Spencermartinsiella nicolii sp. nov., a potential opportunistic pathogenic yeast species isolated from rotting wood in Brazil.

Nineteen isolates representing a candidate for a novel yeast species belonging to the genus Spencermartinsiella were recovered from rotting wood samples collected at different sites in Atlantic Rainforest and Amazonian Forest ecosystems in Brazil. Similarity search of the nucleotide sequence of the intergenic spacer (ITS)-5.8S and large subunit D1/D2 regions of the ribosomal gene cluster showed that this novel yeast is closely related to Spencermartinsiella cellulosicola. The isolates differ by four nucleotide substitutions in the D1/D2 domain and six substitutions and 31 indels in the ITS region from the holotype of S. cellulosicola. Phylogenomic analysis based on 1474 single-copy orthologues for a set of Spencermartinsiella species whose whole genome sequences are available confirmed that the novel species is phylogenetically close to S. cellulosicola. The low average nucleotide identity value of 83% observed between S. cellulosicola and the candidate species confirms that they are distinct. The novel species produced asci with hemispherical ascospores. The name Spencermartinsiella nicolii sp. nov. is proposed. The holotype is CBS 14238T. The MycoBank number is MB855027. Interestingly, the D1/D2 sequence of the S. nicolii was identical to that of an uncultured strain of Spencermartinsiella causing systemic infection in a male adult crocodile (Crocodylus niloticus). The characterization of some virulence factors and antifungal susceptibility of S. nicolii isolates suggest that this yeast may be an opportunistic pathogen for animals, including humans; the isolates grow at 37 °C.

Quality improvement programmes in paediatric sepsis from a global perspective.

Sepsis is a major contributor to poor child health outcomes around the world. The high morbidity, mortality, and societal cost associated with paediatric sepsis render it a global health priority, as summarised in Paper 1 of this Series. Sepsis is characterised by a dysregulated host response to infection that manifests as organ failure, and children are uniquely susceptible to sepsis, as discussed in Paper 2. The focus of this third Series paper is quality improvement in paediatric sepsis. The 2017 WHO resolution on sepsis outlined key aims to reduce the burden of sepsis. As of 2024, only a small number of countries have implemented systematic, paediatric-focused quality improvement programmes to raise sepsis awareness, enhance recognition of sepsis, promote timely treatment, and provide long-term support for paediatric sepsis survivors. We examine programme successes and systematic barriers to quality improvement targeting paediatric sepsis. We highlight the need for programme design to consider the entire patient journey, starting with prevention, caregiver awareness, recognition at home, education of the health-care workforce, development of health-care systems, and establishment of long-term family and survivor support extending beyond the intensive care unit. Building on lessons learnt from existing quality improvement programmes, we outline implementation strategies and measures to enable benchmarking. Ultimately, quality improvement on a global scale can only be accelerated through a global learning platform focusing on paediatric sepsis.

DNA lesions that block transcription induce the death of Trypanosoma cruzi via ATR activation, which is dependent on the presence of R-loops.

Trypanosoma cruzi is the etiological agent of Chagas disease and a peculiar eukaryote with unique biological characteristics. DNA damage can block RNA polymerase, activating transcription-coupled nucleotide excision repair (TC-NER), a DNA repair pathway specialized in lesions that compromise transcription. If transcriptional stress is unresolved, arrested RNA polymerase can activate programmed cell death. Nonetheless, how this parasite modulates these processes is unknown. Here, we demonstrate that T. cruzi cell death after UV irradiation, a genotoxic agent that generates lesions resolved by TC-NER, depends on active transcription and is signaled mainly by an apoptotic-like pathway. Pre-treated parasites with α-amanitin, a selective RNA polymerase II inhibitor, become resistant to such cell death. Similarly, the gamma pre-irradiated cells are more resistant to UV when the transcription processes are absent. The Cockayne Syndrome B protein (CSB) recognizes blocked RNA polymerase and can initiate TC-NER. Curiously, CSB overexpression increases parasites' cell death shortly after UV exposure. On the other hand, at the same time after irradiation, the single-knockout CSB cells show resistance to the same treatment. UV-induced fast death is signalized by the exposition of phosphatidylserine to the outer layer of the membrane, indicating a cell death mainly by an apoptotic-like pathway. Furthermore, such death is suppressed in WT parasites pre-treated with inhibitors of ataxia telangiectasia and Rad3-related (ATR), a key DDR kinase. Signaling for UV radiation death may be related to R-loops since the overexpression of genes associated with the resolution of these structures suppress it. Together, results suggest that transcription blockage triggered by UV radiation activates an ATR-dependent apoptosis-like mechanism in T. cruzi, with the participation of CSB protein in this process.

Fluid accumulation in critically ill children: a systematic review and meta-analysis.

Background: Fluids are often administered for various purposes, such as resuscitation, replacement, maintenance, nutrition, or drug infusion. However, its use is not without risks. Critically ill patients are highly susceptible to fluid accumulation (FA), which is associated with poor outcomes, including organ dysfunction, prolonged mechanical ventilation, extended hospital stays, and increased mortality. This study aimed to assess the association between FA and poor outcomes in critically ill children. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases from inception to May 2024. Relevant publications were searched using the following terms: child, children, infant, infants, pediatric, pediatrics, critically ill children, critical illness, critical care, intensive care, pediatric intensive care, pediatric intensive care unit, fluid balance, fluid overload, fluid accumulation, fluid therapy, edema, respiratory failure, respiratory insufficiency, pulmonary edema, mechanical ventilation, hemodynamic instability, shock, sepsis, acute renal failure, acute kidney failure, acute kidney injury, renal replacement therapy, dialysis, mortality. Paediatric studies were considered eligible if they assessed the effect of FA on the outcomes of interest. The main outcome was all-cause mortality. Pooled analyses were performed by using random-effects models. This review was registered on PROSPERO (CRD42023432879). Findings: A total of 120 studies (44,682 children) were included. Thirty-five FA definitions were identified. In general, FA was significantly associated with increased mortality (odds ratio [OR] 4.36; 95% confidence interval [CI] 3.53-5.38), acute kidney injury (OR 1.98; 95% CI 1.60-2.44), prolonged mechanical ventilation (weighted mean difference [WMD] 38.1 h, 95% CI 19.35-56.84), and longer stay in the intensive care unit (WMD 2.29 days; 95% CI 1.19-3.38). The percentage of FA was lower in survivors when compared to non-survivors (WMD -4.95 [95% CI, -6.03 to -3.87]). When considering only studies that controlled for potential confounding variables, the pooled analysis revealed 6% increased odds of mortality associated with each 1% increase in the percentage of FA (adjusted OR = 1.06 [95% CI, 1.04-1.09). Interpretation: FA is significantly associated with poorer outcomes in critically ill children. Thus, clinicians should closely monitor fluid balance, especially when new-onset or worsening organ dysfunction occurs in oedematous patients, indicating potential FA syndrome. Future research should explore interventions like restrictive fluid therapy or de-resuscitation methods. Meanwhile, preventive measures should be prioritized to mitigate FA until further evidence is available. Funding: None.

A novel post-1950 CE atmospheric 14C record for the tropics using absolutely dated tree rings in the equatorial Amazon.

In this study, we present a comprehensive atmospheric radiocarbon (14C) record spanning from 1940 to 2016, derived from 77 single tree rings of Cedrela odorata located in the Eastern Amazon Basin (EAB). This record, comprising 175 high-precision 14C measurements obtained through accelerator mass spectrometry (AMS), offers a detailed chronology of post-1950 CE (Common Era) 14C fluctuations in the Tropical Low-Pressure Belt (TLPB). To ensure accuracy and reliability, we included 14C-AMS results from intra-annual successive cuts of the tree rings associated to the calendar years 1962 and 1963 and conducted interlaboratory comparisons. In addition, 14C concentrations in 1962 and 1963 single-year cuts also allowed to verify tissue growth seasonality. The strategic location of the tree, just above the Amazon River and estuary areas, prevented the influence of local fossil-CO2 emissions from mining and trade activities in the Central Amazon Basin on the 14C record. Our findings reveal a notable increase in 14C from land-respired CO2 starting in the 1970s, a decade earlier than previously predicted, followed by a slight decrease after 2000, signaling a transition towards the fossil fuel era. This shift is likely attributed to changes in reservoir sources or global atmospheric dynamics. The EAB 14C record, when compared with a shorter record from Muna Island, Indonesia, highlights regional differences and contributes to a more nuanced understanding of global 14C variations at low latitudes. This study not only fills critical spatial gaps in existing 14C compilations but also aids in refining the demarcation of 14C variations over South America. The extended tree-ring 14C record from the EAB is pivotal for reevaluating global patterns, particularly in the context of the current global carbon budget, and underscores the importance of tropical regions in understanding carbon-climate feedbacks.

Distinct roles of the left and right prelimbic cortices in the modulation of ethanol consumption in male mice under acute and chronic social defeat stress.

RATIONALE: Chronic stress exposure disrupts the medial prefrontal cortex's (mPFC) ability to regulate impulses, leading to the loss of control over alcohol drinking in rodents, emphasizing the critical role of this forebrain area in regulating alcohol consumption. Moreover, chronic stress exposure causes lateralization of mPFC functions with volumetric and functional changes, resulting in hyperactivity in the right hemisphere and functional decrease in the left. OBJECTIVES: This study investigated the inhibitory role of the left prelimbic cortex (LPrL) on ethanol consumption induced by chronic social defeat stress (SDS) in male mice and to examine if inactivation of the LPrL causes disinhibition of the right mPFC, leading to an increase in ethanol consumption. We also investigated the role of lateralization and neurochemical alterations in the mPFC related to ethanol consumption induced by chronic SDS. To this end, we examined the activation patterns of ΔFosB, VGLUT2, and GAD67 in the left and right mPFC. RESULTS: Temporarily blocking the LPrL or right PrL (RPrL) cortices during acute SDS did not affect male mice's voluntary ethanol consumption in male mice. When each cortex was blocked in mice previously exposed to chronic SDS, ethanol consumption also remained unaffected. However, male mice with LPrL lesions during chronic SDS showed an increase in voluntary ethanol consumption, which was associated with enhanced ΔFosB/VGLUT2-positive neurons within the RPrL cortex. CONCLUSIONS: The results suggest that the LPrL may play a role in inhibiting ethanol consumption induced by chronic SDS, while the RPrL may be involved in the disinhibition of ethanol consumption.

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.

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.

Pharmacokinetics and therapeutic target attainment of vancomycin in pediatric post-liver transplant patients.

INTRODUCTION: Vancomycin is widely prescribed to treat or prevent Gram-positive infections in pediatric liver transplant recipients. The objective of this prospective cohort study is to describe vancomycin pharmacokinetics and to evaluate the therapeutic target attainment after initial dose regimen. MATERIALS AND METHODS: Patients with previous renal injury were excluded. Vancomycin therapy started with 40‒60 mg/kg/day. The pharmacokinetic parameters were assessed using two steady-state blood samples and the first-order kinetic equations. Therapeutic target was defined as vancomycin 24-hour Area Under the Curve/Minimum Inhibitory Concentration (AUC/MIC) ≥ 400 and < 600. RESULTS: Sixteen patients were included. The found vancomycin clearance, half-life, and volume of distribution were, respectively: 2.1 (1.3‒2.8) mL/kg/min, 3.3 (2.7‒4.4) hours, and 0.7 (0.5‒0.9) L/kg. With the initial dose, only 6 (37 %) patients reached the therapeutic target against Gram-positive pathogens with MIC 1 mg/L. After individual dose adjustments, all patients reached the target. The correlation between trough levels and AUC was low (R2 = 0.5). CONCLUSIONS: Pediatric patients with preserved renal function after liver transplantation have an increased volume of distribution for vancomycin, and most patients present subtherapeutic levels after the standard initial dosing regimen. With the vancomycin AUC-guided monitoring and dosing, it is possible to improve therapeutic target attainment.

Pharmacokinetics and Therapeutic Target Attainment of Meropenem in Pediatric Post-Liver Transplant Patients: Extended vs Intermittent Infusion.

PURPOSE: The aim of this study is to characterize the concentration-time profile, pharmacokinetics parameters, and therapeutic target attainment of meropenem in pediatric post-liver transplant patients according to the duration of infusion. METHODS: This is a prospective cohort of pediatric transplant recipients with preserved renal function receiving meropenem 40 mg/kg every 8 hours. The patients were stratified into 2 groups based on infusion duration: G1 (15 minutes of intermittent infusion) and G1 (3 hours of extended infusion). Two blood samples per child were collected during the same interval within 48 hours of starting the antimicrobial. Meropenem concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were assessed using a noncompartmental analysis. The therapeutic target was defined as 100% of the time above the minimum inhibitory concentration. FINDINGS: Fourteen patients with 28 measured meropenem concentrations were included. Lower values of volume of distribution and meropenem clearance compared with other critically ill pediatric populations were found. All patients achieved the therapeutic target against gram-negative pathogens with a minimum inhibitory concentration of ≤8 mg/L. Patients receiving a 15-minute infusion had higher values of peak and trough concentrations, resulting in unnecessary increased total drug exposure when compared to patients receiving a 3-hour infusion (P < .05). CONCLUSIONS: Meropenem at 120 mg/kg/d attained the therapeutic target against sensitive microorganisms in pediatric liver transplant recipients. The extended infusion should be preferred for patient safety. Because of the pharmacokinetic changes resulting from liver transplantation, individualized meropenem dosing regimens may be necessary.

Knowledge regarding extracorporeal membrane oxygenation management among Brazilian pediatric intensivists: a cross-sectional survey.

OBJECTIVE: To assess Brazilian pediatric intensivists' general knowledge of extracorporeal membrane oxygenation, including evidence for its use, the national funding model, indications, and complications. METHODS: This was a multicenter cross-sectional survey including 45 Brazilian pediatric intensive care units. A convenience sample of 654 intensivists was surveyed regarding their knowledge on managing patients on extracorporeal membrane oxygenation, its indications, complications, funding, and literature evidence. RESULTS: The survey addressed questions regarding the knowledge and experience of pediatric intensivists with extracorporeal membrane oxygenation, including two clinical cases and 6 optional questions about the management of patients on extracorporeal membrane oxygenation. Of the 45 invited centers, 42 (91%) participated in the study, and 412 of 654 (63%) pediatric intensivists responded to the survey. Most pediatric intensive care units were from the Southeast region of Brazil (59.5%), and private/for-profit hospitals represented 28.6% of the participating centers. The average age of respondents was 41.4 (standard deviation 9.1) years, and the majority (77%) were women. Only 12.4% of respondents had taken an extracorporeal membrane oxygenation course. Only 19% of surveyed hospitals have an extracorporeal membrane oxygenation program, and only 27% of intensivists reported having already managed patients on extracorporeal membrane oxygenation. Specific extracorporeal membrane oxygenation management questions were responded to by only 64 physicians (15.5%), who had a fair/good correct response rate (median 63.4%; range 32.8% to 91.9%). CONCLUSION: Most Brazilian pediatric intensivists demonstrated limited knowledge regarding extracorporeal membrane oxygenation, including its indications and complications. Extracorporeal membrane oxygenation is not yet widely available in Brazil, with few intensivists prepared to manage patients on extracorporeal membrane oxygenation and even fewer intensivists recognizing when to refer patients to extracorporeal membrane oxygenation centers.

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.

Identification of miRnas with possible prognostic roles for HAM/TSP.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1-infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.

A higher number of SARS-COV-2 infections in quilombola communities than in the local population in Brazil.

The historical and social vulnerability of quilombola communities in Brazil can make them especially fragile in the face of COVID-19, considering that several individuals have precarious health systems and inadequate access to water. This work aimed to characterize the frequency of SARS-COV-2 infections and the presence of IgM and IgG SARS-CoV-2 antibodies in quilombola populations and their relationship with the presence of risk factors or preexisting chronic diseases in the quilombola communities. We analyzed the sociodemographic and clinical characteristics, serological status, comorbidities, and symptoms of 1,994 individuals (478 males and 1,536 females) from 18 Brazilian municipalities in the State of Sergipe of quilombola communities, which were evaluated at different epidemiological weeks, starting at the 32nd (August 6th) and ending at the 40th (October 3rd) epidemiological week. More than 70% of studied families live in rural areas and they have an extreme poverty social status. Although we found a higher number of SARS-COV-2 infections in quilombola communities than in the local population, their SARS-CoV-2 reactivity and IgM and IgG positivity varied across the communities investigated. Arterial hypertension was the most risk factor, being found in 27.8% of the individuals (9.5% in stage 1, 10.8% in stage 2, and 7.5% in stage 3). The most common COVID-19 symptoms and comorbidities were headache, runny nose, flu, and dyslipidemia. However, most individuals were asymptomatic (79.9%). Our data indicate that mass testing must be incorporated into public policy to improve the health care system available to quilombola populations during a future pandemic or epidemic.

Emotional- and cognitive-like responses induced by social defeat stress in male mice are modulated by the BNST, amygdala, and hippocampus.

Introduction: Chronic exposure to social defeat stress (SDS) has been used to investigate the neurobiology of depressive- and anxiety-like responses and mnemonic processes. We hypothesized that these affective, emotional, and cognitive consequences induced by SDS are regulated via glutamatergic neurons located in the bed nucleus of the stria terminalis (BNST), amygdaloid complex, and hippocampus in mice. Methods: Here, we investigated the influence of chronic SDS on (i) the avoidance behavior assessed in the social interaction test, (ii) the anxiety-like behavior (e.g., elevated plus-maze, and open field tests) (iii) depressive-like behaviors (e.g., coat state, sucrose splash, nesting building, and novel object exploration tests), (iv) the short-term memory (object recognition test), (v) ΔFosB, CaMKII as well as ΔFosB + CaMKII labeling in neurons located in the BNST, amygdaloid complex, dorsal (dHPC) and the ventral (vHPC) hippocampus. Results: The main results showed that the exposure of mice to SDS (a) increased defensive and anxiety-like behaviors and led to memory impairment without eliciting clear depressive-like or anhedonic effects; (b) increased ΔFosB + CaMKII labeling in BNST and amygdala, suggesting that both areas are strongly involved in the modulation of this type of stress; and produced opposite effects on neuronal activation in the vHPC and dHPC, i.e., increasing and decreasing, respectively, ΔFosB labeling. The effects of SDS on the hippocampus suggest that the vHPC is likely related to the increase of defensive- and anxiety-related behaviors, whereas the dHPC seems to modulate the memory impairment. Discussion: Present findings add to a growing body of evidence indicating the involvement of glutamatergic neurotransmission in the circuits that modulate emotional and cognitive consequences induced by social defeat stress.

Haemodynamic support for paediatric septic shock: a global perspective.

Septic shock is a leading cause of hospitalisation, morbidity, and mortality for children worldwide. In 2020, the paediatric Surviving Sepsis Campaign (SSC) issued evidence-based recommendations for clinicians caring for children with septic shock and sepsis-associated organ dysfunction based on the evidence available at the time. There are now more trials from multiple settings, including low-income and middle-income countries (LMICs), addressing optimal fluid choice and amount, selection and timing of vasoactive infusions, and optimal monitoring and therapeutic endpoints. In response to developments in adult critical care to trial personalised haemodynamic management algorithms, it is timely to critically reassess the current state of applying SSC guidelines in LMIC settings. In this Viewpoint, we briefly outline the challenges to improve sepsis care in LMICs and then discuss three key concepts that are relevant to management of children with septic shock around the world, especially in LMICs. These concepts include uncertainties surrounding the early recognition of paediatric septic shock, choices for initial haemodynamic support, and titration of ongoing resuscitation to therapeutic endpoints. Specifically, given the evolving understanding of clinical phenotypes, we focus on the controversies surrounding the concepts of early fluid resuscitation and vasoactive agent use, including insights gained from experience in LMICs and high-income countries. We outline the key components of sepsis management that are both globally relevant and translatable to low-resource settings, with a view to open the conversation to the large variety of treatment pathways, especially in LMICs. We emphasise the role of simple and easily available monitoring tools to apply the SSC guidelines and to tailor individualised support to the patient's cardiovascular physiology.

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.

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.