International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Pharmacokinetic and pharmacodynamic considerations of antibiotics and antifungals in liver transplantation recipients.

The liver plays a major role in drug metabolism. Liver transplantation impacts the intrinsic metabolic capability and extrahepatic mechanisms of drug disposition and elimination. Different levels of inflammation and oxidative stress during transplantation, the process of liver regeneration, and the characteristics of the graft alter the amount of functional hepatocytes and activity of liver enzymes. Binding of drugs to plasma proteins is affected by the hyperbilirubinemia status and abnormal synthesis of albumin and alpha-1-acid glycoproteins. Postoperative intensive care complications such as biliary, circulatory, and cardiac also impact drug distribution. Renally eliminated antimicrobials commonly present reduced clearance due to hepatorenal syndrome and the use of nephrotoxic immunosuppressants. In addition, liver transplantation recipients are particularly susceptible to multidrug-resistant infections due to frequent manipulation, multiple hospitalizations, invasive devices, and frequent use of empiric broad-spectrum therapy. The selection of appropriate anti-infective therapy must consider the pathophysiological changes after transplantation that impact the pharmacokinetics and pharmacodynamics of antibiotics and antifungal drugs.

Potential Impact of Chemical Fungicides on the Efficacy of Metarhizium rileyi and the Occurrence of Pandora gammae on Caterpillars in Soybean Crops.

Entomopathogenic fungi may play a crucial role in the regulation of caterpillar populations in soybean crops, either through natural occurrences or applied as mycopesticides. In the present work, we reported the naturally occurring entomopathogenic fungus Pandora gammae attacking the caterpillar Chrysodeixis includens, with infection rates in field trials ran in two consecutive years in the 10-35% range. As many chemicals are potentially harmful to entomopathogenic fungi, this work aimed to investigate the potential impact of two chemical fungicides (azoxystrobin + benzovindiflupyr and trifloxistrobina + prothioconazole) used to control soybean rust (Phakopsora pachyrhizi) on the natural occurrence of P. gammae and Metarhizium rileyi, as well as the efficacy of the latter fungus applied as different formulations against the soybean caterpillars Anticarsia gemmatalis and C. includens. Under laboratory conditions, fungicides used at field-recommended rates had a considerable negative impact on the germinability of M. riley on the medium surface, and all tested formulations did not protect conidia from damage by these chemicals. This harmful effect also impacted host infectivity, as the larval mortality owing to this fungus was reduced by 30-40% compared to that of the fungicide-free treatments. In field trials conducted in two subsequent years, unformulated and formulated M. rileyi conidia applied to soybean plants produced primary infection sites in caterpillar populations after a single spray. Spraying unformulated or formulated M. rileyi conidia following fungicide application on plants did not affect host infection rates over time. Moreover, the use of M. rileyi-based formulations or chemical fungicide did not interfere with the natural infection rates by P. gammae on its host, C. includens. Although a higher degree of exposure to non-selective fungicides can negatively affect fungal entomopathogens, a single foliar application of fungicides may be harmless to both M. rileyi and P. gammae in soybean fields. Additionally, this work showed that naturally occurring wasps and tachnids also play an important role in the regulation of A. gemmatalis and, notably, C. includens, with parasitism rates above 40-50% in some cases.

Reporting of Social Determinants of Health in Pediatric Sepsis Studies.

OBJECTIVE: Standardized, consistent reporting of social determinants of health (SDOH) in studies on children with sepsis would allow for: 1) understanding the association of SDOH with illness severity and outcomes, 2) comparing populations and extrapolating study results, and 3) identification of potentially modifiable socioeconomic factors for policy makers. We, therefore, sought to determine how frequently data on SDOH were reported, which factors were collected and how these factors were defined in studies of sepsis in children. DATA SOURCES AND SELECTION: We reviewed 106 articles (published between 2005 and 2020) utilized in a recent systematic review on physiologic criteria for pediatric sepsis. DATA EXTRACTION: Data were extracted by two reviewers on variables that fell within the World Health Organization's SDOH categories. DATA SYNTHESIS: SDOH were not the primary outcome in any of the included studies. Seventeen percent of articles (18/106) did not report on any SDOH, and a further 36.8% (39/106) only reported on gender/sex. Of the remaining 46.2% of articles, the most reported SDOH categories were preadmission nutritional status (35.8%, 38/106) and race/ethnicity (18.9%, 20/106). However, no two studies used the same definition of the variables reported within each of these categories. Six studies reported on socioeconomic status (3.8%, 6/106), including two from upper-middle-income and four from lower middle-income countries. Only three studies reported on parental education levels (2.8%, 3/106). No study reported on parental job security or structural conflict. CONCLUSIONS: We found overall low reporting of SDOH and marked variability in categorizations and definitions of SDOH variables. Consistent and standardized reporting of SDOH in pediatric sepsis studies is needed to understand the role these factors play in the development and severity of sepsis, to compare and extrapolate study results between settings and to implement policies aimed at improving socioeconomic conditions related to sepsis.

Operationalizing Appropriate Sepsis Definitions in Children Worldwide: Considerations for the Pediatric Sepsis Definition Taskforce.

Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a "Think globally, act locally" approach is required.

Identification of potential biomarkers and survival analysis for oral squamous cell carcinoma: A transcriptomic study.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. The current study aimed to identify potential biomarkers associated with OSCC survival. MATERIALS AND METHODS: Differentially expressed genes (DEGs) in atypical OSCC cases were identified using two public datasets: The Cancer Genome Atlas and the Gene Expression Omnibus database. Receiver operating characteristic (ROC) analysis was performed to identify the cutoff, and the candidate DEGs related to survival. Kaplan-Meier and Cox regression analysis using the categorized genes were employed to identify genes that impact the overall survival in OSCC. RESULTS: A total of 263 OSCC samples and 105 healthy tissues were used to identify 295 upregulated and 131 downregulated genes expressed only in non-smokers. ROC analyses identified 25 candidate genes associated with death. Survival analyses demonstrated that the following DEGs, namely CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5, are potential OSCC prognostic factors. CONCLUSION: We found that CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5 are associated with a low survival rate in OSCC. However, further studies are needed to validate our findings and facilitate the development of these factors as potential biomarkers for OSCC survival.

Diversity of anamorphic Cordyceps (formerly Isaria) isolated from Brazilian agricultural sites.

A total of 53 anamorphic strains of Brazilian Cordyceps species currently maintained in a government-owned culture collection, were reassessed for diversity and species identity using multi-loci-based phylogenetic methods. The strains used in this study were originally obtained from soil samples or were isolated from insects of the orders Hemiptera, Lepidoptera, Coleoptera and Diptera, mostly from agricultural sites. A Bayesian phylogenetic tree was constructed based on a concatenation of five loci (ITS, LSU, RPB1, RPB2 and TEF). In a few cases of ambiguity, morphological traits were also considered for species delimitations. Considerable variability within the set of strains was detected and six Cordyceps species were identified: C. amoenerosea, C. fumosorosea, C. javanica, C. tenuipes and, for the first time, C. brevistroma and C. spegazzinii are reported in Brazil. Four other taxonomically equivocal groups, closely related to other known taxa (C. amoenerosea, C. cateniannulata, C. polyarthra and C. spegazzinii), were also recognized, although further studies will be required to confirm their identifications or their descriptions as new species. Cordyceps javanica was the most common species in our dataset, originally isolated from soil and several different insect orders, and includes 17 strains from the whitefly, Bemisia tabaci. Interestingly, strains previously identified as C. fumosorosea based on morphology and growth characteristics, were shown to be C. javanica, including the active ingredients of some commercial mycoinsecticides. Cordyceps farinosa, usually mentioned in the literature as occurring in Brazil, was not found in our study. Since most strains were from insect crop pests, further studies with hosts from non-agricultural settings or from environmental samples would be advisable for a deeper understanding of the occurrence of anamorphic Cordyceps in Brazil.

Akanthomyces diversity in Brazil and their pathogenicity to plant-sucking insects.

Currently, species within the genus Akanthomyces are poorly studied and explored compared to other hypocrealean entomopathogenic fungi employed as commercial biocontrol agents. This study aimed to molecularly identify 23 Brazilian Akanthomyces strains, most originally isolated from aphids and scales (n = 22), and one from the coffee leaf rust, and further investigate their pathogenicity to six plant-sucking insects as a means to better understand their host spectra. We also explored the capacity of A. muscarius CG935 for blastospore production via liquid fermentation. Akanthomyces dipterigenus, A. muscarius, A. lecanii, and two unidentified species were recognized as naturally occurring in Brazil. Akanthomyces dipterigenus CG829 and A. muscarius CG935 were highly virulent to nymphs of Bemisia tabaci (67.5-85.4% confirmed mortality) and the aphid Aphis fabae (74.6-75.3%), but only the first strain was virulent to the mealybug Planococcus sp. (80.9%). Akanthomyces lecanii CG824 was weakly virulent to all tested insects. None of the strains were pathogenic to the thrips Caliothrips phaseoli, and all strains showed low virulence to the wooly whitefly Aleurothrixus floccosus and the scale Duplachionaspis divergens. Submerged liquid fermentation yields varied from 1.72 × 109 (day 2) to 3.90 × 109 (day 5) blastospores mL-1. Blastospores or aerial conidia from A. muscarius CG935, at a single concentration of 1 × 107 viable propagules mL-1, resulted in 67.5-83.1% mortality of B. tabaci nymphs within 8 days post-treatment. Overall, these results encourage additional studies that could lead to the development of new mycopesticides based on Akanthomyces strains.

Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study.

Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.

Primary lacrimal gland sebaceous carcinoma - case presentation and literature review.

Primary sebaceous carcinoma of the lacrimal gland (PSCLG) is the rarest lacrimal gland (LG) tumor, often belatedly diagnosed, worsening the prognosis. We present a 68-year-old man with a large, indurated mass in the left orbital outer quadrant, visible at the conjunctival upper temporal fornix, extending to the lower fornix, with left gaze restriction. The lesion was not related to the eyelid or other periocular tissues. Excisional biopsy revealed the PSCLG diagnosis. There are only eight others previous PSCLGs. Males are the most affected. Indurated mass in the lacrimal fossa, with eyelid in "S" shape is the most common presentation. Image exams are suggestive, but histological and immunohistochemical evaluations showing a single tumor cell line within LG are mandatory for definitive diagnosis. Larger and more extensive lesions can have a poor prognosis, but early detection can favor the outcome.

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce.

OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract. DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

Latin American Consensus on the Management of Sepsis in Children: Sociedad Latinoamericana de Cuidados Intensivos Pediátricos [Latin American Pediatric Intensive Care Society] (SLACIP) Task Force: Executive Summary.

Objective: The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. Design: A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs, and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish, and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021, the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations, although 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically in Latin American countries. The consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America.

Molecular characterization and sequence analysis of four Brazilian rice stripe necrosis virus isolates.

Rice (Oryza sativa L.) is an important food crop for humanity, being cultivated in tropical and temperate regions of the world. This study reports the nearly complete genome sequences of four Brazilian rice stripe necrosis virus (RSNV) isolates. The nucleotide sequences of the RNA1 and RNA2 genome segments of these Brazilian isolates were 96.5 to 99.9% identical, indicating their close phylogenetic relationship to each other. Phylogeny and recombination analysis indicated that the genome of one of the isolates consisted of RNA segments of different origins, suggesting that a reassortment event had occurred.

Gender-related differences in the modulation of anthropometric, biochemical, and immune markers by physical activity in hypertensive and diabetic individuals.

Systemic arterial hypertension (SAH) and type 2 diabetes mellitus (T2DM) compose the two major noncommunicable chronic inflammatory diseases. Physical activity has been shown as a promising complementary approach to control the systemic inflammation. However, it is still unclear whether this modulation is gender-dependent. The objective of this study was evaluate the gender-related influence of physical activity on the inflammatory response and biochemical profile of individuals with SAH and T2DM. An international physical activity questionnaire was applied to 376 individuals diagnosed with SAH and T2DM in order to access their exercises routine and was evaluated the influence of physical activity in biochemical, anthropometrical, and immunological markers involved in these disorders in men and women. Even though active individuals have exhibited lower serum levels of IL-1ß, IFN-γ, TNF-α, and IL-17A, the ratios between IL-10 and all inflammatory cytokines were higher in men than in women. Physically active individuals also demonstrated increased HDL/LDL and HDL/VLDL ratios. Moreover, multiple correlations revealed that in active women both IL-10 and TNF-α serum levels positively correlate with fasting glucose levels, and were negatively associated with HDL levels. Our findings suggest that gender-related differences dictate a distinct crosstalk between inflammatory and biochemical markers in physically active individuals.

Serotonin activates glycolysis and mitochondria biogenesis in human breast cancer cells through activation of the Jak1/STAT3/ERK1/2 and adenylate cyclase/PKA, respectively.

BACKGROUND: Although produced by several types of tumours, the role of serotonin on cancer biology is yet to be understood. METHODS: The effects of serotonin (5-HT) on human breast cancer cells proliferation, signalling pathways and metabolic profile were evaluated by cytometry, western blotting, qPCR, enzymology and confocal microscopy. RESULTS: Our results revealed that incubation of MCF-7 cells with 10 µM 5-HT increased cell growth rate by 28%, an effect that was prevented by the 5-HTR2A/C antagonist, ketanserin. Conversely, increasing concentrations of 5-HT promoted glucose consumption and lactate production by MCF-7 cells. We also showed that increased glucose metabolism is provoked by the upregulation of pyruvate kinase M2 (PKM2) isoform through 5-HTR2A/C-triggered activation of Jak1/STAT3 and ERK1/2 subcellular pathways. However, we noticed a decrease in the rate of produced lactate per consumed glucose as a function of the hormone concentration, suggesting a disruption of the Warburg effect. The latter effect is due to 5-HTR2A/C-dependent mitochondrial biogenesis and metabolism, which is triggered by adenylyl cyclase/PKA, enhancing the oxidation of lactate within these cells. CONCLUSIONS: We showed that serotonin, through 5-HTR2A/C, interferes with breast cancer cells proliferation and metabolism by triggering two distinct signalling pathways: Jak1/STAT3 that boosts glycolysis through upregulation of PKM2, and adenylyl cyclase/PKA that enhances mitochondrial biogenesis.

COVID-19 PICU guidelines: for high- and limited-resource settings.

BACKGROUND: Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic co-morbidities are likely to develop critical illness. Recently, a multisystem inflammatory syndrome (MIS-C) has been described in children with some of these patients requiring care in the pediatric ICU. METHODS: An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. RESULTS: This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed anti-viral drugs, anti-inflammatory or anti-thrombotic therapies are also described. CONCLUSION: Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing this data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. IMPACT: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2. Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae. These guidelines can be adapted to both high- and limited-resource settings.

Assessment of the diversity of Brazilian entomopathogenic fungi in the genus Beauveria.

We combined matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) along with sequencing of the B locus intergenic region (Bloc) to assess the diversity of Brazilian species within the anamorphic genus Beauveria. A total of 121 strains maintained in a government-owned culture collection and isolated from a range of hosts/substrates over a long time span (1981-2015) were assessed. Strains were collected in five of six Brazilian biomes, mostly in the Atlantic Forest (42.2%) and Cerrado (29.8%), primarily from insect pests of crops. All strains were subjected to MS, and those not accurately identified by this technique were genomically analyzed. Among the outcomes of this study, four taxa from the genus Beauveria were recognized, with the great majority of strains belonging to B. bassiana s.str. (93.4%), followed by B. caledonica (2.5%), B. pseudobassiana (2.5%) and B. amorpha (1.6%). B. bassiana s.str. was found in all biomes and isolated from a wide range of hosts/substrates. Due to low numbers, associations of the remaining Beauveria species with specific hosts or habitats/biomes were not clear, except that all three B. caledonica strains were found only in the Cerrado biome and were associated with adults of the banana weevil, Cosmopolites sordidus (Col.:Curculionidae). B. pseudobassiana is reported for the first time on the South American continent, in a subtropical region and from two insect orders not yet associated with this taxon. We also showed that some strains previously ascribed to B. brongniartii were misidentifications. The biodiversity of Beauveria analyzed in our study was comparatively low. The geographic origins of strains used in our study were biased towards biomes with intense human interventions. Future surveys on more conserved, less environmentally disturbed biomes, such as Caatinga, Pampa, Pantanal, and Amazon are needed for a more comprehensive picture of the diversity of Beauveria and related genera in Brazil.

Trypanosoma cruzi RNA-binding protein ALBA30 aggregates into cytoplasmic foci under nutritional stress.

Trypanosoma cruzi, the causative agent of Chagas disease, has a complex life cycle that requires the adaptation to different environments. In the absence of traditional mechanisms for regulation of gene expression, this parasite relies on posttranscriptional control events, which allow the progression of its life cycle in different hosts and stress conditions. In this context, different stress conditions trigger the aggregation of RNA-binding proteins and their target mRNAs into cytoplasmic foci known as RNA granules, which act as RNA-sorting centers. In this study, we have characterized the T. cruzi RNA-binding protein ALBA30 during nutritional stress conditions. Using a recombinant form of TcALBA30 to facilitate its detection (rTcALBA30), we showed that this protein resides in the cytoplasm in normal growth conditions but is recruited into cytoplasmic foci after starvation. Moreover, evaluation of rTcALBA30 in parasites that reached the stationary phase of growth also showed the recruitment of this protein into cytoplasmic foci. Our results indicate that, similar to TbALBA3, TcALBA30 aggregates into stress granules in parasites submitted to nutritional stress.

Seroprevalence of SARS-CoV-2 IgM and IgG antibodies in an asymptomatic population in Sergipe, Brazil.

OBJECTIVE: To estimate the prevalence of SARS-CoV-2 antibodies in an asymptomatic population in the state of Sergipe, Brazil.
. METHODS: This cross-sectional study with stratified sampling (sex and age) included serological immunofluorescent tests for IgM and IgG on samples from 3 046 asymptomatic individuals. Sample collection was performed in wet-markets of the 10 most populous cities of Sergipe, Brazil. Exclusion criteria included symptomatic individuals and health workers. The presence of comorbidities was registered.
. RESULTS: Of the 3 046 participants, 1 577 (51.8%) were female and 1 469 (48.2%) were male; the mean age was 39.76 (SD 16.83) years old. 2 921 tests were considered valid for IgM and 2 635 for IgG. Of the valid samples, 347 (11.9% [CI 10.7%-13.1%]) tested positive for IgM and 218 (8.3% [CI 7.2%-9.4%]) tested positive for IgG. Women over 40 had the highest prevalence for IgM (group C, p=0.006; group D p=0.04). The capital Aracaju displayed the highest prevalence for both antibodies; 83 (26.3% [CI 21.6%-31.6%]) tested positive for IgM and 35 (14.6% [CI 10.4%-19.7%]) for IgG. The most prevalent comorbidities were hypertension (64/123 individuals) and diabetes (29/123).
. CONCLUSIONS: A high prevalence of SARS-CoV-2 antibodies was found among asymptomatic persons in Sergipe. Women over 40 showed the highest rates. The capital, Aracaju, displayed the highest seroprevalence. Surveys like this one are important to understand how the virus spreads and to help authorities to plan measures to control it. Repeated serologic testing are required to track the progress of the epidemic.

OBJETIVO: estimar la prevalencia de anticuerpos dirigidos contra el SARS-CoV-2 en una población asintomática del estado de Sergipe, Brasil. MÉTODOS: estudio transversal con muestreo estratificado (por sexo y edad) que incluyó pruebas serológicas de inmunofluorescencia para IgM e IgG en muestras de 3 046 individuos asintomáticos. La recolección de muestras se realizó en los mercados húmedos de las 10 ciudades más pobladas de Sergipe, Brasil. Se excluyó a los individuos sintomáticos y a los trabajadores de la salud. Se registró la presencia de comorbilidades. RESULTADOS: De los 3 046 participantes, 1 577 (51,8%) eran mujeres y 1 469 (48,2%) varones; la edad promedio fue de 39,76 (SD 16,83) años. Se consideraron válidas 2 921 pruebas para la IgM y 2 635 para la IgG. De las muestras válidas, 347 (11,9% [CI 10,7%-13,1%]) resultaron positivas para IgM y 218 (8,3% [CI 7,2%-9,4%]) para IgG. Las mujeres mayores de 40 años tuvieron la mayor prevalencia de IgM (grupo C, p=0,006; grupo D, p=0,04). Aracaju, la capital del estado, mostró la mayor prevalencia para ambos anticuerpos; 83 (26,3% [CI 21,6%-31,6%]) resultaron positivas para IgM y 35 (14,6% [CI 10,4%-19,7%]) para IgG. Las comorbilidades más frecuentes fueron la hipertensión (64/123 individuos) y la diabetes (29/123). CONCLUSIONES: Se encontró una alta prevalencia de anticuerpos contra el SARS-CoV-2 en personas asintomáticas en Sergipe. Las mujeres mayores de 40 años mostraron las tasas más altas. La capital, Aracaju, mostró la mayor seroprevalencia. Las encuestas como esta son importantes para comprender cómo se propaga el virus y para ayudar a las autoridades a planificar medidas de control. Se requieren pruebas serológicas repetidas para dar seguimento al progreso de la epidemia.