De novo design of potent and selective mimics of IL-2 and IL-15.

We describe a de novo computational approach for designing proteins that recapitulate the binding sites of natural cytokines, but are otherwise unrelated in topology or amino acid sequence. We use this strategy to design mimics of the central immune cytokine interleukin-2 (IL-2) that bind to the IL-2 receptor ßγc heterodimer (IL-2Rßγc) but have no binding site for IL-2Rα (also called CD25) or IL-15Rα (also known as CD215). The designs are hyper-stable, bind human and mouse IL-2Rßγc with higher affinity than the natural cytokines, and elicit downstream cell signalling independently of IL-2Rα and IL-15Rα. Crystal structures of the optimized design neoleukin-2/15 (Neo-2/15), both alone and in complex with IL-2Rßγc, are very similar to the designed model. Neo-2/15 has superior therapeutic activity to IL-2 in mouse models of melanoma and colon cancer, with reduced toxicity and undetectable immunogenicity. Our strategy for building hyper-stable de novo mimetics could be applied generally to signalling proteins, enabling the creation of superior therapeutic candidates.

De Novo Human Angiotensin-Converting Enzyme 2 Decoy NL-CVX1 Protects Mice From Severe Disease After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections.

Non-natural MUC1 Glycopeptide Homogeneous Cancer Vaccine with Enhanced Immunogenicity and Therapeutic Activity.

Glycopeptides derived from the glycoprotein mucin-1 (MUC1) have shown potential as tumor-associated antigens for cancer vaccine development. However, their low immunogenicity and non-selective conjugation to carriers present significant challenges for the clinical efficacy of MUC1-based vaccines. Here, we introduce a novel vaccine candidate based on a structure-guided design of an artificial antigen derived from MUC1 glycopeptide. This engineered antigen contains two non-natural amino acids and has an α-S-glycosidic bond, where sulfur replaces the conventional oxygen atom linking the peptide backbone to the sugar N-acetylgalactosamine. The glycopeptide is then specifically conjugated to the immunogenic protein carrier CRM197 (Cross-Reactive Material 197), a protein approved for human use. Conjugation involves selective reduction and re-bridging of a disulfide in CRM197, allowing the attachment of a single copy of MUC1. This strategy results in a chemically defined vaccine while maintaining both the structural integrity and immunogenicity of the protein carrier. The vaccine elicits a robust Th1-like immune response in mice and generates antibodies capable of recognizing human cancer cells expressing tumor-associated MUC1. When tested in mouse models of colon adenocarcinoma and pancreatic cancer, the vaccine is effective both as a prophylactic and therapeutic use, significantly delaying tumor growth. In therapeutic applications, improved outcomes were….

Mental Health and Emotional Disorders During the COVID-19 Pandemics: Prevalence and Extent in PICU Staff.

OBJECTIVES: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p < 0.001), and depression symptoms (32.5% vs 15%; p < 0.001), with superior PCL-5 scores for PTSD ( p < 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p < 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p < 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.

Sleep in multiple sclerosis and neuromyelitis optica spectrum disorder-the SEMN study.

PURPOSE: This study aimed to (1) evaluate in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) the presence of sleep disorders such as hypersomnia, fatigue, risk of apnea, and the presence of restless legs syndrome/Willis-Ekbom disease (RLS/WED); (2) evaluate quality of sleep in patients with MS and NMOSD; and (3) correlate them with clinical and imaging data. METHODS: The study was cross-sectional and was carried out in the sector of demyelinating diseases of the neurology service of HUGV-UFAM, Manaus, Brazil, from January 2017 to December 2020. RESULTS: Our sample consisted of 60 patients, 41 with MS and 19 with NMOSD. We found that patients with MS and NMOSD have poor sleep quality (65%) and hypersomnia (53% in MS; 47% in NMOSD), but low risk of apnea by STOP-BANG. The frequency of RLS/WE found was 14% in MS, and 5% in NMOSD. No correlation existed between sleep quality, number of relapses, and sleep quality for the Expanded Disability Status Scale (EDSS), i.e., fatigue/illness duration. CONCLUSION: Patients with MS and NMOSD have poor sleep quality, excessive sleepiness, and are at low risk for OSA, yet the frequency of RLS/WED is like that of the general population. There does not seem to be a significant difference between these sleep disorders in these demyelinating diseases of the CNS.

The neurotoxic mechanism of Jack Bean Urease in insects involves the interplay between octopaminergic and dopaminergic pathways.

In the last decades, the entomotoxicity of JBU and its derived peptides became an object of study, due mainly to the ubiquitous interaction of these compounds with different species of insects and their potential as natural insecticides. In this work, we investigated the neurotoxic effects of JBU in Nauphoeta cinerea cockroaches by dissecting pharmacologically the monoaminergic pathways involved. Selective pharmacological modulators for monoaminergic pathways in in vivo and ex vivo experimental models were employed. Thus, the analysis of N. cinerea neurolocomotory behavior demonstrated that JBU (1.5 and 3 µg/g) induces a significant decrease in the exploratory activity. In these assays, pretreatment of animals with phentolamine, SCH23390 or reserpine, interfered significantly with the response of JBU. Using in vivo abductor metathoracic preparations JBU (1.5 µg/g) induced progressive neuromuscular blockade, in 120 min recordings. In this set of experiments, the previous treatment of the animals with phentolamine, SCH23390 or reserpine, completely inhibited JBU-induced neuromuscular blockade. The recordings of spontaneous compound neural action potentials in N. cinerea legs showed that JBU, only in the smallest dose, significantly decreased the number of potentials in 60 min recordings. When the animals were pretreated with phentolamine, SCH23390, or reserpine, but not with mianserin, there was a significant prevention of the JBU-inhibitory responses on the action potentials firing. Meanwhile, the treatment of the animals with mianserin did not affect JBU's inhibitory activity. The data presented in this work strongly suggest that the neurotoxic response of JBU in N. cinerea involves a cross talking between OCTOPAMIN-ergic and DOPAMIN-ergic nerve systems, but not the SEROTONIN-ergic neurotransmission. Further molecular biology studies with expression of insect receptors associated with voltage clamp techniques will help to discriminate the selectivity of JBU over the monoaminergic transmission.

Health education provided by nurses to children and young people: parents' assessment.

BACKGROUND: Healthy literacy is a determinant key children/teenager's health and health outcomes. The aim of this study to identify the parents' assessment about Health Education practice to children and teenagers. METHODS: We opted for a descriptive, quantitative and cross-sectional research, with a non-probabilistic convenience sample. The inclusion criteria were: being a parent who uses attending children health appointments in primary health care; being a parent who has a child hospitalized and is accompanying him/her in the pediatric hospital inpatient ward. A questionnaire survey was built with three sections: sample characterization, Health Education practices performed by nurses (5 questions) and a scale that measured Health Education Assessment Scale (HEAS), which contained 48 items and was validated. It was applied from September to December 2018. RESULTS: The survey was filled in by 113 parents. The results showed that 100% (n = 113) of the parents feel comfortable to talk with nurses about children/teenagers health; 79.6% (n = 90) consider that nurses have time availability for the doubts clarification; 61.9% (n = 70) point out that nurses identify child/teenager needs; Healthy eating" (60.2%; n = 68), the "National Vaccination Plan" (53.1%; n = 60) and "Harmful behaviors prevention" (46.9%; n = 53) are the most important topics; 56.6% (n = 64) of the parents, when in doubt, turn first to the pediatrician, and 66.4% (n = 75) considered that this practice was equal important, compared with other nursing interventions. DISCUSSION: This study shows that Health Education provided by nurses is based on the need's identification, with a perspective of involvement and participation, promoting health and conscious changes which reinforces the nurses' position as health educators.

The role of the perioperative prone position in the low recurrence of pressure injuries in the pelvic region.

OBJECTIVE: A pressure injury (PI) is a localised area of damage to the skin and/or underlying soft tissue as a result of a sustained mechanical loading. There are three key aetiological mechanisms to PI formation-direct cell deformation, inflammatory oedema and ischaemic damage-which are typically activated sequentially to drive a spiral of injury. This article discusses the role of the perioperative prone position as a rational approach to reducing the recurrence of pelvic PI after reconstructive surgery. METHOD: Patients with deep PI in the pelvic region, who were operated on from 2011 to 2019, were retrospectively evaluated. The protocol of care included training in the prone position, followed by maintenance of the prone position for 4-6 weeks postoperatively. The reconstruction was performed with fasciocutaneous and myocutaneous local or regional flaps. RESULTS: The study evaluated a total of 26 patients. The rate of recurrence of PIs was 15.4% (4/26) in the mean follow-up of 54 months. Regarding postoperative complications, four cases of partial dehiscence of the suture occurred. CONCLUSION: This perioperative protocol of maintaining a prone position seems to be safe for the patient, and it can be used to prevent or reduce the recurrence of deep PIs on the pelvic region after reconstructive surgery.

Social Fear in US Infants: The Roles of Hair and Salivary Cortisol.

Elevated social fear in infancy poses risk for later social maladjustment and psychopathology. Hair cortisol concentration (HCC), an index of cumulative cortisol exposure, and diurnal salivary cortisol slope, a biomarker of acute stress regulation, have been associated with social fear behaviors in childhood; however, no research has addressed their relations in infancy. Elucidating potential biomarkers of infant social fear behaviors, as well as environmental factors associated with these biomarkers, may grant insights into the ontogeny of fear behaviors that increase risk for internalizing and externalizing psychopathologies later in life. The current study used multiple linear regression to examine if infant HCC, infant diurnal cortisol slope, and income-to-needs ratios (ITN) were differentially associated with observed social fear responses to a Stranger Approach task at 12 months. Using a sample of 90 infants (Mage = 12.26m, SD = 0.81m, 50% female), results indicated that increased infant HCC was associated with increased distress vocalizations during the Stranger Approach task, while steeper diurnal cortisol slope was associated with fewer distress vocalizations. Ordinary least squares path analyses did not reveal group differences between economically strained and non-strained infants in how cortisol measures and social fear responses related. Findings underscore very early psychobiological correlates of fearfulness that may increase risk for fear-related disorders and adverse mental health symptomology across childhood.

Quantum Information of the Aharanov-Bohm Ring with Yukawa Interaction in the Presence of Disclination.

We investigate quantum information by a theoretical measurement approach of an Aharanov-Bohm (AB) ring with Yukawa interaction in curved space with disclination. We obtained the so-called Shannon entropy through the eigenfunctions of the system. The quantum states considered come from Schrödinger theory with the AB field in the background of curved space. With this entropy, we can explore the quantum information at the position space and reciprocal space. Furthermore, we discussed how the magnetic field, the AB flux, and the topological defect influence the quantum states and the information entropy.

Cannabidiol for Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: REM sleep behaviour disorder (RBD) is a common non-motor feature of Parkinson's disease (PD). Cannabidiol (CBD) is one of the main non-psychoactive components of Cannabis sativa and may represent an alternative route for treating RBD. OBJECTIVE: This study assessed the efficacy and safety of CBD for RBD in PD. METHODS: We conducted a phase II/III, double-blind, placebo-controlled clinical trial in 33 patients with RBD and PD. Patients were randomized 1:1 to CBD in doses of 75 to 300mg or matched capsules placebo and were followed up for 14 weeks. The primary outcomes were the frequency of nights with RBD, CGI-I, and CGI-S. RESULTS: CBD showed no difference to placebo for primary outcomes. Regarding secondary outcomes, we observed a significant improvement in average sleep satisfaction from the 4th to 8th week in the CBD versus placebo group with P = 0.049 and P = 0.038, respectively. CONCLUSION: CBD, as an adjunct therapy, showed no reduction in RBD manifestations in PD patients. A transient improvement in sleep satisfaction with a dose of 300mg has been noted. © 2021 International Parkinson and Movement Disorder Society.

Prevalence of childhood anaemia in Brazil: still a serious health problem: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of anaemia in Brazilian children up to 83·9 months old. DESIGN: Systematic review and meta-analysis, using databases PubMed, Scopus, SciELO, Lilacs, Google Scholar, Periódicos Capes, Arca, Biblioteca Virtual em Saúde, Microsoft Academic Search and Cochrane Library using search terms: anaemia, prevalence, child and Brazil. PROSPERO Registration number: CRD42020208818. SETTING: Cross-sectional, cohort, case-control and intervention studies published between 2007 and 2020 were searched, excluding those who assessed children with an illness or chronic condition. The main outcome was anaemia prevalence. Random effects models based on the inverse variance method were used to estimate pooled prevalence measures. Sensitivity analyses removed studies with high contribution to overall heterogeneity. PARTICIPANTS: From 6790 first screened, 134 eligible studies were included, totalling 46 978 children aged zero to 83·9 months analysed, with adequate regions representativeness. RESULTS: Pooled prevalence of anaemia was 33 % (95 % CI 30, 35). Sensitivity analyses showed that withdrawal of studies that contributed to high heterogeneity did not influence national average prevalence. CONCLUSIONS: Childhood anaemia is still a serious public health problem in Brazil, exposing 33 % of Brazilian children to the anaemia repercussions. The main limitation of the study is the estimation of national prevalence based on local surveys, but a large number of studies were included, with representation in all regions of the country, giving strength to the results. In Brazil, more public policies are needed to promote supplementation, fortification and access to healthy eating to reduce the high level of anaemia among children.

Do the new triatomine species pose new challenges or strategies for monitoring Chagas disease? An overview from 1979-2021.

Chagas disease persists as one of the most important, and yet most neglected, diseases in the world, and several changes in its epidemiological aspects have been recorded since its discovery. Currently, some of the most relevant changes are related to: (i) the reduction in the incidence of the endemic due to the control of the most important vectors, Triatoma infestans and Rhodnius prolixus, in many countries; (ii) the migration of human populations spreading cases of the disease throughout the world, from endemic to non-endemic areas, transforming Chagas disease into a global threat; and (iii) new acute cases and deaths caused by oral transmission, especially in the north of Brazil. Despite the reduction in the number of cases, new challenges need to be responded to, including monitoring and control activities aiming to prevent house infestation by the secondary vectors from occurring. In 1979, Lent & Wygodzinsky(1) published the most complete review of the subfamily Triatominae, encompassing 111 recognised species in the taxon. Forty-two years later, 46 new species and one subspecies have been described or revalidated. Here we summarise the new species and contextualise them regarding their ecology, epidemiologic importance, and the obstacles they pose to the control of Chagas disease around the world.

Optical Camera Communication as an Enabling Technology for Microalgae Cultivation.

Optical Camera Communication (OCC) systems have a potential application in microalgae production plants. In this work, a proof-of-concept prototype consisting of an artificial lighting photobioreactor is proposed. This reactor optimises the culture's photosynthetic efficiency while transmitting on-off keying signals to a rolling-shutter camera. Upon reception, both signal decoding and biomass concentration sensing are performed simultaneously using image processing techniques. Moreover, the communication channel's theoretical modelling, the data rate system's performance, and the plant distribution requirements and restrictions for a production-scale facility are detailed. A case study is conducted to classify three different node arrangements in a real facility, considering node visibility, channel capacity, and space exploitation. Finally, several experiments comprising radiance evaluation and Signal-to-Noise Ratio (SNR) computation are performed at different angles of view in both indoor and outdoor environments. It is observed that the Lambertian-like emission patterns are affected by increasing concentrations, reducing the effective emission angles. Furthermore, significant differences in the SNR, up to 20 dB, perceived along the illuminated surface (centre versus border), gradually reduce as light is affected by greater dispersion. The experimental analysis in terms of scattering and selective wavelength attenuation for green (Arthrospira platensis) and brown (Rhodosorus marinus) microalgae species determines that the selected strain must be considered in the development of this system.

Parascapular Sub-Iliocostalis Plane Block: Comparative Description of a Novel Technique for Posterior Rib Fractures.

We describe a new analgesic technique, parascapular sub-iliocostalis plane block (PSIP), for lateral-posterior rib fractures as an alternative to other regional techniques in a high-risk patient who suffered a decompensation of her cardiorespiratory function after posterior chest trauma. We performed a continuous ultrasound-guided left PSIP block in the sub-iliocostalis plane next to the fourth rib to optimize analgesia and minimize complications. The patient had total pain relief with marked improvement in her cardiorespiratory condition. No complications were reported. The efficacy of the PSIP block may potentially depend on different mechanisms of action: (1) direct action in the fracture site by craniocaudal myofascial spread underneath the erector spinae muscle (ESM); (2) spread to deep layers through tissue disruption caused by trauma, to reach the proximal intercostal nerves; (3) further medial spread through deeper layers to the midline to block the posterior and ventral spinal nerves; (4) medial spread below the ESM, to reach the posterior spinal nerves (more reliably than rhomboid intercostal / sub-serratus [RISS] block); and (5) lateral spread in the sub-serratus (SS) plane to reach the lateral cutaneous branches of the intercostal nerves; while avoiding significant negative hemodynamic effects associated with techniques such as the paravertebral block (PVB), erector spinae plane (ESP) block or its variations, or thoracic epidural analgesia (TEA). A comparative comprehensive overview of the regional techniques described for posterior chest trauma is presented, including TEA, PVB, ESP block, retrolaminar block, mid-point to transverse process block, costotransverse foramen block, RISS, and serratus anterior plane (SAP) block.

Professional football in times of COVID-19: did the home advantage effect disappear in European domestic leagues?

This study aimed to examine how the home advantage (HA) and home teams' performances changed in European football leagues (German Bundesliga, Spanish La Liga, English Premier League, Portuguese Primeira Liga and Italian Serie A) with the measures imposed by legal authorities to deal with the COVID-19 pandemic (no audience, five substitutions and "cooling breaks"). The HA (Pollard's rescaled method) and home performance-related statistics of matches contested before (n = 491) and after (n = 491) the 2019-2020 season break were calculated and compared, for each league and for all five, using the paired t-test or the Wilcoxon signed-rank test. Overall, the HA did not significantly decrease in European leagues (from 16.4% to 11.6%; trivial effect size [ES]); however, a one-sample t-test revealed that the HA after the COVID-19 break was significantly greater than 0% (small ES). While the HA completely disappeared in the Bundesliga (large ES), its effects remained stable in La Liga (small ES), Premier League and Primeira Liga (trivial ES), and even increased in Serie A (medium ES) after the return. Home teams' performances in these leagues were influenced to different extents by the COVID-19 situation, especially by playing behind closed doors. Altogether, significant decreases were observed for total shots, tackles (medium ES), shots on target and pass success (small ES). Therefore, the role of crowd support seems to vary depending on the context characteristics in which football is played. Also, the augmented "information transfer" from coaches to players during COVID-19 matches might have masked the crowd effects on the HA.

Chronic Insomnia in Patients With Parkinson Disease: Which Associated Factors Are Relevant?

BACKGROUND: Insomnia complaints are frequent in Parkinson disease (PD), affecting up to 55% of patients. Factors related to insomnia in PD are multifactorial and may be associated with the degenerative process of the disease, comorbidities related to aging, and medication use. The aim of this study is to determine the factors associated with the presence of chronic insomnia in patients with PD. METHOD: A cross-sectional study was performed involving 63 consecutive patients with PD from an outpatient clinic. Participants underwent clinical interviews with neurologists and a psychiatrist and were assessed with standardized scales (Epworth Sleepiness Scale, Parkinson's Disease Questionnaire, Pittsburgh Sleep Quality Index and, for individuals with a diagnosis of restless legs syndrome(RLS)/Willis-Ekbom disease (WED), the International RLS/WED grading scale) and video-polysomnography. RESULTS: The main factors associated with chronic insomnia in PD were the habit of staying in bed without sleeping, large rapid eye movement (REM) sleep latency, high Pittsburgh Sleep Quality Index scores, and absence of obstructive sleep apnea (OSA). CONCLUSION: Insomnia in PD is related to specific factors including inadequate sleep habits, REM sleep latency, absence of OSA, and quality of sleep.

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity.

The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

The Impact of the Novel Coronavirus on Brazilian PICUs.

OBJECTIVES: To study the impact of the coronavirus disease 2019 pandemic, considering the physical distancing and schools closing, on the characteristics of admission and epidemiology on Brazilian PICUs. DESIGN: Observational, multicenter, time series analysis, of electronic medical records from 15 PICU in Brazil. Data consisted of all March, April, and May PICU admissions from 2017 to 2020. SETTING: Fifteen private PICUs in Brazil. PATIENTS: Pediatric patients admitted to the PICU from March to May since 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The period from March 11, 2020, to March 17, 2020, was considered the "intervention point" studied, corresponding to the suspension of school activities and the beginning of physical distancing in Brazil. During the pandemic period studied, there were 28 cases of coronavirus disease 2019 (one death). The mean age was higher (p = 0.000), the length of stay was shorter (p = 0.000), but mortality rates were similar among the periods (p = 0.36). The model estimated a reduction of 1,483 PICU admissions from March 2020 to May 2020. At the end of May, there was an estimated drop of -146.6 bronchiolitis admissions (95% CI, -242.8 to -50.3; p = 0.016); -71 asthma admissions (95% CI, -93.6 to -48.63; p = 0.000); and -59 community-acquired pneumonia admissions (95% CI, -74.7 to -43.3; p = 0.000) per period. The model showed no effect of the "intervention" (physical distancing) on hospitalization rates for epilepsy, diarrhea, sepsis, bacterial meningitis, or surgery when analyzed individually. When assessed together, the model estimated a reduction of 73.6 admissions (95% IC, -132 to -15.2; p = 0.43). CONCLUSIONS: The coronavirus disease 2019 pandemic strongly affected Brazilian PICUs, reducing admissions, length of stay, and the epidemiological profile. The measures to oppose the coronavirus disease 2019 pandemic may have prevented thousands of PICU hospitalizations across the country.

Exploring the Microalga Euglena cantabrica by Pressurized Liquid Extraction to Obtain Bioactive Compounds.

In the present study, the chemical composition of the microalga Euglena cantabrica was investigated. The extraction of bioactive compounds was done using pressurized liquid extraction (PLE) at different temperatures (40-180 °C) and using green solvents (ethanol-water mixtures). A statistical design of experiments was used to optimize the maximum antioxidant capacity of the extracts by response surface methodology. The antioxidant capacity was determined through the inhibition of 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, while the chemical analyses of the extracts were carried out using different chromatographic techniques. Chlorophylls and carotenoids were analyzed by high-performance liquid chromatography coupled to a diode array detector and mass spectrometry (HPLC-DAD-MS/MS) and carbohydrates by gas chromatography with flame ionization detection (GC-FID) and high-pressure size-exclusion chromatography coupled to an evaporative light-scattering detector (HPSEC-ELSD). The results showed different possibilities for the extraction conditions, depending on the desired bioactivity or chemical composition. Briefly, (i) mixtures of ethanol-water containing around 40% ethanol at 180 °C gave the best antioxidant capacity, (ii) mixtures containing around 50% ethanol at 110 °C gave the best yield of ß-glucan paramylon, and (iii) the use of pure ethanol at a low temperature (40 °C) is the best choice for the recovery of carotenoids such as diatoxanthin. Summing up, E. cantabrica seems to be a good candidate to be used in biorefinery to obtain different bioactive compounds.