The discovery of antibiotics has significantly transformed the outcomes of bacterial infections in the last decades. However, the development of antibiotic resistance mechanisms has allowed an ...increasing number of bacterial strains to overcome the action of antibiotics, decreasing their effectiveness against infections they were developed to treat. This study aimed to evaluate the antibacterial activity of synthetic coumarins Staphylococcus aureus in vitro and analyze their interaction with the MepA efflux pump in silico. The Minimum Inhibitory Concentration (MIC) determination showed that none of the test compounds have antibacterial activity. However, all coumarin derivatives decreased the MIC of the standard efflux inhibitor ethidium bromide, indicating antibacterial synergism. On the other hand, the C14 derivative potentiated the antibacterial activity of ciprofloxacin against the resistant strain. In silico analysis showed that C9, C11, and C13 coumarins showed the most favorable interaction with the MepA efflux pump. Nevertheless, due to the present in silico and in vitro investigation limitations, further experimental research is required to confirm the therapeutic potential of these compounds in vivo.
•The docking assay demonstrated a possible interactions between the coumarins and MepA efflux pump.•Compounds C9, C11, and C13 showed a better interaction with the MepA efflux pump.•All coumarin assayed reduced the MIC of ethidium bromide.
Purpose
Chemotherapy treatment can lead to cardiovascular toxicity and physical impairment prior to autologous hematopoietic stem cell transplantation (auto-HSCT). Cardiovascular adjustments during ...exercise and the exercise capacity remain unknown in patients prior to auto-HSCT. Thus, the hemodynamic responses during exercise and exercise capacity were evaluated using a novel effort test in patients prior to auto-HSCT.
Methods
Thirty patients prior to auto-HSCT (BMT group: 44.6 ± 14.1 years) and 23 control participants (CON group: 43.9 ± 16.6 years) performed the 6-Minute Step Test (6MST) to assess their exercise capacity and the hemodynamic responses during exercise. Systolic and diastolic blood pressure (SBP and DBP), heart rate (HR), and oxygen saturation (SpO
2
) were measured during the test. Rate-pressure product (RPP) was calculated multiplying SBP by HR. The highest HR value recorded during the test was compared with the maximum HR predicted by age and was used as % of maximum HR (%HRmax).
Results
The number of steps up and down performed by the BMT group was lower than CON (108.8 ± 25.3 vs. 127.5 ± 34.4 steps,
P
= 0.02). The BMT group showed a higher magnitude of increase in SBP and RPP during the 6MST when compared to CON (ΔSBP: 18.5 ± 11.45 vs. 8.30 ± 18.46 mmHg,
P
= 0.01; and ΔRPP: 8197.3 ± 3829.1 vs. 6170.9 ± 3568.9 mmHg beats min
−1
,
P
= 0.05). The BMT group exhibited higher SpO2 and HR values throughout the protocol (
P
< 0.05), reaching a higher %HRmax than CON group (76.9 ± 9.6 vs. 66.4 ± 8.9%,
P
< 0.01).
Conclusions
Patients with indication for auto-HSCT have exacerbated chronotropic and pressor responses during exercise and reduced exercise capacity in the 6MST.
The increase in antibiotic resistance rates has attracted the interest of researchers for antibacterial compounds capable of potentiating the activity of conventional antibiotics. Coumarin ...derivatives have been reported to develop effective antibacterials with possible new mechanisms of action for treating infectious diseases caused by bacteria with a profile of drug resistance. In this context, the aim of the present study we have now prepared one variety of new synthetic coumarins evaluating the pharmacokinetic and chemical similarity in silico, their antimicrobial activity against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), and potential for the modulation of antibiotic resistance against Staphylococcus aureus (SA10) and Escherichia coli (EC06) clinical isolate bacteria by in vitro assay. The antibacterial activity and antibiotic-enhancing properties were evaluated by the broth microdilution method and pharmacokinetically characterized according to the Lipinsk rule of 5 and had their similarity analyzed in databases such as ChemBL and CAS SciFinder. The results demonstrated that only compound C13 showed significant antibacterial activity (MIC ≤256 μg/mL), and all other coumarins did not display relevant antibacterial activity (MIC ≥1024 μg/mL). However, they did modulate the antibiotics activities to norfloxacin and gentamicin, except, compound C11 to norfloxacin against Staphylococcus aureus (SA10). The in silico properties prediction and drug-likeness results demonstrated that all coumarins presented a good drug-likeness score with no violations and promising in silico pharmacokinetic profiles showing that they have the potential to be developed into an oral drug. The results indicate that the coumarin derivatives showed good in vitro antibacterial activity. These new coumarin derivatives also demonstrated the capacity to modulate antibiotic resistance with potential synergy action for current antimicrobials assayed, as antibiotic adjuvants, to reduce the emergence of antimicrobial resistance.
•All of the coumarin derivatives have antibiotic-enhancing properties.•The C13 derivative demonstrated clinically relevant antibacterial effects.•In silico analysis indicates that these compounds have characteristics to their use as oral drugs.
In order to search nanofiller for controlling release of drugs lamellar α-zirconium phosphate (α-ZrP) was modified with ether-amine oligomer (E-A). Synthesis and chemical modification followed ...specific reaction conditions and different EA:ZrP ratios. Infrared spectra showed strong interaction between P-OH and NH2 groups. Thermogravimetric curves showed that ether-amine oligomer was incorporated by ZrP. Interlamellar space of α-ZrP increased at least four times indicating intercalation. The relaxometry analysis indicated that α-ZrP molecular mobility changed according to the etheramine amount. The scanning electron microscopy/energy dispersive analysis revealed the presence of octadecylamine inside the α-ZrP galleries. The results showed that P-OH group (Brønsted acid) and amine group (Brønsted base) reacted to each other, resulting in an ionic bond PO-+ 3 HN--(CH2 -CH2 -O) m-(CH2 -C-H(CH3 )-O)n -. Partially intercalated nanofiller were achieved.
The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary ...healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs.
A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors.
A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval CI = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 95% CI = 0.68-1.18, p = 0.08) than patients who presented six or more diseases (OR = 1.12 95% CI = 1.02-2.01, p < 0.01). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 95% CI = 1.92-3.12, p < 0.01) than patients who took three to four drugs (OR = 0.93 95% CI = 0.74-1.11, p = 0.06). No significant difference was found with regard to sex (OR = 1.08 95% CI 0.48-2.02, p = 0.44).
The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.
IntroductionDeficits in episodic memory following traumatic brain injury (TBI) are common and affect independence in activities of daily living. Transcranial direct current stimulation (tDCS) and ...concurrent cognitive training may contribute to improve episodic memory in patients with TBI. Although previous studies have shown the potential of tDCS to improve cognition, the benefits of the tDCS applied simultaneously to cognitive training in participants with neurological disorders are inconsistent. This study aims to (1) investigate whether active tDCS combined with computer-assisted cognitive training enhances episodic memory compared with sham tDCS; (2) compare the differences between active tDCS applied over the left dorsolateral prefrontal cortex (lDLPFC) and bilateral temporal cortex (BTC) on episodic memory and; (3) investigate inter and intragroup changes on cortical activity measured by quantitative electroencephalogram (qEEG).Methods and analysisA randomised, parallel-group, double-blind placebo-controlled study is conducted. Thirty-six participants with chronic, moderate and severe closed TBI are being recruited and randomised into three groups (1:1:1) based on the placement of tDCS sponges and electrode activation (active or sham). TDCS is applied for 10 consecutive days for 20 min, combined with a computer-based cognitive training. Cognitive scores and qEEG are collected at baseline, on the last day of the stimulation session, and 3 months after the last tDCS session. We hypothesise that (1) the active tDCS group will improve episodic memory scores compared with the sham group; (2) differences on episodic memory scores will be shown between active BTC and lDLPFC and; (3) there will be significant delta reduction and an increase in alpha waves close to the location of the active electrodes compared with the sham group.Ethics and disseminationThis study was approved by Hospital das Clínicas, University of São Paulo Ethical Institutional Review Border (CAAE: 87954518.0.0000.0068).Trial registration numberNCT04540783.
The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in ...diagnosis.
A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations.
Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0-297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (
=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after,
=0.02).
The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.
Resumo Fundamento: A deficiência de testosterona (DT) é uma condição prevalente em nosso meio e ainda muito negligenciada. A hipertensão arterial (HA) é um de seus possíveis fatores associados. ...Objetivos: Determinar a prevalência de DT em uma população masculina hipertensa e os fatores associados à sua ocorrência, como idade, tempo de diagnóstico de HA, número de classes de anti-hipertensivos, índice de massa corporal (IMC), diabetes, dislipidemia, doença renal crônica (DRC), sintomas positivos de DT (questionário ADAM positivo) e uso de espironolactona. Métodos: Estudo transversal com aplicação do questionário ADAM, e avaliação de dados bioquímicos, clínicos e antropométricos. Os pacientes foram estratificados em grupos de DT e testosterona normal. As variáveis categóricas foram comparadas pelo teste do qui-quadrado e as variáveis contínuas pelo teste de Mann-Witney; as variáveis com significância (p<0,05) foram submetidas à regressão linear multivariada. Resultados: A prevalência de DT foi de 26,8%. Houve associação entre DT e IMC (p=0,0007), mas não houve com idade (p=0,0520), tempo de diagnóstico de HA (p=0,1418), número de classes de anti-hipertensivos (p=0,0732), diabetes (p=0,1112); dislipidemia (p=0,3888); presença de DRC (p=0,3321); uso de espironolactona (p=0,3546) e questionário ADAM positivo (p=0,2483). Conclusões: A prevalência de DT foi alta e houve associação positiva com IMC. A testosterona total (TT) declinou 8,44 ng/dL com o aumento de 1 kg/m2 no IMC e caiu 3,79 ng/dL com o avanço em um ano na idade.
Abstract Background: Testosterone deficiency (TD) is a prevalent condition in our midst and still very neglected. Arterial hypertension (AH) is one of the possible associated factors. Objectives: To determine the prevalence of TD in a hypertensive male population and the factors associated with its occurrence, such as age, time since hypertension diagnosis, number of antihypertensive classes, body mass index (BMI), diabetes, dyslipidemia, chronic kidney disease (CKD), positive symptoms of TD (positive ADAM questionnaire) and use of spironolactone. Methods: Cross-sectional study with administration of the ADAM questionnaire, assessment of biochemical, clinical, and anthropometric data. Patients were stratified into DT and normal testosterone groups. Categorical variables were compared using the chi-squared test and continuous variables using the Mann-Witney test; variables with significance (p<0,05) were analyzed by multivariable linear regression. Results: The prevalence of TD was 26.36%. There was an association between TD and body mass index (BMI) (p=0.0007) but there was no association with age (p=0.0520), time of hypertension diagnosis (p=0.1418), number of classes of antihypertensive drugs (p=0.732), diabetes (p=0.1112); dyslipidemia (p=0.3888); CKD (p=0.3321); use of spironolactone (p=0.3546) or positive ADAM questionnaire (p=0.2483). Conclusions: TD was highly prevalent and positively associated with BMI. Total testosterone (TT) declined by 8.44ng/dL with a one unit increase in BMI and dropped by 3.79ng/dL with a one-year increase in age.
As medidas de isolamento introduzidas para reduzir a propagação da doença causada pelo SARS-CoV-2 (COVID-19) tiveram efeitos sobre a mobilidade humana e relações sociais, com impacto sobre a saúde ...mental e práticas sexuais. Nesse estudo de corte transversal, investigamos a influência da pandemia da COVID-19 sobre o uso da profilaxia pré-exposição ao HIV (PrEP) entre pacientes do ambulatório de um serviço público em São Paulo, Brasil.
Usuários de PrEP foram convidados a participar do estudo entre agosto e dezembro de 2020, respondendo a um questionário de autopreenchimento ou aplicado por um investigador do estudo. Foram coletados dados a respeito do impacto da COVID-19 sobre hábitos sexuais, práticas de prevenção para infecções sexualmente transmissíveis, acesso a serviços de testagem e tratamento. Variáveis associadas à piora no acesso à saúde sexual ou aumento da vulnerabilidade sexual durante a pandemia foram exploradas em análises univariadas.
Foram incluídos 209 participantes, com mediana de idade de 33 anos; a maioria declarou-se com gênero masculino (98%) e raça/cor branca (71%). A maioria diminuiu o número de parceiros sexuais totais (77%) e casuais (78%) durante a pandemia. A pandemia não alterou de forma significativa o uso de preservativos ou o acesso a serviços de saúde sexual. A redução no uso de PrEP foi observada em cerca de um quinto dos entrevistados. Não encontramos associações entre fatores sociodemográficos e maior vulnerabilidade ao HIV; entre participantes que relataram trabalho em regime integral, 6% tiveram redução do acesso aos serviços de saúde sexual, comparado a 15% entre participantes em regime parcial de trabalho ou desempregados (p = 0,031).
Os impactos de longo prazo das restrições do COVID-19 nos comportamentos sexuais de grupos vulneráveis precisam ser monitorados porque podem prenunciar flutuações na cobertura de prevenção e risco de infecção por HIV. Políticas de apoio social e de cuidado à saúde, feitas sob medida durante períodos de redução de mobilidade e acesso aos serviços devem ser disponibilizadas para essas populações. Os desafios para a PrEP e o acesso aos testes sorológicos exigirão a implementação de soluções inovadoras para evitar a expansão da epidemia de HIV e a colisão de pandemias.
ABSTRACT Purpose: to review the literature available on electrophysiological findings on ABR with chirp stimuli in newborns. Methods: articles were searched in PubMed, MEDLINE, Scopus, Web of ...Science, LILACS, and SciELO. Papers published in English and Portuguese between 2010 and 2020 were selected, including those that addressed ABR with air-conduction broadband chirp stimuli in newborns, that assessed ABR with a specific frequency, and that compared ABR results with chirp and click stimuli. Articles that assessed only bone-conduction results, duplicates, literature reviews, case reports, letters, and editorials were excluded. Literature review: the search strategy resulted in nine selected articles. Four studies (44.4%) analyzed ABR wave amplitude and latency with chirp stimuli, three studies (33.3%) compared the time of ABR procedures between chirp and click stimuli, two studies (22.2%) analyzed only amplitude, and two (22.2%), verified the specificity of ABR with chirp stimuli in neonatal hearing screening. Conclusion: chirp stimuli elicit responses with greater amplitudes, lower latencies, and shorter examination time than those with click stimuli in newborns.
RESUMO Objetivo: revisar a literatura disponível sobre os achados eletrofisiológicos do PEATE por estímulo chirp em recém-nascidos. Métodos: a busca dos artigos foi realizada nas bases de dados PubMed, Medline, Scopus, Web of Science, LILACS e Scielo. Foram selecionados artigos publicados em Inglês e Português, entre 2010 e 2020. Foram incluídos artigos que contemplavam o uso do PEATE por estímulo chirp banda larga por via aérea em recém-nascidos; que avaliavam o PEATE por frequência específica e que comparavam os resultados do PEATE por estímulo chirp e clique. Aqueles que avaliavam somente resultados por via óssea, artigos repetidos nas bases de dados, artigos de revisão de literatura, relato de casos, cartas e editoriais foram excluídos. Revisão da Literatura: a estratégia de busca resultou na seleção de nove artigos. Quatro estudos (44,4%) analisaram amplitude e latência das ondas do PEATE por estímulo chirp, três (33,3%) compararam o tempo de realização do PEATE por clique e chirp, dois estudos (22,2%) analisaram somente o parâmetro amplitude e dois (22,2%) verificaram a especificidade do PEATE por chirp na triagem auditiva neonatal. Conclusão: o estímulo chirp possibilita respostas com maiores amplitudes, maiores latências e menor tempo de realização do exame quando comparado ao estímulo clique em recém-nascidos.
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