Microalgae extracts modulates the immune response in Trypanosoma cruzi-infected human cells.

Chagas disease (CD) is caused by the hemoflagellate protozoan Trypanosoma cruzi. The control of the infection depends of the innate and acquired immune response of host. Moreover, CD plays a significant role in the immune response, and, in this context, microalgae can be an interesting alternative due to its immunomodulatory and trypanocidal effects. This study aimed to evaluate, in vitro, immunomodulatory potentials of the aqueous extracts of Chlorella vulgaris and Tetradesmus obliquus. Both microalgae extracts (ME) were obtained by sonication, and the selectivity index (SI) was determined by assays of inhibitory concentration (IC50) in T. cruzi trypomastigotes cells; as well as the cytotoxic concentrations (CC50) in human peripheral mononuclear cells (PBMC). The immune response was evaluated in T. cruzi-infected PBMC using the IC50 value. ME led to inhibition of T. cruzi trypomastigotes after 24 h of treatment, in which the IC50 values were 112.1 µg/ml to C. vulgaris and 15.8 µg ml-1 to T. obliquus. On the other hand, C. vulgaris did not affect the viability of PBMCs in concentrations up to 1000 µg ml-1, while T. obliquus was non-toxic to PBMCs in concentrations up to 253.44 µg ml-1. In addition, T. obliquus displayed a higher SI against T. cruzi (SI = 16.8), when compared with C. vulgaris (SI = 8.9). C. vulgaris decreased the levels of IFN, indicating a reduction of the inflammatory process; while T. obliquus displayed an interesting immunomodulatory effect, since discretely increased the levels of TNF and stimulated the production of the anti-inflammatory cytokine IL-10. This study confirms that ME are effective against T. cruzi trypomastigotes, and may able to control the parasitemia and preventing the progress of CD while regulating the inflammatory process.

Benznidazole treatment decreases IL-6 levels in Trypanosoma cruzi-infected human adipocytes differentiated from adipose tissue-derived stem cells.

BACKGROUND: Trypanosoma cruzi, which causes Chagas disease (CD), is a versatile haemoparasite that uses several strategies to evade the host's immune response, including adipose tissue (AT), used as a reservoir of infection. As it is an effective barrier to parasite evasion, the effectiveness of the drug recommended for treating CD, Benznidazole (BZ), may be questionable. OBJECTIVE: To this end, we evaluated the parasite load and immunomodulation caused by BZ treatment in the culture of adipocytes differentiated from human adipose tissue-derived stem cells (ADSC) infected with T. cruzi. METHODS: The ADSC were subjected to adipogenic differentiation. We then carried out four cultures in which we infected the differentiated AT with trypomastigote forms of the Y strain of T. cruzi and treated them with BZ. After the incubation, the infected AT was subjected to quantitative polymerase chain reaction (qPCR) to quantify the parasite load and transmission electron microscopy (TEM) to verify the infection. The supernatant was collected to measure cytokines, chemokines, and adipokines. FINDINGS: We found elevated secretion of IL-6, CXCL-10/IP-10, CCL2/MCP-1, CCL5/RANTES, and leptin in infected fat cells. However, treatment with BZ promoted a decrease in IL-6. MAIN CONCLUSION: Therefore, we believe that BZ has a beneficial role as it reduces inflammation in infected fat cells.

Study of association of the rs2275913 IL-17A single nucleotide polymorphism and susceptibility to cutaneous leishmaniasis caused by Leishmania braziliensis.

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is the most spread clinical form of leishmaniasis in Brazil. However, only a few part of the people infected develop clinically perceptive disease, suggesting the influence of human genetic components in the CL pathogeny. The rs2275913 SNP is the nucleotide variant of the IL17A gene. The A allele is associated with a vast number of infectious and non-infectious diseases. Here, we investigated the association of the rs2275913 SNP (G/A) from IL-17A and two forms of susceptibility to CL in Brazil by case-control study. Furthermore, we evaluated the functional relevance of this SNP during the immune response of the host and analyzed its impact in the parasite elimination. Weak associations of A allele with susceptibility to L. braziliensis infection or to symptomatic CL were observed, and a tendency of A allele carriers to be more susceptible to infection and cutaneous disease. Functional analysis of the Th17 cell phenotypes revealed lower frequencies of CD4+ IL-17+ cells in samples of infected people with AA/AG genotypes. Furthermore, people carrying the A allele maintain higher parasite loads, reinforcing the genetic susceptibility findings. This study adds knowledge about the influence of a significant genetic variation on IL-17 promoter on CL pathogenesis, and may contribute to enhance the knowledge about the role of IL-17 in the L. braziliensis infections.

Interaction between peripheral blood mononuclear cells and Trypanosoma cruzi-infected adipocytes: implications for treatment failure and induction of immunomodulatory mechanisms in adipose tissue.

Background/Introduction: Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi, which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added. Methods: We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping. Results: Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi. Discussion: Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host's immune response and the pharmacological action of BZ.

Dynamics of the Trypanosoma cruzi infection in adipose tissue: Assessing gene expression of PNPLA2, FASN, and ACAT1 under Benzonidazole treatment and indirect mononuclear immune cells interaction.

Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2.

Green microalgae as a potential source of trypanocide compounds.

Due to the limitations of Chagas disease therapy, microalgae can be promising in the search of new trypanocidal compounds, since these organisms produce bioactive compounds with large pharmaceutical applications, including antiparasitic effects. In this work, trypanocidal activity of aqueous extract of Tetradesmus obliquus and, for the first time, aqueous extract of Chlorella vulgaris, were evaluated against trypomastigote forms of Trypanosoma cruzi. In addition, cytotoxic activity in Vero cells was evaluated. Our results showed that C. vulgaris and T. obliquus present trypanocidal activity (IC50 = 32.9 µg ml-1 and 36.4 µg ml-1, respectively), however, C. vulgaris did not present cytotoxic effects in Vero cells (CC50 > 600 µg ml-1) and displayed a higher selectivity against trypomastigotes forms of T. cruzi (SI > 18). Thus, microalgae extracts, such as aqueous extract of C. vulgaris, are promising potential candidates for the development of natural antichagasic drugs.

Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise.

Obesity is an epidemic disease most commonly caused by a combination of increased energy intake and lack of physical activity. The cholinergic system has been shown to be involved in the regulation of food intake and energy expenditure. Moreover, physical exercise promotes a reduction of fat pads and body mass by increasing energy expenditure, but also influences the cholinergic system. The aim of this study is to evaluate the interaction between physical exercise (swimming) and central cholinergic activity in rats treated with monosodium glutamate (MSG, a model for obesity) during infancy. Our results show that MSG treatment is able to induce obesity in male and female rats. Specifically, MSG-treated rats presented a reduced body mass and nasoanal length, and increased perigonadal and retroperitoneal fat pads in relation to the body mass. Physical exercise was able to reduce body mass in both male and female rats, but did not change the fat pads in MSG-treated rats. Increased food intake was only seen in MSG-treated females submitted to exercise. Cholinergic activity was increased in the cortex of MSG-treated females and physical exercise was able to reduce this activity. Thalamic cholinergic activity was higher in sedentary MSG-treated females and exercised MSG-treated males. Hypothalamic cholinergic activity was higher in male and female MSG-treated rats, and was not reduced by exercise in the 2 sexes. Taken together, these results show that MSG treatment and physical exercise have different effects in the cholinergic activity of males and females.

Distinguishing SARS-CoV-2 bonafide re-infection from pre-existing minor variant reactivation.

Different groups have recently reported events of SARS-CoV-2 reinfection, where patients had a sequence of positive-negative-positive RT-PCR tests. However, such events could be explained by different scenarios such as intermittent viral shedding, bonafide re-infection or multiple infection with alternating predominance of different viruses. Analysis of minor variants is an important tool to distinguish between these scenarios. Using ARTIC network PCR amplification and next-generation sequencing, we obtained SARS-CoV-2 sequences from two timepoints (with a time span of 102 days) of a patient followed at the Brazilian National Cancer Institute. Within-host variant analysis evidenced three single nucleotide variants (SNVs) at the consensus viral sequence in the second timepoint that were already present in the first timepoint as minor variants. Another five SNVs found in the second timepoint were not detected in the first sample sequenced, suggesting an additional infection by a yet another new virus. Our observation shed light into the existence of different viral populations that are present in dynamic frequencies and fluctuate during the course of SARS-CoV-2 infection. The detection of these variants in distinct disease events of an individual highlights a complex interplay between viral reactivation from a pre-existing minority variant and reinfection by a different virus.

Nrf2, NF-κB and PPARß/δ mRNA Expression Profile in Patients with Coronary Artery Disease.

BACKGROUND: Oxidative stress and inflammation are present in coronary artery disease (CAD) and are linked to the activation of the transcription nuclear factor kappa B (NF-κB). To attenuate these complications, transcription factors like nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) can be activated to inhibit NF-κB. However, the available data on expression of NF-κB, Nrf2 and PPARß/δ in CAD patients are limited. OBJECTIVE: To evaluate the expression of the transcription factors NF-κB and Nrf2 and PPAR𝛽/𝛿 in CAD patients. METHODS: Thirty-five patients (17 men, mean age 62.4 ? 7.55 years) with CAD and twelve patients (5 men, mean age 63.50 ? 11.46 years) without CAD were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and processed for mRNA expression of Nrf2, NF-κB, NADPH: quinone oxidoreductase 1 (NQO1) and PPARß/δ mRNAs using quantitative real-time polymerase chain reaction (qPCR). p < 0.05 was considered statistically significant. RESULTS: There was no difference in the mRNA expressions of Nrf2 (1.35 ? 0.57), NF-κB (1.08 ? 0.50) or in the antioxidant enzyme NQO1 (1.05 ? 0.88) in the CAD group compared to the group without CAD (1.16 ? 0.76, 0.95 ? 0.33, 0.81 ? 0.55, respectively). However, PPARß/δ was highest expressed in the CAD group (1.17 ? 0.86 vs. 0.56 ? 0.34, p = 0.008). CONCLUSION: The main finding of this study was the PPARß/δ being more expressed in the PBMC of patients with CAD compared to the control group, whereas no differences were observed in Nrf2 or NF-κB mRNA expressions.

Physical activity but not sedentary time is associated with vitamin D status in adolescents: study of cardiovascular risk in adolescents (ERICA).

BACKGROUND/OBJECTIVES: The association between active lifestyle components and vitamin D status in adolescents remains relatively unexplored. We aimed to investigate independent and joint associations of moderate-to-vigorous physical activity (MVPA) and screen time with serum 25-hydroxyvitamin D [25(OH)D] concentrations in adolescents. METHODS: This multicenter cross-sectional study involved 1152 Brazilian adolescents (age 12-17 years). Serum 25(OH)D was measured in a single laboratory and categorized as ≤20, 21-29, or ≥30 ng/mL. Demographic and lifestyle characteristics were assessed by self-reports. Ordered logistic regression was used to investigate potential associations of being physically active (MVPA ≥ 300 min/week) and excessive screen time (>2 h/day) with serum 25(OH)D concentrations. RESULTS: The prevalence of higher serum 25(OH)D concentrations (≥30 ng/mL) was 36.4%. In adjusted models, being physically active was associated with higher serum 25(OH)D concentrations only in boys [proportional odds ratio (POR) = 2.04, 95% CI 1.42-2.93], while excessive screen time was not associated with serum 25(OH)D. Adolescents who were physically active and limited their screen time had higher odds of a higher serum 25(OH)D concentration, but the association was significant only for boys (POR = 2.11, 95% CI 1.19-3.74). CONCLUSIONS: MVPA may play an important role in increasing serum 25(OH)D concentrations in adolescence, especially for boys, regardless of screen time.

Virulence of Listeria monocytogenes isolated from the cheese dairy environment, other foods and clinical cases.

The virulence potential of 51 Listeria monocytogenes isolates, including strains from cheese, cheese production environments and from human cases of listeriosis, was evaluated in this study. The isolates were used to infect HT-29 cell monolayers in an in vitro test of virulence, based on a plaque-forming assay (PFA). Fifteen selected isolates were used for subcutaneous footpad inoculation in mice and subsequent recovery of the bacterium from the spleen 3 days after inoculation. In the PFA, two isolates from milk (serovar 1/2a) were not significantly different (P<0.05) from the low-virulence strain (442) used as reference. Thirty-three isolates were not significantly different (P<0.05) from the virulent strain (EGDe) used as reference. Nine isolates were significantly more virulent (highly virulent) than the EGDe strain and seven isolates were significantly less virulent. The nine highly virulent isolates were either from humans (four), from cheese dairy environments (two isolates of a strain were found persistently in two dairies), from cheese (one), from milk (one) and the reference strain for serovar 1/2b (CECT 936). The two milk isolates with low virulence in the PFA were found to be virulent in mice. In conclusion, all the isolates from food and food-related environments were potentially virulent or highly virulent. These results stress the risk of listeriosis associated with the consumption of cheese contaminated with L. monocytogenes, and once more emphasize the importance of good manufacturing practices (GMPs) together with sanitation standard operating procedures (SSOPs) throughout the food chain.

Pulsed-field gel electrophoresis (PFGE) analysis of Listeria monocytogenes isolates from different sources and geographical origins and representative of the twelve serovars.

Multiplex-PCR (MPCR) serogrouping and pulsed-field gel electrophoresis (PFGE) subtyping analysis are currently used by several public and private laboratories for the characterization of Listeria monocytogenes. In this study a set of 80 L. monocytogenes isolates belonging to the twelve serovars was used to investigate (i) the typeability of the rare serovars, (ii) the ability of PFGE analysis with ApaI and AscI to differentiate serovars within MPCR serogroups and (iii) the association of molecular types with the specific source or geographical origin of the isolates. With the exception of three isolates (rare serovars 4a and 4c) that were not amenable to restriction with ApaI, all the other analyzed isolates were subtyped by both enzymes. PFGE discriminated the 80 isolates into 62 combined ApaI and AscI PFGE patterns (pulsotypes), but could not differentiate serovars within MPCR serogroups, in which isolates from different serovars displaying the same pulsotype were found. Clustering analysis suggests that for some pulsotypes grouping according to Portuguese origin or source can be suggested. On the other hand, some L. monocytogenes clones are widely distributed. Two pulsotypes from Portuguese human isolates were identical to the ones displayed by human outbreak clones in the UK and in the USA and Switzerland, respectively, although they were not temporally matched. Computer-assisted data analysis of large and diverse PFGE type databases will improve the correct interpretation of subtyping data in epidemiological studies and in tracing routes and sources of contamination in the food industry.

Listeria monocytogenes cells under nutrient deprivation showed reduced ability to infect the human intestinal cell line HT-29.

PURPOSE: This study aimed to evaluate the effect of two types of stress, cold and nutritional, on the viability and the in vitro virulence of the foodborne pathogenic bacteria Listeria monocytogenes. METHODOLOGY: Ten diverse isolates were kept in phosphate-buffered saline (PBS) at optimal (37 °C) or at refrigeration temperature (7 °C), for 1 and 7 days. The viability of the cells [log colony-forming units (c.f.u.)/ml] and their in vitro virulence, before and after storage in these conditions, were investigated. In vitro virulence (log PFA) was evaluated using the human intestinal epithelial cell line HT-29 in plaque-forming assays (PFAs).Results/Key findings. In general, when compared with the conditions at 37 °C, the exposure at 7 °C for 7 days seemed to increase the resistance of the isolates to nutritional stress. Nutritional stress per se acted significantly to decrease the in vitro virulence of the isolates. After 7 days of nutrient deprivation, whether at optimal or at refrigeration temperature, the majority of the isolates assumed a low-virulence phenotype. CONCLUSION: Our results suggest that when L. monocytogenes are in refrigerated post-processing environments that are unable to support their growth they may increase their resistance to nutritional stress and may decrease their virulence. This should be considered when performing risk assessments for refrigerated ready-to-eat (RTE) foods.

Impacto de Marcadores Inflamatórios no Prognóstico de Pacientes Oncológicos Internados no Instituto Nacional de Câncer com SARS-CoV-2 na Primeira Onda da Pandemia no Brasil / Impact of Inflammatory Markers on the Prognosis of Patients with Cancer Admitted to the National Cancer Institute with SARS-CoV-2 in the First Wave of the Pandemic in Brazil / Impacto de los Marcadores Inflamatorios en el Pronóstico de Pacientes con Cáncer Ingresados en el Instituto Nacional del Cáncer con SARS-CoV-2 en la Primera Ola de la Pandemia en el Brasil

Introdução: O intenso processo inflamatório desencadeado pela covid-19 tem sido apontado por diversos autores. Objetivo: Avaliar o impacto de marcadores inflamatórios no prognóstico de pacientes com tumores sólidos internados com SARS-CoV-2/covid-19 na primeira onda da pandemia no Brasil. Método: Estudo de coorte com pacientes maiores de 18 anos com câncer, internados em um centro público de referência no tratamento oncológico, com SARS-CoV-2/covid-19, no período de março a setembro de 2020. Os seguintes marcadores inflamatórios foram analisados: razão neutrófilo-linfócito (RNL), derivação da razão neutrófilo-linfócito (dRNL) e razão plaqueta-linfócito (RPL). Foi considerado desfecho deste estudo a ocorrência de óbito durante a internação hospitalar. A associação entre as variáveis independentes e o desfecho foi analisada por meio de regressão logística univariada e múltipla. Resultados: Dos 185 pacientes, a maioria apresentava idade < 65 anos (61,1%), performance status (PS) ≥ 2 (82,4%) e estavam em tratamento oncológico (80,0%). O câncer de mama foi o tumor mais frequente (26,5%). Para a maior parte dos casos, o tempo de internação foi ≥ 5 dias (59,5%) e ocorreu em unidade de tratamento intensivo (84,3%). Durante a internação, 86 (46,5%) pacientes evoluíram para óbito. Na análise ajustada, apenas a RNL elevada (≥ 4,44) esteve associada ao risco de morrer (OR 3,54; IC 95%; 1,68 - 7,46; p = 0,001). Conclusão: A RNL se mostrou um importante marcador prognóstico, e níveis acima do seu valor mediano estiveram relacionados ao aumento do risco de morte durante a internação hospitalar

Introduction: The intense inflammatory process triggered by COVID-19 has been pointed out by several authors. Objective: To evaluate the impact of inflammatory markers on the prognosis of patients with solid tumors hospitalized with SARS-CoV-2/COVID-19 in the first wave of the pandemic in Brazil. Method: A cohort study of patients >18 years old with cancer, hospitalized at a public cancer treatment reference center, with SARS-CoV-2/COVID-19 from March to September 2020. The following inflammatory markers were analyzed: neutrophil-lymphocyte ratio (NLR), derivation of the neutrophil-lymphocyte ratio (dNLR) and platelet-lymphocyte ratio (PLR). The outcome of this study was death during hospitalization. The association between the independent variables and the outcome was analyzed using univariate and multiple logistic regression. Results: Of the 185 patients, most were aged < 65 years (61.1%), had performance status (PS) ≥ 2 (82.4%) and were in cancer treatment (80.0%). Breast cancer was the most frequent tumor (26.5%). For the majority of the cases, the length of hospital stay was ≥ 5 days (59.5%) and occurred in the intensive treatment unit (84.3%). During hospitalization, 86 (46.5%) patients progressed to death. In the adjusted analysis only high NLR (≥ 4.44) was associated with the risk of death (OR 3.54; 95% CI; 1.68 - 7.46; p = 0.001). Conclusion: NLR proved to be an important prognostic marker, and levels above its median value were related to an increased risk of death during hospitalization

Introducción: El papel de la inflamación desencadenada por la COVID-19 ha sido señalado por varios autores. Objetivo: Evaluar el impacto de los marcadores inflamatorios en el pronóstico de pacientes con tumores sólidos hospitalizados por SARS-CoV-2/COVID-19 en la primera ola de la pandemia en el Brasil. Método: Estudio de cohorte con pacientes >18 años con cáncer, ingresados en un centro público de referencia en el tratamiento del cáncer, con SARS-CoV-2/COVID-19 de marzo a septiembre de 2020. Se evaluaron los siguientes marcadores inflamatorios: relación neutrófilos-linfocitos (RNL), derivación de la relación neutrófilos-linfocitos (dRNL) y relación plaquetas-linfocitos (RPL). Se consideró como desenlace de este estudio la ocurrencia de muerte durante la hospitalización. La asociación entre las variables independientes y el desenlace se analizó mediante regresión logística univariada y múltiple. Resultados: De los 185 pacientes hospitalizados, la mayoría tenía una edad < 65 años (61,1%), un performance status (PS) ≥ 2 (82,4%) y estaban en tratamiento oncológico (80,0 %). El cáncer de mama fue el tumor más frecuente (26,5%). Para la mayoría de los casos, el tiempo de hospitalización fue ≥ 5 días (59,5%) y ocurrió en la unidad de tratamiento intensivo (84,3%). Durante la hospitalización, 86 (46,5%) pacientes terminaron falleciendo. En el análisis ajustado, solo una RNL alta (≥ 4,44) se asoció con el riesgo de muerte (OR 3,54; IC 95%; 1,68 - 7,46; p = 0,001). Conclusión: La RNL demostró ser un importante marcador pronóstico, y los niveles por encima de su valor medio se relacionaron con un mayor riesgo de muerte durante la hospitalización

Benznidazole treatment decreases IL-6 levels in Trypanosoma cruzi-infected human adipocytes differentiated from adipose tissue-derived stem cells

BACKGROUND Trypanosoma cruzi, which causes Chagas disease (CD), is a versatile haemoparasite that uses several strategies to evade the host's immune response, including adipose tissue (AT), used as a reservoir of infection. As it is an effective barrier to parasite evasion, the effectiveness of the drug recommended for treating CD, Benznidazole (BZ), may be questionable. OBJECTIVE To this end, we evaluated the parasite load and immunomodulation caused by BZ treatment in the culture of adipocytes differentiated from human adipose tissue-derived stem cells (ADSC) infected with T. cruzi. METHODS The ADSC were subjected to adipogenic differentiation. We then carried out four cultures in which we infected the differentiated AT with trypomastigote forms of the Y strain of T. cruzi and treated them with BZ. After the incubation, the infected AT was subjected to quantitative polymerase chain reaction (qPCR) to quantify the parasite load and transmission electron microscopy (TEM) to verify the infection. The supernatant was collected to measure cytokines, chemokines, and adipokines. FINDINGS We found elevated secretion of IL-6, CXCL-10/IP-10, CCL2/MCP-1, CCL5/RANTES, and leptin in infected fat cells. However, treatment with BZ promoted a decrease in IL-6. MAIN CONCLUSION Therefore, we believe that BZ has a beneficial role as it reduces inflammation in infected fat cells.

Tratamento da broncodisplasia pulmonar: uma revisão sistemática / Treatment of pulmonary broncodysplasia: a systematic review

Introdução: Displasia broncopulmonar (DBP) é uma grave complicação entre pré-termos, com incidência inversamente proporcional à idade gestacional. Resulta de processo inflamatório com desenvolvimento pulmonar anormal, gerando graves consequências. Apesar de serem limitadas e não afetarem substancialmente a evolução da doença, as opções terapêuticas para prevenção e tratamento da DBP são importantes, porém carecem de melhor elucidação. Objetivos: Abordar aspectos recentes da literatura quanto à prevenção e tratamento da DBP. Métodos: Revisão de literatura na base de dados MEDLINE, em 2021, incluindo ensaios clínicos controlados e randomizados, realizados em humanos e nos últimos 5 anos, excluindo estudos não diretamente relacionados ao tema. Resultados: A incidência de DBP foi menor naqueles casos leves expostos à budesonida inalatória, óleo de peixe intravenoso contendo emulsão lipídica (OP) e ácido docosahexaenoico (DHA). Houve aumento da sobrevida com uso de hidrocortisona em baixas doses, dexametasona com redução gradual da dose, por 42 dias, e dexametasona associada a corticosteroides pós-natais (este ainda com redução dos prejuízos no neurodesenvolvimento). Hidrocortisona, dexametasona, dipropianato de hidrofluoalcano-beclometasona inalado e OP reduziram o tempo ou a necessidade de ventilação e oxigenoterapia. A mortalidade foi menor nos estudos envolvendo hidrocortisona e elevada no que avaliou budesonida. As principais complicações foram sepse, retinopatia, hemorragia intraventricular e enterocolite necrosante, nos estudos abordando DHA, hidrocortisona, dexametasona e óxido nítrico inalado. Conclusão: Abordagens terapêuticas satisfatórias foram os glicocorticoides associado à terapia ventilatória e à abordagem precoce. Não houve benefícios com uso de ventilação com insuflações sustentadas, administração de dipropionato de hidrofluoralcano-beclometasona inalada e DHA.

Introduction: Bronchopulmonary dysplasia (BPD) is a complication among preterms, with an incidence inversely proportional to gestational age. It results from an inflammatory process that causes abnormal lung development, with severe consequences. Although therapeutic options are limited and do not substantially strike the course of the disease, they are important tools and need further elucidation. Purpose: Address the most recent aspects of the literature regarding the prevention and treatment of BPD. Methods: A literature review was carried out in the MEDLINE database, in 2021, in which only controlled and randomized clinical studies performed in humans in the last 5 years were included. Studies that were not directly related to the theme were excluded. Results: The incidence of BPD was lower in those cases exposed to inhaled budesonide, intravenous fish oil containing lipid emulsion (FO) and docosahexaenoic acid (DHA). There was improvement in survival with a lowdose use of hydrocortisone, dexamethasone with gradual dose reduction, and dexamethasone associated with postnatal corticosteroids (which generated reduction in neurodevelopmental impairments as well). Hydrocortisone, dexamethasone, inhaled hydrofluoalkane-beclomethasone dipropynate and FO reduced the time or need for ventilation and oxygen therapy. The main complications were sepsis, retinopathy, intraventricular hemorrhage and necrotizing enterocolitis in studies that addressed DHA, hydrocortisone, dexamethasone and inhaled nitric oxide. Conclusion: The therapeutic approaches that proved to be conclusive were the use of glucocorticoids associated with ventilatory therapy and an early approach. No benefits were found with the use of ventilation with sustained inflation, administration of inhaled hydrofluoralkane-beclomethasone dipropionate and DHA.

Lactobacillus plantarum LB95 impairs the virulence potential of Gram-positive and Gram-negative food-borne pathogens in HT-29 and Vero cell cultures.

Listeria monocytogenes, Salmonella enterica and verocytotoxigenic Escherichia coli (VTEC) are amongst the most important agents responsible for food outbreaks occurring worldwide. In this work, two Lactobacillus spp. strains (LABs), Lactobacillus plantarum (LB95) and Lactobacillus paraplantarum (LB13), previously isolated from spontaneously fermenting olive brines, and two reference probiotic strains, Lactobacillus casei Shirota and Lactobacillus rhamnosus GG, were investigated for their ability to attenuate the virulence of the aforementioned pathogens using animal cell culture assays. In competitive exclusion assays, the relative percentages of adhesion and invasion of S. enterica subsp. enterica serovar Enteritidis were significantly reduced when the human HT-29 cell line was previously exposed to LB95. The relative percentage of invasion by Listeria monocytogenes was significantly reduced when HT-29 cells were previously exposed to LB95. In the cytotoxicity assays, the cell-free supernatant of the co-culture (CFSC)of VTEC with LB95 accounted for the lowest value obtained amongst the co-cultures of VTEC with LABs, and was significantly lower than the value obtained with the co-culture of VTEC with the two probiotic reference strains. The cytotoxicity of CFSC of VTEC with both LB95 and LB13 exhibited values not significantly different from the cell-free supernatant of the nonpathogenic E. coli B strain. Our results suggested that LB95 may be able to attenuate the virulence of Gram-positive and Gram-negative food-borne pathogens; together with other reported features of these strains, our data reveal their possible use in probiotic foods due to their interesting potential in preventing enteric infections in humans.

Perfil epidemiológico do escorpionismo em crianças no estado de Pernambuco, 2015-2019 / Epidemiological profile of scorpionism in children in the state of Pernambuco, 2015-2019 / Perfil epidemiológico del escorpionismo en niños del estado de Pernambuco, 2015-2019

Objetivo: Analisar o perfil epidemiológico do escorpionismo em crianças, no Estado de Pernambuco, nos anos de 2015 a 2019. Métodos: Trata-se de um estudo ecológico, de caráter exploratório, cujo dados foram extraídos do Sistema de Informação de Agravos de Notificação (fichas de notificação preenchidas no período de 2015 a 2019). A análise dos dados foi realizada por meio do Statistical Package for the Social Sciences versão 20.0. Resultados: Entre 2015 e 2019 foram registrados 17.825 acidentes com escorpiões em crianças de até 14 anos no Estado de Pernambuco. A faixa etária mais acometida foi a de 5 a 9 anos (32,70%). Crianças de 0 a 4 anos de idade apresentaram duas vezes mais chances de apresentar quadro clínico grave (p: <0,001; OR: 2,353; IC95%:1,650 ­ 4,782). Conclusão: Houve uma elevada taxa de agravos no período analisado, especialmente em crianças em início de vida escolar, suscitando medidas de prevenção mais eficazes.(AU)

Objective: To analyze the epidemiological profile of scorpionism in children, in the State of Pernambuco, in the years 2015 to 2019. Methods: This is an ecological, exploratory study, whose data were extracted from the Notifiable Diseases Information System (data sheets). notification completed from 2015 to 2019). Data analysis was performed using the Statistical Package for the Social Sciences version 20.0. Results: Between 2015 and 2019 there were 17,825 accidents involving scorpions in children up to 14 years old in the State of Pernambuco. The most affected age group was 5 to 9 years old (32.70%). Children from 0 to 4 years of age were twice as likely to have a severe clinical condition (p: <0.001; OR: 2.353; 95% CI: 1.650 - 4.782). Conclusion: There was a high rate of injuries in the analyzed period, especially in children at the beginning of school life, giving rise to more effective prevention measures.(AU)

Objetivo: Analizar el perfil epidemiológico del escorpionismo en niños, en el estado de Pernambuco, en los años 2015 a 2019. Métodos: Este es un estudio exploratorio ecológico, cuyos datos fueron extraídos del Sistema de Información de Enfermedades Notificables (fichas técnicas). notificación completada de 2015 a 2019). El análisis de los datos se realizó utilizando el Statistical Package for the Social Sciences versión 20.0. Resultados: Entre 2015 y 2019 se produjeron 17,825 accidentes con escorpiones en niños de hasta 14 años en el estado de Pernambuco. El grupo de edad más afectado fue el de 5 a 9 años (32,70%). Los niños de 0 a 4 años tenían el doble de probabilidades de tener una enfermedad clínica grave (p: <0,001; OR: 2,353; IC del 95%: 1,650 - 4,782). Conclusión: Hubo una alta tasa de lesiones en el período analizado, especialmente en niños al inicio de la vida escolar, dando lugar a medidas de prevención más efectivas.(AU)

Performance and economic viability of tambaqui, Colossoma macropomum, selectively bred for weight gain

Tambaqui, Colossoma macropomum, is one of the most produced species in Brazilian fish farming, which has boosted the development of new technologies to increase its productivity. The aim of this study was to evaluate production performance in two second-generation tambaqui stocks selectively bred for weight gain in a semi-intensive rearing system and assess its influence on total production cost. We analyzed 300 fish (initial mean weight and standard length of 160 g and 17 cm, respectively) of two families (A and B, 150 fish each). The fish were individually marked with microchips and stocked in an 800-m2 excavated pond. For economic analysis, the obtained performance data were extrapolated for a fish farm with a 10-ha pond, adopting the Total Production Cost methodology. After 270 days of farming, the fish from family B were significantly superior (p < 0.05) for all analyzed performance parameters (final weight = 1965.0 g; weight gain = 1786.7 g; biomass gain = 255.2 kg) and morphometric growth in relation to the fish from family A (final weight = 1881.0 g; weight gain = 1737.5 g; biomass gain: 217.7 kg). The total production cost estimations indicated that fish from family B would allow for a 4% reduction in the average fixed cost and a 1% decrease in the total average production cost. (AU)

Nuts and Cardiovascular Diseases: Focus on Brazil Nuts

Cardiovascular diseases (CVD) are the main cause of death globally and most CVD can be prevented by addressing their risk factors, such as an unhealthy diet. Many authors have studied the benefits of nut consumption on CVD. Nuts contain high amounts of vegetable protein, unsaturated fatty acids, dietary fibers, vitamins, minerals and many other bioactive compounds, like phytosterols and phenolic compounds, which are able to reduce cholesterol levels and promote antioxidant and anti-inflammatory effects, thereby reducing cardiovascular risks. This review aims to describe studies involving the consumption of nuts, including Brazil nuts and CVD risk factors with positive results in the improvement of lipid profile, glucose metabolism, vascular function, and inflammatory and oxidative stress biomarkers