Utrasound as a method for confirming the positioning of enteral catheters in critically ill patients.

AIM: To evaluate the agreement between the bedside ultrasound in a single epigastric window and the plain X-ray to confirm the positioning of the enteral catheter in critically ill patients. MATERIAL AND METHODS: This was an observational, cross-sectional study conducted in two Intensive Care Units of a university hospital. The ultrasound exams were carried out immediately after the introduction of the enteral catheter, using only the epigastric window, with an injection of 5 ml of air associated with 5 ml of saline solution. In all cases, the plain radiography was taken to confirm the positioning of the enteral catheter and to define the beginning of nutritional therapy. RESULTS: This study included 83 patients, the positioning of the enteral catheter was confirmed by plain radiography in all cases and by ultrasound in 81 (97.6%) patients. The median duration of the ultrasound exam was 2 (2-3) minutes, while the time spent between the request for the X-ray and the release of the exam for a doctor's appointment was 225 (120-330) minutes. CONCLUSION: Bedside ultrasound proved to be an effective, quick, and safe method to confirm the position of the enteral catheter in critically ill patients.

Seasonal and circadian variation of non-volatile metabolites in Lippia alba leaves.

The present study describes the seasonal and circadian variations of the major compounds from Lippia alba leaves. SPSS was used to identify, quantify, and associate the variations in the secondary metabolites of this species through HPLC/DAD analysis of the leaves hydroethanolic extracts of six selected L. alba specimens. For the circadian study, the samples were collected at four different daily hours in each year's season. For the seasonal study, the samples were collected monthly from the same individuals for two consecutive years (2018 and 2019). These samples were analyzed and quantified using a validated HPLC method for flavonoids, iridoids, and phenyl ethanoid glycoside. Mussaenoside, acteoside, and tricin-7-O-diglucuronide showed a moderate positive correlation between their biosynthesis and the precipitation index, while epi-loganin had a moderate negative correlation. Acteoside showed a moderate positive correlation between the minimum registered temperature and its production. Compared with previous studies, a drastic reduction (about 95%) in the production of tricin-7-O-diglucuronide compared with previous study and this difference could be attributed to the plant's aging. Thus, the data demonstrated that lower temperatures and high rainfall could favor the production of the major L. alba active compounds (acteoside and tricin-7-O-diglucuronide) and that older plants harm their production.

Clinical characteristics and outcomes in COVID-19 in kidney transplant recipients: a propensity score matched cohort study.

Patients with chronic kidney disease (CKD), especially those on dialysis or who have received a kidney transplant (KT), are considered more vulnerable to severe COVID-19. This susceptibility is attributed to advanced age, a higher frequency of comorbidities, and the chronic immunosuppressed state, which may exacerbate their susceptibility to severe outcomes. Therefore, our study aimed to compare the clinical characteristics and outcomes of COVID-19 in KT patients with those on chronic dialysis and non-CKD patients in a propensity score-matched cohort study. This multicentric retrospective cohort included adult COVID-19 laboratory-confirmed patients admitted from March/2020 to July/2022, from 43 Brazilian hospitals. The primary outcome was in-hospital mortality. Propensity score analysis matched KT recipients with controls - patients on chronic dialysis and those without CKD (within 0.25 standard deviations of the logit of the propensity score) - according to age, sex, number of comorbidities, and admission year. This study included 555 patients: 163 KT, 146 on chronic dialysis, and 249 non-CKD patients (median age 57 years, 55.2% women). With regards to clinical outcomes, chronic dialysis patients had a higher prevalence of acute heart failure, compared to KT recipients, furthermore, both groups presented high in-hospital mortality, 34.0 and 28.1%, for KT and chronic dialysis patients, respectively. When comparing KT and non-CKD patients, the first group had a higher incidence of in-hospital dialysis (26.4% vs. 8.8%, p < 0.001), septic shock (24.1% vs. 12.0%, p = 0.002), and mortality (32.5% vs. 23.3%, p = 0.039), in addition to longer time spent in the intensive care unit (ICU). In this study, chronic dialysis patients presented a higher prevalence of acute heart failure, compared to KT recipients, whereas KT patients had a higher frequency of complications than those without CKD, including septic shock, dialysis during hospitalization, and in-hospital mortality as well as longer time spent in the ICU.

AB2CO risk score for in-hospital mortality of COVID-19 patients admitted to intensive care units.

PURPOSE: To develop a mortality risk score for COVID-19 patients admitted to intensive care units (ICU), and to compare it with other existing scores. MATERIALS AND METHODS: This retrospective observational study included consecutive adult patients with laboratory-confirmed COVID-19 admitted to ICUs of 18 hospitals from nine Brazilian cities, from September 2021 to July 2022. Potential predictors were selected based on the literature review. Generalized Additive Models were used to examine outcomes and predictors. LASSO regression was used to derive the mortality score. RESULTS: From 558 patients, median age was 69 years (IQR 58-78), 56.3 % were men, 19.7 % required mechanical ventilation (MV), and 44.8 % died. The final model comprised six variables: age, pO2/FiO2, respiratory function (respiratory rate or if in MV), chronic obstructive pulmonary disease, and obesity. The AB2CO had an AUROC of 0.781 (95 % CI 0.744 to 0.819), good overall performance (Brier score = 0.191) and an excellent calibration (slope = 1.063, intercept = 0.015, p-value = 0.834). The model was compared with other scores and displayed better discrimination ability than the majority of them. CONCLUSIONS: The AB2CO score is a fast and easy tool to be used upon ICU admission.

Corrigendum: Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit.

[This corrects the article DOI: 10.3389/fmed.2023.1130218.].

Systematic Review and Meta-Analysis of Congenital Toxoplasmosis Diagnosis: Advances and Challenges.

Objective: To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis. Methods: PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum." We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis. Results: Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or T. gondii DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity. Conclusion: Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and T. gondii recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Assessment of the ABC2-SPH risk score to predict invasive mechanical ventilation in COVID-19 patients and comparison to other scores.

Background: Predicting the need for invasive mechanical ventilation (IMV) is important for the allocation of human and technological resources, improvement of surveillance, and use of effective therapeutic measures. This study aimed (i) to assess whether the ABC2-SPH score is able to predict the receipt of IMV in COVID-19 patients; (ii) to compare its performance with other existing scores; (iii) to perform score recalibration, and to assess whether recalibration improved prediction. Methods: Retrospective observational cohort, which included adult laboratory-confirmed COVID-19 patients admitted in 32 hospitals, from 14 Brazilian cities. This study was conducted in two stages: (i) for the assessment of the ABC2-SPH score and comparison with other available scores, patients hospitalized from July 31, 2020, to March 31, 2022, were included; (ii) for ABC2-SPH score recalibration and also comparison with other existing scores, patients admitted from January 1, 2021, to March 31, 2022, were enrolled. For both steps, the area under the receiving operator characteristic score (AUROC) was calculated for all scores, while a calibration plot was assessed only for the ABC2-SPH score. Comparisons between ABC2-SPH and the other scores followed the Delong Test recommendations. Logistic recalibration methods were used to improve results and adapt to the studied sample. Results: Overall, 9,350 patients were included in the study, the median age was 58.5 (IQR 47.0-69.0) years old, and 45.4% were women. Of those, 33.5% were admitted to the ICU, 25.2% received IMV, and 17.8% died. The ABC2-SPH score showed a significantly greater discriminatory capacity, than the CURB-65, STSS, and SUM scores, with potentialized results when we consider only patients younger than 80 years old (AUROC 0.714 [95% CI 0.698-0.731]). Thus, after the ABC2-SPH score recalibration, we observed improvements in calibration (slope = 1.135, intercept = 0.242) and overall performance (Brier score = 0.127). Conclusion: The ABC2-SPHr risk score demonstrated a good performance to predict the need for mechanical ventilation in COVID-19 hospitalized patients under 80 years of age.

Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal-fetal interface.

Introduction: Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection. Methods: In this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants. Results: Our results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease T. gondii proliferation, whereas T. cruzi infection increases T. gondii proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α production. Discussion: In conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor T. gondii infection.

Rhythmic profile of memory T and B-cells along childhood and adolescence.

Immunobiography describes the life-long effects of exogenous or endogenous stimuli on remodeling of immune cell biology, including the development of memory T and B-cells. The present study aimed at investigating the rhythms of changes in phenotypic features of memory T and B-cells along childhood and adolescence. A descriptive-observational investigation was conducted including 812 healthy volunteers, clustered into six consecutive age groups (9Mths-1Yr; 2Yrs; 3-4Yrs; 5-7Yrs; 8-10Yrs; 11-18Yrs). Immunophenotypic analysis of memory T-cell (CD4+ and CD8+) and B-cell subsets were performed by flow cytometry. The results pointed out that memory-related biomarkers of T and B-cells displayed a bimodal profile along healthy childhood and adolescence, regardless of sex. The first stage of changes occurs around 2Yrs, with predominance of naive cells, while the second and more prominent wave occurs around the age 8-10Yrs, with the prevalence of memory phenotypes. The neighborhood connectivity profile analysis demonstrated that the number of correlations reaches a peak at 11-18Yrs and lower values along the childhood. Males presented higher and conserved number of correlations when compared to females. Altogether, our results provide new insights into immunobiography and a better understanding of interactions among the cellular subsets studied here during childhood and adolescence.

Temporal validation of the MMCD score to predict kidney replacement therapy and in-hospital mortality in COVID-19 patients.

BACKGROUND: Acute kidney injury has been described as a common complication in patients hospitalized with COVID-19, which may lead to the need for kidney replacement therapy (KRT) in its most severe forms. Our group developed and validated the MMCD score in Brazilian COVID-19 patients to predict KRT, which showed excellent performance using data from 2020. This study aimed to validate the MMCD score in a large cohort of patients hospitalized with COVID-19 in a different pandemic phase and assess its performance to predict in-hospital mortality. METHODS: This study is part of the "Brazilian COVID-19 Registry", a retrospective observational cohort of consecutive patients hospitalized for laboratory-confirmed COVID-19 in 25 Brazilian hospitals between March 2021 and August 2022. The primary outcome was KRT during hospitalization and the secondary was in-hospital mortality. We also searched literature for other prediction models for KRT, to assess the results in our database. Performance was assessed using area under the receiving operator characteristic curve (AUROC) and the Brier score. RESULTS: A total of 9422 patients were included, 53.8% were men, with a median age of 59 (IQR 48-70) years old. The incidence of KRT was 8.8% and in-hospital mortality was 18.1%. The MMCD score had excellent discrimination and overall performance to predict KRT (AUROC: 0.916 [95% CI 0.909-0.924]; Brier score = 0.057). Despite the excellent discrimination and overall performance (AUROC: 0.922 [95% CI 0.914-0.929]; Brier score = 0.100), the calibration was not satisfactory concerning in-hospital mortality. A random forest model was applied in the database, with inferior performance to predict KRT requirement (AUROC: 0.71 [95% CI 0.69-0.73]). CONCLUSION: The MMCD score is not appropriate for in-hospital mortality but demonstrates an excellent predictive ability to predict KRT in COVID-19 patients. The instrument is low cost, objective, fast and accurate, and can contribute to supporting clinical decisions in the efficient allocation of assistance resources in patients with COVID-19.

Hepatic damage caused by flaviviruses: A systematic review.

Flaviviruses infect arthropods and mammals and their pathologies are a considerable global health problem, affecting about 400 million people per year. The symptoms of these flaviviruses range from mild manifestations such as nausea, vomiting, and headache to more serious cases such as hemorrhage, meningitis, microcephaly, kidney, and liver failure. This review aims to compile the morphological changes that occur due to infections caused by dengue, yellow fever, and Zika viruses, as well as to describe possible mechanisms of action of such flaviviruses in the liver. PRISMA guidelines were used to search for studies associating flavivirus with liver disorders. Two independent reviewers selected the studies on PubMed/Medline, Web of Science, and Scopus search platforms. The SYRCLE software was used for the evaluation of the study's quality. Eighteen experimental articles were included. The experimental animals often used in experiments were monkeys (5 %), hamsters (10 %), chicken embryos (10 %), and mice (75 %). It is evident that there is a strong hepatic interaction with flaviviruses, and the main hepatic alterations found were steatosis, apoptosis, necrosis, hemorrhage, elevation of ALT and AST levels, and total bilirubin. Flavivirus infection, in general, trigger an upregulation of pro-inflammatory cytokines, leading to structural changes in mitochondria that activate cascades of cellular death and promote insulin resistance. The majority of the studies primarily focus on dengue and yellow fever viruses, while the findings related to Zika virus exposure are still relatively limited and require further investigation.

Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit.

Objectives: To assess the ABC2-SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score). Materials and methods: Consecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC2-SPH was used as the reference score, and comparisons between ABC2-SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality. Results: ABC2-SPH had an area under the curve of 0.716 (95% CI 0.693-0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC2-SPH and SAPS-3, 4C Mortality Score, and the novel severity score. Conclusion: ABC2-SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients.

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy.

The conventional treatment of congenital toxoplasmosis is mainly based on the combination of sulfadiazine and pyrimethamine. However, therapy with these drugs is associated with severe side effects and resistance, requiring the study of new therapeutic strategies. There are currently many studies with natural products, including Copaifera oleoresin, showing actions against some pathogens, as Trypanosoma cruzi and Leishmania. In the present study, we investigated the effects of the leaf hydroalcoholic extract and oleoresin from Copaifera multijuga against Toxoplasma gondii in human villous (BeWo) and extravillous (HTR8/SVneo) trophoblast cells, as well as in human villous explants from third-trimester pregnancy. For this purpose, both cells and villous explants were infected or not with T. gondii, treated with hydroalcoholic extract or oleoresin from C. multijuga and analyzed for toxicity, parasite proliferation, cytokine and ROS production. In parallel, both cells were infected by tachyzoites pretreated with hydroalcoholic extract or oleoresin, and adhesion, invasion and replication of the parasite were observed. Our results showed that the extract and oleoresin did not trigger toxicity in small concentrations and were able to reduce the T. gondii intracellular proliferation in cells previously infected. Also, the hydroalcoholic extract and oleoresin demonstrated an irreversible antiparasitic action in BeWo and HTR8/SVneo cells. Next, adhesion, invasion and replication of T. gondii were dampened when BeWo or HTR8/SVneo cells were infected with pretreated tachyzoites. Finally, infected and treated BeWo cells upregulated IL-6 and downmodulated IL-8, while HTR8/SVneo cells did not change significantly these cytokines when infected and treated. Finally, both the extract and oleoresin reduced the T. gondii proliferation in human explants, and no significant changes were observed in relation to cytokine production. Thus, compounds from C. multijuga presented different antiparasitic activities that were dependent on the experimental model, being the direct action on tachyzoites a common mechanism operating in both cells and villi. Considering all these parameters, the hydroalcoholic extract and oleoresin from C. multijuga can be a target for the establishment of new therapeutic strategy for congenital toxoplasmosis.

Macrophage Migration Inhibitory Factor contributes to drive phenotypic and functional macrophages activation in response to Toxoplasma gondii infection.

Cytokines are small molecules secreted by numerous cells. Macrophage Migration Inhibitory Factor (MIF) is a cytokine initially described due to its function of inhibiting random macrophage migration. Currently, new functions have been described for MIF, such as stimulating inflammatory functions in response to infections by microorganisms including, Toxoplasma gondii. However, the primordial MIF function related to macrophages has been little addressed. The main purpose of the study was to recapitulate MIF function on macrophages in response to T. gondii infection. To achieve this goal, peritoneal macrophages were collected from C57BL/6WT and Mif1-/- mice after recruitment with thioglycolate. Macrophages were cultured, treated with 4-Iodo-6-phenylpyrimidine (4-IPP), and infected or not by T. gondii for 24 h. Following this, the culture supernatant was collected for cytokine, urea and nitrite analysis. In addition, macrophages were evaluated for phagocytic activity and T. gondii proliferation rates. Results demonstrated that T. gondii infection triggered an increase in MIF production in the WT group as well as an increase in the secretion of IL-10, TNF, IFN-γ, IL-6 and IL-17 in the WT and Mif1-/- macrophages. Regarding the comparison between groups, it was detected that Mif1-/- macrophages secreted more IL-10 compared to WT. On the other hand, the WT macrophages produced greater amounts of TNF, IFN-γ, IL-6 and IL-17. Urea production was more pronounced in Mif1-/- macrophages while nitrite production was higher in WT macrophages. T. gondii showed a greater ability to proliferate in Mif1-/- macrophages and these cells also presented enhanced phagocytic activity. In conclusion, T. gondii infection induces macrophage activation inciting cytokine production. In presence of MIF, T. gondii infected macrophages produce pro-inflammatory cytokines compatible with the M1 activation profile. MIF absence caused a dramatic reduction in pro-inflammatory cytokines that are balanced by increased levels of urea and anti-inflammatory cytokines. These macrophages presented increased phagocytic capacity and shared features activation with the M2 profile.

Mechanical ventilation and death in pregnant patients admitted for COVID-19: a prognostic analysis from the Brazilian COVID-19 registry score.

BACKGROUND: The assessment of clinical prognosis of pregnant COVID-19 patients at hospital presentation is challenging, due to physiological adaptations during pregnancy. Our aim was to assess the performance of the ABC2-SPH score to predict in-hospital mortality and mechanical ventilation support in pregnant patients with COVID-19, to assess the frequency of adverse pregnancy outcomes, and characteristics of pregnant women who died. METHODS: This multicenter cohort included consecutive pregnant patients with COVID-19 admitted to the participating hospitals, from April/2020 to March/2022. Primary outcomes were in-hospital mortality and the composite outcome of mechanical ventilation support and in-hospital mortality. Secondary endpoints were pregnancy outcomes. The overall discrimination of the model was presented as the area under the receiver operating characteristic curve (AUROC). Overall performance was assessed using the Brier score. RESULTS: From 350 pregnant patients (median age 30 [interquartile range (25.2, 35.0)] years-old]), 11.1% had hypertensive disorders, 19.7% required mechanical ventilation support and 6.0% died. The AUROC for in-hospital mortality and for the composite outcome were 0.809 (95% IC: 0.641-0.944) and 0.704 (95% IC: 0.617-0.792), respectively, with good overall performance (Brier = 0.0384 and 0.1610, respectively). Calibration was good for the prediction of in-hospital mortality, but poor for the composite outcome. Women who died had a median age 4 years-old higher, higher frequency of hypertensive disorders (38.1% vs. 9.4%, p < 0.001) and obesity (28.6% vs. 10.6%, p = 0.025) than those who were discharged alive, and their newborns had lower birth weight (2000 vs. 2813, p = 0.001) and five-minute Apgar score (3.0 vs. 8.0, p < 0.001). CONCLUSIONS: The ABC2-SPH score had good overall performance for in-hospital mortality and the composite outcome mechanical ventilation and in-hospital mortality. Calibration was good for the prediction of in-hospital mortality, but it was poor for the composite outcome. Therefore, the score may be useful to predict in-hospital mortality in pregnant patients with COVID-19, in addition to clinical judgment. Newborns from women who died had lower birth weight and Apgar score than those who were discharged alive.

Effects of Rooibos (Aspalathus linearis) on the Testicular Parenchyma of Adult BALB/C Mice Submitted to a Hypercaloric Diet

Oxidative stress due to obesity plays a detrimental role in the testicular microenvironment and sperm parameters. We explored the impact of a hypercaloric diet in male BALB/c mice as a condition to trigger damage to the spermatogenic process and the antioxidant effect of Aspalathus linearis as well. We used a hypercaloric diet in animals divided into 3 groups: Control, Hypercaloric diet control (HC) and Hypercaloric diet and Rooibos infusion (HCR). Morphometric parameters, enzyme dosages, cell viability, and tubular histopathology were evaluated. Body weight increased in HCR animals at weeks 3, 4, and 8. We found a reduction in seminiferous epithelium height, with an increase in the tubular diameter of the HCR group. Catalase levels were lower in HC and HCR, while carbonyl protein was decreased in HC. We estimate that it induces oxidative stress (OS) capable of affecting the seminiferous epithelium and that the infusion of A. linearis does not demonstrate a potential benefit in cell preservation.

Doxycycline hyclate may damage testicular germinal epithelium in Wistar rats

Broad-spectrum antimicrobial doxycycline acts as an inhibitor of protein synthesis and it is widely used in the clinical treatment of various infections by microorganisms that are sensitive to the drug, as well as in animal feed. Its liposolubility guarantees its high tissue bioavailability, being associated with several biochemical changes in the organism and potentially adverse effects on reproduction. This study aims to evaluate the effects of the action of doxycycline on spermatogenesis to provide a complete analysis of the tubular and interstitial compartments and to identify possible changes in the testicular parenchyma. Adult male Wistar rats were divided into three groups: one control (water), and two treated with doxycycline at the doses of 10mg/kg and 30mg/kg, for 30 days. After euthanasia and sample processing, the following parameters were evaluated: a) tubular diameter and height of the seminiferous epithelium; b) volumetric proportions (%) and volumes (mL) of the components of the testicular parenchyma; c) counting testicular germ cell populations; d) evaluation of cell viability. The results of the comparative evaluation between the experimental groups demonstrated a significant increase in the diameter and area of the tubular lumen and a reduction in the count of spermatogonia in the experimental group that received doxycycline hyclate at a dose of 30mg/kg. In the same experimental group, an increase in the overall yield of spermatogenesis was found as a consequence of the increase in the mitotic index.

The ethanolic extract of the fungus Trichoderma stromaticum decreases the Toxoplasma gondii replication in vitro and ameliorates the experimental toxoplasmosis in vivo.

Trichoderma are fungi that are well-known to inhibit the growth of a variety of plant pathogens. Currently, there is an increasing search for new drugs to treat toxoplasmosis. The aims of this study were to investigate the effect of ExtTs in the control of Toxoplasma gondii proliferation in vitro and the course of toxoplasmosis in a mouse model. Firstly, the cytotoxicity of the ExtTs was evaluated by cultivating macrophages with different concentrations of the extract and cell viability was assessed by the MTT assay. Next, the infectivity of the T. gondii treated with extract was analyzed by infecting J774 macrophages. To evaluate the effect of the ExtTs in vivo, C57BL/6 mice were infected orally with T. gondii, ME-49, treated daily with ExtTs, and clinical, biochemical and histological changes were monitored. It was demonstrated that the extract did not affect the host cellular viability and, the treatment of parasites with ExtTs altered their morphology and decreased their ability to proliferate inside macrophages. Additionally, the treatment of mice with ExtTs decreased the parasitism and inflammation in the small intestine and liver of infected mice in parallel with increased IL-10/TNF ratio systemically and prevented alterations to serum VLDL and triglyceride levels. Thus, ExtTs could be considered an alternative/complementary therapy to control toxoplasmosis.

Polarisation of human macrophages towards an M1 subtype triggered by an atypical Brazilian strain of Toxoplasma gondii results in a reduction in parasite burden.

Toxoplasma gondii Nicolle et Manceaux, 1909, the etiologic agent of toxoplasmosis, was considered a clonal population with three distinct genetic lineages (I, II and III); however, sequence analysis of different strains has revealed distinct atypical genotypes. Macrophages are essential for immunity against toxoplasmosis and differential cell regulation may affect the course of the disease. In this context, our study aims to investigate the infection by TgChBrUD2, a highly virulent atypical Brazilian strain of T. gondii, on the activation and polarisation of human macrophages. Human macrophage-like cells obtained from THP-1 cells were infected with TgChBrUD2, RH or ME49 strains of T. gondii to evaluate the impact of parasite infection on macrophage polarisation. Our results indicate that the TgChBrUD2 and ME49 strains of T. gondii induced a classic activation of human macrophages, which was confirmed by the high rate of spindle-shaped macrophages, low amount of urea and increase in the levels of nitrite, as well as the down-regulation of M2-markers. In contrast, RH strain promoted an alternative activation of macrophages. The polarisation of human macrophages towards an M1 subtype mediated by TgChBrUD2 and ME49 strains resulted in a low parasite burden, with high levels of IL-6 and MIF. Finally, the M2 subtype triggered by the RH strain culminated in a lower intracellular proliferation index. We concluded that the atypical (TgChBrUD2) and clonal (ME49) strains are able to elicit an M1 subtype, which results in parasitism control, partially explained by the high levels of IL-6 and MIF produced during the infection by these genotypes. In contrast, the clonal (RH) strain promoted a macrophage polarisation towards an M2 subtype, marked by a high parasite burden, with a weak modulation of pro-inflammatory cytokines. Thus, atypical strains can present different mechanisms of pathogenicity and transmissibility compared to clonal strains, as well as they can use distinct strategies to evade the host's immune response and ensure their survival.