding the results of the echocardiography of the neonates with a positive test, two were normal, seven were cases of patent foramen ovale (PFO), and one was a case (0,017%) with interatrial communication (IAC) diagnosis. In the same period, five neonates with CCHD were born, symptomatic, diagnosed by physical examination, and referred to neonatal intensive care units (NICU) before taking the neonatal cardiac screening (< 24 hours of life). Conclusion The prevalence of positive pulse oximetry tests was 0.17% and none CCHD was detected. Five cases of CCHD were born in this period, but they were diagnosed before the recommend time to perform the screening test.

Food preference of Phylloicus sp. (Insecta: Trichoptera): experimental study with plant species from the Cerrado / Preferência alimentar de Phylloicus sp. (Insecta: Trichoptera): trabalho experimental com espécies vegetais do Cerrado

Abstract The aquatic insects of the genus Phylloicus play a crucial role in aquatic ecosystems, shredding leaves and contributing to nutrient cycling in streams. Therefore, this genus is often used in laboratory experiments. However, in Cerrado regions such as Araguaia, these studies are impractical due to a lack of knowledge about basic aspects, such as their feeding preferences for local plants. Hence, our objective is to determine the native plant species in the Araguaia region preferred as food by Phylloicus. We conducted an experimental study comparing the consumption of three native Cerrado plant species: Casearia sylvestris, Astronium fraxinifolium, and Ficus guaranítica by Phylloicus. To assess differences in consumption, we performed an Analysis of Variance. The results revealed that Phylloicus larvae exhibited a feeding preference for Casearia sylvestris (F = 9.71; p = 0.004). This finding will contribute to the development of future experimental studies using Phylloicus in the Araguaia region, as understanding the feeding preferences of animals used in experiments is essential for their maintenance in the laboratory.

Resumo Os insetos aquáticos do gênero Phylloicus desempenham um papel essencial nos ecossistemas aquáticos, fragmentando folhas e contribuindo para a ciclagem de nutrientes nos riachos. Por isso, esse gênero é frequentemente utilizado em experimentos de laboratório. No entanto, em regiões de Cerrado como o Araguaia, esses trabalhos são inviáveis por não se conhecer aspectos básicos como a sua preferência alimentar por plantas locais. Por isso, nosso objetivo é responder quais são as espécies vegetais nativas da região do Araguaia preferidas para a alimentação de Phylloicus. Fizemos um trabalho experimental comparando o consumo de três espécies vegetais nativas do Cerrado: Casearia sylvestris, Astronium fraxinifolium e Ficus guaranítica pelos Phylloicus. Para avaliar as diferenças no consumo, realizamos uma Análise de Variância. Os resultados obtidos revelaram que as larvas de Phylloicus demonstraram preferência alimentar por Casearia sylvestris (F = 9.71; p = 0.004). Esse achado ajudará no desenvolvimento de futuros trabalhos experimentais utilizando Phylloicus na região do Araguaia, uma vez que é essencial o conhecimento da preferência alimentar dos animais utilizados nos experimentos para sua manutenção em laboratório.

Purinergic signaling influences the neuroinflammatory outcomes of a testosterone-derived synthetic in female rats: Resistance training protective effects on brain health.

Physical exercise is recognized as a non-pharmacological approach to treat and protect against several neuroinflammatory conditions and thus to prevent brain disorders. However, the interest in ergogenic resources by athletes and bodybuilding practitioners is widespread and on the rise. These substances shorten the process of performance gain and improve aesthetics, having led to the prominent use and abuse of hormones in the past years. Recent evidence has shown that the purinergic system, composed of adenine nucleotides, nucleosides, enzymes, and receptors, participates in a wide range of processes within the brain, such as neuroinflammation, neuromodulation, and cellular communication. Here, we investigated the effects of the anabolic androgenic steroid (AAS) testosterone (TES) at a dose of 70 mg/kg/week in female rats and the neuroprotective effect of resistance exercise related to the purinergic system and oxidative stress parameters. Our findings showed a decrease in ATP and ADO hydrolysis in treated and trained animals. Furthermore, there was an increase in the density of purinoceptors (P2X7 and A2A) and inflammatory markers (IBA-1, NRLP3, CASP-1, IL-1ß, and IL-6) in the cerebral cortex of animals that received AAS. On the other hand, exercise reversed neuroinflammatory parameters such as IBA-1, NLRP3, CASP-1, and IL-1ß and improved antioxidant response and anti-inflammatory IL-10 cytokine levels. Overall, this study shows that the use of TES without indication or prescription disrupts brain homeostasis, as demonstrated by the increase in neuroinflammation, and that the practice of exercise can protect brain health.

Trend of pediatric leprosy in an endemic area in Northeast of Brazil, 2008-2018.

BACKGROUND: The incidence of leprosy in children is an important indicator of the disease's tendency in the general population and suggests intense circulation and transmission of Mycobacterium leprae. OBJECTIVES: To describe the clinical, epidemiological characteristics and temporal dynamics of leprosy cases in children under 15 years of age from 2008 to 2018 in an endemic municipality. METHODS: A descriptive study with an analytical approach was carried out with data from leprosy cases registered in the Brazilian Information System on Notifiable Diseases for the municipality of Cabo de Santo Agostinho, Pernambuco, Brazil. RESULTS: Between 2008 and 2018, 112 new cases of leprosy were registered. Most cases were classified as paucibacillary leprosy and occurred in children living in urban areas. There was no significant difference in the incidence of leprosy during the study period. Only 4.5% of the sample presented reactional episodes, but a high number of cases were not evaluated for the occurrence of reactions. CONCLUSIONS: The findings of this study show a high incidence of paucibacillary leprosy in children and adolescents, which reveals active transmission in the community and failures in the detection of new multibacillary cases among adults. Children between 10 and 14 years old are more vulnerable to M. leprae infection and mainly develop paucibacillary leprosy.

Incidence of Delirium in Critically Ill Patients With and Without COVID-19.

BACKGROUND: It is known that patients with COVID-19 are at high risk of developing delirium. The aim of the study was to compare the incidence of delirium between critically ill patients with and without a diagnosis of COVID-19. METHODS: This is a retrospective study conducted in a southern Brazilian hospital from March 2020 to January 2021. Patients were divided into two groups: the COVID-19 group consisted of patients with a diagnosis of COVID-19 confirmed by reverse transcription-polymerase chain reaction (RT-PCR) or serological tests who were admitted to specific ICUs. The non-COVID-19 group consisted of patients with other surgical and medical diagnoses who were admitted to non-COVID ICUs. All patients were evaluated daily using the Intensive Care Delirium Screening Checklist (ICDSC). The two cohorts were compared in terms of the diagnosis of delirium. RESULTS: Of the 649 patients who remained more than 48 h in the ICU, 523 were eligible for the study (COVID-19 group: 292, non-COVID-19 group: 231). There were 119 (22.7%) patients who had at least one episode of delirium, including 96 (32.9%) in the COVID-19 group and 23 (10.0%) in the non-COVID-19 group (odds ratio [OR] 4.42; 95% confidence interval [CI], 2.69 to 7.26; p < 0.001). Among patients mechanically ventilated for two days or more, the incidence of delirium did not differ between groups (COVID-19: 89/211, 42.1% vs non-COVID-19: 19/47, 40.4%; p = 0.82). Logistic regression showed that the duration of mechanical ventilation was the only independent factor associated with delirium (p = 0.001). CONCLUSION: COVID-19 can be associated with a higher incidence of delirium among critically ill patients, but there was no difference in this incidence between groups when mechanical ventilation lasted two days or more.

Genetic effects in a progressive model of parkinsonism induced by reserpine.

OBJECTIVE AND METHODS: We investigated the locomotor, emotional, physiological, and neurobiological effects induced by low-dose reserpine repeated treatment (0.1 mg/kg; 14 injections) in males from the Lewis (LEW), Spontaneously Hypertensive Rats (SHR), and SHR.LEW-(D4Rat76-D4Mgh11) (SLA16) isogenic rat strains, which have different genetic backgrounds on chromosome 4. Behavioral responses in the catalepsy, open-field, and oral movements' tests were coupled with blood pressure, body weight, and striatal tyrosine hydroxylase (TH) level assessments to establish neurobiological comparisons between reserpine-induced impairments and genetic backgrounds RESULTS: Results revealed the SHR strain was more sensitive in the catalepsy test and exhibited higher TH immunoreactivity in the dorsal striatum. The SLA16 strain presented more oral movements, suggesting increased susceptibility to develop oral dyskinesia. CONCLUSIONS: Our results showed the efficacy of repeated treatment with a low dose of reserpine and demonstrated, for the first time, the genetic influence of a specific region of chromosome 4 on the expression of these effects.

Time from kidney failure onset to transplantation and its impact on growth in pediatric patients.

BACKGROUND: In children with kidney failure, the longer the duration of dialysis the greater the impact on growth deficit, quality of life, and life expectancy. The aim of this research is to test whether there was a shortening of treatment time from kidney failure to transplantation in pediatric patients and whether this time interval impacted height. METHODS: Observational retrospective cohort study from 2005 to 2018. The first outcome variable was time to transplantation in years, while the second was height/age standard deviation score (SDS) at transplantation. Cox regression models were used to analyze time from disease to transplantation and linear regression was employed to test the association of the year of kidney failure onset with height. RESULTS: A total of 780 children were evaluated and 517 underwent kidney transplantation after a median time of 1.9 years (IQR = 1.0-4.0). The variables significantly associated with time to transplant were: year of kidney failure onset (HR = 1.07; 95% CI: 1.05-1.10; p < .001), age at kidney failure onset <12 years (HR = 0.59; 95% CI: 0.49-0.71; p < .001), living in different state as transplant center (HR = 0.63; 95% CI: 0.53-0.77; p < .001), and undergoing blood transfusion before transplantation (HR = 0.63; 95% CI: 0.53-0.75; p < .001). Regarding growth, for each 1-year increase in the epoch of kidney failure onset, a 0.05 SDS raise in height/age is expected (p < .001). CONCLUSION: Children with recent kidney failure onset had significantly lower time to the outcome and this reduction was associated with a less severe growth deficit.

Inhibition of α-Glycosidase by Lippia dulcis Trevir. (Verbenaceae) Preparations, Quantification of Verbascoside, and Study of Its Molecular Docking.

This study aimed to quantify verbascoside (VEB), perform molecular docking studies of VEB with the α-glucosidase (GL) of Bacillus stearothermophilus, and evaluate the inhibition of the enzyme by L. dulcis preparations. The substrate concentration and presence of reduced glutathione were evaluated for their effect on the in vitro inhibition of the GL enzyme. Assays were also performed in the presence and absence of simulated gastric fluid. The antidiabetic fractions 2 and 3 were the most inhibited GL, but their activity were significantly decreased in the presence of gastric fluid. Chromatographic analyses confirmed the predominant presence of VEB in the samples. The samples had VEB concentrations between 49.9 and 243.5 mg/g. Simulation of the molecular docking of VEB were consistent with its GL-inhibitory activity. It can conclude that the crude ethanol extract and fractions show inhibitory activity against the GL enzyme.

Neuromodulatory effect of the combination of metformin and vitamin D3 triggered by purinergic signaling in type 1 diabetes induced-rats.

Several studies have indicated the vitamin D deficiency in the development of macro- and microvascular complications of diabetes mellitus (DM) including DM-related cognitive dysfunction. The purinergic system plays an important role in the modulation of a variety of mechanisms, including neuroinflammation, plasticity, and cell-cell communication. In addition, purines, their receptors, and enzymes can regulate the purinergic axis at different levels in type 1 DM (T1DM). This study evaluated the effects of vitamin D3 alone or in combination with metformin in the behavioral performance of streptozotocin-induced T1DM rats. The effects of this combination on the metabolism of ATP and ADP were also studied by NTPDase (CD39), AMP by 5'-nucleotidase (CD73), and adenosine by adenosine deaminase (E-ADA) in the brain and peripheral lymphocytes of type 1 diabetic STZ-induced rats. The results showed that anxiety and memory loss from the DM condition reverted after 30 days of vitamin D3 treatment. Furthermore, the DM state affected systemic enzymes, with no effect on the central enzymes hydrolyzing extracellular nucleotides and nucleosides. Vitamin D3 treatment positively regulated ectonucleotidase (NTPDase and 5'-nucleotidase) activity, E-ADA, and the purinergic receptors as a mechanism to prevent oxidative damage in the cerebral cortex of T1DM rats. A neuroprotector effect of vitamin D3 through adenosine signaling was also observed, by regulating A1 and A2A receptors proteins levels. The present findings suggest that purinergic signaling through vitamin D3 modulation may be a novel alternative strategy for T1DM treatment, and may compensate for the negative changes in the central nervous system.

Effects of combination of Cryptococcus gattii and IFN-γ, IL-4 or IL-27 on human bronchial epithelial cells.

BACKGROUND: Airway epithelial cells are crucial for the establishment of cryptococcosis. In experimental cryptococcosis, the Th2 immune response is associated with host susceptibility, while Th1 cells are associated with protection. The absence of IL-27 receptor alpha in mice favor the increase Cryptococcus neoformans burden in the lung. Here, we evaluated the effects of the combination of IL-4, IFN-γ or IL-27 with C. gattii on human bronchial epithelial cells (BEAS-2B). METHODS: BEAS-2B were stimulated with IL-4, IFN-γ or IL-27 (100 ng/mL) and/or live yeast forms of C. gattii (multiplicities of infection (MOI) of 1-100) and vice-versa, as well as with heat-killed cells of C. gattii for 24 h. RESULTS: None of the C. gattii MOIs had cytotoxic effects on BEAS-2B when compared to control. The cells stimulated by cytokines (IL-4, IFN-γ or IL-27) followed by live yeast forms of C. gattii (MOI of 100) infection and vice-versa demonstrated a reduction in IL-6, IL-8 and/or CCL2 production and activation of STAT6 (induced by IL-4) and STAT1 (induced by IL-27 or IFN-γ) when compared to cells stimulated with C. gattii, IL-4, IFN-γ or IL-27. In the combination of cytokines and heat-killed cells of C. gattii, no inhibition of these inflammatory parameters was observed. The growth of C. gattii was increased while the phagocytosis of live yeast forms of C. gattii in the BEAS-2B were reduced in the presence of IL-4, IFN-γ or IL-27. Conclusion The association of live yeast forms, but not heat-killed yeast forms, of C. gattii with IL-4, IFN-γ or IL-27 induced an anti-inflammatory effect.

Food Aversion during Cancer Treatment: A Systematic Review.

Individuals with cancer often present food aversion after initiation of anti-tumor treatment, which may impair nutritional status. We aim to assess the prevalence and factors associated with food aversion during cancer treatment. Articles from three databases were searched: MEDLINE, EMBASE and Cochrane Library. English was used, with no restriction on the year of publication. Inclusion criteria were original articles that evaluated food aversion in adults and the elderly undergoing chemotherapy and/or radiotherapy treatment. Fifteen articles were included. A high prevalence of food aversion (21-62%) was observed, with meat considered the most aversive food. The aversion is usually transient and may be due to gastrointestinal problems, such as nausea and vomiting, caused by chemotherapy or radiotherapy treatment, and even psychological and emotional issues. Offering a new food before the beginning of treatment seems to be an effective strategy to reduce aversion, combined with nutritional and psychological monitoring. Cancer patients have a high prevalence of food aversion. Multidisciplinary care can minimize the consequences of cancer treatment.

Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps.

Scientists have systematically investigated the hereditary bases of behaviors since the 19th century, moved by either evolutionary questions or clinically-motivated purposes. The pioneer studies on the genetic selection of laboratory animals had already indicated, one hundred years ago, the immense complexity of analyzing behaviors that were influenced by a large number of small-effect genes and an incalculable amount of environmental factors. Merging Mendelian, quantitative and molecular approaches in the 1990s made it possible to map specific rodent behaviors to known chromosome regions. From that point on, Quantitative Trait Locus (QTL) analyses coupled with behavioral and molecular techniques, which involved in vivo isolation of relevant blocks of genes, opened new avenues for gene mapping and characterization. This review examines the QTL strategy applied to the behavioral study of emotionality, with a focus on the laboratory rat. We discuss the challenges, advances and limitations of the search for Quantitative Trait Genes (QTG) playing a role in regulating emotionality. For the past 25 years, we have marched the long journey from emotionality-related behaviors to genes. In this context, our experiences are used to illustrate why and how one should move forward in the molecular understanding of complex psychiatric illnesses. The promise of exploring genetic links between immunological and emotional responses are also discussed. New strategies based on humans, rodents and other animals (such as zebrafish) are also acknowledged, as they are likely to allow substantial progress to be made in the near future.

A prática da episiotomia no Brasil / The practice of episiotomy in Brazil / La práctica de la episiotomía en Brasil

O parto é um processo fisiológico e natural que pode ser vivenciado sem complexidades pelas parturientes e bebês. A violência obstétrica atinge mulheres em seu processo reprodutivo e ocorre entre os períodos de gestação, parto e puerpério. Ocorre pelo desrespeito a sua autonomia, seu corpo e seus processos reprodutivos, utilizando procedimentos cientificamente desnecessários, podendo ser praticada de forma física, verbal, psicológica, sexual e negligência da assistência. Objetivo: Identificar a ocorrência de episiotomias realizadas, suas principais indicações e quando essa prática se torna uma violência. Materiais e métodos: Trata-se de uma revisão integrativa da literatura, considerando a questão norteadora: a episiotomia se torna um evento necessário ou uma violência? Para tanto, a busca de artigos ocorreu por meio da biblioteca virtual de saúde (BVS), utilizando as bases de dados LILACS, MEDLINE e BDENF. Os critérios para inclusão dos artigos foram: publicações entre os anos 2018 e 2023, no idioma português e inglês. Foram excluídos desta pesquisa os artigos sem relação direta com o tema, dissertações/teses. Resultados/Discussão: Após analisar os 312 artigos encontrados e aplicar os filtros, constatou-se que 200 deles não possuíam relação com o tema em questão, restando assim, 112 artigos para leitura de título e resumo. Em seguida, foram excluídos mais 91 artigos por não abrangerem o escopo desta pesquisa, por estarem em duplicidade ou por se tratar de dissertações/teses, resultando em um total de 21 artigos selecionados para o estudo que destacaram: mulheres que passaram por procedimentos de intervenção como a episiotomia relataram sequelas, como dores e dificuldades em retomar as atividades sexuais. A prática adotada, deve ser realizada apenas em casos de distocia ou 4866Arquivos de Ciências da Saúde da UNIPAR, Umuarama, v.27, n.9, p.4865-4892, 2023. ISSN 1982-114Xsofrimento fetal, com a autorização da parturiente. Mulheres submetidas à episiotomia, relatam dificuldades para realizar atividades diárias e habituais, comprometendo suas necessidades fisiológicas. Parturientes que tiveram acompanhamento adequado realizado pelo enfermeiro obstetra apresentaram menores taxas de realização de episiotomia, recuperação com maior índice de satisfação, ressaltando à importância da humanização do parto e redução de práticas desnecessárias para que o nascimento ocorra. As evidências apresentadas nesta revisão apoiam a necessidade de uma reavaliação crítica das práticas de episiotomia. Orientações adequadas, treinamento e maior conscientização dos profissionais de saúde são essenciais para garantir que a episiotomia seja realizada de forma criteriosa, respeitando a fisiologia e a integridade do corpo da mulher. Além disso, a implementação de abordagens de atendimento humanizado e consentimento informado é crucial para reduzir a prevalência de episiotomias desnecessárias e minimizar potenciais efeitos negativos na qualidade de vida das mulheres. Cada vez mais a episiotomia é realizada sem levar em conta nenhum critério de indicação, não respeitando limites da fisiologia, do corpo da mulher e do processo do nascer, causando inúmeros malefícios. Considerações finais: Em síntese, as evidências apresentadas apoiam a necessidade de uma reavaliação crítica na adoção da prática da episiotomia, que perpassa pela formação, capacitação e educação permanente dos profissionais que assistem a mulher durante o parto. Orientações adequadas, treinamento e maior conscientização dos profissionais de saúde são essenciais para garantir que a episiotomia seja realizada de forma criteriosa, respeitando a fisiologia e a integridade do corpo da mulher.

Childbirth is a physiological and natural process that can be experienced without complexities by parturients and babies. Obstetric violence affects women in their reproductive process and occurs between the periods of pregnancy, childbirth and puerperium. It occurs by disrespecting their autonomy, their body and their reproductive processes, using scientifically unnecessary procedures, and can be practiced physically, verbally, psychologically, sexually and negligence of care. Objective: To identify the occurrence of episiotomies performed, their main indications and when this practice becomes violence. Materials and methods: This is an integrative literature review, considering the guiding question: does episiotomy become a necessary event or a violence? To this end, the search for articles occurred through the virtual health library (VHL), using the LILACS, MEDLINE and BDENF databases. The criteria for inclusion of the articles were: publications between the years 2018 and 2023, in Portuguese and English. Articles with no direct relation to the theme, dissertations/theses were excluded from this research. Results/Discussion: After analyzing the 312 articles found and applying the filters, it was found that 200 of them were not related to the topic in question, thus leaving 112 articles for reading the title and abstract. Then, 91 more articles were excluded because they did not cover the scope of this research, because they were in duplicate or because they were dissertations/theses, resulting in a total of 21 articles selected for the study that highlighted: women who underwent intervention procedures such as episiotomy reported sequelae, such as pain and difficulties in resuming sexual activities. The practice adopted should be performed only in cases of dystocia or fetal distress, with the authorization of the parturient. Women undergoing episiotomy report difficulties in performing daily and usual activities, compromising their physiological needs. Parturients who had adequate follow-up performed by the obstetric nurse had lower rates of episiotomy, recovery with a higher satisfaction rate, highlighting the importance of humanizing childbirth and reducing unnecessary practices for birth to occur. The evidence presented in this review support the need for a critical reassessment of episiotomy practices. Appropriate guidance, training and increased awareness of health care providers are essential to ensure that episiotomy is performed judiciously, respecting the physiology and integrity of the woman's body. In addition, the implementation of humanized care approaches and informed consent is crucial to reduce the prevalence of unnecessary episiotomies and minimize potential negative effects on women's quality of life. Episiotomy is increasingly performed without taking into account any indication criteria, not respecting the limits of physiology, the woman's body and the birth process, causing numerous harms. Final considerations: In summary, the evidence presented supports the need for a critical reassessment in the adoption of the practice of episiotomy, which includes the training, qualification and permanent education of professionals who assist women during childbirth. Adequate guidance, training and greater awareness of health professionals are essential to ensure that episiotomy is performed carefully, respecting the physiology and integrity of the woman's body.

El parto es un proceso fisiológico y natural que puede ser vivido sin complejidades por parturientas y bebés. La violencia obstétrica afecta a las mujeres en su proceso reproductivo y ocurre entre los periodos de embarazo, parto y puerperio. Ocurre por la falta de respeto a su autonomía, a su cuerpo y a sus procesos reproductivos, utilizando procedimientos científicamente innecesarios, y puede ser practicada física, verbal, psicológica, sexual y negligencia de cuidados. Objetivo: Identificar la ocurrencia de episiotomías realizadas, sus principales indicaciones y cuando esa práctica se torna violencia. Materiales y métodos: Se trata de una revisión bibliográfica integradora, considerando la pregunta orientadora: ¿la episiotomía se convierte en un hecho necesario o en violencia? Para ello, la búsqueda de artículos se realizó a través de la biblioteca virtual de salud (BVS), utilizando las bases de datos LILACS, MEDLINE y BDENF. Los criterios de inclusión de los artículos fueron: publicaciones entre 2018 y 2023, en portugués e inglés. Fueron excluidos de esta investigación artículos sin relación directa con el tema, disertaciones/tesis. Resultados/Discusión: Después de analizar los 312 artículos encontrados y aplicar los filtros, se constató que 200 de ellos no estaban relacionados con el tema en cuestión, quedando así 112 artículos para la lectura del título y resumen. Luego, 91 artículos más fueron excluidos por no abarcar el alcance de esta investigación, por estar duplicados o por tratarse de disertaciones/tesis, resultando en un total de 21 artículos seleccionados para el estudio que destacaron: las mujeres sometidas a procedimientos de intervención como la episiotomía relataron secuelas, como dolor y dificultades para retomar las actividades sexuales. La práctica adoptada sólo debería realizarse en casos de distocia o sufrimiento fetal, con la autorización de la parturienta. Las mujeres sometidas a episiotomía relatan dificultades en la realización de las actividades cotidianas y habituales, comprometiendo sus necesidades fisiológicas. Las parturientas que tuvieron un seguimiento adecuado realizado por la enfermera obstétrica presentaron menores tasas de episiotomía, recuperación con una mayor tasa de satisfacción, destacando la importancia de humanizar el parto y reducir las prácticas innecesarias para que ocurra. Las pruebas presentadas en esta revisión apoyan la necesidad de una reevaluación crítica de las prácticas de episiotomía. La orientación adecuada, la formación y una mayor concienciación de los profesionales sanitarios son esenciales para garantizar que la episiotomía se realice con criterio, respetando la fisiología y la integridad del cuerpo de la mujer. Además, la aplicación de enfoques asistenciales humanizados y el consentimiento informado son cruciales para reducir la prevalencia de episiotomías innecesarias y minimizar los posibles efectos negativos en la calidad de vida de las mujeres. La episiotomía se realiza cada vez más sin tener en cuenta ningún criterio de indicación, sin respetar los límites de la fisiología, el cuerpo de la mujer y el proceso del parto, causando numerosos daños. Consideraciones finales: En resumen, las pruebas presentadas apoyan la necesidad de una reevaluación crítica de la adopción de la episiotomía, que incluya la formación, cualificación y educación permanente de los profesionales que asisten a las mujeres durante el parto. La orientación adecuada, la formación y una mayor concienciación de los profesionales de la salud son esenciales para garantizar que la episiotomía se realice con cuidado, respetando la fisiología y la integridad del cuerpo de la mujer.

Efeitos da nanopartícula de ácido poli lático-co-glicólico (PLGA) associada ao cloridrato de metformina na doença periodontal em ratos diabéticos / Effects of polylactic-co-glycolic acid (PLGA) nanoparticle associated with metformin hydrochloride on periodontal disease in diabetic rats

Existe uma associação entre diabetes e a periodontite, e a Metformina (MET) além de controlar os níveis glicêmicos, tem apresentado efeitos antiinflamatórios e na diminuição da perda óssea periodontal. Ao se veicular a MET a um sistema de nanopartículas pode-se apresentar a vantagem de aumento da eficácia terapêutica. Objetivos: esse estudo consistiu na avaliação dos efeitos antiinflamatórios, perda óssea e disponibilidade in vitro/in vivo de uma nanopartícula de ácido poli lático-co-glicólico (PLGA) associada à MET em um modelo de periodontite induzida por ligadura. Materiais e métodos: o PLGA carreado com diferentes doses da MET foi caracterizado pelo seu diâmetro médio, tamanho da partícula, índice de polidispensão e eficiência de aprisionamento. Foram utilizados ratos machos da linhagem Wistar, divididos aleatoriamente, em grupos controles e experimentais com diferentes doses de MET associadas ou não ao PLGA, os quais receberam diferentes tratamentos. Amostras de maxilas e tecidos gengivais foram utilizadas para avaliação de perda óssea e inflamação, por meio da microtomografia computadorizada, histopatológico, imunohistoquímica, análise de citocinas inflamatórias e expressão gênica de proteínas por RT-PCR quantitativo. Para o ensaio de liberação in vitro, utilizou-se o dispositivo de células de difusão vertical de Franz estáticas. Para a disponibilidade in vivo, as amostras de sangue foram coletadas em diferentes intervalos de tempo e analisadas por cromatografia líquida de alta eficiência acoplado a espectrometria de massas (HPLC-MS/MS). Resultados: o diâmetro médio das nanopartículas de PLGA carreadas com MET estava em um intervalo de 457,1 ± 48,9 nm (p <0,05) com um índice de polidispersidade de 0,285 (p <0,05), potencial Z de 8,16 ± 1,1 mV (p <0,01) e eficiência de aprisionamento (EE) de 66,7 ± 3,73. O tratamento com a MET 10 mg / kg + PLGA mostrou uma baixa concentração de células inflamatórias, fraca imunomarcação para RANKL, Catepsina K, OPG e osteocalcina. Diminuição dos níveis de IL-1ß e TNF-α (p <0,05), aumento da expressão gênica do AMPK (p <0,05) e diminuição do NF-κB p65, HMGB1 e TAK-1 (p <0,05). O 10 mg/kg MET + PLGA foi liberado no ensaio in vitro sugerindo um modelo cinético de difusão parabólica com um perfil de liberação que atinge 50% de seu conteúdo em 2h e permanece em liberação constante em torno de 60% até o final de 6h. O ensaio in vivo mostrou o volume aparente de distribuição Vz/F (10 mg/kg MET + PLGA, 46,31 mL/kg vs. 100 mg/kg MET + PLGA, 28,8 mL/kg) e o tempo médio de residência MRTinf (PLGA + MET 10 mg /kg, 37,66h vs. MET 100 mg/kg, 3,34h). Conclusão: o PLGA carreado com MET diminuiu a inflamação e a perda óssea na periodontite em ratos diabéticos. O 10 mg/kg MET + PLGA teve uma taxa de eliminação mais lenta em comparação com o MET 100 mg/kg. A formulação modifica os parâmetros farmacocinéticos, como volume de distribuição aparente e tempo médio de residência (AU).

There is an association between diabetes and periodontitis, and Metformin (MET) in addition to controlling glycemic levels, has shown anti-inflammatory effects and decreased periodontal bone loss. By transferring MET to a nanoparticle system, the advantage of increasing therapeutic efficacy can be presented. Objectives: this study consisted of evaluating the antiinflammatory effects, bone loss and in vitro/in vivo availability of a polylactic-co-glycolic acid (PLGA) nanoparticle associated with MET in a ligature-induced periodontitis model. Materials and methods: PLGA loaded with different doses of MET was characterized by its mean diameter, particle size, polydispension index and entrapment efficiency. Male Wistar rats were used, randomly divided into control and experimental groups with different doses of MET associated or not with PLGA, which received different treatments. Samples of jaws and gingival tissues were used to assess bone loss and inflammation, using computed microtomography, histopathology, immunohistochemistry, analysis of inflammatory cytokines and gene expression of proteins by quantitative RT-PCR. For the in vitro release assay, the static Franz vertical diffusion cell device was used. For in vivo availability, blood samples were collected at different time intervals and analyzed by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Results: the mean diameter of MET-loaded PLGA nanoparticles was in the range of 457.1 ± 48.9 nm (p <0.05) with a polydispersity index of 0.285 (p <0.05), Z potential of 8.16 ± 1.1 mV (p <0.01) and trapping efficiency (EE) of 66.7 ± 3.73. Treatment with MET 10 mg/kg + PLGA showed a low concentration of inflammatory cells, weak immunostaining for RANKL, Cathepsin K, OPG and osteocalcin. Decreased IL-1ß and TNF-α levels (p <0.05), increased AMPK gene expression (p <0.05) and decreased NF-κB p65, HMGB1 and TAK-1 (p <0. 05). The 10 mg/kg MET + PLGA was released in the in vitro assay suggesting a kinetic model of parabolic diffusion with a release profile that reaches 50% of its content in 2h and remains in constant release around 60% until the end of 6h . The in vivo assay showed the apparent volume of distribution Vz/F (10 mg/kg MET + PLGA, 46.31 mL/kg vs. 100 mg/kg MET + PLGA, 28.8 mL/kg) and the mean MRTinf residency (PLGA + MET 10 mg/kg, 37.66h vs. MET 100 mg/kg, 3.34h). Conclusion: MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats. 10 mg/kg MET + PLGA had a slower rate of elimination compared to 100 mg/kg MET. The formulation modifies pharmacokinetic parameters such as apparent volume of distribution and mean residence time (AU).