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Background/Objectives : Cytokine storm in severe COVID-19 is responsible for irreversible tissue damage and death. Soluble mediators from the TNF superfamily, their correlation with clinical outcome, and the use of TNF receptors as a potent predictor for clinical outcome were evaluated. Methods : Severe COVID-19 patients had the levels of soluble mediators from the TNF superfamily quantified and categorized according to the clinical outcome (death versus survival). Statistical modeling was performed to predict clinical outcomes. Results : COVID-19 patients have elevated serum levels from the TNF superfamily. Regardless of sex and age, the sTNFRI levels were observed to be significantly higher in deceased patients from the first weeks following the onset of symptoms. We analyzed hematological parameters and inflammatory markers, and there was a difference between the groups for the following factors: erythrocytes, hemoglobin, hematocrit, leukocytes, neutrophils, band cells, lymphocytes, monocytes, CRP, IL-8, IFN-γ, IL-10, IL-6, IL-4, IL-2, leptin MIF sCD40L, and sTNFRI ( p < 0.05). A post hoc analysis showed an inferential capacity over 70% for some hematological markers, CRP, and inflammatory mediators in deceased patients. sTNFRI was strongly associated with death, and the sTNFRI/sTNFRII ratio differed between outcomes ( p < 0.001; power above 90%), highlighting the impact of these proteins on clinical results. The final logistic model, including sTNFRI/sTNFRII and CRP, indicated high sensitivity, specificity, accuracy, and an eight-fold higher odds ratio for an unfavorable outcome. Conclusions : The joint use of the sTNFRI/sTNFRII ratio with CRP proves to be a promising tool to assist in the clinical management of patients hospitalized for COVID-19.

The industries are searching for greener alternatives for their productions due to the rising concern about the environment and creation of waste and by-products without industrial utility for that specific line of products. This investigation describes the development of two stable nanostructured lipid carriers (NLCs): one is the formulation of a standard NLC, and the other one is the same NLC formulation associated with a natural deep eutectic solvent (NaDES). The research presents the formulation paths of the NLCs through completeness, which encompass dynamic light scattering (DLS), zeta potential tests, and pH. Transmission electron microscopy (TEM) and confocal microscopy were performed to clarify the morphology. Cytotoxicity tests with zebrafish were realized, and the results are complementary to the in vitro outcomes reached with fibroblast L132 tests by the MTT technique and the zymography test. Infrared spectroscopy and X-ray diffractometry tests elucidated the link between the physicochemical characteristics of the formulation and its behavior and properties. Different cooling techniques were explored to prove the tailorable properties of the NLCs for any industrial applications. In conclusion, the compiled results show the successful formulation of new nanocarriers based on a sustainable, eco-friendly, and highly tailorable technology, which presents low cytotoxic potential.

As a result of human activities and natural dispersal, exotic species can be brought to new areas, where they become established and spread, becoming invaders. These species are responsible for the loss of biodiversity and cause ecosystemic harm throughout the world. In this paper, we report the rapid, broad geographic expansion of the invasive fly Drosophila nasuta in Brazil. An 84% increase was found in its area of occupation in the country compared to previous studies. The present data reveal its arrival to the Pantanal wetlands in a location more than one thousand kilometers from the closest previous record in the Cerrado biome. We present the first record of D. nasuta in the Atlantic Forest in the states of Paraíba and Bahia. We report its introduction in the Amazon Forest in the state of Amazonas approximately 700 kilometers from previous records. The relative abundance of D. nasuta in this biome increased fivefold in comparison to a previous study. In the first decade of invasion in Brazil, D. nasuta has already colonized more than half of the country. The present data reveal its invasive potential and underscore the importance of following up the possible negative effects of this biological invasion.

Background: To mitigate mortality among critically ill COVID-19 patients, both during their Intensive Care Unit (ICU) stay and following ICU discharge, it is crucial to measure its frequency, identify predictors and to establish an appropriate post-ICU follow-up strategy., Methods: In this multicentre, prospective cohort study, we included 586 critically ill COVID-19 patients., Results: We observed an overall ICU mortality of 20.1% [95%CI: 17.1% to 23.6%] (118/586) and an overall hospital mortality of 25.4% [95%CI: 22.1% to 29.1%] (149/586). For ICU survivors, 30 days (early) post-ICU mortality was 5.3% [95%CI: 3.6% to 7.8%] (25/468) and one-year (late) post-ICU mortality was 7.9% [95%CI: 5.8% to 10.8%] (37/468). Pre-existing conditions/comorbidities were identified as the main independent predictors of mortality after ICU discharge: hypertension and heart failure were independent predictors of early mortality; and hypertension, chronic kidney disease, chronic obstructive pulmonary disease and cancer were independent predictors of late mortality., Conclusion: Early and late post-ICU mortality exhibited an initial surge (in the first 30 days post-ICU) followed by a subsequent decline over time. Close monitoring of critically ill COVID-19 post-ICU survivors, especially those with pre-existing conditions, is crucial to prevent adverse outcomes, reduce mortality and to establish an appropriate follow-up strategy., Competing Interests: The authors of this manuscript have the following competing interests: Mariana M S Santos acknowledges having been awarded a research grant (PD/BD/150529/2019) from Fundação para a Ciência e a Tecnologia (FCT). Regis G Rosa discloses research grants from Pfizer and lecture fees from Novartis, both unrelated to the work submitted herein. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The remaining authors have no competing interests to disclose., (Copyright: © 2023 Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Infectious diseases are a major health concern worldwide, especially as they are one of the main causes of mortality in underdeveloped and developing countries. Those that are considered emerging and re-emerging are characterized by unpredictability, high morbidity and mortality, exponential spread, and substantial social impact. These characteristics highlight the need to create an "on demand" control method, with rapid development, large-scale production, and wide distribution. In view of this, RNA vaccines have been investigated as an effective alternative for the treatment and prevention of infectious diseases since they can meet those needs and are considered safe, affordable, and totally synthetic. Therefore, this systematic review aimed to evaluate the use of RNA vaccines for infectious diseases from experimental, in vivo, and in vitro studies. PubMed, Web of Science, and Embase were searched for suitable studies. Additionally, further investigations, such as grey literature checks, were performed. A total of 723 articles were found, of which only 41 met the inclusion criteria. These studies demonstrated the potential of using RNA vaccines to control 19 different infectious diseases, of which COVID-19 was the most studied. Similarly, viruses comprised the largest number of reported vaccine targets, followed by protozoa and bacteria. The mRNA vaccines were the most widely used, and the intramuscular route of administration was the most reported. Regarding preclinical experimental models, mice were the most used to evaluate the impact and safety of the RNA vaccines developed. Thus, although further studies and evaluation of the subject are necessary, it is evident that RNA vaccines can be considered a promising alternative in the treatment and prophylaxis of infectious diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Despite the considerable morbidity and mortality of yellow fever virus (YFV) infections in Brazil, our understanding of disease outbreaks is hampered by limited viral genomic data. Here, through a combination of phylogenetic and epidemiological models, we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modeling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centers in the Southeast. Phylodynamic analysis unraveled the circulation of three distinct lineages and provided proof of the directionality of a known spatial corridor that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with eco-epidemiology can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.

Introduction: The effectiveness of human immunodeficiency virus (HIV) post-exposure prophylaxis (PEP) depends on adherence to the protocol, which includes taking antiretrovirals (ARVs) and attending visits. We examined the adherence rate to antiretroviral agents and follow-up visits identifying the associated characteristics of adherence and the reasons for not attending HIV PEP consultations in a specialized service in São Paulo, Brazil., Methodology: This was a cross-sectional study with health service users who had an indication for PEP due to sexual exposure in an HIV/AIDS service from April to October 2019. The health service users were followed-up throughout the prophylaxis cycle. Adherence was determined through self-reports on antiretroviral agent use and attendance to follow-up consultations., Results: Association measures were employed to identify adherence-related characteristics. The sample analyzed included 91 users. The mean age was 32.5 years old (SD = 9.8). The largest share was white-skinned (49.5%), men who have sex with other men (62.2%), male (86.8%), and undergraduate/graduate students (65.9%). Adherence totaled 56.7% and health insurance was the associated characteristic (p = 0.039). Work (55.9%), using a private service (15.2%), forgetfulness (11.8%) and considering follow-up unnecessary (11.8%) were the main reasons for not attending the follow-up appointments., Conclusions: Few users do attend HIV PEP consultations. The users without health insurance had the highest adherence percentage whereas work was mentioned as a reason for not attending HIV PEP consultations., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Marcos Morais Santos Silva, Luciane Simões Duarte, Lucia Yasuko Izumi Nichiata.)

SARS-CoV-2 (COVID-19) infection is responsible for causing a disease with a wide spectrum of clinical presentations. Predisposition to thromboembolic disease due to excessive inflammation is also attributed to the disease. The objective of this study was to characterize the clinical and laboratory aspects of hospitalized patients, in addition to studying the pattern of serum cytokines, and associate them with the occurrence of thromboembolic events., Methodology: A retrospective cohort study with 97 COVID-19 patients hospitalized from April to August 2020 in the Triângulo Mineiro macro-region was carried out. A review of medical records was conducted to evaluate the clinical and laboratory aspects and the frequency of thrombosis, as well as the measurement of cytokines, in the groups that presented or did not present a thrombotic event., Results: There were seven confirmed cases of thrombotic occurrence in the cohort. A reduction in the time of prothrombin activity was observed in the group with thrombosis. Further, 27.8% of all patients had thrombocytopenia. In the group that had thrombotic events, the levels of IL1b, IL-10, and IL2 were higher ( p < 0.05)., Conclusions: In the studied sample, there was an increase in the inflammatory response in patients with thrombotic events, confirmed by the increase in cytokines. Furthermore, in this cohort, a link was observed between the IL-10 percentage and an increased chance of a thrombotic event.

Background: C:N:P homeostasis in plants guarantees optimal levels of these nutrients in plant metabolism. H However, one of the causes to the effects of deficit irrigation is the loss of C:N:P homeostasis in leaves and stems that causes reduction in the growth of sugarcane. Being able to measure the impact of water deficit on C:N:P homeostasis in plants from the stoichiometric ratios of the concentrations of these nutrients in leaves and stems. This loss causes a decrease in nutritional efficiency, but can be mitigated with the use of silicon. Silicon favors the homeostasis of these nutrients and crop productivity. The magnitude of this benefit depends on the absorption of Si by the plant and Si availability in the soil, which varies with the type of soil used. Thus, this study aims to evaluate whether the application of Si via fertigation is efficient in increasing the absorption of Si and whether it is capable of modifying the homeostatic balance of C:N:P of the plant, causing an increase in nutritional efficiency and consequently in the production of biomass in leaves and stems of sugarcane ratoon cultivated with deficient and adequate irrigations in different tropical soils., Results: Water deficit caused biological losses in concentrations and accumulation of C, N, and P, and reduced the nutrient use efficiency and biomass production of sugarcane plants cultivated in three tropical soils due to disturbances in the stoichiometric homeostasis of C:N:P. The application of Si increased the concentration and accumulation of Si, C, N, and P and their use efficiency and reduced the biological damage caused by water deficit due to the modification of homeostatic balance of C:N:P by ensuring sustainability of the production of sugarcane biomass in tropical soils. However, the intensity of attenuation of such deleterious effects stood out in plants cultivated in Eutrophic Red Oxisols. Si contributed biologically by improving the performance of sugarcane ratoon with an adequate irrigation due to the optimization of stoichiometric ratios of C:N:P; increased the accumulation and the use efficiency of C, N, and P, and promoted production gains in biomass of sugarcane in three tropical soils., Conclusion: Our study shows that fertigation with Si can mitigate the deleterious effects of deficient irrigation or potentiate the beneficial effects using an adequate irrigation system due to the induction of a new stoichiometric homeostasis of C:N:P, which in turn improves the nutritional efficiency of sugarcane cultivated in tropical soils., (© 2023. The Author(s).)

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis ( L.b ) is one of the most clinically relevant pathogens that affects the skin and mucosa, causing single or multiple disfiguring and life-threatening injuries. Even so, the few treatment options for patients have significant toxicity, high dropout rates, high cost, and the emergence of resistant strains, which implies the need for studies to promote new and better treatments to combat the disease. Zinc oxide nanocrystals are microbicidal and immunomodulatory agents. Here, we develop new Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages of silver oxide (AgO) nanocrystals (x = 49%, 65%, and 68%) that could act as an option for tegumentary leishmaniasis treatment. Our findings showed that 65% and 68% of AgO inhibit the extra and intracellular replication of L.b. and present a high selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression of surface receptors, and cytokine production by human peripheral blood mononuclear cells toward a proinflammatory phenotype. These results point to new Ag-ZnO/AgO nanocomposites as a promising option for L. braziliensis treatment.

Phenolic compounds are natural dyes contained in sugarcane juice and represent an important parameter in industrial processing, as they significantly affect the color formation of raw sugar. This study investigated the relationship between color formation and phenolic compounds during a Very High Polarization (VHP) sugar manufacturing process, in which the RB92579 genotype represents about 50% of the processed sugarcane. The products evaluated during the industrial processing of sugarcane were: raw juice, mixed juice, lime-treated juice, clarified juice, syrup, massecuite, and VHP sugar. The polyphenols catechin (CAT), chlorogenic acid (CGA), caffeic acid (CAF), vanillin (VAN), syringaldehyde (SYR), p-coumaric acid (p-COU), coumarin (CUM), and rutin (RUT) were quantified by high-performance liquid chromatography (HPLC). The highest concentrations of CGA and SYR were obtained from the sucrose crystallization product (massecuite), similarly to the parameters of color, total phenols and the total polyphenol content. CGA was the predominant polyphenol in the samples of clarified juice, syrup, massecuite and VHP sugar, with the latter presenting concentrations above 50%. The presence of phenolic compounds provided different indices of color during the production process. In this context, chlorogenic acid (CGA) was the compound that presented the most expressive results, contributing significantly to the formation of color in sugarcane processing products, which is a fact that has not yet been reported in the literature. The color of the VHP sugar crystals also had a positive relationship with the concentration of phenolics, with greater evidence for CGA., (© 2022. The Author(s).)

Background: Ultramarathons with distances over 180 km might lead to different results regarding participation, performance, and age compared to shorter runs of 50 and 100 km., Objective: To evaluate ultramarathons with distances above 180 km in relation to runners' peak age and performance., Method: s. Verification of the quantity of competitions in runs over 180 km by continents in the period 2000 to 2020 and evaluation of the individual results of 13,300 athletes after 2010., Results: Europe stood out with the largest number of organized events, followed by Asia and North America. The age peak performance (PP) in men and women averaged 45 years old with relationship between sex × years ( F = 3.612, p < 0.001; η 2 = 0.003). Men accounted for more than 80% of the runners and showed a reduction in PP from 2015 onwards ( p < 0.001). Competitions between 180 and 240 km were the most frequent, particularly after 2016, surpassing the number of marathons over 360 km ( p < 0.001). Men and women showed higher velocity in distances ( p < 0.001) from 180 to 240 km when compared to 241 to 300 k m, 301 to 360 km, and >360 km courses., Conclusions: The decade between 2010 and 2020 showed an increase in the number of Ultramarathon running events. Europe had the highest number. Women had low participation. Performance progression fell, a fact associated with an increase in the number of participants and not specifically related to a decline in athletic performance over the years., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Raphael Fabricio de Souza et al.)

COVID-19, also known as coronavirus disease 2019, is an infectious viral disease caused by SARS-CoV-2, a novel coronavirus. Since its emergence, its epidemiology has been explored; however, for some regions of the world, COVID-19's behavior, incidence, and impact remain unclear. In continental nations like Brazil, this lack of knowledge results in nonuniform control, prevention, and treatment measures, which can be controversial in some locations. This study aimed to describe the epidemiological profile of patients with COVID-19 in the macroregion of Triângulo Sul in the state of Minas Gerais (MG), Brazil. Between March 25 and October 21, 2020, data were collected and statistically analyzed from 395 hospitalized patients in the city of Uberaba, MG, suspected to have moderate or severe forms of the disease. Of the 395 suspected cases, 82% were confirmed to be positive for COVID-19. The mean age of positive patients was 58.4 years, and 60.76% were male. Following these patients throughout their hospitalization, a mortality rate of 31.3% was observed. In the population positive for COVID-19, the risk of death increased by 4% for each year of the patient's age. Likewise, the older the patient, the longer their hospitalization and the higher the risk of developing acute respiratory failure. Among the treatments tested in patients, heparin was associated with protection against mortality, and the absence of anticoagulant use was linked to a more than six times greater risk of death. Finally, comorbidities in patients with COVID-19 were positively correlated with increased hospitalization time. In summary, this study revealed that age, presence of comorbidities, length of hospitalization, and drug treatment considerably altered COVID-19's lethality. To understand infection rates and the factors involved in COVID-19's lethality, knowledge of the local epidemiology is necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Silva, Rodrigues, Abadia, Alves da Silva, Andrade e Silva, Desidério, Farnesi-de-Assunção, Costa-Madeira, Barbosa, Bernardes e Borges, Hortolani Cunha, Pereira, Helmo, Lemes, Barbosa, Trevisan, Obata, Bueno, Mundim, Oliveira-Scussel, Monteiro, Ferreira, Machado, Ferreira-Paim, Moraes-Souza, da Silva, Rodrigues Júnior and Oliveira.)

Objective: To analyze conditions which interfere with adherence to HIV post-sexual exposure prophylaxis., Method: Cross-sectional study conducted in two health care services specializing in HIV/AIDS in São Paulo city. Interviewees included men and women who were eighteen or older, sought care due to consensual sexual relation, and had a recommendation for prophylaxis. The questionnaires which compose the social reproduction index and adherence to prophylaxis were used as parameters. Non-parametric Kruskal-Wallis and Mann-Whitney tests and summation of the employed instrument through programs Excel® and Statistical Package for the Social Sciences® were performed. Ethical principles have been respected., Results: Forty-nine users have been identified; their mean age was 34.7 and they were predominantly men (95.9%). Out of these, 83.6% were men who have sex with men. The conditions which correlated with adherence (p<0.05) were taking post-sexual exposure prophylaxis prior to that appointment and continuing to take the medication., Conclusion: Health professionals are responsible for establishing rapport with service users, especially during the first appointment, to contribute to adherence interventions plans.

Mevalonate kinase deficiency (MKD) is an autosomal recessive disorder in humans that causes systemic autoinflammatory problems to children. Previously, we used a yeast model to show that MKD results in mitochondrial malfunctioning that may finally induce mitophagy. Here, we proved that MKD indeed induced general autophagy as well as mitophagy in yeast, but these mechanisms did not go to completion. Therefore, the limitation of mevalonate kinase activity produces dysfunctional mitochondria that might not be recycled, causing metabolic dysfunctions in the cells. Understanding this mechanism may provide a piece in solving the nonspecific autoinflammatory response puzzle observed in MKD patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cancer during pregnancy is rarely studied due to its low incidence (1:1000). However, as a result of different sociocultural and economic changes, women are postponing pregnancy, so the number of pregnant women with cancer has been increasing in recent years. The importance of studying cancer during pregnancy is not only based on maternal and foetal prognosis, but also on the evolutionary mechanisms of the cell biology of trophoblasts and neoplastic cells, which point out similarities between and suggest new fields for the study of cancer. Moreover, the magnitude of how cancer factors can affect trophoblastic cells, and vice versa, in altering the foetus's nutrition and health is still a subject to be understood. In this context, the objective of this narrative review was to show that some researchers point out the importance of supplementing branched-chain amino acids, especially leucine, in experimental models of pregnancy associated with women with cancer. A leucine-rich diet may be an interesting strategy to preserve physiological placenta metabolism for protecting the mother and foetus from the harmful effects of cancer during pregnancy.

Background: Longevity, combined with a higher prevalence of obesity, particularly visceral obesity, has been associated with an increased risk of cardiovascular diseases. Insulin resistance (IR) is an important link between visceral obesity and cardiovascular diseases. An important association has been found between sagittal abdominal diameter, visceral obesity and IR. The objective of this study is to evaluate sagittal abdominal diameter as a marker of visceral obesity and correlate it with IR in older primary health care patients., Methods: A cross-sectional study was performed with 389 patients over 60 years of age (70.6 ± 6.9), of whom 74% were female. Their clinical, anthropometric and metabolic profiles were assessed and their fasting serum insulin level was used to calculate the homeostasis model assessment insulin resistance (HOMA-IR). Sagittal abdominal diameter was measured in the supine position at the midpoint between the iliac crest and the last rib with abdominal calipers., Results: Sagittal abdominal diameter was significantly correlated with anthropometric measures of general and visceral obesity and with HOMA-IR in both genders. There was no change in the association between sagittal abdominal diameter and HOMA-IR after adjusting for age, sex, diabetes and hypertension., Conclusion: It is feasible to use sagittal abdominal diameter in older primary care patients as a tool to evaluate visceral obesity, which is an indicator of cardiovascular risk., (Institute of Geriatric Cardiology.)

Lawsone is a natural naphthoquinone present in the henna leaf extract with several cytotoxic activities and used as precursor for synthesis of various pharmaceutical compounds. Its biological activities are thought to be the result of oxidative stress generated, although the hydroxy group at position C-2 in its structure tends to reduce its electrophilic potential. In view of lack of knowledge on its activity, the present work aimed to elucidate the biological effect of lawsone using the yeast Saccharomyces cerevisiae. In the model strain BY4741 it was defined 229 mmol/L as the minimal inhibitory concentration (MIC). Using 172 mmol/L as sub-MIC value it was observed that yap1 deletion mutant was sensitive to lawsone independent the presence of oxygen. Lawsone affected yeast growth in glycerol, indicating interference in the respiratory metabolism. Intracellular content of thiol groups did not indicate intensive oxidative stress and the presence of the anti-oxidant N-acetylcysteine (NAC) exacerbated lawsone toxicity. By analysing the sensitivity of atg mutant strains and the localization of GFP-Atg8 fusion protein, it was concluded that lawsone primarily produces mitochondrial malfunctioning, leading to indirect oxidative stress. It triggers the autophagic response that ultimately induces mitophagy.

Importance: The effects of intensive care unit (ICU) visiting hours remain uncertain., Objective: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium., Design, Setting and Participants: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018., Interventions: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation., Main Outcomes and Measures: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory)., Results: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, -1.7% [95% CI, -6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, -0.8% [95% CI, -2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, -3.8% [95% CI, -4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, -1.6 [95% CI, -2.3 to -0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, -1.2 [95% CI, -2.0 to -0.4]; P = .003) were significantly better with flexible visitation., Conclusions and Relevance: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium., Trial Registration: ClinicalTrials.gov Identifier: NCT02932358.

Introduction: Carriers of oncohematological diseases are at high risk for hepatitis B virus (HBV) infection., Objective and Method: To investigate the epidemiology of HBV infection in Goiânia, Central Brazil, 322 individuals with oncohematological diseases (leukemias, Hodgkin lymphoma and non-Hodgkin lymphoma) were interviewed and blood samples were collected for the detection of serological markers of HBV-DNA by polymerase chain reaction (PCR). Medical records of participants were also reviewed., Results: Non-Hodgkin's lymphomas (n=99) and chronic myeloid leukemia (n=108) were the most frequent oncohematological diseases. The overall prevalence of HBV was 13.97% (45/322). Of the total participants, 8.69% (28/322) presented isolated positivity for anti-HBs, suggesting low vaccine coverage. HBV-DNA was detected in 25% (1/4) of HBsAg positive samples and in 25% (3/12) of anti-HBc isolated, suggesting HBV occult infection. All samples were identified as subgenotype A1. Entries in patient records and the findings of this investigation suggest anti-HBc seroconversion during oncologic treatment. Age 50 years or over and use of a central catheter during therapy were associated with HBV exposure., Conclusion: The low frequency of hepatitis B immunized individuals, detection of HBV DNA in HBsAg negative samples, and the suggestion of HBV exposure during treatment evidenced the potential for health-related viral dissemination in people with oncohematological diseases in our region, reinforcing the importance of serological monitoring, vaccination against hepatitis B, and adoption of strict infection control measures in these individuals., (Copyright © 2019 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

The aims of this work were to re-describe all parasitic stages of Rhipicephalus sanguineus sensu stricto, to select and deposit a neotype, and to characterize some of its diagnostic molecular traits. A male of R. sanguineus s.s. collected in Montpellier, France, was designated as neotype. The diagnostic characters unique to the male of R. sanguineus s.s. are: spiracular plate elongated and subtriangular in shape with a dorsal prolongation narrow and usually visible dorsally, with the dorsal prolongation narrower than the width of the adjacent festoon; punctations of the scutum moderate in number and unequal in size; marginal groove conspicuous, deep and punctate; posteromedian groove distinct and elongated, and posterolateral grooves often sub-circular, shorter than posteromedian groove; adanal plates long, wide, and subtriangular in shape, with a clear concavity in its inner margin and posterior margin broadly rounded or truncated; accessory adanal plates with the posterior end pointed, narrower than the width of adjacent festoon. The female of R. sanguineus s.s. can be diagnosed by a combination of broadly U-shaped genital aperture, spiracular plate with a narrow dorsal prolongation visible dorsally, basis capituli hexagonal with broad lateral angles, and scutum barely longer than broad with posterior margin sinuous and punctations moderate in number and unequal in size, larger and more numerous along cervical fields. The nymph has a basis capituli sub-triangular dorsally with lateral angles slightly curved and presence of ventral processes, scutum approximately as long as broad with lateral margins nearly straights, posterior margin broadly rounded, and cervical grooves short and sigmoid in shape extending posteriorly to the level of the eyes. The larva is characterized by basis capituli broader than long with lateral angles short and slightly curved and with posterior margin slightly convex, cervical grooves short, shallow and subparallel, and scutum almost twice broader than long. The phylogenetic analysis of DNA sequences support R. sanguineus s.s. as a well-defined taxon when compared with other species of the R. sanguineus group: R. turanicus s.s., R. camicasi, R. guilhoni, R. sulcatus, R. pusillus, R. rossicus and R. leporis. Molecularly R. sanguineus s.s. also encompasses the so-called "temperate lineage" from the New World (Argentina, southern Brazil, Chile, Uruguay, and USA). The evidence currently available supports the presence of R. sanguineus s.s. in Europe (France, Italy, Spain, Switzerland and Portugal) and America (Argentina, Brazil, Chile, Uruguay and U.S.A.), but further studies are needed to determine the exact geographic range of this taxon., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Mevalonate kinase deficiency (MKD) an orphan drug rare disease affecting humans with different clinical presentations, is still lacking information about its pathogenesis; no animal or cell model mimicking the genetic defect, mutations at MVK gene, and its consequences on the mevalonate pathway is available. Trying to clarify the effects of MVK gene impairment on the mevalonate pathway we used a yeast model, the erg12-d mutant strain Saccharomyces cerevisiae (orthologous of MKV) retaining only 10% of mevalonate kinase (MK) activity, to describe the effects of reduced MK activity on the mevalonate pathway. Since shortage of isoprenoids has been described in MKD, we checked this observation using a physiologic approach: while normally growing on glucose, erg12-d showed growth deficiency in glycerol, a respirable carbon source, that was not rescued by supplementation with non-sterol isoprenoids, such as farnesol, geraniol nor geranylgeraniol, produced by the mevalonate pathway. Erg12-d whole genome expression analysis revealed specific downregulation of RSF2 gene encoding general transcription factor for respiratory genes, explaining the absence of growth on glycerol. Moreover, we observed the upregulation of genes involved in sulphur amino acids biosynthesis that coincided with the increasing in the amount of proteins containing sulfhydryl groups; upregulation of ubiquinone biosynthesis genes was also detected. Our findings demonstrated that the shortage of isoprenoids is not the main mechanism involved in the respiratory deficit and mitochondrial malfunctioning of MK-defective cells, while the scarcity of ubiquinone plays an important role, as already observed in MKD patients.

Introduction: Flexible intensive care unit (ICU) visiting hours have been proposed as a means to improve patient-centred and family-centred care. However, randomised trials evaluating the effects of flexible family visitation models (FFVMs) are scarce. This study aims to compare the effectiveness and safety of an FFVM versus a restrictive family visitation model (RFVM) on delirium prevention among ICU patients, as well as to analyse its potential effects on family members and ICU professionals., Methods and Analysis: A cluster-randomised crossover trial involving adult ICU patients, family members and ICU professionals will be conducted. Forty medical-surgical Brazilian ICUs with RFVMs (<4.5 hours/day) will be randomly assigned to either an RFVM (visits according to local policies) or an FFVM (visitation during 12 consecutive hours per day) group at a 1:1 ratio. After enrolment and follow-up of 25 patients, each ICU will be switched over to the other visitation model, until 25 more patients per site are enrolled and followed. The primary outcome will be the cumulative incidence of delirium among ICU patients, measured twice a day using the Confusion Assessment Method for the ICU. Secondary outcome measures will include daily hazard of delirium, ventilator-free days, any ICU-acquired infections, ICU length of stay and hospital mortality among the patients; symptoms of anxiety and depression and satisfaction among the family members; and prevalence of burnout symptoms among the ICU professionals. Tertiary outcomes will include need for antipsychotic agents and/or mechanical restraints, coma-free days, unplanned loss of invasive devices and ICU-acquired pneumonia, urinary tract infection or bloodstream infection among the patients; self-perception of involvement in patient care among the family members; and satisfaction among the ICU professionals., Ethics and Dissemination: The study protocol has been approved by the research ethics committee of all participant institutions. We aim to disseminate the findings through conferences and peer-reviewed journals., Trial Registration: NCT02932358., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)