Mapping the Landscape: Simulation Centers in Portugal.

INTRODUCTION: Simulation-based training has emerged as a vital component of healthcare education. This study aims to characterize Portuguese simulation centers concerning their geographic distribution and key features, providing stakeholders with valuable insights to inform strategic decisions. METHODS: A cross-sectional survey-based study was conducted over two years (2021-2023) to investigate the geographical dispersion and characteristics of simulation centers in Portugal. Descriptive statistics and thematic analysis were used to analyze data. RESULTS: Twenty-three Portuguese simulation centers were included. Major urban areas and coastal regions bring together 20 simulation centers (86.96%). A large percentage (71.93%) of centers were affiliated with academic institutions, while five centers (21.74%) were clinically affiliated. Emergency care, Anesthesiology and Intensive Medicine, Pediatrics, and Gynecology and Obstetrics were identified as the national key areas of intervention. DISCUSSION: Significant geographical disparity raises concerns about unequal access to professional training opportunities using simulation. Centers should be encouraged to incorporate developing technologies and innovative pedagogical methodologies and to expand their training repertoire into relatively uncharted territories. CONCLUSION: Several issues have been identified within the national simulation network. Stakeholders and policymakers should prioritize equitable access, bolster the prevalence of clinical affiliated centers, foster innovation, and facilitate strategic coordination.

Aerobic exercise attenuates dysautonomia, cardiac diastolic dysfunctions, and hemodynamic overload in female mice with atherosclerosis.

Cardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions.

Antimicrobial and optical properties of a new biogenic silica-coated silver nanoparticles incorporated into experimental resin.

Background: Evaluate the effects of incorporating silica-coated silver nanoparticles (Ag@SiO2 NPs) into odontological clinic resin materials. Material and Methods: Silver nanoparticles coated with silicon dioxide were added to the experimental resin matrix at 1, 3, and 5wt%. Degree of conversion (DC), optical properties (total transmittance and color change), and microstructural analysis were evaluated. Materials were tested for silver ion release, cytotoxicity in dental pulp fibroblasts, Streptococcus mutans biofilm growth by Colony-Forming Unit (CFU) and confocal laser scanning microscopy (CLSM). Results: Groups had a similar DC, despite significant differences observed in transmittance and color change analysis for all groups with NPs. Silver ion release values were below the detection limit after 72h for all groups, and NPs incorporation did not show a statistical difference from the control on pulp fibroblasts assay. After 72h, the CFU count was significantly reduced by 74% from 3wt% of Ag@SiO2NPs. CLSM evaluation on S. mutans colonies showed a dose-dependent decrease in the emitted fluorescence. Conclusions: The application of Ag@SiO2 NPs in a resinous matrix, demonstrates a significant reduction of S. mutans CFU in oral biofilm, at concentrations from 3wt%, without an increase in cytotoxicity. The reduced transmittance values did not affect the DC, although a significant color change was perceived in all concentrations. Key words:Nanoparticles, Silver Compounds, Composite Dental Resin, Anti-Bacterial Agent, Optical Imaging.

Hydroxytakakiamide and Other Constituents from a Marine Sponge-Associated Fungus Aspergillus fischeri MMERU23, and Antinociceptive Activity of Ergosterol Acetate, Acetylaszonalenin and Helvolic Acid.

An unreported prenylated indole derivative hydroxytakakiamide (4) was isolated, together with the previously described ergosterol (1), ergosterol acetate (2), and (3R)-3-(1H-indol-3-ylmethyl)-3, 4-dihydro-1H-1,4-benzodiazepine-2,5-dione (3), from the column fractions of the crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus fischeri MMERU 23. The structure of 4 was elucidated by the interpretation of 1D and 2D NMR spectral data and high-resolution mass spectrum. The absolute configuration of the stereogenic carbon in 3 was proposed to be the same as those of the co-occurring congeners on the basis of their biogenetic consideration and was supported by the comparison of its sign of optical rotation with those of its steroisomers. The crude ethyl acetate extract and 2 were evaluated, together with acetylaszonalenin (5) and helvolic acid (6), which were previously isolated from the same extract, for the in vivo antinociceptive activity in the mice model. The crude ethyl acetate extract exhibited antinociceptive activity in the acetic acid-induced writhing and formalin tests, while 2, 5, and 6 displayed the effects in the late phase of the formalin test. On the other hand, neither the crude ethyl acetate extract nor 2, 5, and 6 affected the motor performance of mice in both open-field and rotarod tests. Additionally, docking studies of 2, 5, and 6 were performed with 5-lipoxygenase (5-LOX) and phosphodiesterase (PDE) enzymes, PDE4 and PDE7, which are directly related to pain and inflammatory processes. Molecular docking showed that 6 has low affinity energy to PDE4 and PDE7 targets while retaining high affinity to 5-LOX. On the other hand, while 2 did not display any hydrogen bond interactions in any of its complexes, it achieved overall better energy values than 6 on the three antinociceptive targets. On the other hand, 5 has the best energy profile of all the docked compounds and was able to reproduce the crystallographic interactions of the 5-LOX complex.

Monitoring Staphylococcus aureus nasal colonization murine model using a bioluminescent methicillin-resistant S. aureus (MRSA).

Staphylococcus aureus nasal carriage is considered a risk factor for infections, and the development of nasal decolonization strategies is highly relevant. Despite they are not naturally colonized by Staphylococcus, mice are a good model for S. aureus nasal colonization. Murine models are easy to manipulate, and inter-laboratory reproducibility makes them suitable for nasal colonization studies. Strategies using bioluminescent bacteria allow for the monitoring of infection over time without the need to sacrifice animals for bacterial quantification. In this study, we evaluated S. aureus nasal colonization in three mouse strains (BALB/c, C57BL/6, and Swiss Webster) using a bioluminescent strain (SAP231). In vitro, a visible Bioluminescent Signal Emission (BLSE) was observed until 106 bacteria and detected by IVIS® imaging system up to 104 cells. Animals were inoculated with one or two doses of approximately 109 colony-forming units (CFU) of SAP231. Swiss Webster mice showed the longest colonization time, with some animals presenting BLSE for up to 140 h. In addition, BLSE was higher in this strain. BALB/c and C57BL/6 strains showed consistent BLSE results for 48 h. BLSE intensity was higher in Swiss Webster inoculated with both doses. Three different positions for image capture were evaluated, with better results for the lateral and ventrodorsal positions. After the loss of BLSE, bacterial quantification was performed, and Swiss Webster mice presented more bacteria in the nasal cavity (approximately 105 CFU) than the other strains. Our results demonstrate that bioluminescent S. aureus allow monitoring of nasal colonization and estimation of the bacterial burden present in live animals until 48 h.

Iron-carbohydrate complexes treating iron anaemia: Understanding the nano-structure and interactions with proteins through orthogonal characterisation.

Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data and clinical studies are available for these products, evidence-based correlation between physicochemical properties of iron-carbohydrate complexes and clinical outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early interactions between NPs and blood upon IV injection are key to understanding how differences in physicochemical characteristics of iron-carbohydrate complexes cause variance in clinical outcomes. We therefore investigated the core-ligand structure of two clinically relevant iron-carbohydrate complexes, iron sucrose (IS) and ferric carboxymaltose (FCM), and their interactions with two structurally different human plasma proteins, human serum albumin (HSA) and fibrinogen, using a combination of cryo-scanning transmission electron microscopy (cryo-STEM), x-ray diffraction (XRD), small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS). Using this orthogonal approach, we defined the nano-structure, individual building blocks and surface morphology for IS and FCM. Importantly, we revealed significant differences in the surface morphology of the iron-carbohydrate complexes. FCM shows a localised carbohydrate shell around its core, in contrast to IS, which is characterised by a diffuse and dynamic layer of carbohydrate ligand surrounding its core. We hypothesised that such differences in carbohydrate morphology determine the interaction between iron-carbohydrate complexes and proteins and therefore investigated the NPs in the presence of HSA and fibrinogen. Intriguingly, IS showed significant interaction with HSA and fibrinogen, forming NP-protein clusters, while FCM only showed significant interaction with fibrinogen. We postulate that these differences could influence bio-response of the two formulations and their clinical outcome. In conclusion, our study provides orthogonal characterisation of two clinically relevant iron-carbohydrate complexes and first hints at their interaction behaviour with proteins in the human bloodstream, setting a prerequisite towards complete understanding of the correlation between physicochemical properties and clinical outcome.

Exercise-induced potentiation of the acute hypoxic ventilatory response: Neural mechanisms and implications for cerebral blood flow.

A given dose of hypoxia causes a greater increase in pulmonary ventilation during physical exercise than during rest, representing an exercise-induced potentiation of the acute hypoxic ventilatory response (HVR). This phenomenon occurs independently from hypoxic blood entering the contracting skeletal muscle circulation or metabolic byproducts leaving skeletal muscles, supporting the contention that neural mechanisms per se can mediate the HVR when humoral mechanisms are not at play. However, multiple neural mechanisms might be interacting intricately. First, we discuss the neural mechanisms involved in the ventilatory response to hypoxic exercise and their potential interactions. Current evidence does not support an interaction between the carotid chemoreflex and central command. In contrast, findings from some studies support synergistic interactions between the carotid chemoreflex and the muscle mechano- and metaboreflexes. Second, we propose hypotheses about potential mechanisms underlying neural interactions, including spatial and temporal summation of afferent signals into the medulla, short-term potentiation and sympathetically induced activation of the carotid chemoreceptors. Lastly, we ponder how exercise-induced potentiation of the HVR results in hyperventilation-induced hypocapnia, which influences cerebral blood flow regulation, with multifaceted potential consequences, including deleterious (increased central fatigue and impaired cognitive performance), inert (unchanged exercise) and beneficial effects (protection against excessive cerebral perfusion).

Proteomic Profiling of Plasma- and Gut-Derived Extracellular Vesicles in Obesity.

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.

Antimicrobial Activity on Streptococcus mutans and Enterococcus faecalis of Cyperus articulatus Ethanolic Extracts.

Oral diseases are one of the biggest public health problems worldwide, caused by opportunistic pathogens such as Streptococcus mutans and Enterococcus faecalis. Cyperus articulatus (priprioca) is a plant conventionally used in traditional medicine in the Amazon region. However, little is known about the possible dentistry-related uses of extracts from the rhizomes and solid waste generated by the extraction of essential oils from this vegetable. This study aimed to investigate the chemical composition of volatile compounds and antimicrobial activity through the Minimum Inhibitory Concentration test (MIC and assessment of the toxicity by Hens Egg Test-Chorion Allantoic Membrane (HET-CAM) of the ethanolic extracts from Cyperus articulatus intact rhizomes and solid waste. We identified sesquiterpenes as the main constituents, strong antimicrobial activity of the ethanolic extract of intact rhizomes against S. mutans (MIC = 0.29 mg/mL), moderate antimicrobial activity against E. faecalis of the extract obtained from the solid waste (MIC = 1.17 mg/mL), and absence of toxicity for both tested extracts. The absence of irritation and the antibacterial activity of the ethanolic extract from C. articulatus rhizomes and solid waste reveal its potential for use in the alternative control of bacteria that cause oral infections and may present economic viability as a raw material for dental products.

The Impact of Motor, Non-Motor, and Social Aspects on the Sexual Health of Men Living with Parkinson's Disease.

Background: Sexual health (SH) is influenced by several biological, mental, and social factors that may be negatively impacted by Parkinson's disease (PD). Despite its prevalence and relevance for quality of life, the factors that affect SH in men with PD (MwPD) are still poorly understood. Objectives: To investigate the impact of motor, non-motor, and social aspects on the SH in MwPD. Methods: We conducted a cross-sectional study of 80 men (mean-age 53.55±10.8) in stages 1-3 of Hoehn and Yahr classification (H&Y), who reported having an active sex life in the last six months. The following data were collected for each person: 1) Demographic and clinical features; 2) global cognitive capacity (T-MoCA); 3) Non-Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part I); 4) Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part II); 5) Fatigue (FSS); 6) Self-esteem (RSES); 7) Sleep disorder (PDSS); 8) Couple relationship quality (DAS); 9) Depressive signals (BDI); 10) Short-term sexual health by International Index of Erectile Function (IIFE); and 11) Long-term sexual health by Sexual Quotient-Male (SQ-M). Results: Our results showed that although several motor, non-motor, and social factors were correlated with SH, only motor disability levels in daily living predicted short-term SH and erectile dysfunction, while only depression predicted long-term SH in MwPD. Age, disease onset, and medication daily dosage were not correlated with SH. Conclusions: Our findings confirm that multidimensional factors can affect the SH of MwPD and emphasize that only a multi-professional team can offer proper care to improve SH in MwPD.

Is There a Relationship between Anthropometric Indices and Muscular, Motor, and Cardiorespiratory Components of Health-Related Fitness in Active European Older Adults?

The aging process induces alterations in the body, resulting in changes in both health-related fitness and specific anthropometric measures. These changes often pose health risks for older adults. The aim of the present study was to investigate whether there is an association between anthropometric indices and muscular, motor, and cardiorespiratory components of health-related fitness in active European older adults. This study included 2687 European older adults, comprising 1999 women and 688 men, with an average age of 70.05 ± 5.5 years. The assessment included health-related fitness using the Senior Fitness Test and anthropometric indices, such as the body adiposity index, body mass index, conicity index, waist-to-hip ratio, and waist-to-height ratio, among others. The results indicated that gender significantly influences the values of physical performance and anthropometric parameters, making them incomparable. The degree of correlation between anthropometric indices and muscular, motor, and cardiorespiratory components of fitness depends on each anthropometric index analysed. The anthropometric index most correlated with physical fitness performance parameters is the waist-to-height ratio (WHR), followed by the body mass index (BMI). Cardiorespiratory endurance and balance are the two physical parameters most correlated with anthropometric indices.

Beta-Adrenergic Blockade in Advanced Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Multicentric Study.

Introduction The standard treatment of cancer has dramatically improved with immune checkpoint inhibitors (ICIs). Despite their proven advantage, many patients fail to exhibit a meaningful and lasting response. The beta-adrenergic signalling pathway may hold significant promise due to its role in promoting an immunosuppressive milieu within the tumour microenvironment. Inhibiting ß-adrenergic signalling could enhance ICI activity; however, blocking this pathway for this purpose has yielded conflicting results. The primary objective of this study was to evaluate the effect of beta-blocker use on overall survival and progression-free survival during ICI therapy. Methods A multicentric, retrospective, observational study was conducted in four Portuguese institutions. Patients with advanced non-small cell lung cancer treated with ICIs between January 2018 and December 2019 were included. Those using beta blockers for non-oncological reasons were compared with non-users. Results Among the 171 patients included, 36 concomitantly received beta blockers and ICIs. No significant increase was found in progression-free survival among patients who took ß-blockers (HR 0.74, 95% confidence interval (CI) 0.48-1.12, p = 0.151), and no statistically significant difference was found in overall survival. An apparent trend was observed towards better outcomes in the beta-blocker group, with a median overall survival of 9.93 months in the group not taking ß-blockers versus 14.90 months in the ß-blocker group (p = 0.291) and a median progression-free survival of 5.37 in the group not taking ß-blockers versus 10.87 months in the ß-blocker group (p = 0.151). Nine (25%) patients in the beta-blocker group and 16 (12%) in the non-beta-blocker group were progressive disease-free at the end of follow-up. This difference between the two groups is statistically significant (p = 0.047). Conclusion Our study found no statistically significant evidence that beta blockers enhance the effectiveness of immunotherapy. Using adrenergic blockade to modulate the immune system shows promise, warranting the need to develop prospective clinical studies.

Soil fertility impact on recruitment and diversity of the soil microbiome in sub-humid tropical pastures in Northeastern Brazil.

Soil fertility is key point to pastures systems and drives the microbial communities and their functionality. Therefore, an understanding of the interaction between soil fertility and microbial communities can increase our ability to manage pasturelands and maintain their soil functioning and productivity. This study probed the influence of soil fertility on microbial communities in tropical pastures in Brazil. Soil samples, gathered from the top 20 cm of twelve distinct areas with diverse fertility levels, were analyzed via 16S rRNA sequencing. The soils were subsequently classified into two categories, namely high fertility (HF) and low fertility (LF), using the K-Means clustering. The random forest analysis revealed that high fertility (HF) soils had more bacterial diversity, predominantly Proteobacteria, Nitrospira, Chloroflexi, and Bacteroidetes, while Acidobacteria increased in low fertility (LF) soils. High fertility (HF) soils exhibited more complex network interactions and an enrichment of nitrogen-cycling bacterial groups. Additionally, functional annotation based on 16S rRNA varied between clusters. Microbial groups in HF soil demonstrated enhanced functions such as nitrate reduction, aerobic ammonia oxidation, and aromatic compound degradation. In contrast, in the LF soil, the predominant processes were ureolysis, cellulolysis, methanol oxidation, and methanotrophy. Our findings expand our knowledge about how soil fertility drives bacterial communities in pastures.

Active Low-Density Polyethylene-Based Films by Incorporating α-Tocopherol in the Free State and Loaded in PLA Nanoparticles: A Comparative Study.

In this work, alpha-tocopherol (α-TOC) was encapsulated in poly(lactic acid) nanoparticles (PLA NPs) and added to low-density polyethylene (LDPE) films with the aim of producing an active film for food packaging applications. PLA NPs loaded with α-TOC were produced through nanoprecipitation and dried using two methods (freeze-dryer and oven). LDPE-based films with final polymeric matrix concentrations of 10 and 20 g/kg were then produced through blow extrusion. The results showed that LDPE-based films loaded with α-TOC can be produced using blow extrusion, and a good distribution of PLA NPs can be obtained within the LDPE matrix as observed using scanning electron microscopy (SEM). The mechanical properties were affected by the incorporation of α-TOC and PLA NPs loaded with α-TOC, with the observation of a decrease in tensile strength and Young's Modulus values and an increase in elongation at break. Regarding water vapor permeability, the films showed a reduction in the values with the addition of α-TOC and PLA NPs loaded with α-TOC compared to the LDPE film (control). Films with α-TOC in the free state and loaded in PLA NPs showed antioxidant activity, but their behavior was affected by the encapsulation process.

Oil-in-water emulsion loaded with optimized antioxidant blend improved the shelf-life of trout (Oncorhynchus mykiss) fillets: a study with simplex-centroid design.

This study aimed to obtain optimized mixture with three essential oils (EOs) for maximum antioxidant activity through the augmented simplex-centroid mixture design and evaluate the effect of this optimized blend on total aerobic psychrotrophic count (TAPC), lipid and protein oxidation, instrumental color parameters and texture profile in rainbow trout fillets at refrigerated storage for nine days. Considering the DPPH and FRAP assays, the ideal EO blend was 66% lemongrass and 34% oregano. During refrigerated storage, this blend at 2000 ppm was equally effective as BHT (100 ppm) (p > 0.05), mitigating the discoloration (a* and b*), lipid, and protein oxidation in 38.83%, 12.95%, 76.13%, and 35.13%, respectively, besides shows greater effectiveness for preserving texture changes (p < 0.05) and extending the shelf life in 13 h. The lemongrass + oregano EO blend reveals a promising natural alternative to enhance the quality of rainbow trout fillets under refrigerated storage. Furthermore, the multiresponse optimization showed to be a strong ally in enabling the use of these EOs by food industries.

Alarming patterns of moderate and high-risk alcohol use among transgender women in Goiás, Central Brazil.

Background: Scant studies have examined alcohol consumption among transgender women in Latin America. This cross-sectional study estimated the prevalence and associated factors of risky alcohol use among transgender women in Goiás, a state located in the center of Brazil. Methods: Participants were 440 transgender women (median age = 35 years, interquartile range = 9) recruited through respondent-driven sampling. All participants were interviewed about sociodemographic characteristics, violence, and risk behavior. Alcohol use was assessed using the alcohol use disorders identification test (AUDIT). An AUDIT score greater than or equal to eight was considered as risky alcohol consumption. Logistic regression analysis was used to examine predictors of risky alcohol use, and p-values <0.05 were considered significant. Results: The majority were young, single, sex workers. Most transgender women had used alcohol in the previous year (85.7%), and more than half (56.6%) reported binge drinking and risky alcohol consumption (60.2%). There was a high overlap between sexual behavior, drugs, and alcohol use. Using alcohol during sex (adjusted odds ratio [aOR]: 2.9; 95% confidence interval [CI]: 1.7-4.8), cocaine/crack use (aOR: 2.3; 95% CI: 1.5-3.7) and having a drug user as a sexual partner (aOR: 2.9; 95% CI: 1.5-5.9) were independently associated with risky alcohol consumption. Conclusion: Alcohol consumption was highly prevalent, and drugs seem to play an important role in risky alcohol consumption among transgender women Goiás. These findings support stakeholders to promote intervention strategies to reduce this pattern of alcohol consumption and reduce the burden of substance use disorders among transgender women.

Modified Procedure for Simple and Rapid Collection of Zebrafish Fluid Samples for Biochemical Analyses.

This study addresses the challenge of collecting blood samples from zebrafish for biochemical analysis. Traditional methods are cumbersome due to low blood flow and rapid coagulation. Based on a previously published technique, we simplified the process by applying an anticoagulant solution directly to the incision site. The modified protocol involves immersing the fish in an ice bath, making a cross-sectional incision, and immediately applying anticoagulant solution. Centrifugation of the specimens provides a streamlined and efficient approach to zebrafish fluid sample collection, compatible with classic biochemical marker analyses.

The Use of Honey for Cicatrization and Pain Control of Obstetric Wounds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Several studies point to antibacterial properties and beneficial effects of honey on scar tissue formation, which is a low-cost and easy-to-use option. This study aimed to compare honey versus a placebo for cicatrization and pain control of obstetric wounds, and determine if one is superior to the other, in terms of efficacy, through a meta-analysis. METHODS: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. Two independent investigators identified randomized controlled trials (RCTs) comparing honey and a placebo for obstetric wounds. The primary outcomes were wound healing and pain control. RESULTS: Five randomized controlled trials and 353 patients were included, of whom, 177 (50.1%) were treated with honey. Differences were not found in the final wound healing between the honey and placebo groups (MD -0.34; 95% CI -1.13, 0.44; p = 0.39); however, there was a decrease in pain levels in the middle of the treatment (SMD -0.54; 95% CI 0.83 to 0.25, p = 0.03), reduction in the use of pain medication (ORR 0.26; 95% CI 0.08, 0.86; p = 0.03), increase in personal satisfaction in women who underwent the intervention (ORR 0.81; 95% CI 0.65, 0.98), and reduction in complications. CONCLUSION: According to the study results, honey treatments showed greater efficiency and provided benefits to the patients by accelerating wound healing and decreasing reported pain.

Hollow-fiber liquid phase microextraction for determination of fluoxetine in human serum by nano-liquid chromatography coupled to high resolution mass spectrometry.

Therapeutic drug monitoring (TDM) is a personalized care tool based on the determination of a target drug concentration in human serum. An antidepressant drug of interest for such investigations is fluoxetine (FXT), due to a severe impact of genetic polymorphisms on its metabolism. A bioanalytical method employed for TDM purposes must exhibit satisfactory selectivity and detectability, which becomes more difficult due to highly complex biological matrices. In this study, a highly selective bioanalytical method for the determination of FXT in human serum is proposed, which provides excellent clean-up efficiency based on a low cost hollow fiber liquid-phase microextraction (HF-LPME) sample preparation step and nano-liquid chromatography coupled to high-resolution mass spectrometry (nano-LC-HRMS). HF-LPME was performed using a two-phase "U" configuration, with 6 cm fiber, 20 µL of 1-octanol acting as supported liquid membrane, and ammonium hydroxide (pH 10) as the donor phase with NaCl (10 % m/v) and methanol (5 % v/v) as additives, requiring only 250 µL of the sample. The procedure was conducted for 30 min under a 750 rpm stirring rate. Gradient elution was carried out employing an acetonitrile-water as mobile phase, the composition of 30:70 to 100:00 (v/v) for 15 min, using formic acid 0.1 % (v/v) as an additive. MS1 was acquired in an Orbitrap mass analyzer, while MS2 was acquired in a linear trap quadrupole. Satisfactory linearity (Pearson's r = 0.99709) was obtained for a concentration range of 0.02 to 2.5 µg mL-1, which is compatible with the therapeutic and toxic range for FXT. The developed method presents adequate precision (1.61 to 7.45 %) and accuracy (95 to 114 %) and allows the dilution of high concentration samples in a 1:4 ratio (v/v), enabling its application for forensic serum samples. To our knowledge, this is the first study reporting a method based on HF-LPME and nano-LC-HRMS with any analytical purpose, especially with a TDM focus.

Altered locomotor muscle metaboreflex control of ventilation in patients with COPD.

We investigated the locomotor muscle metaboreflex control of ventilation, circulation, and dyspnea in patients with chronic obstructive pulmonary disease (COPD). Ten patients [forced expiratory volume in 1 second (FEV1; means ± SD) = 43 ± 17% predicted] and nine age- and sex-matched controls underwent 1) cycling exercise followed by postexercise circulatory occlusion (PECO) to activate the metaboreflex or free circulatory flow to inactivate it, 2) cold pressor test to interpret whether any altered reflex response was specific to the metaboreflex arc, and 3) muscle biopsy to explore the metaboreflex arc afferent side. We measured airflow, dyspnea, heart rate, arterial pressure, muscle blood flow, and vascular conductance during reflexes activation. In addition, we measured fiber types, glutathione redox balance, and metaboreceptor-related mRNAs in the vastus lateralis. Metaboreflex activation increased ventilation versus free flow in patients (∼15%, P < 0.020) but not in controls (P > 0.450). In contrast, metaboreflex activation did not change dyspnea in patients (P = 1.000) but increased it in controls (∼100%, P < 0.001). Other metaboreflex-induced responses were similar between groups. Cold receptor activation increased ventilation similarly in both groups (P = 0.46). Patients had greater type II skeletal myocyte percentage (14%, P = 0.010), lower glutathione ratio (-34%, P = 0.015), and lower nerve growth factor (NGF) mRNA expression (-60%, P = 0.031) than controls. Therefore, COPD altered the locomotor muscle metaboreflex control of ventilation. It increased type II myocyte percentage and elicited redox imbalance, potentially producing more muscle metaboreceptor stimuli. Moreover, it decreased NGF expression, suggesting a downregulation of metabolically sensitive muscle afferents.NEW & NOTEWORTHY This study's integrative physiology approach provides evidence for a specific alteration in locomotor muscle metaboreflex control of ventilation in patients with COPD. Furthermore, molecular analyses of a skeletal muscle biopsy suggest that the amount of muscle metaboreceptor stimuli derived from type II skeletal myocytes and redox imbalance overcame a downregulation of metabolically sensitive muscle afferents.