Crosstalk between cytokines, inflammation and pulmonary arterial hypertension in heart transplant patients.

BACKGROUND: Heart transplant (HT) is a therapeutic option for patients with advanced heart failure (HF) refractory to optimized treatment. Patients with advanced HF often develop pulmonary arterial hypertension (PAH). PAH is defined as a condition in which the mean pulmonary artery pressure is greater than 20 mmHg. Inflammation is an important aspect of PAH development. In this context, the objective of this work was to evaluate the relationship between the inflammatory process and the development of HAP in patients undergoing HT. METHODS: The levels of interleukins IL-6, IL-1ß and TNF-α were obtained by ELISA and associated with CD68+ and CD66b neutrophil counts using the immunofluorescence technique in fragments of the pulmonary arteries of donors and patients with or without chagasic cardiomyopathy subjected to HT. RESULTS: The results showed a positive, statistically significant correlation (p < 0.05) between right atrium pressure levels and IL-6. Furthermore, negative, moderate, and statistically significant correlations (p < 0.05) were observed between the variables cardiac index and TNF-α, and between the levels of transpulmonary pressure grandient and TNF-α. The study also revealed the presence of a statistically significant difference (p < 0.05) between patients who died within 30 days and the highest number of CD68 cells per square micrometer in the vessel of the donor and recipient patient. CONCLUSION: Suggesting the presence of a pro-inflammatory profile in HT patients, independent of measured pulmonary artery pressure levels.

Chemical Characterization, Phenolic Compounds Quantification, and Assessment of Antioxidant and Anti-Acetylcholinesterase Activities of Byrsonima sericea DC fruits.

Byrsonima sericea is a species native to Brazil that is widely used in traditional medicine. The seed ethanol extract (SEE) had the highest content of total phenols (179.35 mg GAE g-1 extract) and flavonoids (10.42 mg QE g-1 extract) and was the most active in relation to antioxidant activity (DPPH: IC50 =4.25 µg mL-1 and ABTS: IC50 =4.82 µg mL-1 ). The peel/pulp ethanol extract (PEE) had the best anticholinesterase activity (IC50 =6.02 µg mL-1 ). Chromatographic investigation identified gallic acid, isoquercitrin, quercetin and amentoflavone in SEE, and gallic acid, isoquercitrin, quercetin and rutin in PEE. Six fatty acid methyl esters and seven triterpenes were identified, highlighting oleic acid in the seed hexane extract (61.85 %) and in the peel/pulp hexane extract (52.61 %), and betulin in the peel/pulp hexane extract (5.25 %). The substances and biological activities identified in B. sericea characterize this fruit as a functional food for future studies.

Neurobrucellosis.

PURPOSE OF REVIEW: Brucellosis is one of the most common zoonosis worldwide, affecting 500 000 people, annually. Neurobrucellosis incidence is approximately 4%, and it is almost always heterogeneous. As there are no typical clinical features, its diagnosis is frequently misdiagnosing by other infections. RECENT FINDINGS: Neurobrucellosis picture includes meningitis, meningoencephalitis, encephalitis, cranial neuropathies, intracranial hypertension, sinus thrombosis, hemorrhages radiculitis, peripheral neuropathy, myelitis, and psychiatric manifestations. The diagnosis should be based on symptoms and signs suggestive of neurobrucellosis, not explained by other neurological disease, cerebrospinal fluid analysis, a positive Brucella serology or culture, and a response to specific antibiotics, with a significant improvement of cerebrospinal fluid parameters. SUMMARY: Neurobrucellosis can be insidious, and despite its global distribution, it is still unrecognized and frequently goes unreported. The understanding of the current epidemiology is necessary for eradication of the disease in humans, as well as the disease control in animals and prevention based on occupational hygiene and food hygiene.

Performance of the National Institute of Infectious Diseases disability scale in HTLV-1-associated myelopathy/tropical spastic paraparesis.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic disabling disease. However, there is a lack of an adequate and specific health measurement instrument validated and with good performance to assess their degree of physical disability. This led us to carry out this study and to evaluate the performance of Fiocruz's National Institute of Infectious Diseases (IDS) disability scale, a specific instrument for HAM/TSP. Ninety-two HAM/TSP patients participated in the study. One researcher applied the IDS, IPEC scale, Disability Status Scale (DSS), Expanded DSS (EDSS), Osame scale, Beck Depression Inventory, and the WHOQOL-BREF questionnaire. In parallel, blindly, and separately, other researchers applied the IDS. An inter-rater reliability analysis of the IDS, correlation analysis with the other scales, and depression and quality of life questionnaires were performed. The applicability of the IDS was also evaluated. The IDS showed high reliability in all scores. The inter-rater reliability test for the total IDS score was 0.94 (0.82-0.98) on its four dimensions. The scale adequately indicated the different degrees of disability, presenting a distribution similar to normal. There was a high correlation with the other scales (Spearman coefficients > 0.80, p < 0.001). The scale had good acceptance among users and a short application time. IDS for HAM/TSP was reliable, consistent, easy, and fast to use. It can be used for both prospective evaluations and clinical trials. The present study supports the IDS as a valid instrument to measure disability in patients with HAM/TSP compared to previously used scales.

Metataxonomy of acid mine drainage microbiomes from the Santa Catarina Carboniferous Basin (Southern Brazil).

Mining activities generate large quantities of wastes that significantly alter the biogeochemistry and ecological structure of entire river basins. Microbial communities that develop in these areas present a variety of survival and adaptation mechanisms. Knowing this diversity at the molecular level is strategic both for understanding adaptive processes and for identifying genomes with potential use in bioremediation and bioprospecting. In this work, prokaryotic and eukaryotic communities were evaluated by meta-taxonomics (16S and 18S amplicons) in sediments and water bodies impacted by acid mine drainage in an important coal mining area in southern Brazil. Five sampling stations were defined on a gradient of impacts (pH 2.7-4.25). Taxon diversity was directly proportional to pH, being greater in sediments than in water. The dominant prokaryotic phyla in the samples were Proteobacteria, Actinobacteria, Acidobacteria, OD1, Nitrospirae, and Euryarchaeota, and among the eukaryotes, algae (Ochrophyta, Chlorophyta, Cryptophyceae), fungi (Basidiomycota, Ascomycota, and Cryptomycota), and protists (Ciliophora, Heterolobosea, Cercozoa). The prokaryotic genera Leptospirillum, Acidithiobacillus, Acidiphilium, Thiomonas, Thermogymnomonas, and Acidobacterium, and the eukaryotic genera Pterocystis and Poteriospumella were associated with more acidic conditions and higher metal concentrations, while the prokaryotic genera Sediminibacterium, Gallionella Geothrix, and Geobacter were more abundant in transitional environments.

Prevalence of vitamin A deficiency in women of childbearing age in Brazil: a systematic review and meta-analysis.

Vitamin A is an essential micronutrient, especially during pregnancy. We aimed to assess the prevalence of vitamin A deficiency in Brazilian women of childbearing age. We conducted a systematic review with meta-analysis of studies that assessed vitamin A deficiency in women of childbearing age following the registered protocol (CRD42020171856). Independent peer researchers selected the studies retrieved from MEDLINE, Embase, Scopus and other sources. Data from the eligible studies were extracted in pairs and assessed for methodological quality. The prevalence of vitamin A deficiency (< 0·70 µmol/l or <0·20 µg/dl) and 95 % CI was combined by meta-analysis, and heterogeneity was estimated by I2. Out of 3610 screened records, thirty-two studies were included, which assessed 12 577 women from 1965 to 2017, mostly in maternity hospitals. Main limitations of the studies were in sample frame (30/32) and sampling method (29/32). Deficiency occurred in 13 % (95 % CI 9·4, 17·2 %; I² = 97 %) of all women and was higher in pregnant women (16·1 %; 95 % CI 5·6, 30·6 %; I² = 98 %) than non-pregnant women (12·3 %; 95 % CI 8·4, 16·8 %; I² = 96 %). The prevalence increased according to the decade, from 9·5 % (95 % CI 1·9­21·6 %; I² = 98 %) up to 1990, 10·8 % (95 % CI 7·9, 14·2 %; I² = 86 %) in the 2000s and 17·8 % (95 % CI 8·7, 29·0 %; I² = 98 %) in the 2010s. Over 10 % of Brazilian women in childbearing age were deficient in vitamin A. Higher prevalence was observed in pregnant women, and deficiency seemed to be increasing over the decades. Low representativeness of the studies, mainly based on convenience sampling that included pregnant, postpartum, lactating and non-pregnant women, as well as high heterogeneity, limits the findings.

Patients' perspectives on the relevance of biosimilars' outcomes in oncology: qualitative study with nominal group technique.

PURPOSE: We aimed to rate the importance of outcomes from a systematic review about biosimilars in oncology from patients' perspective. METHODS: This is a qualitative research with nominal group technique. Patients with cancer were selected by convenience sampling and invited for two mediated virtual meetings in 2022. Twelve outcomes from a systematic review on biosimilars for oncology developed following a protocol were explained in plain language to participants who classified them as critical, important, or not important according to the Grading of Recommendations Assessment, Development and Evaluation approach. We employed Iramuteq software for lexical categorization of the meeting transcripts, and content analysis for interpretation. RESULTS: Five women participated (three had metastatic cancer, one non-metastatic, one recurrent). Six outcomes were classified as critical: duration of response, progression-free survival, pathological complete response, overall survival, severe adverse events, and quality of life; three as important: mortality, event-free survival, and objective response; and three as non-important: neutralizing anti-drug antibody, any adverse event, and non-neutralizing anti-drug antibody. Duration of response, pathological complete response, severe adverse events, and quality of life were considered secondary in the review protocol, but critical by the patients. The main themes influencing the importance classification were related to the disease (progression and control) and treatment (recognition and healthcare setting). CONCLUSION: Patients rated most outcomes as critical or important, some of them previously regarded as secondary by the researchers, which reinforces the need to include stakeholders' perspectives in oncology research. Aspects of the disease progression and treatment effects influenced participants' judgment on outcomes' relevance.

Pharmaceutical policies: effects of policies regulating drug marketing.

BACKGROUND: The costs of developing new treatments and bringing them to the market are substantial. The pharmaceutical industry uses drug promotion to gain a competitive market share, and drive sale volumes and industry profitability. This involves disseminating information about new treatments to relevant targets. However, conflicts of interest can arise when profits are prioritised over patient care and its benefits. Drug promotion regulations are complex interventions that aim to prevent potential harm associated with these activities. OBJECTIVES: To assess the effects of policies that regulate drug promotion on drug utilisation, coverage or access, healthcare utilisation, patient outcomes, adverse events and costs. SEARCH METHODS: We searched Epistemonikos for related reviews and their included studies. To find primary studies we searched MEDLINE, CENTRAL, Embase, EconLit, Global Index Medicus, Virtual Health Library, INRUD Bibliography, two trial registries and two sources of grey literature. All databases and sources were searched in January 2023. SELECTION CRITERIA: We planned to include studies that assessed policies regulating drug promotion to consumers, healthcare professionals or regulators and third-party payers, or any combination of these groups.In this review we defined policies as laws, rules, guidelines, codes of practice, and financial or administrative orders made by governments, non-government organisations or private insurers. One of the following outcomes had to be reported: drug utilisation, coverage or access, healthcare utilisation, patient health outcomes, any adverse effects (unintended consequences), and costs. The study had to be a randomised or non-randomised trial, an interrupted time series analysis (ITS), a repeated measures (RM) study or a controlled before-after (CBA) study. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed eligibility for inclusion of studies. When consensus was not reached, any disagreements were discussed with a third review author.  We planned to use the criteria suggested by Cochrane Effective Practice and Organisation of Care (EPOC) to assess the risk of bias of included studies. For randomised trials, non-randomised trials, and CBA studies, we planned to estimate relative effects, with 95% confidence intervals (CI). For dichotomous outcomes, we planned to report the risk ratio (RR) when possible and adjusted for baseline differences in the outcome measures. For ITS and RM, we planned to compute changes along two dimensions: change in level and change in slope. We planned to undertake a structured synthesis following EPOC guidance.  MAIN RESULTS: The search yielded 4593 citations, and 13 studies were selected for full-text review. No study met the inclusion criteria. AUTHORS' CONCLUSIONS: We sought to assess the effects of policies that regulate drug promotion on drug use, coverage or access, use of health services, patient outcomes, adverse events, and costs, however we did not find studies that met the review's inclusion criteria. As pharmaceutical policies that regulate drug promotion have untested effects, their impact, as well as their positive and negative influences, is currently only a matter of opinion, debate, informal or descriptive reporting. There is an urgent need to assess the effects of pharmaceutical policies that regulate drug promotion using well-conducted studies with high methodological rigour.

Frequency of osteonecrosis in bisphosphonate users submitted to dental procedures: A systematic review.

OBJECTIVE: To determine the frequency of osteonecrosis of the jaw in bisphosphonate users submitted to dental procedures. METHODS: This systematic review searched the sources: MEDLINE, EMBASE, Web of Science, Scopus, and Virtual Health Library, with no restriction on language or publication date. Reviewers, in pairs and independently, selected the studies, extracted their data, and assessed the risk of bias. Meta-analyses were pooled using the DerSimonian and Laird random effects model. RESULTS: A total of 27 studies (5391 participants) were included. The most reported bisphosphonates were zoledronate (n = 17 studies) and alendronate (n = 19) for treating cancers (n = 11) and osteoporosis (n = 16), respectively. Twelve studies were of low methodological quality. The frequency of osteonecrosis was 2.7% (95% CI: 0.9-5.2%) and proved higher for intravenous [6.9% (0.7-17.3%)] than oral [0.2% (0.9-5.2%)] bisphosphonate use. No association between longer treatment duration and greater frequency of osteonecrosis was observed. CONCLUSIONS: Higher frequency of osteonecrosis was observed in intravenous bisphosphonate users submitted to dental extraction. Further studies collecting more detailed information on the bisphosphonates used and of greater methodological rigor are warranted to confirm these findings and better inform prescribers, dental surgeons, and other professionals on risks of bisphosphonate use in this patient group.

Low-pressure ozone injection system: relationship between reaction kinetics and physical properties of grains.

BACKGROUND: The ozonation of grains in a closed system at low pressure is a strategy with the potential for treating packaged products. Research is necessary to characterize the reaction kinetics of ozone in this type of injection system so that it is possible to design chambers and determine the ozone concentrations suitable for commercial-scale applications. The objective of this study was therefore to characterize the low-pressure ozone injection system in relation to the physical properties of the grains and determine possible changes in their quality. Samples (5 kg each) of common beans, cowpea beans, corn, popcorn kernels, paddy rice, and polished rice were exposed to ozone in a 70 L hypobaric chamber. Initially, the internal pressure of the chamber was reduced to 500 hPa. Then, ozone was injected at a concentration of 32.10 g m-3 at a volumetric flow rate of 1 L min-1 until reaching a pressure of 1000 hPa. To relate the decomposition of ozone to the grains that were being evaluated, different physical properties were determined, and quality analysis was conducted. RESULTS: Ozone gas half-life outside and inside the package depended on the grain type. Ozone decomposition was quickest in polished rice and slowest in common beans. The half-life of the different grains ranged from 17.8 to 52.9 and 16.4 to 52.9 min, outside and inside the package, respectively. Considering the physical properties, specific surface (Ss), surface area (SA), and sphericity (φ) exhibited a significant correlation with the decomposition rate constant (k) of ozone. However, the variables volume (V), permeability (K), porosity (ε), and specific mass (ρ) showed no correlation with k. CONCLUSION: The physical properties of grain influenced the reaction kinetics of ozone gas during the low-pressure injection process. Ozone gas injection at low pressures did not alter the quality attributes of the grains under study. © 2022 Society of Chemical Industry.

Toxicity of allyl isothiocyanate applied in systems with or without recirculation for controlling Sitophilus zeamais, Rhyzopertha dominica, and Tribolium castaneum in corn grains.

BACKGROUND: The application of allyl isothiocyanate (AITC) has been proposed as an alternative to control stored-grain insects. However, AITC is a compound with a low diffusion coefficient, making its distribution throughout the grain mass difficult. Therefore, the objective of the present study was to evaluate the effectiveness of AITC applied in systems with or without recirculation for controlling Sitophilus zeamais (Mots. 1855) (Coleoptera: Curculionidae), Rhyzopertha dominica (Fabr.) (Coleoptera: Bostrichidae), and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) infesting a corn grain mass. The assays used a polyvinyl chloride (PVC) prototype, dimensioned 1.60 m in length, 0.30 m in diameter, and a static capacity of 60 kg of grains. AITC toxicity to insects was evaluated at the base, 0.5 m from the base, and top of the grain column (1.0 m). Different concentrations of AITC were tested for an exposure period of 48 h. RESULTS: In the system without AITC recirculation, insect mortality was verified only at the base of the grain column. However, insect mortality was considered uniform at the different positions of the column when the AITC recirculation system was adopted. In this system, there was also a marked reduction in the instantaneous population growth rate of S. zeamais, T. castaneum, and R. dominica, and a decrease in the dry matter loss of the grains, when the AITC concentrations were increased. CONCLUSION: AITC recirculation proved to be a viable strategy for protecting grains against the species S. zeamais, R. dominica, and T. castaneum. AITC fumigation ultimately did not cause changes in grain quality. © 2023 Society of Chemical Industry.

Inflammatory Cytokine Patterns Associated with Neurological Diseases in Coronavirus Disease 2019.

Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Perceived discrimination in health services and associated factors in Manaus Metropolitan Region, Brazil: a cross-sectional population-based study.

Objectives: Discrimination is the differentiated treatment of individuals due to prejudgments. Discriminatory practices in health care result in negative effects on patients' health. In Brazil, skin color represents the main form of racial discrimination, which may have an impact on the accessibility and quality of health care. The Brazilian Amazon lacks investigations on this topic at the population level. This study aims to estimate the prevalence of perceived discrimination in health services and associated factors in the Manaus Metropolitan Region, state of Amazonas, Brazil.Design: A population-based cross-sectional study was conducted with a probabilistic sample of adults interviewed in 2015. The associated factors were investigated by calculating the prevalence ratio (PR) using Poisson regression with robust variance.Results: A total of 4,001 participants were included. The overall prevalence of perceived discrimination was 12.9% (95% confidence interval [CI]: 11.8-13.9%). When compared to the reference categories, women (PR = 1.43; 95%CI: 1.20-1.70), individuals with brown skin color (Brazilian mixed race; PR = 1.33; 95%CI: 1.04-1.71), people who suffer from hypertension (PR = 1.27;95%CI: 1.03-1.57), and people who frequently used health services (p≤0.03) experienced more discrimination from health professionals.Conclusions: The prevalence of perceived discrimination in health services in Manaus Metropolitan Region is frequent and is associated with ethnic, social and health-related factors. Investments in inclusive public health policies and a better quality of health assistance are required to tackle this problem.

Methods: A new protocol for in vitro red blood cell glycation.

During diabetes, the characteristic hyperglycemia can induce red blood cell glycation. Several researchers have proposed different protocols to perform an in vitro model to study this phenomenon. In this article, some of the most important in vitro glycation protocols available in the bibliography were compared to each other. The incubation parameters as the suspension medium, glucose concentration, red blood cell concentration, time, and temperature were analyzed. Also, several assays were carried out in our laboratory, and glycated hemoglobin, erythrocyte aggregation and viscoelasticity were determined for the protocol validation. Based on the bibliographic analysis and our experimental results, an optimal protocol for in vitro glycation of red blood cells is presented.

Seroprevalence of Epstein-Barr virus and cytomegalovirus infections in Presidente Figueiredo, Amazonas, Brazil.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections affect around 95% of the world's population. In Brazil, there are few epidemiological reports related to EBV and CMV infection, especially in the western Amazon region. This study aimed to estimate the seroprevalence of EBV and CMV infection in individuals residents in Presidente Figueiredo, Amazonas, Brazil. Blood samples of 443 individuals were tested for the presence of anti-EBV and anti-CMV IgG antibodies through an enzyme-linked immunosorbent assay. EBV (95.9%; 95% CI: 0.94;0.98), CMV (96.8%; 95% CI: 0.95;0.98) and CMV/EBV (93%;95% CI: 0.91-0.95) coinfection were highly prevalent in the study population. Children (1 to 5 years) not attending school were less susceptible to EBV (OR 0.15; 95% CI: 0.05-0.52; p = 0.017) and CMV infections (OR 0.05; 95% CI: 0.02 - 0.17; p < 0.0001). Teenagers at high school showed increased susceptibility to CMV infection (OR 4.65; 95%CI: 1.43-15.08; p = .013) and EBV/CMV co-infection (OR 3.04; 95%CI: 1.44-6.45; p = 0.005). The seroprevalence of CMV and EBV infections were preeminent and tend to increase with age in the study population. Either attendance to a daycare facility or primary school before the age of 5 years may increase the susceptibility to EBV or CMV infection.

Polymorphisms in HTLV-1 Tax-responsive elements in HTLV-1-associated myelopathy/tropical spastic paraparesis patients are associated with reduced proviral load but not with disease progression.

Human T-lymphotropic virus type 1 (HTLV-1) provirus expression is mainly directed by Tax-responsive elements (TRE) within the long terminal repeats (LTR). Mutations in TRE can reduce provirus expression and since a high proviral load (PVL) is a risk factor for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we evaluated polymorphisms in the 5' LTR and the association with PVL and disease progression. HTLV-1 LTR and tax sequences derived from asymptomatic carriers (AC) and HAM/TSP patients followed in a longitudinal study were analysed according to PVL and clinical severity. Individuals infected with HTLV-1 presenting the canonical TRE, considering strain ATK-1 as the consensus, displayed sustained higher PVL. By contrast, an LTR A125G mutation in TRE was associated with slightly reduced PVL only in HAM/TSP patients, although it did not influence the speed of disease progression. Moreover, this polymorphism was frequent in Latin American strains of the HTLV-1 Cosmopolitan Transcontinental subtype. Therefore, polymorphisms in the 5' TRE of HTLV-1 may represent one of the factors influencing PVL in HAM/TSP patients, especially in the Latin American population. Indeed, higher PVL in the peripheral blood has been associated with an increased inflammatory activity in the spinal cord and to a poorer prognosis in HAM/TSP. However, this event was not associated with TRE polymorphisms.

In vitro alteration on erythrocytes mechanical properties by propofol, remifentanil and vecuronium.

Several studies report flow disturbance and microcirculation disorders upon anesthesia treatment. These alterations are often related to blood rheology changes. In this work, it was attempted to make a detailed description of the alterations in erythrocyte mechanical properties by the action of propofol, remifentanil, and vecuronium. For this, an in vitro study was performed on red blood cell samples from healthy donors incubated with solutions of propofol (4 µg/mL whole blood), remifentanil (10 ng/mL plasma), and vecuronium (0.15 µg/mL plasma). Erythrocyte viscoelastic parameters were determined by octuplicate using a Reómetro Eritrocitario. Also, a Wilcoxon signed rank-test with Yates correction for continuity was performed to analyze the overall alteration in the mechanical properties of erythrocytes. Statistical analysis showed that the three studied anesthetics changed the erythrocyte mechanical properties at different parts of the membrane. These results would imply an interaction of these anesthetics with the erythrocyte membrane. Finally, this could conduce to alterations in microcirculation.

Gender differences in the use of atypical antipsychotics in early-onset schizophrenia: a nationwide population-based study in Brazil.

BACKGROUND: The use of atypical antipsychotics for the treatment of schizophrenia and other mental disorders in populations under 18 years of age is increasing worldwide. Little is known about treatment patterns and the influence of gender differences, which may be a predictor of clinical outcomes. The aim of this study was to investigate gender differences in the use of atypical antipsychotics in patients with early-onset schizophrenia (EOS) assisted by the public health system in Brazil. METHODS: We conducted a cross-sectional study of outpatients with EOS aged 10 to 17 years who received at least one provision of atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a large Brazilian pharmaceutical assistance programme. Data were retrieved from a nationwide administrative database from 2008 to 2017. RESULTS: Of the 49,943 patients with EOS, 63.5% were males, and the mean age was 13.6 years old. The patients were using risperidone (62.5%), olanzapine (19.6%), quetiapine (12.4%), ziprasidone (3.3%) and clozapine (2.2%). We found gender differences, especially in the 13-17 year age group (65.1% for males vs. 34.9% for females, p < 0.001), in the use of risperidone (72.1% for males vs. 27.9% for females, p < 0.001) and olanzapine (66.5% for males vs. 33.5% for females, p < 0.001). Only in the 13 to 17 years age group were the prescribed doses of olanzapine (p = 0.012) and quetiapine (p = 0.041) slightly higher for males than for females. CONCLUSIONS: Our findings showed gender differences among patients diagnosed with EOS and who received atypical antipsychotics. More attention should be devoted to gender differences in research and clinical practice.

Essential oil from leaves of Eugenia calycina Cambes: Natural larvicidal against Aedes aegypti.

BACKGROUND: Eugenia calycina is an endemic species in the Brazilian savannah (the Cerrado) and it is threatened with extinction. Several species of Eugenia are used as insecticides or insect repellents. No data are available on the larvicidal activity of E. calycina. The chemical composition of the essential oil (EO) from leaves of Eugenia calycina was analyzed by gas chromatography coupled to mass spectrometry (GC-MS) and the larvicidal activity against Aedes aegypti larvae in the third stage of development was studied. RESULTS: Oxygenated and non-oxygenated sesquiterpenes were identified, and the main compounds were bicyclogermacrene, spathulenol, and ß-caryophyllene. The EO was fractionated in a chromatographic column and three compounds were isolated and identified: spathulenol, aromadendrane-4ß,10α-diol, and 1ß-11-dihydroxy-5-eudesmene. It is the first time that the last two compounds have been identified in E. calycina. The exposure times in the larvicidal test were 24 h and 48 h and the LC50 values obtained were 199.3 and 166.4 µg mL-1 . The cytotoxicity of the EO in mammalian cells (HeLa and Vero) was evaluated for 24 and 48 h of incubation. The cytotoxic concentrations of the EO for HeLa and Vero cells (266.8 ± 46.5 and 312.1 ± 42.5 µg mL-1 , respectively) in 48 h of exposure were higher than the LC50 , showing low cytotoxicity at the concentration exhibiting larvicidal activity, resulting in a positive selectivity index. CONCLUSION: These results indicate that the EO of E. calycina showed high activity against the A. aegypti larvae but lower cytotoxicity to mammalian cells. The leaves of E. calycina are therefore a very promising source of natural larvicidal products. © 2020 Society of Chemical Industry.