Correlation between individual autoantibodies and clinical features in primary biliary cholangitis: results of a retrospective longitudinal study.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an immune-mediated liver disease. The immunological profile seems to relate to clinical prognosis. This study aims to determine the role of autoantibodies in the course of liver disease and in the response to ursodeoxycholic acid. METHODS: Between January 2016 and December 2020, 143 patients with PBC who underwent immunological liver profile evaluation were enrolled. All data were extracted retrospectively from electronic clinical records. Chi-square test, Fisher's exact test and Mann-Whitney test were used to evaluate the relationship between autoantibodies and biochemical parameters, clinical outcomes and therapeutic response scores. A significance level of 0.05 was used. RESULTS: Antimitochondrial antibodies were present in 91.6%, antiglycoprotein-210 antibody (anti-gp210) in 18.2% and anti-Sp100 in 19.6% of patients. The incidence of liver-related death was higher in patients with autoimmune hepatitis variants. The occurrence of cirrhosis or portal hypertension was not linked to the presence of any of the autoantibodies tested. No relationship was found with the probability of dying or being transplanted. Patients with anti-Sp100 antibodies had higher baseline levels of aspartate aminotransferase and alanine aminotransferase and lower immunoglobulin M levels. Patients with anti-gp210 were more likely to have a lower median transplant-free survival rate and higher median risk of liver transplant or liver-related death using the GLOBE and UK-PBC scores. CONCLUSION: Our findings confirm a strong association between anti-gp210 antibodies and a worse outcome. The association between anti-Sp100 and hepatic lesions requires further elucidation.

Therapeutic effects and the impact of statins in the prevention of ulcerative colitis in preclinical models: A systematic review.

Ulcerative Colitis (UC) is a chronic inflammatory condition of the large intestines. Although great advances have been made in the management of the disease with the introduction of immunomodulators and biological agents, the treatment of UC is still a challenge. So far, there are no definitive therapies for this condition. Statins are potent inhibitors of cholesterol biosynthesis, possess beneficial effects on primary and secondary prevention of coronary heart disease, and have high tolerability and safety. Furthermore, they may have potential roles in UC management due to their possible anti-inflammatory, immunomodulatory, and antioxidant activities. This systematic review aimed to gather information about the potential benefits of statins for managing UC, reducing inflammation and disease remission in animal models. A systematic search was performed in PubMed/MEDLINE, Scopus, Web of Science, and Virtual Health Library. The data were summarized in tables and critically analyzed. After the database search, 21 relevant studies were identified as eligible for this review. Preclinical studies using several colitis-induction protocols and various statins have shown numerous beneficial effects of these drugs on reducing disease activity, inflammatory profile, oxidative stress, and general clinical parameters of animals with UC. These studies revealed the potential of statins against the pathogenesis of UC. However, there are still important gaps regarding the molecular mechanisms of action of statins, leading to some contradictory results. Thus, more research on the molecular level to determine the roles of statins in colitis should be carried out to elucidate their mechanisms of action.

Pathogenicity and virulence of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, an infectious disease with one of the highest morbidity and mortality rates worldwide. Leveraging its highly evolved repertoire of non-protein and protein virulence factors, Mtb invades through the airway, subverts host immunity, establishes its survival niche, and ultimately escapes in the setting of active disease to initiate another round of infection in a naive host. In this review, we will provide a concise synopsis of the infectious life cycle of Mtb and its clinical and epidemiologic significance. We will also take stock of its virulence factors and pathogenic mechanisms that modulate host immunity and facilitate its spread. Developing a greater understanding of the interface between Mtb virulence factors and host defences will enable progress toward improved vaccines and therapeutics to prevent and treat tuberculosis.

A Single Bout of High Heels Dancing Causes an Increase in Circulating Markers of Muscle Tissue Degradation and MMP-3 in Young Healthy Women.

Prolonged wearing of high heels can cause chronic injury and inflammation. Herein, we investigated the presence of muscle injury, inflammation, and neutrophil function in young women after a single bout of stiletto dance class. Sixteen volunteers (23.4 ± 3.8 years; 61.7 ± 8.1 kg; 23.4 ± 2.3 kg/m2; and 27.2 ± 3.8% body fat) participated in the study. The plasma biomarkers matrix metalloproteinase 3 (MMP-3), muscle damage (myoglobin (Mb), total creatine kinase (CK), and lactate dehydrogenase (LDH)), and inflammation (interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-α), interleukin (IL]-1ß, and IL-6) were quantified before and immediately after a single stiletto class (60 min) of moderate intensity. After class, our data showed that the plasma concentration of MMP-3, Mb, and CK increased by 56% (p = 0.04; d = 0.8), 113% (p = 0.007; d = 1.1), and 21% (p < 0.001; d = 0.4), respectively. Reactive oxygen species produced by neutrophils and the plasma concentration of IL-8, TNF-α, IL-1ß, and IL-6 were not affected under the study conditions. We concluded that a single bout of stiletto dance class caused muscle damage but did not alter the plasma concentration of proinflammatory cytokines. These findings are crucial in preventing the progress of chronic injuries that are often noted in dancers with synovitis and arthritis.

Leukocyte metabolism in obese type 2 diabetic individuals associated with COVID-19 severity.

Recent studies show that the metabolic characteristics of different leukocytes, such as, lymphocytes, neutrophils, and macrophages, undergo changes both in the face of infection with SARS-CoV-2 and in obesity and type 2 diabetes mellitus (DM2) condition. Thus, the objective of this review is to establish a correlation between the metabolic changes caused in leukocytes in DM2 and obesity that may favor a worse prognosis during SARS-Cov-2 infection. Chronic inflammation and hyperglycemia, specific and usual characteristics of obesity and DM2, contributes for the SARS-CoV-2 replication and metabolic disturbances in different leukocytes, favoring the proinflammatory response of these cells. Thus, obesity and DM2 are important risk factors for pro-inflammatory response and metabolic dysregulation that can favor the occurrence of the cytokine storm, implicated in the severity and high mortality risk of the COVID-19 in these patients.

Cross-mapping of nursing diagnoses and interventions in decompensated heart failure.

OBJECTIVE: To map the terms recorded in medical records of patients with decompensated heart failure for nursing diagnoses and interventions from the NANDA International and Nursing Interventions Classification. METHOD: This is an exploratory and descriptive research, carried out by a cross-mapping study. Data were collected from 107 medical records of a Hospital Institute in the city of Rio de Janeiro/Brazil, in a period between October 2017 to February 2019. The diagnoses and interventions mapped were assessed by four clinical experts. Data analysis was performed using the content validation index and the Fleiss Kappa. RESULTS: The most frequent nursing diagnoses were: risk for infection (74.8%), decreased cardiac output (55.1%) and excessive fluid volume (49.5%). The interventions were: vital signs monitoring (79.4%), fluid monitoring (72.9%) and positioning (52.3%). CONCLUSION: The research mapped 32 titles of nursing diagnoses from NANDA-I and 21 nursing interventions from NIC. The diagnoses and interventions mapped will contribute to the quality of the nurses' records and patient safety.

Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils.

Visceral leishmaniasis (VL) is often associated with hematologic manifestations that may interfere with neutrophil response. Lipophosphoglycan (LPG) is a major molecule on the surface of Leishmania promastigotes, which has been associated with several aspects of the parasite-vector-host interplay. Here, we investigated how LPG from Leishmania (L.) infantum, the principal etiological agent of VL in the New World, influences the initial establishment of infection during interaction with human neutrophils in an experimental setting in vitro. Human neutrophils obtained from peripheral blood samples were infected with either the wild-type L. infantum (WT) strain or LPG-deficient mutant (∆lpg1). In this setting, ∆lpg1 parasites displayed reduced viability compared to WT L. infantum; such finding was reverted in the complemented ∆lpg1+LPG1 parasites at 3- and 6-h post-infection. Confocal microscopy experiments indicated that this decreased survival was related to enhanced lysosomal fusion. In fact, LPG-deficient L. infantum parasites more frequently died inside neutrophil acidic compartments, a phenomenon that was reverted when host cells were treated with Wortmannin. We also observed an increase in the secretion of the neutrophil collagenase matrix metalloproteinase-8 (MMP-8) by cells infected with ∆lpg1 L. infantum compared to those that were infected with WT parasites. Furthermore, collagen I matrix degradation was found to be significantly increased in ∆lpg1 parasite-infected cells but not in WT-infected controls. Flow cytometry analysis revealed a substantial boost in production of reactive oxygen species (ROS) during infection with either WT or ∆lpg1 L. infantum. In addition, killing of ∆lpg1 parasites was shown to be more dependent on the ROS production than that of WT L. infantum. Notably, inhibition of the oxidative stress with Apocynin potentially fueled ∆lpg1 L. infantum fitness as it increased the intracellular parasite viability. Thus, our observations demonstrate that LPG may be a critical molecule fostering parasite survival in human neutrophils through a mechanism that involves cellular activation and generation of free radicals.

Doppler abnormalities and perinatal outcomes in pregnant women with early-onset fetal growth restriction.

OBJECTIVE: To compare Doppler alterations and perinatal outcomes in pregnant women who evolved with early- and late-onset fetal growth restriction (FGR). METHODS: A retrospective, observational cohort study with pregnant women who evolved with FGR treated between January 2018 and April 2019, in which all live births from singleton pregnancies, over 24 weeks, with FGR ultrasound diagnosis and under 2700 g weight were included in the study. RESULTS: Pregnancies with early-onset FGR were more associated with hypertensive disorders (p = .00) and placental vascular insufficiency, resulting in a high degree of umbilical artery Doppler involvement (p = .00) in a short period of pregnancy and higher rates of adverse perinatal outcomes (p = .00). The time of prenatal follow-up of early- and late-onset FGR cases was similar, but the degree of prematurity of the former made the evolution more unfavorable. CONCLUSION: Early-onset FGR had a lower prevalence but was associated with higher maternal and fetal morbidity and mortality than late-onset FGR.

Cross-mapping of nursing diagnoses and interventions in decompensated heart failure / Mapeo cruzado de diagnósticos e intervenciones de enfermería en insuficiencia cardíaca descompensada / Mapeamento cruzado dos diagnósticos e intervenções de enfermagem na insuficiência cardíaca descompensada

ABSTRACT Objective To map the terms recorded in medical records of patients with decompensated heart failure for nursing diagnoses and interventions from the NANDA International and Nursing Interventions Classification. Method This is an exploratory and descriptive research, carried out by a cross-mapping study. Data were collected from 107 medical records of a Hospital Institute in the city of Rio de Janeiro/Brazil, in a period between October 2017 to February 2019. The diagnoses and interventions mapped were assessed by four clinical experts. Data analysis was performed using the content validation index and the Fleiss Kappa. Results The most frequent nursing diagnoses were: risk for infection (74.8%), decreased cardiac output (55.1%) and excessive fluid volume (49.5%). The interventions were: vital signs monitoring (79.4%), fluid monitoring (72.9%) and positioning (52.3%). Conclusion The research mapped 32 titles of nursing diagnoses from NANDA-I and 21 nursing interventions from NIC. The diagnoses and interventions mapped will contribute to the quality of the nurses' records and patient safety.

RESUMEN Objetivo Mapear los términos registrados en los registros médicos de pacientes con insuficiencia cardíaca descompensada para los diagnósticos e intervenciones de enfermería de NANDA International y la clasificación de las intervenciones de enfermería. Método Investigación exploratoria, descriptiva, realizada mediante mapeo cruzado. La recolección de datos se realizó en 107 historias clínicas de un hospital de la ciudad de Río de Janeiro / RJ, en el período comprendido entre octubre de 2017 y febrero de 2019. Los diagnósticos e intervenciones mapeados fueron evaluados por cuatro expertos. El análisis de los datos se realizó utilizando el índice de validación de contenido y el Kappa de Fleiss. Resultados: Los diagnósticos de enfermería más frecuentes fueron: riesgo de infección (74,8%), disminución del gasto cardíaco (55,1%) y volumen excesivo de líquidos (49,5%). Las intervenciones mapeadas fueron: monitoreo de signos vitales (79.4%) y posicionamiento (52.3%). Conclusión La investigación mapeó 32 títulos de diagnóstico de enfermería NANDA-I y 21 intervenciones de enfermería NIC. Los diagnósticos y las intervenciones mapeadas contribuirán a la calidad del registro de enfermeras y la seguridad del paciente.

RESUMO Objetivo Mapear os termos registrados em prontuários de pacientes com insuficiência cardíaca descompensada para diagnósticos e intervenções de enfermagem da NANDA Internacional e Classificação de Intervenções de Enfermagem. Método Pesquisa exploratória, descritiva, realizada através do mapeamento cruzado. Os dados foram coletados em 107 prontuários de um hospital do município do Rio de Janeiro/RJ, no período entre outubro de 2017 e fevereiro de 2019. Os diagnósticos e intervenções mapeados foram avaliados por quatro peritos. A análise dos dados foi realizada pelo índice de validação de conteúdo e o Kappa de Fleiss. Resultados Os diagnósticos de enfermagem mais frequentes foram: risco de infecção (74,8%), débito cardíaco diminuído (55,1%) e volume de líquidos excessivo (49,5%). As intervenções foram: monitoração de sinais vitais (79,4%), monitoração hídrica (72,9%) e posicionamento (52,3%). Conclusão A pesquisa mapeou 32 títulos de diagnósticos de enfermagem da NANDA-I e 21 intervenções de enfermagem da NIC. Os diagnósticos e intervenções mapeados irão contribuir para a qualidade do registro de enfermeiros e segurança do paciente.

Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms.

The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration.

Investigating the Phagocytosis of Leishmania using Confocal Microscopy.

Phagocytosis is an orchestrated process that involves distinct steps: recognition, binding, and internalization. Professional phagocytes take up Leishmania parasites by phagocytosis, consisting of recognizing ligands on parasite surfaces by multiple host cell receptors. Binding of Leishmania to macrophage membranes occurs through complement receptor type 1 (CR1) and complement receptor type 3 (CR3) and Pattern Recognition Receptors. Lipophosphoglycan (LPG) and 63 kDa glycoprotein (gp63) are the main ligands involved in macrophage-Leishmania interactions. Following the initial recognition of parasite ligands by host cell receptors, parasites become internalized, survive, and multiply within parasitophorous vacuoles. The maturation process of Leishmania-induced vacuoles involves the acquisition of molecules from intracellular vesicles, including monomeric G protein Rab 5 and Rab 7, lysosomal associated membrane protein 1 (LAMP-1), lysosomal associated membrane protein 2 (LAMP-2), and microtubule-associated protein 1A/1B-light chain 3 (LC3). Here, we describe methods to evaluate the early events occurring during Leishmania interaction with the host cells using confocal microscopy, including (i) binding (ii) internalization, and (iii) phagosome maturation. By adding to the body of knowledge surrounding these determinants of infection outcome, we hope to improve the understanding of the pathogenesis of Leishmania infection and support the eventual search for novel chemotherapeutic targets.

Prospective study of ventricular function and myocardial deformation related to survival in acute Chagas disease: an experimental animal model.

Chagas disease (CD) has been changing from an endemic Latino-American disease to a condition found outside endemic regions, due to migratory movements. Although often subclinical, its acute phase can be lethal. This study aimed to assess survival during the acute phase of CD and its relationship with ventricular function in an experimental model. To this end, 30 Syrian hamsters were inoculated with Trypanosoma cruzi (IG) and other 15 animals received saline solution (CG). Groups were monitored daily and submitted to echocardiography in two moments: before the challenge and 15 days post-infection. Left ventricular ejection fraction (LVEF) and global longitudinal myocardial strain (GLS) of the LV were measured. The IG was divided into groups of animals with and without clinical signs of disease. ANOVA for mixed models was used to compare ventricular function parameters. Survival analysis was studied using Kaplan-Meier curves and the log-rank test. The follow-up lasted 60 days. LVEF in IG was reduced through time (53.80 to 43.55%) compared to CG (57.86 to 59.73%) (p=0.002). There was also a reduction of GLS (-18.97% to -12.44%) in the IG compared to CG (p=0.012). Twelve animals from IG died compared to one animal from CG. Eleven out of the 12 animals from the IG group died before presenting with clinical signs of infection. Survival was reduced in the IG compared to CG over time (p=0.02). The reduced survival during the acute phase of this experimental model of Chagas disease was related to the significant reduction of LV function. The mortality rate in the IG was higher in the group presenting with clinical signs of infection.

17-AAG-Induced Activation of the Autophagic Pathway in Leishmania Is Associated with Parasite Death.

The heat shock protein 90 (Hsp90) is thought to be an excellent drug target against parasitic diseases. The leishmanicidal effect of an Hsp90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), was previously demonstrated in both in vitro and in vivo models of cutaneous leishmaniasis. Parasite death was shown to occur in association with severe ultrastructural alterations in Leishmania, suggestive of autophagic activation. We hypothesized that 17-AAG treatment results in the abnormal activation of the autophagic pathway, leading to parasite death. To elucidate this process, experiments were performed using transgenic parasites with GFP-ATG8-labelled autophagosomes. Mutant parasites treated with 17-AAG exhibited autophagosomes that did not entrap cargo, such as glycosomes, or fuse with lysosomes. ATG5-knockout (Δatg5) parasites, which are incapable of forming autophagosomes, demonstrated lower sensitivity to 17-AAG-induced cell death when compared to wild-type (WT) Leishmania, further supporting the role of autophagy in 17-AAG-induced cell death. In addition, Hsp90 inhibition resulted in greater accumulation of ubiquitylated proteins in both WT- and Δatg5-treated parasites compared to controls, in the absence of proteasome overload. In conjunction with previously described ultrastructural alterations, herein we present evidence that treatment with 17-AAG causes abnormal activation of the autophagic pathway, resulting in the formation of immature autophagosomes and, consequently, incidental parasite death.

Headache as an Adverse Reaction to the Use of Medication in the Elderly: A Pharmacovigilance Study.

There is a consensus that elderly individuals are quite vulnerable to adverse drug reactions (ADRs), and headaches are one of the most frequent clinical presentations of central nervous system problems in the general population, which can be an ADR. The purpose of our work was to analyze reports of "headache" associated ADRs in the elderly sent to the Portuguese Pharmacovigilance System (PPS), and also which drugs were more frequently associated with this adverse reaction. A retrospective analysis of suspected ADR reports involving patients aged 65 years or older received by the PPS in the last 10 years was conducted. A search of all the terms associated with the High Level Term "headache" was performed. All duplicate reports were excluded from the analysis. A total of 155 ADRs reports were included, in which 15 reported isolated "headache" as suspected ADR, while the remaining 140 ADRs reports reported "headache" together with several other adverse reactions. Most reports of "headache" ADR occurred in women (74.8%; n = 116). About half (46.5%; n = 72) of the ADR reports were considered serious. Anti-viral medication, anti-depressants, anti-dyslipidemic agents and central nervous system-acting analgesics were the most frequent drugs associated with "headache" ADR reports in this population. In elderly patients, most ADR reports involving headaches occurred in women and a high percentage (46.5%) were considered serious. Thus, it is important that healthcare professionals pay more attention to headaches reported as ADRs in the elderly and drugs suspected to cause them, in order to increase knowledge about this type of reaction and contribute towards safely using drugs in this age group.

Feasibility and reference intervals assessed by conventional and speckle-tracking echocardiography in normal hamsters.

OBJECTIVES: This study aimed to determine feasibility, reference intervals, and reproducibility of left ventricular ejection fraction (LVEF) and speckle-tracking echocardiography (STE) in adult Syrian hamsters. BACKGROUND: Syrian hamster is an experimental model for several heart diseases. Echocardiography allows the evaluation of structure and function with bidimensional conventional techniques and STE. However, there is no data regarding reference values for bidimensional LVEF and myocardial strain in hamsters. METHODS: A total of 135 female Syrian hamsters were anesthetized and studied with a small animal dedicated echocardiography system. Echocardiography measurements were obtained from M-mode and B-mode images. Feasibility and 95% reference intervals were obtained for LVEF using three different approaches: LVEF_Teichholz (from M-mode linear measurements), LVEF_BMode (from area-length method), and LVEF_ STE (from strain), and for global longitudinal (GLS), circumferential (GCS), and radial (GRS) endocardial strain. Reproducibility was assessed as intra-class correlation coefficients. RESULTS: Feasibility of LVEF and endocardial strain was high (95% in FEVE_Teichholz, 93% in the LVEF_BMode, 84% in the LVEF_STE, 84% from PSLAX, and 80% from PSSAX). Values of LVEF_Teichholz were significantly higher than values of LVEF_BMode, and LVEF_STE-derived methods (59.0 ± 5.8, 53.8 ± 4.7, 46.3 ± 5.7, p < 0.0001). The 95% reference intervals for GLS, GCS, and GRS were respectively -13.6(-7.5;-20.4)%, -20.5 ± 3.1%, and + 34,7 ± 7.0%. Intra-class correlation coefficients were 0.49 - 0.91 for LVEF measurements, 0.73 - 0.92 for STE, with better results for LVEF_Teichholz and GLS. CONCLUSIONS: Evaluation of LVEF by several methods and STE parameters is feasible in hamsters. Reference intervals for LVEF and STE obtained for this experimental animal model can be applied at future research.

North Pacific warming shifts the juvenile range of a marine apex predator.

During the 2014-2016 North Pacific marine heatwave, unprecedented sightings of juvenile white sharks (Carcharodon carcharias) emerged in central California. These records contradicted the species established life history, where juveniles remain in warmer waters in the southern California Current. This spatial shift is significant as it creates potential conflicts with commercial fisheries, protected species conservation, and public safety concerns. Here, we integrate community science, photogrammetry, biologging, and mesoscale climate data to describe and explain this phenomenon. We find a dramatic increase in white sharks from 2014 to 2019 in Monterey Bay that was overwhelmingly comprised of juvenile sharks < 2.5 m in total body length. Next, we derived thermal preferences from 22 million tag measurements of 14 juvenile sharks and use this to map the cold limit of their range. Consistent with historical records, the position of this cold edge averaged 34° N from 1982 to 2013 but jumped to 38.5° during the 2014-2016 marine heat wave. In addition to a poleward shift, thermally suitable habitat for juvenile sharks declined 223.2 km2 year-1 from 1982 to 2019 and was lowest in 2015 at the peak of the heatwave. In addition to advancing the adaptive management of this apex marine predator, we discuss this opportunity to engage public on climate change through marine megafauna.

Melatonin, Zinc, and Vitamin C: Potential Adjuvant Treatment for COVID-19 Patients.

The use of nutraceutical approaches may regulate the immune system, performing a potential strategy to contain the worst outcomes of COVID-19. We reviewed the current evidence surrounding nutritional/nutraceutical approaches for the therapy in patients with COVID-19. We searched the PubMed database to report randomized controlled trials (RCTs) and observational research that used melatonin, zinc, or vitamin C supplementation as an intervention for COVID-19 treatment. To date, we found only three concluded studies that assessed zinc supplementation and melatonin therapy in patients with COVID-19, but with inconclusive data, relatively small sample size, and early termination of the trial. On the other hand, vitamin C therapy appears to reduce hyperinflammation and improve the oxygen support status of patients with COVID-19. However, a large part of this research involves pilot trials, and there are still conflicting data regarding mortality rate, mechanical ventilation, and duration of symptoms of patients with COVID-19. Melatonin, zinc, and vitamin C supplementation should be investigated further on the nutritional status-immune response, and data from ongoing trials are needed to understand these molecules as a therapy strategy in patients COVID-19.

Genetics and regulation of nitrogen fixation in Paenibacillus brasilensis PB24.

Biological nitrogen fixation (BNF), performed by diazotrophic prokaryotes, is responsible for reducing dinitrogen (N2) present in the biosphere into biologically available forms of nitrogen. Paenibacillus brasilensis PB24 is a diazotrophic Gram-positive bacterium and is considered ecologically and industrially important because it is able to produce antimicrobial substances and 2,3-butanediol. However, the genetics and regulation of its nitrogen fixing (nif) genes have never been assessed so far. Therefore, the present study aimed to (i) identify the structural and regulatory genes related to BNF in the PB24 genome, (ii) perform comparative genomics analysis of the nif operon among different Paenibacillus species and (iii) study the expression of these genes in the presence and absence of NH4. Strain PB24 showed a nif operon composed of nine genes (nifBHDKENXhesAV), with a conserved synteny (with small variations) among the Paenibacillus species evaluated. BNF regulatory genes, glnK and amtB (encoding GlnK signal transduction protein and AmtB transmembrane protein, respectively) and glnR and glnA genes (encoding the transcription factor GlnR and glutamine synthetase) were found in the PB24 genome. Primers were designed for qPCR amplification of the nitrogenase structural (nifH, nifD and nifK) and regulatory (glnA and amtB) BNF genes. The structural gene expression in PB24 was up- and downregulated in the absence and presence of NH4, respectively. The gene expression levels indicated a GlnR-mediated repression of genes associated with ammonium import (amtBglnK) and BNF (nif genes). Additionally, the regulatory mechanism of GlnR in P. brasilensis PB24 differed from the other Paenibacillus evaluated, considering the different distribution of binding sites recognized by GlnR.

Produção de riscos, consumo, necropolítica e desigualdades: expressividades midiáticas da pandemia no contexto brasileiro / Risk production, consumption, necropolitics and inequalities: media expressiveness of the pandemic in the brazilian context

A pandemia do novo coronavírus (SARS-CoV-2) produziu, e permanece produzindo, diversas significações em torno da vida da população brasileira, onde as mídias comunicacionais permanecem presentes nas veiculações acerca dos desdobramentos dessa conjuntura. Este estudo objetiva analisar informações veiculadas no contexto da pandemia, buscando compreender e explicitar aspectos ancorados nas produções dos discursos, os sentidos produzidos, bem como as materialidades expressas através do comportamento de consumo e acumulação da população, suscitados pela pandemia. Foram analisadas dez matérias jornalísticas, veiculadas na internet entre março e abril de 2020, à luz da psicossociologia do risco, inspirados em autores como Ulrich Beck e Mary Jane Spink; dos comportamentos de consumo, principalmente a partir de Jurandir Freire Costa, e sob as lentes da necropolítica de Achille Mbembe. Os comportamentos analisados expõem problemas sociais crônicos, onde o consumo exacerbado procura sustentar o cenário ilusório de segurança frente ao avanço do vírus, esvaziando prateleiras, em atos que desassistem aqueles que não têm recursos financeiros para garantir seus próprios insumos, operando em favor de tecnologias necropolíticas. Na atividade midiática encontram-se incitações ao consumo e uma amplificação da sensação de medo diante da suposta escassez anunciada.

The new coronavirus (SARS-CoV-2) pandemic produced and continues to produce, several meanings around the life of the Brazilian population, where the communication media remain present in the news about the developments of this situation. This study aims to analyze information conveyed in the context of the pandemic, seeking to understand and explain aspects anchored in the production of the speeches, the meanings produced, as well as the materialities expressed through consumption and accumulation behavior of the population, raised by the pandemic. Ten journalistic articles, published on the Internet between March and April 2020, were analyzed in the light of risk psychosociology, inspired by authors such as Ulrich Beck and Mary Jane Spink; consumer behavior, mainly from Jurandir Freire Costa, and under the necropolitics' lens of Achille Mbembe. The analyzed behaviors expose chronic social problems, where the exacerbated consumption seeks to sustain the illusory scenario of security face the advance of the virus, emptying shelves, in acts that neglect those who do not have financial resources to guarantee their inputs, operating in favor of necropolitical technologies. In media activity, there are incitements to consumption and amplification of the feeling of fear in the face of the supposed shortage announced.

Betulinic Acid Exerts Cytoprotective Activity on Zika Virus-Infected Neural Progenitor Cells.

Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barré syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2+ NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2+ and Casp3+ NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs.