The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition.

Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking, we propose that CYM blocks the interaction of cytochrome c with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that will be instrumental in driving informed management of the use of this fungicide.

A prolonged intensive care unit stay defines a worse long-term prognosis - Insights from the critically ill mortality by age (Cimba) study.

BACKGROUND: Patients with critical illness often survive the intensive care unit (ICU) at a cost of prolonged length of stay (LOS) and slow recovery. This chronic critically ill disease may lead to long-term poor outcomes, especially in older or frail patients. OBJECTIVES: The main goal of this study was to address the characteristics and outcomes of patients with prolonged ICU LOS. Mainly, short- and long-term admissions were compared to identify risk factors for persistent critical illness and to characterise the impact on ICU, hospital, and long-term mortality. METHODS: Subanalysis of a retrospective, multicentric, observational study addressing the 2-year outcome of patients admitted to Portuguese ICUs (the Cimba study). Patients were segregated according to an ICU LOS of ≥14 days. RESULTS: Data from 37 118 patients were analysed, featuring a median ICU LOS of 4 days (percentile: 25-75 2-9), and a mortality of 16.1% in the ICU, 24.0% in the hospital, and 38.7% after 2 years. A total of 5334 patients (14.4%) had an ICU LOS of ≥14 days (corresponding to 48.9% of all ICU patients/days). Patients with prolonged LOS were more often younger (52.8% vs 46.4%, were ≤65 years of age , p < 0.001), although more severe (Simplified Acute Physiology Score II: 49.1 ± 16.9 vs 41.8 ± 19.5, p < 0.001), and had higher ICU and hospital mortality (18.3% vs 15.7%, and 31.2 vs 22.8%, respectively). Prolonged ICU LOS was linked to an increased risk of dying during the 2-year follow-up (adjusted Cox proportional hazard: 1.65, p < 0.001). CONCLUSION: Prolonged LOS is associated with a long-term impact on patient prognosis. More careful planning of care should incorporate these data.

Montelukast and cefoperazone act as antiquorum sensing and antibiofilm agents against Pseudomonas aeruginosa.

AIMS: Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control. METHODS AND RESULTS: The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of Ps. aeruginosa biofilms. Cefoperazone inhibited the Pqs system by hindering the production of the autoinducer molecules 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal or PQS), corroborating in silico results. Pseudomonas aeruginosa pyocyanin production was reduced by 50%. The combination of the antibiotics cefoperazone and ciprofloxacin was synergistic for Ps. aeruginosa biofilm control. On the other hand, montelukast had no relevant effects on the inhibition of the Pqs system and against Ps. aeruginosa biofilm. CONCLUSION: This study provides for the first time strong evidence that cefoperazone interacts with the Pqs system, hindering the formation of the autoinducer molecules HHQ and PQS, reducing Ps. aeruginosa pathogenicity and virulence. Cefoperazone demonstrated a potential to be used in combination with less effective antibiotics (e.g. ciprofloxacin) to potentiate the biofilm control action.

Dual action of benzaldehydes: Inhibiting quorum sensing and enhancing antibiotic efficacy for controlling Pseudomonas aeruginosa biofilms.

Quorum sensing (QS) has a central role in biofilm lifestyle and antimicrobial resistance, and disrupting these signaling pathways is a promising strategy to control bacterial pathogenicity and virulence. In this study, the efficacy of three structurally related benzaldehydes (4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde)) in disrupting the las and pqs systems of Pseudomonas aeruginosa was investigated using bioreporter strains and computational simulations. Additionally, these benzaldehydes were combined with tobramycin and ciprofloxacin antibiotics to evaluate their ability to increase antibiotic efficacy in preventing and eradicating P. aeruginosa biofilms. To this end, the total biomass, metabolic activity and culturability of the biofilm cells were determined. In vitro assays results indicated that the aromatic aldehydes have potential to inhibit the las and pqs systems by > 80 %. Molecular docking studies supported these findings, revealing the aldehydes binding in the same pocket as the natural ligands or receptor proteins (LasR, PQSA, PQSE, PQSR). Benzaldehydes were shown to act as virulence factor attenuators, with vanillin achieving a 48 % reduction in pyocyanin production. The benzaldehyde-tobramycin combination led not only to a 60 % reduction in biomass production but also to a 90 % reduction in the metabolic activity of established biofilms. A similar result was observed when benzaldehydes were combined with ciprofloxacin. 4-Hydroxybenzaldehyde demonstrated relevant action in increasing biofilm susceptibility to ciprofloxacin, resulting in a 65 % reduction in biomass. This study discloses, for the first time, that the benzaldehydes studied are potent QS inhibitors and also enhancers of antibiotics antibiofilm activity against P. aeruginosa.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

Oropharyngeal colostrum immunotherapy and risk reduction of mortality in very low birth weight premature newborns: a clinical trial.

OBJECTIVE: To evaluate the effect of oropharyngeal colostrum immunotherapy (OCI) on the mortality of preterm newborns (PTNB) with very low birth weight (VLBW). METHOD: Non-randomized clinical trial, carried out with 138 mother-child pairs attended at a public maternity hospital. The treatment group used raw colostrum, dripping 4 drops (0.2 ml) into the oropharyngeal mucosa, totaling 8 administrations in 24 h, up to the 7th complete day of life (OCI). The control group was composed of newborns admitted to the same maternity hospital before the implementation of the OCI. Analyzes were performed: descriptive, bivariate, multiple logistic regression, and survival analysis, with a significance level of 5% and 95% CI. RESULTS: The treatment group had an RR of death of 0.26 (95% CI = 0.07-0.67; p = 0.00), adjusted for maternal age, marital status, gestational hypertension, type of delivery, number of prenatal visits, and birth weight. Number Needed to Treat (NNT) demonstrated that for every 5 individuals treated with OCI, one death was prevented NNT = 4.9 (95% CI = 1.84-5.20); however, for PTNB with VLBW who remained hospitalized for 50, 100 and 150 days, the NNT reduces to 4, 4 and 3, respectively. CONCLUSION: The OCI proved to be a beneficial intervention, since it reduced the risk of mortality in PTNB with VLBW when compared to the control group.

Critically ill patients with high predicted mortality: Incidence and outcome.

OBJECTIVE: As calculated by the severity scores, an unknown number of patients are admitted to the Intensive Care Unit (ICU) with a very high risk of death. Clinical studies have poorly addressed this population, and their prognosis is largely unknown. DESIGN: Post hoc analysis of a multicenter, cohort, longitudinal, observational, retrospective study (CIMbA). SETTING: Sixteen Portuguese multipurpose ICUs. PATIENTS: Patients with a Simplified Acute Physiology Score II (SAPS II) predicted hospital mortality above 80% on admission to the ICU (high-risk group); A comparison with the remaining patients was obtained. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Hospital, 30 days, 1 year mortality. RESULTS: We identified 4546 patients (59.9% male), 12.2% of the whole population. Their SAPS II predicted hospital mortality was 89.0±5.8%, whilst the observed mortality was lower, 61.0%. This group had higher mortality, both during the first 30 days (aHR 3.52 [95% CI 3.34-3.71]) and from day 31 to day 365 after ICU admission (aHR 1.14 [95%CI 1.04-1.26]), respectively. However, their hospital standardized mortality ratio was similar to the other patients (0.69 vs. 0.69, P=.92). At one year of follow-up, 30% of patients in the high-risk group were alive. CONCLUSIONS: Roughly 12% of patients admitted to the ICU for more than 24h had a SAPS II score predicted mortality above 80%. Their hospital standardized mortality was similar to the less severe population and 30% were alive after one year of follow-up.

Colostrum immunotherapy and length of hospital stay in preterm infants: an intervention study / Imunoterapia de colostro e tempo de internamento de prematuros: estudo de intervenção

Abstract Objectives: to evaluate the effect of oropharyngeal colostrum immunotherapy on the length of hospital stay in preterm newborns with very low birth weight. Methods: interventional ambispective study, which consisted of eight daily administrations of 0.2 ml (four drops) of colostrum, totaling up to 56 syringes (for up to seven days). The control was historic. The main independent variable: length of hospital stay (days). Survival analysis was performed using the Kaplan-Meier Method and the survival effect was estimated - Log Rank Test (Mantel-Cox) and Breslow Test (Generalized Wilcoxon). A significance level of 5% was adopted. Results: of the 109 mother/child pairs, 56 were part of the treatment and 53 were part of the control group. There was no association between oropharyngeal colostrum immunotherapy and length of stay for preterm newborns with very low birth weight in the general sample. However, after stratification, a shorter hospital stay (42 versus 51 days, HR= 1.78, CI95%=1.02-3.09, p=0.04) was demonstrated among premature infants with ≥28 gestational weeks undergoing oropharyngeal colostrum immunotherapy. Conclusions: we found an association between oropharyngeal colostrum immunotherapy and shorter median length of hospital stay in the subgroup of premature infants ≥ 28 weeks of gestational age, but we did not find significant differences in those <28 weeks.

Resumo Objetivos: avaliar o efeito da imunoterapia orofaríngea de colostro no tempo de internamento hospitalar de recém-nascidos pré-termos de muito baixo peso. Métodos: estudo de intervenção, ambispectivo, que consistiu em oito administrações diárias de 0,2 ml (quatro gotas) de colostro, totalizando até 56 seringas (por até sete dias). O controle foi histórico. A variável independente principal: tempo de permanência hospitalar (dias). Realizada análise de sobrevivência pelo Método de Kaplan-Meier e estimado o efeito da sobrevida - Teste de Log Rank (Mantel-Cox) e Teste de Breslow (Wilcoxon Generalizado). Adotou-se o nível de significância de 5%. Resultados: das 109 duplas mães/filho, 56 fizeram parte da análise do grupo tratamento e 53 do controle. Não houve associação entre imunoterapia orofaríngea de colostro e tempo de internamento de recém-nascidos pré-termos de muito baixo peso na amostra geral. Após estratificação demonstrou-se menor tempo de permanência hospitalar (43 versus 51 dias, HR=1,78, IC95%= 1,02-3,09, p=0,04) entre os prematuros com ≥28 semanas gestacionais submetidos a imunoterapia orofaríngea de colostro. Conclusões: encontrou-se associação entre imunoterapia orofaríngea de colostro e menor mediana de tempo de internamento hospitalar no subgrupo de prematuros ≥ 28 semanas de idade gestacional, porém não foram encontradas diferenças significativas naqueles < 28 semanas.

Oropharyngeal colostrum immunotherapy and risk reduction of mortality in very low birth weight premature newborns: a clinical trial

Abstract Objective To evaluate the effect of oropharyngeal colostrum immunotherapy (OCI) on the mortality of preterm newborns (PTNB) with very low birth weight (VLBW). Method Non-randomized clinical trial, carried out with 138 mother-child pairs attended at a public maternity hospital. The treatment group used raw colostrum, dripping 4 drops (0.2 ml) into the oropharyngeal mucosa, totaling 8 administrations in 24 h, up to the 7th complete day of life (OCI). The control group was composed of newborns admitted to the same maternity hospital before the implementation of the OCI. Analyzes were performed: descriptive, bivariate, multiple logistic regression, and survival analysis, with a significance level of 5% and 95% CI. Results The treatment group had an RR of death of 0.26 (95% CI = 0.07-0.67; p= 0.00), adjusted for maternal age, marital status, gestational hypertension, type of delivery, number of prenatal visits, and birth weight. Number Needed to Treat (NNT) demonstrated that for every 5 individuals treated with OCI, one death was prevented NNT = 4.9 (95% CI = 1.84-5.20); however, for PTNB with VLBW who remained hospitalized for 50, 100 and 150 days, the NNT reduces to 4, 4 and 3, respectively. Conclusion The OCI proved to be a beneficial intervention, since it reduced the risk of mortality in PTNB with VLBW when compared to the control group.

Comparative resistome, mobilome, and microbial composition of retail chicken originated from conventional, organic, and antibiotic-free production systems.

The aim of this study was to investigate the microbial composition, and the profiles of antimicrobial resistance genes (ARGs, resistome) and mobile genetic elements (mobilome) of retail chicken carcasses originated from conventional intensive production systems (CO), certified antimicrobial-free intensive production systems (AF), and certified organic production systems with restricted antimicrobial use (OR). DNA samples were collected from 72 chicken carcasses according to a cross-sectional study design. Shot-gun metagenomics was performed by means of Illumina high throughput DNA sequencing followed by downstream bioinformatic analyses. Gammaproteobacteria was the most abundant bacterial class in all groups. Although CO, AF, and OR did not differ in terms of alpha- and beta-microbial diversity, the abundance of some taxa differed significantly across the groups, including spoilage-associated organisms such as Pseudomonas and Acinetobacter. The co-resistome comprised 29 ARGs shared by CO, AF and OR, including genes conferring resistance to beta-lactams (blaACT-8, 10, 13, 29; blaOXA-212;blaOXA-275 and ompA), aminoglycosides (aph(3')-IIIa, VI, VIa and spd), tetracyclines (tet KL (W/N/W and M), lincosamides (inu A,C) and fosfomycin (fosA). ARGs were significantly less abundant (P < 0.05) in chicken carcasses from AF and OR compared with CO. Regarding mobile genetic elements (MGEs), transposases accounted for 97.2% of the mapped genes. A higher abundance (P = 0.037) of MGEs was found in CO compared to OR. There were no significant differences in ARGs or MGEs diversity among groups according to the Simpson´s index. In summary, retail frozen chicken carcasses from AF and OR systems show similar ARGs, MGEs and microbiota profiles compared with CO, even though the abundance of ARGs and MGEs was higher in chicken carcasses from CO, probably due to a higher selective pressure.

Associação entre parto cesáreo e pressão arterial elevada em pré-escolares: um estudo transversal / Association between cesarean section and high blood pressure among early elementary schoolchildren: a cross-sectional study / Asociación entre los partos por cesárea y la presión arterial alta en preescolares: un estudio transversal

O parto cesáreo é apontado como fator de risco para diversas doenças crônicas. Neste estudo, objetivou-se averiguar a associação entre parto cesáreo e pressão arterial (PA) de crianças de 6 anos. Trata-se de estudo transversal conduzido em Feira de Santana (BA), com 635 pares de mãe e filho. O tipo de parto foi categorizado em cesárea e vaginal. A PA foi aferida por meio de esfigmomanometria e considerada elevada quando atingiu níveis iguais ou maiores ao percentil 90 para idade, sexo e altura. Razões de prevalência brutas (RPbruta) e ajustadas (RPajustada) e respectivos intervalos de confiança de 95% (IC95%) foram estimados via regressão logística múltipla. A cesariana ocorreu em 46,5% dos casos, as prevalências de pressão arterial sistólica (PAS) e diastólica (PAD) elevadas foram de 17,2% e 5,6%, respectivamente. O excesso de peso foi verificado em 28,6% das crianças. A maior prevalência de PAS elevada foi observada entre as crianças que nasceram por cesariana (61%) em relação às que nasceram por parto vaginal (RPbruta: 1,51; IC95%: 1,07-2,14; RPajustada: 1,61; IC95%: 1,05-2,46). A idade materna ao nascimento da criança foi fator de interação na associação principal, assim, as crianças nascidas via parto vaginal exibiram maior prevalência de PAS elevada, comparadas às nascidas via cesárea. O parto cesáreo se associou à PAS elevada aos 6 anos de idade.

Cesarean delivery is considered a risk factor for several chronic diseases. This study aimed to investigate the association between cesarean section and blood pressure (BP) in 6-year-old children. This is a cross-sectional study carried out in Feira de Santana, (BA) with 635 mother-child pairs. The type of birth was categorized into cesarean and vaginal. The BP was measured by using sphygmomanometry and considered high when it reached levels equal or higher than the 90th percentile for age, gender, and height. Crude (PRcrude) and adjusted (PRadjusted) prevalence rate and respective 95% confidence intervals (95%CI) were estimated by multiple logistic regression. Cesarean section occurred in 46.5% of the cases, the prevalence of high systolic (SBP) and diastolic (DBP) blood pressure were 17.2% and 5.6%, respectively. Excess weight was verified in 28.6% of the children. The highest prevalence of high SBP was among children who were born by cesarean section (61%) compared with those who were born vaginally (PRcrude: 1.51; 95%CI: 1.07-2.14; PRadjusted: 1.61; 95%CI %: 1.05-2.46). Maternal age at the birth of the child was an interaction factor in the main association, thus, children born vaginally had a higher prevalence of elevated SBP, compared with those born via cesarean section. Cesarean section was associated with increased SBP at six years of age.

El parto por cesárea presenta un factor de riesgo para varias enfermedades crónicas. El objetivo de este estudio fue investigar la asociación entre el parto por cesárea y la presión arterial (PA) en niños de 6 años de edad. Se trata de un estudio transversal, realizado en Feira de Santana, en Bahía (Brasil), con 635 pares de madre e hijo. El tipo de parto se clasificó en cesárea y vaginal. La PA se midió mediante esfigmomanometría y se consideró alta cuando alcanzó niveles más altos o iguales al percentil 90 para edad, sexo y talla. Las razones de prevalencia crudas (RPcrudas) y ajustadas (RPajustadas) y los respectivos intervalos de confianza del 95% (IC del 95%) se estimaron mediante regresión logística múltiple. La cesárea ocurrió en el 46,5%, las prevalencias de presión arterial sistólica (PAS) y diastólica (PAD) altas fueron el 17,2% y el 5,6%, respectivamente. El exceso de peso se presentó en el 28,6% de los niños. La mayor prevalencia de PAS alta se observó entre los niños nacidos por cesárea (61%) en comparación con los nacidos por vía vaginal (RPcruda: 1,51; IC95%: 1,07-2,14; RPajustada: 1,61; IC95%: 1,05-2,46). La edad materna al nacimiento del niño fue un factor de interacción en la principal asociación, así, los niños nacidos por vía vaginal tuvieron una mayor prevalencia de PAS elevada en comparación con los nacidos por cesárea. El parto por cesárea se asoció con un aumento de la PAS a los 6 años de edad.

Effectiveness of Self-Adhesive Resin Luting Cement in CAD-CAM Blocks-A Systematic Review and Meta-Analysis.

Self-adhesive resin cements (SARCs) are used because of their mechanical properties, ease of cementation protocols, and lack of requirements for acid conditioning or adhesive systems. SARCs are generally dual-cured, photoactivated, and self-cured, with a slight increase in acidic pH, allowing self-adhesiveness and increasing resistance to hydrolysis. This systematic review assessed the adhesive strength of SARC systems luted to different substrates and computer-aided design and manufacturing (CAD/CAM) ceramic blocks. The PubMed/MedLine and Science Direct databases were searched using the Boolean formula [((dental or tooth) AND (self-adhesive) AND (luting or cement) AND CAD-CAM) NOT (endodontics or implants)]. Of the 199 articles obtained, 31 were selected for the quality assessment. Lava Ultimate (resin matrix filled with nanoceramic) and Vita Enamic (polymer-infiltrated ceramic) blocks were the most tested. Rely X Unicem 2 was the most tested resin cement, followed by Rely X Unicem > Ultimate > U200, and µTBS was the test most used. The meta-analysis confirmed the substrate-dependent adhesive strength of SARCs, with significant differences between them and between SARCs and conventional resin-based adhesive cement (α < 0.05). SARCs are promising. However, one must be aware of the differences in the adhesive strengths. An appropriate combination of materials must be considered to improve the durability and stability of restorations.

Receptor-Based Virtual Screening of Large Libraries in a Multi-Level In Silico Approach.

Structure-based drug design (SBDD) has become an alternative to high throughput screening (HTS) as it reduces experimental costs and time. It works like a funnel, filtering out compounds that do not show good affinity (or score) toward a particular target, with known 3D structure.Here, we describe a protocol for structure-based drug design using a multi-level in silico approach, combining Molecular Docking, Virtual Screening, Molecular Dynamics Simulations and Free energy calculations to find new lead molecules for experimental testing, predict binding affinities and characterize binding modes.

Silver(I) 1,10-Phenanthroline Complexes Are Active against Fonsecaea pedrosoi Viability and Negatively Modulate Its Potential Virulence Attributes.

The genus Fonsecaea is one of the etiological agents of chromoblastomycosis (CBM), a chronic subcutaneous disease that is difficult to treat. This work aimed to evaluate the effects of copper(II), manganese(II) and silver(I) complexes coordinated with 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione (phendione) on Fonsecaea spp. Our results revealed that most of these complexes were able to inhibit F. pedrosoi, F. monophora and F. nubica conidial viability with minimum inhibitory concentration (MIC) values ranging from 0.6 to 100 µM. The most effective complexes against F. pedrosoi planktonic conidial cells, the main etiologic agent of CBM, were [Ag(phen)2]ClO4 and [Ag2(3,6,9-tdda)(phen)4].EtOH, (tdda: 3,6,9-trioxaundecanedioate), displaying MIC values equal to 1.2 and 0.6 µM, respectively. These complexes were effective in reducing the viability of F. pedrosoi biofilm formation and maturation. Silver(I)-tdda-phen, combined with itraconazole, reduced the viability and extracellular matrix during F. pedrosoi biofilm development. Moreover, both silver(I) complexes inhibited either metallo- or aspartic-type peptidase activities of F. pedrosoi as well as its conidia into mycelia transformation and melanin production. In addition, the complexes induced the production of intracellular reactive oxygen species in F. pedrosoi. Taken together, our data corroborate the antifungal action of metal-phen complexes, showing they represent a therapeutic option for fungal infections, including CBM.

Critically ill patient mortality by age: long-term follow-up (CIMbA-LT).

BACKGROUND: The past years have witnessed dramatic changes in the population admitted to the intensive care unit (ICU). Older and sicker patients are now commonly treated in this setting due to the newly available sophisticated life support. However, the short- and long-term benefit of this strategy is scarcely studied. METHODS: The Critically Ill patients' mortality by age: Long-Term follow-up (CIMbA-LT) was a multicentric, nationwide, retrospective, observational study addressing short- and long-term prognosis of patients admitted to Portuguese multipurpose ICUs, during 4 years, according to their age and disease severity. Patients were followed for two years after ICU admission. The standardized hospital mortality ratio (SMR) was calculated according to the Simplified Acute Physiology Score (SAPS) II and the follow-up risk, for patients discharged alive from the hospital, according to official demographic national data for age and gender. Survival curves were plotted according to age group. RESULTS: We included 37.118 patients, including 15.8% over 80 years old. The mean SAPS II score was 42.8 ± 19.4. The ICU all-cause mortality was 16.1% and 76% of all patients survive until hospital discharge. The SAPS II score overestimated hospital mortality [SMR at hospital discharge 0.7; 95% confidence interval (CI) 0.63-0.76] but accurately predicted one-year all-cause mortality [1-year SMR 1.01; (95% CI 0.98-1.08)]. Survival curves showed a peak in mortality, during the first 30 days, followed by a much slower survival decline thereafter. Older patients had higher short- and long-term mortality and their hospital SMR was also slightly higher (0.76 vs. 0.69). Patients discharged alive from the hospital had a 1-year relative mortality risk of 6.3; [95% CI 5.8-6.7]. This increased risk was higher for younger patients [21.1; (95% CI 15.1-39.6) vs. 2.4; (95% CI 2.2-2.7) for older patients]. CONCLUSIONS: Critically ill patients' mortality peaked in the first 30 days after ICU admission. Older critically ill patients had higher all-cause mortality, including a higher hospital SMR. A long-term increased relative mortality risk was noted in patients discharged alive from the hospital, but this was more noticeable in younger patients.

Relações entre Paixão pelo Trabalho, Bem-Estar e Autoeficácia Ocupacional em Treinadores Esportivos / Relationship between Passion for Work, Well-Being and Occupational Self-Efficiency in Sports Coaches / Relaciones entre la pasión por el trabajo, el bienestar y la autoeficiencia laboral en los entrenadores deportivos

O objetivo deste estudo foi verificar as associações entre a paixão pelo trabalho, bem-estar e autoeficácia ocupacional em treinadores esportivos. Participaram do estudo 139 treinadores de ambos os sexos (71,2% masculino). Foram observados efeitos positivos da paixão harmoniosa sobre afetos positivos e autoeficácia ocupacional, e efeitos negativos sobre afetos negativos. A paixão obsessiva predisse positivamente os afetos negativos. Ainda, identificou-se o papel mediador dos afetos positivos na relação entre paixão harmoniosa e autoeficácia ocupacional. Corroborando as hipóteses teóricas, os resultados sugerem a importância do envolvimento harmonioso com a atividade profissional, seu potencial sobre experiências de emoções positivas e percepção de competência para o enfrentamento dos desafios profissionais.

The aim of this study was to verify the associations between passion for work, well-being and occupational self-efficacy in sports coaches. 139 coaches of both sexes participated (71.2% male). Positive effects of harmonious passion have been observed on positive affects and occupational self-efficacy, and negative effects on negative affects. Obsessive passion positively predicted negative affects. Still, the mediating role of positive affects in the relationship between harmonious passion and occupational self-efficacy was identified. Corroborating the theoretical hypotheses, the results suggest the importance of harmonious involvement with professional activity, its potential on positive emotional experiences and perception of competence to face professional challenges.

El objetivo de este estudio fue verificar las asociaciones entre la pasión por el trabajo, el bienestar y la autoeficacia laboral en entrenadores deportivos. Participaron 139 entrenadores de ambos sexos (71,2% hombres). Se han observado efectos positivos de la pasión armoniosa sobre los afectos positivos y la autoeficacia ocupacional, y efectos negativos sobre los afectos negativos. La pasión obsesiva predijo positivamente los afectos negativos. Aún así, se identificó el papel mediador de los afectos positivos en la relación entre la pasión armoniosa y la autoeficacia ocupacional. Corroborando las hipótesis teóricas, los resultados apuntan a la importancia de la implicación armónica con la actividad profesional, su potencialidad sobre experiencias emocionales positivas y percepción de competencia para afrontar retos profesionales.

Food consumption pattern and excess weight in preschoolers: a cross-sectional study / Padrão de consumo alimentar e excesso de peso em pré-escolares: estudo transversal / Patrón de consumo de alimentos y sobrepeso en niños en edad preescolar: estudio transversal

Background and objectives: children's food-related lifestyle brought changes in their weight status and eating patterns. We aimed to investigate the association between food consumption pattern and excess weight in preschoolers aged six. Methods: a cross-sectional analysis of a prospective birth cohort, in 2004, in Feira de Santana-BA. Food consumption frequency was verified, characterized by patterns and established through a food frequency questionnaire, validated in a previous study, in pattern 1: milk, vegetables, cereals, legumes, fruits and fish; pattern 2: snacks, soda/artificial juice, oils, sweets and coffee/tea; pattern 3: sausages, fast food, ketchup/mayonnaise and egg; pattern 4: red meat and chicken. Excess weight was defined according to the World Health Organization criteria. The main association was assessed using Pearson's chi-square test and Poisson regression. Results: a total of 618 children were investigated. Excess weight occurred in 28.6%, and pattern 3 frequency was 68%. In the bivariate analysis, only pattern 3 was associated with children's excess weight (PR: 1.23; 95%CI: 1.01-1.63). In the multivariate analysis, the prevalence of excess weight children who consumed pattern 3 was 50% (adjustedPR: 1.50; 95%CI: 1.01­1.93). Conclusion: moderate/high consumption of sausages, fast food, ketchup/mayonnaise and eggs was associated with excess weight among children in the sample.(AU)

Justificativa e objetivos: o estilo de vida das crianças relacionado à alimentação trouxe mudanças no estado de peso e no padrão alimentar. Objetivou-se averiguar a associação entre o padrão de consumo alimentar e o excesso de peso em pré-escolares aos seis anos de idade. Métodos: análise transversal, de uma coorte prospectiva de nascimento, em 2004, em Feira de Santana-BA. Verificou-se a frequência do consumo alimentar, caracterizado por padrões e estabelecido por meio do questionário de frequência alimentar, validado em um estudo prévio, em padrão 1: leite, verduras, cereais, leguminosas, frutas e pescados; padrão 2: salgadinhos, refrigerantes/sucos artificiais, óleos, doces e cafés/chás; padrão 3: embutidos, fast food, ketchup/maionese e ovo; padrão 4: carnes vermelhas e frango. O excesso de peso foi definido segundo os critérios da Organização Mundial da Saúde. A associação principal foi avaliada mediante Teste Qui-Quadrado de Pearson e regressão de Poisson. Resultados: investigaram-se 618 crianças. O excesso de peso ocorreu em 28,6%, e a frequência do padrão 3 foi de 68%. Na análise bivariada, somente o padrão 3 se associou com o excesso de peso da criança (RP: 1,23; IC95%: 1,01-1,63). Na análise multivariada, a prevalência de crianças que consumiam o padrão 3 com excesso de peso foi de 50% (RPajustado: 1,50; IC95%: 1,01­1,93). Conclusão: o consumo moderado/alto de embutidos, fast food, ketchup/maionese e ovo se associou com o excesso de peso entre as crianças.(AU)

Justificación y objetivos: el estilo de vida de los niños relacionado con la alimentación trajo cambios en su estado de peso y patrones de alimentación. El objetivo fue investigar la asociación entre el patrón de consumo de alimentos y el sobrepeso en preescolares de seis años. Métodos: análisis transversal de una cohorte prospectiva de nacimiento, en 2004, en Feira de Santana-BA. Se verificó la frecuencia de consumo de alimentos, caracterizada por patrones y establecida a través del cuestionario de frecuencia de alimentos, validado en un estudio previo, en el patrón 1: leche, verduras, cereales, legumbres, frutas y pescado; patrón 2: bocadillos, refrescos/jugos artificiales, aceites, dulces y café/té; patrón 3: salchichas, fast food, salsa de tomate/mayonesa y huevo; patrón 4: carnes rojas y pollo. El exceso de peso se definió según los criterios de la Organización Mundial de la Salud, la asociación principal se evaluó mediante la prueba de chi-cuadrado de Pearson y regresión de Poisson. Resultados: 618 niños fueron investigados. El exceso de peso se presentó en el 28,6% y la frecuencia del patrón 3 fue del 68%. En el análisis bivariado, solo el patrón 3 se asoció con el exceso de peso del niño (RP: 1,23; IC95%: 1,01-1,63). En el análisis multivariado, la prevalencia de niños con sobrepeso que consumieron el patrón 3 fue del 50% (RPajustado: 1,50; IC95%: 1,01­1,93). Conclusión: el consumo moderado/alto de salchichas, fast food, ketchup/mayonesa y huevos se asoció con sobrepeso entre los niños de la muestra.(AU)

Liposomal Formulations Loaded with a Eugenol Derivative for Application as Insecticides: Encapsulation Studies and In Silico Identification of Protein Targets.

A recently synthesized new eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate, with a high insecticidal activity against Sf9 (Spodoptera frugiperda) insect cells, was encapsulated in the liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and 100% dioleoylphosphatidylglycerol (DOPG), aiming at the future application as insecticides. Compound-loaded DOPG liposomes have sizes of 274 ± 12 nm, while Egg-PC:Ch liposomes exhibit smaller hydrodynamic diameters (69.5 ± 7 nm), high encapsulation efficiency (88.8 ± 2.7%), higher stability, and a more efficient compound release, thus, they were chosen for assays in Sf9 insect cells. The compound elicited a loss of cell viability up to 80% after 72 h of incubation. Relevantly, nanoencapsulation maintained the toxicity of the compound toward insect cells while lowering the toxicity toward human cells, thus showing the selectivity of the system. Structure-based inverted virtual screening was used to predict the most likely targets and molecular dynamics simulations and free energy calculations were used to demonstrate that this molecule can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase. The results are promising for the future application of compound-loaded nanoliposome formulations as crop insecticides.

Antibacterial, Antiparasitic, and Cytotoxic Activities of Chemical Characterized Essential Oil of Chrysopogon zizanioides Roots.

This study aimed to investigate the chemical composition as well as the antibacterial, antiparasitic, and cytotoxic potentialities of the Brazilian Chrysopogon zizanioides root essential oil (CZ-EO) In addition, CZ-EO cytotoxicity to LLCMK2 adherent epithelial cells was assessed. The major compounds identified in CZ-EO were khusimol (30.0 ± 0.3%), ß-eudesmol (10.8 ± 0.3%), α-muurolene (6.0 ± 0.1%), and patchouli alcohol (5.6 ± 0.2%). CZ-EO displayed optimal antibacterial activity against Prevotella nigrescens, Fusobacterium nucleatum, Prevotella melaninogenica, and Aggregatibacter actinomycetemcomitans, with Minimum Inhibitory Concentration (MIC) values between 22 and 62.5 µg/mL and Minimum Bactericidal Concentration (MBC) values between 22 and 400 µg/mL. CZ-EO was highly active against the L. amazonensis promastigote and amastigote forms (IC50 = 7.20 and 16.21 µg/mL, respectively) and the T. cruzi trypomastigote form (IC50 = 11.2 µg/mL). Moreover, CZ-EO showed moderate cytotoxicity to LLCMK2 cells, with CC50 = 565.4 µg/mL. These results revealed an interesting in vitro selectivity of CZ-EO toward the L. amazonensis promastigote and amastigote forms (Selectivity Index, SI = 78.5 and 34.8, respectively) and the T. cruzi trypomastigote form (SI = 50.5) compared to LLCMK2 cells. These results showed the promising potential of CZ-EO for developing new antimicrobial, antileishmanial, and antitrypanosomal drugs.

Depressive and Anxiety Symptoms in Severe COVID-19 Survivors: A Prospective Cohort Study.

The coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, leading to increased concerns about long-term patients' neuropsychiatric consequences. This study aims to describe the presence of depressive and anxiety symptoms in severe COVID-19 survivors and to identify associated baseline, in-hospital and post-discharge factors. This study is part of the MAPA longitudinal project conducted with severe COVID-19 patients admitted in Intensive Care Medicine Department (ICMD) of a University Hospital (CHUSJ) in Porto, Portugal. Patients with ICMD length of stay ≤ 24 h, terminal illness, major auditory loss or inability to communicate at follow-up assessment were excluded. All participants were assessed by telephone post-discharge (median = 101 days), with a comprehensive protocol assessing depressive and anxiety symptoms, cognition, Intensive Care Unit (ICU) memories recall and health-related quality of life. Out of a sample of 56 survivors (median age = 65; 68% males), 29% and 23% had depressive and anxiety symptoms, respectively. Depressive and anxiety symptoms were significantly more prevalent among younger survivors and were associated with cognitive complaints, emotional and delusions ICU memories and fear of having COVID-19 sequelae, sleep problems and pain after discharge (all p < 0.05). An important proportion of these survivors suffers from depression and anxiety symptoms post-discharge, namely younger ones and those who reported more cognitive complaints, ICU memories, fear of having COVID-19 sequelae, sleep problems and pain. These findings highlight the importance of psychological consequences assessment and planning of appropriate and multidisciplinary follow-up care after hospitalization due to COVID-19.