Retinoblastoma is the most common primary intraocular tumor in childhood. Intra-arterial chemotherapy is becoming the standard of care for both first-line and rescue therapy, thus improving survival ...rates and decreasing the adverse effects of retinoblastoma treatment. Cardiorespiratory adverse events during general anesthesia for intra-arterial chemotherapy, including decreased lung compliance and bradycardia, have been described, but data regarding associated factors are still lacking. We aimed to assess the characteristics of patients and procedures associated with cardiorespiratory events during intra-arterial chemotherapy.
We performed a prospective monocenter observational study in children diagnosed with retinoblastoma undergoing intra-arterial chemotherapy under general anesthesia. The occurrence of cardiorespiratory events was registered. We also assessed clinical and procedural characteristics potentially associated with these events.
A cardiorespiratory event was observed in 22 (12.5%) procedures, predominantly a decrease in tidal volume observed in 16 (9%) procedures. The median age was lower in the procedures with a cardiorespiratory event (20.43 SD, 11.76 months versus 30.11 SD, 24.17 months) (
< .05). Other variables such as bilateral disease or a previous intra-arterial chemotherapy treatment were not associated with the occurrence of a cardiorespiratory event.
In children undergoing intra-arterial chemotherapy for retinoblastoma treatment, cardiorespiratory events were observed in 12.5% of procedures. Lower age was associated with this complication. Although predominantly mild, these events should have prompt diagnosis and treatment to prevent further deterioration and worse outcomes.
As humans age, their immune system undergoes modifications, including a low-grade inflammatory status called inflammaging. These changes are associated with a loss of physical and immune resilience, ...amplifying the risk of being malnourished and frail. Under the COVID-19 scenario, inflammaging increases the susceptibility to poor prognostics. We aimed to bring the current concepts of inflammaging and its relationship with frailty and COVID-19 prognostic; highlight the importance of evaluating the nutritional risk together with frailty aiming to monitor older adults in COVID-19 scenario; explore some compounds with potential to modulate inflammaging in perspective to manage the COVID-19 infection. Substances such as probiotics and senolytics can help reduce the high inflammatory status. Also, the periodic evaluation of nutrition risk and frailty will allow interventions, assuring the appropriate care.
Abstract Since the classic studies of Alexander Flemming, Penicillium strains have been known as a rich source of antimicrobial substances. Recent studies have identified novel metabolites produced ...by Penicillium sclerotiorum that have antibacterial, antifouling and pharmaceutical activities. Here, we report the isolation of a P. sclerotiorum (LM 5679) from Amazonian soil and carry out a culture-based study to determine whether it can produce any novel secondary metabolite(s) that are not thus-far reported for this genus. Using a submerged culture system, secondary metabolites were recovered by solvent extract followed by thin-layer chromatography, nuclear magnetic resonance, and mass spectroscopy. One novel secondary metabolite was isolated from P. sclerotiorum (LM 5679); the phenolic compound 5-pentadecyl resorcinol widely known as an antifungal, that is produced by diverse plant species. This metabolite was not reported previously in any Penicillium species and was only found once before in fungi (that time, in a Fusarium). Here, we discuss the known activities of 5-pentadecyl resorcinol in the context of its mode-of-action as a hydrophobic (chaotropicity-mediated) stressor.
Resumo Desde os estudos clássicos de Alexander Flemming, as cepas de Penicillium são conhecidas como uma fonte rica em substâncias antimicrobianas. Estudos recentes identificaram novos metabólitos produzidos pela espécie Penicillium sclerotiorum com atividades antibacteriana, anti-incrustante e farmacêutica. Aqui, relatamos o isolamento de uma colônia de P. sclerotiorum (LM 5679) do solo amazônico e relatamos também o estudo baseado em cultura para determinar se ele pode produzir qualquer novo metabólito (s) secundário (s) que não foram relatados até agora para este gênero. Usando um sistema de cultura submerso, os metabólitos secundários foram recuperados por extrato de solvente seguido por cromatografia em camada delgada, ressonância magnética nuclear e espectroscopia de massa. Um novo metabólito secundário foi isolado de P. sclerotiorum (LM 5679); o composto fenólico 5-pentadecil resorcinol que é amplamente conhecido como um antifúngico que é produzido por diversas espécies de plantas. Este metabólito não foi relatado anteriormente em nenhuma espécie de Penicillium, e foi encontrado apenas uma vez em fungos (Fusarium). Aqui, discutimos as atividades conhecidas do 5-pentadecil resorcinol no contexto de seu modo de ação como um estressor hidrofóbico (mediado pela caotropicidade).
Obesity is associated with metabolic and physiological effects in the gut. In this study, we evaluated the anti-inflammatory effect of trypsin inhibitor isolated from tamarind seeds (TTI) in vitro ...(interaction with lipopolysaccharide (LPS) and inhibitory activity against human neutrophil elastase (HNE)), and using intestinal co-cultures of Caco-2:HT29-MTX cell lines inflamed with TNF-α (50 ng/mL) and a Wistar rat model of diet-induced obesity (n = 15). TTI was administered to animals by gavage (10 days), and the treated group (25 mg/kg/day) was compared to animals without treatment or treated with a nutritionally adequate diet. In the in vitro study, it showed inhibitory activity against HNE (93%). In co-cultures, there was no protection or recovery of the integrity of inflamed cell monolayers treated with TTI (1.0 mg/mL). In animals, TTI led to lower plasma concentrations of TNF-α and IL-6, total leukocytes, fasting glucose, and LDL-c (p < 0.05). The intestines demonstrated a lower degree of chronic enteritis, greater preservation of the submucosa, and greater intestinal wall thickness than the other groups (p = 0.042). Therefore, the better appearance of the intestine not reflected in the intestinal permeability added to the in vitro activity against HNE point to possibilities for new studies and applications related to this activity.
Candida auris and Candida haemulonii are two emerging opportunistic pathogens that have caused an increase in clinical cases in the recent years worldwide. The differentiation of some Candida species ...is highly laborious, difficult, costly, and time-consuming depending on the similarity between the species. Thus, this study aimed to develop a new, faster, and less expensive methodology for differentiating between C . auris and C. haemulonii based on near-infrared (NIR) spectroscopy and multivariate analysis. C. auris CBS10913 and C. haemulonii CH02 were separated in 15 plates per species, and three isolated colonies of each plate were selected for Fourier transform near-infrared (FT-NIR) analysis, totaling 90 spectra. Subsequently, principal component analysis (PCA) and variable selection algorithms, including the successive projections algorithm (SPA) and genetic algorithm (GA) coupled with linear discriminant analysis (LDA), were employed to discern distinctive patterns among the samples. The use of PCA, SPA, and GA algorithms associated with LDA achieved 100% sensitivity and specificity for the discriminations. The SPA-LDA and GA-LDA algorithms were essential in selecting the variables (infrared wavelengths) of most importance for the models, which could be attributed to binding of cell wall structures such as polysaccharides, peptides, proteins, or molecules resulting from yeasts’ metabolism. These results show the high potential of combined FT-NIR and multivariate analysis techniques for the classification of Candida -like fungi, which can contribute to faster and more effective diagnosis and treatment of patients affected by these microorganisms.
Parkinson's disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive ...impairment. To test this in PD, we promoted a lesion within the substantia nigra
of rats using the neurotoxin rotenone. In the sequence, the animals were supplemented with folic acid and vitamin B12 for 14 consecutive days and subjected to the object recognition test. We observed an impairment in object recognition memory after rotenone administration, which was prevented by supplementation (
< 0.01). Supplementation may adjust gene expression through efficient DNA methylation. To verify this, we measured the expression and methylation of the kynureninase gene (
), whose product metabolizes neurotoxic metabolites often accumulated in PD as kynurenine. Supplementation prevented the decrease in
expression induced by rotenone in the substantia nigra (
< 0.05), corroborating the behavioral data. No differences were observed concerning the methylation analysis of two CpG sites in the
promoter. Instead, we suggest that folic acid and vitamin B12 increased global DNA methylation, reduced the expression of
inhibitors, maintained Kynu-dependent pathway homeostasis, and prevented the memory impairment induced by rotenone. Our study raises the possibility of adjuvant therapy for PD with folic acid and vitamin B12.
The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain.
To ...determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy.
Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS.
An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning.
The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality.
A total of 1010 patients (37.5% female; mean SD age, 50.9 17.4 years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio HR, 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.
In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.
clinicaltrials.gov Identifier: NCT01374022.
Background The natural history of latent rheumatic heart disease (RHD) detected by echocardiography remains unclear. We aimed to assess the accuracy of a simplified score based on the 2012 World ...Heart Federation criteria in predicting mid-term RHD echocardiography outcomes in children from 4 different countries. Methods and Results Patient-level baseline and follow-up data of children with latent RHD from 4 countries (Australia, n=62; Brazil, n=197; Malawi, n=40; New Zealand, n=94) were combined. A simplified echocardiographic scoring system previously developed from Brazilian and Ugandan cohorts, consisting of 5 point-based variables with respective weights, was applied: mitral valveanterior leaflet thickening (weight=3), excessive leaflet tip motion (3), regurgitation jet length ≥2 cm (6), aortic valve focal thickening (4), and any regurgitation (5). Unfavorable outcome was defined as worsening diagnostic category, persistent definite RHD or development/worsening of valve regurgitation/stenosis. The score model was updated using methods for recalibration. 393 patients (314 borderline, 79 definite RHD) with median follow-up of 36 (interquartile range, 25-48) months were included. Median age was 14 (interquartile range, 11-16) years and secondary prophylaxis was prescribed to 16%. The echocardiographic score model applied to this external population showed significant association with unfavorable outcome (hazard ratio, 1.10; 95% CI, 1.04-1.16;
=0.001). Unfavorable outcome rates in low (≤5 points), intermediate (6-9), and high-risk (≥10) children at 3-year follow-up were 14.3%, 20.8%, and 38.5% respectively (
<0.001). The updated score model showed good performance in predicting unfavorable outcome. Conclusions The echocardiographic score model for predicting RHD outcome was updated and validated for different latent RHD populations. It has potential utility in the clinical and screening setting for risk stratification of latent RHD.
The purpose of this study was to demonstrate the usefulness of lectin obtained from Talisia esculenta (TEL) seeds as a tool to recognize and study Microsporum canis. For this purpose, we investigated ...the antifungal and marker action of this lectin and the relationship of these effects with the presence of carbohydrates on the structure of this fungus. The in vitro antifungal activity of TEL was analysed by broth microdilution assay. In addition, TEL was assessed against the arthroconidia present on hairs obtained from infected dogs and cats. The affinity of fluorescein isothiocyanate (FITC)-labelled TEL for macroconidia and arthroconidia of M. canis was also tested. The effects of TEL on the growth of the M. canis strains began with 0·125 mg ml⁻¹, and 100% inhibition was obtained with a concentration of 2 mg ml⁻¹. The addition of carbohydrates, especially N-acetyl-glucosamine and d-mannose, inhibited these antifungal effects. TEL was able to inhibit the growth of arthroconidial chitin-rich forms of M. canis obtained from hairs of infected animals and strains cultured in Sabouraud agar. FITC-labelled TEL efficiently marked macroconidial and arthroconidial forms of M. canis, as shown by fluorescent microscopy. These results show that the inhibitory effects of TEL on M. canis growth may be related to the interaction of lectin with the carbohydrates present at the micro-organism's surface, mainly d-mannose and N-acetyl-glucosamine. Talisia esculenta can be used as an important tool in the biochemical study of M. canis or as a molecule to recognize this dermatophyte in infected tissue.
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