Trypanocidal potential of synthetic p-aminochalcones: In silico and in vitro evaluation.

Chagas disease (CD) is a neglected tropical disease of worldwide health concern, caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi), endemic in Latin America and present in North America and Europe. The WHO recommended drug for CD, benznidazole has low safety profile and several limitations. Therefore, an entity with better therapeutic potential to treat CD is required. Chalcones are an important class of compounds, which have shown antichagasic potential. Thus, the objective of this study was to evaluate the activity of synthetic p-aminochalcones against T. cruzi. Chalcones 1 and 2 were synthesized by Claisen-Schmidt condensation and characterized by both spectroscopic and theoretical methods. Initially, they were submitted to molecular docking simulations using cruzain and trypanothione reductase (TR) enzymes. It was expected to observe the possible interactions of chalcones with the catalytic site and other important regions of these main pharmacological targets of T. cruzi. Their cytotoxicity within host cells were assessed by MTT reduction assay using LLC-MK2 cells, with CC50 = 85.6 ± 9.2 µM and 1115 ± 381.7 µM for chalcones 1 and 2, respectively. These molecules were also tested against epimastigote and trypomastigote life forms of T. cruzi, causing reduction in the number of viable parasites. For the evaluation of the effect on intracellular amastigotes, infected LLC-MK2 cells were incubated with the chalcones for 24 h, causing reduction in the percentage of infected cells and the number of amastigotes/100 cells. Finally, flow cytometry assays were performed for analyzing cell death mechanisms (7-AAD/AxPE labelling), cytoplasmic ROS accumulation (DCFH-DA assay) and mitochondrial transmembrane potential disruption (Rho123 assay). Both chalcones (1 and 2) caused membrane damage, ROS accumulation and mitochondrial depolarization. In conclusion, the synthetic p-aminochalcones presented trypanocidal effect, causing membrane damage and oxidative stress. Their mechanism of action may be related to cruzain and TR inhibition.

Association of serum lipoproteins and inflammatory parameters derived from the blood test with renal function in COVID-19 outpatients

Abstract Changes in lipoprotein metabolism are among the main causes of hemodynamic impairment in renal function. COVID-19 is an multisystemic inflammatory disease, aggravating this situation. This cross-sectional study investigated the relationship of serum lipoprotein profile with inflammatory parameters and renal function in 95 COVID-19 outpatients in comparison with 173 with flu-like symptoms. Serum samples were collected for the determination of total cholesterol and fractions, apolipoproteins (Apo A-I and Apo B), urea (sUr) and creatinine (sCr). The glomerular filtration rate (eGFR) was calculated. Neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios were calculated as inflammatory parameters derived from the blood tests. COVID-19 patients presented lower high-density lipoprotein cholesterol (HDL-c) (47.90 ± 1.543 vs. 51.40 ± 0.992) and higher PLR (190.9 ± 9.410 vs. 137.6 ± 5.534) and NLR (3.40 ± 0.22 vs. 2.80 ± 0.15). Both NLR and PLR correlated with each other (r = 0.639). Furthermore, the Apo B/Apo A-I ratio was correlated with PLR (r = 0.5818) and eGFR (r = -0.2630). COVID-19 patients classified as at high risk of developing acute myocardial infarction based on the Apo B/ Apo A-I ratio had higher values for sUr/sCr. Thus, serum apolipoproteins, PLR, and NLR could be related to renal dysfunction in COVID-19.

Plants with Therapeutic Potential for Ischemic Acute Kidney Injury: A Systematic Review.

Acute kidney injury (AKI) is a complex condition which has an intricate pathology mostly involving hemodynamic, inflammatory, and direct toxic effects at the cellular level with high morbidity and mortality ratios. Renal ischemic reperfusion injury (RIRI) is the main factor responsible for AKI, most often observed in different types of shock, kidney transplantation, sepsis, and postoperative procedures. The RIRI-induced AKI is accompanied by increased reactive oxygen species generation together with the activation of various inflammatory pathways. In this context, plant-derived medicines have shown encouraging nephroprotective properties. Evidence provided in this systemic review leads to the conclusion that plant-derived extracts and compounds exhibit nephroprotective action against renal ischemic reperfusion induced-AKI by increasing endogenous antioxidants and decreasing anti-inflammatory cytokines. However, there is no defined biomarker or target which can be used for treating AKI completely. These plant-derived extracts and compounds are only tested in selected transgenic animal models. To develop the results obtained into a therapeutic entity, one should apply them in proper vertebrate multitransgenic animal models prior to further validation in humans.

Assessment of knowledge regarding tracheostomy care and management of early complications among healthcare professionals / Avaliação do conhecimento sobre cuidados com a traqueostomia e manejo de complicações precoces entre profissionais de saúde

Abstract Introduction: Tracheostomy is commonly performed surgical procedure in ENT practice. Postoperative care is the most important aspect for achieving good patient outcomes. Unavailability of standard guidelines on tracheostomy management and inadequate training can make this basic practice complex. The nursing staff and doctors play a very important role in bedside management, both in the ward and in the intensive care unit (ICU) setup. Therefore, it is crucial that all healthcare providers directly involved in providing postoperative care to such patients can do this efficiently. Objectives: The objective of this study is to assess the knowledge regarding identification and management of tracheostomy-related emergencies and early complications among healthcare professionals so as to improve practice and further standardization. Methods: Cross-sectional observational study included two hundred and fifty-four doctors and nurses from four large tertiary care hospitals. The questions used were simple and straightforward regarding tracheostomy suctioning, cuff care, cuff management, tube blockage, and feeding management in patients with tracheostomy. Results: Based on evidence from our study, knowledge level regarding tracheostomy care ranges from 48% to 52% with knowledge scores above 50% being considered satisfactory. Significant gaps in knowledge exist in various aspects of tracheostomy care and management among healthcare professionals. Conclusion: Our findings demonstrated an adequate knowledge level among health care professionals ranging from 48% to 52% with knowledge scores above 50% being considered satisfactory and revealed that gaps in knowledge still exist in various aspects of tracheostomy care and management.

HIGHLIGHTS Healthcare workers should be well versed in identifying tracheostomy management, its complications and responding accordingly. Doctors and nurses (131 =52%) possessed good knowledge about various aspects of tracheostomy care and management. The poorest scores were regarding cuff pressure (38.9%), suction pressure (39.4%) and first response in tube blockade (31.1%). Higher scores were found in age group 26 to 30 years (54.2%) and those having 1-3 years of clinical experience (41.2%). No statistically significant assoiation of knowledge regarding tracheostomy care was apparent with age, gender or years of practice.

Resumo Introdução: A traqueostomia é um procedimento cirúrgico comumente feito na prática otorrinolaringológica. O cuidado pós-operatório é o aspecto mais importante para alcançar bons resultados para o paciente. A indisponibilidade de diretrizes padrão para o manejo da traqueostomia e o treinamento inadequado podem tornar complexa essa prática básica. A equipe de enfermagem e os médicos desempenham um papel muito importante no manejo à beira do leito, tanto na enfermaria quanto na unidade de terapia intensiva (UTI). Portanto, é crucial que todos os profissionais de saúde diretamente envolvidos na prestação de cuidados pós-operatórios a esses pacientes possam fazer isso de forma eficiente. Objetivo: Avaliar o conhecimento sobre a identificação e manejo de emergências relacionadas à traqueostomia e complicações precoces entre os profissionais de saúde, a fim de melhorar a prática e sua padronização. Método: Estudo observacional transversal que incluiu 254 médicos e enfermeiras de quatro grandes hospitais terciários. As perguntas foram simples e diretas em relação à aspiração da traqueostomia, cuidados com o cuff, manejo do cuff, obstrução da cânula e manejo da alimentação em pacientes traqueostomizados. Resultado: Com base nas evidências de nosso estudo, o nível de conhecimento sobre os cuidados com a traqueostomia varia de 48% a 52%, com escores de conhecimento acima de 50% considerados satisfatórios. Existem lacunas significativas no conhecimento em vários aspectos dos cuidados e manejo da traqueostomia entre os profissionais de saúde. Conclusão: Nossos achados demonstraram um nível de conhecimento adequado entre os profissionais de saúde, variação de 48% a 52%, com escores de conhecimento acima de 50% considerados satisfatórios e revelaram que ainda existem lacunas no conhecimento em vários aspectos do tratamento e manejo do paciente traqueostomizado.

DESTAQUES Profissionais de saúde devem estar bem familiarizados com a identificac¸ão do manejo da traqueostomia, suas complicac¸ões e como agir de acordo com a necessidade. Médicos e enfermeiras (131 = 52%) possuíam bons conhecimentos sobre vários aspectos dos cuidados e manejo da traqueostomia. Os piores escores foram em relac¸ão à pressão adequada do cuff (38,9%), à pressão de aspirac¸ão adequada (39,4%) e primeiros socorros em caso de obstruc¸ão da cânula (31,1%). Os melhores escores foram encontrados no grupo 26 a 30 anos (54,2%) e aqueles com experiência clínica de 1-3 anos (41,2%). Não houve associac¸ão estatisticamente significante entre o conhecimento sobre os cuidados com a traqueostomia, idade e gênero e os anos de prática de médicos e enfermeiras.

(-)-α-Bisabolol as a protective agent against epithelial renal cytotoxicity induced by amphotericin B.

INTRODUCTION: Amphotericin B (AmB), used for systemic fungal infections, has a limited clinical application because of its high nephrotoxicity. Natural antioxidant and anti-inflammatory substances have been widely studied for protection against drug-induced nephrotoxicity. α-Bisabolol (BIS) has demonstrated a nephroprotective effect on both in vitro and in vivo models. AIMS: The aim of this work was to evaluate the effect of BIS against AmB-induced nephrotoxicity in vitro. MATERIAL AND METHODS: LLC-MK2 cells were pre- and post-treated with non-toxic BIS concentrations and/or AmB IC50 (13.97 µM). Cell viability was assessed by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Flow cytometry analyses were used to assess cell death mechanism, production of reactive oxidative stress (ROS) and mitochondrial transmembrane potential. Kidney Injury Molecule-1 (KIM-1) levels were measured via ELISA. KEY FINDINGS: The present work showed that BIS pretreatment (125; 62.5 and 31.25 µM) increased cell viability when compared to the group treated only with AmB IC50. AmB treatment induced both necrosis (7-AAD-labeled cells) and late apoptosis (AnxV-labeled). BIS was able to prevent the occurrence of these events. These effects were associated with a decrease of ROS accumulation, improving transmembrane mitochondrial potential and protecting against tubular cell damage, highlighted by the inhibition of KIM-1 release after BIS treatment. SIGNIFICANCE: BIS presented a potential effect on model of renal cytotoxicity induced by AmB, bringing perspectives for the research of new nephroprotective agents.

Assessment of knowledge regarding tracheostomy care and management of early complications among healthcare professionals.

INTRODUCTION: Tracheostomy is commonly performed surgical procedure in ENT practice. Postoperative care is the most important aspect for achieving good patient outcomes. Unavailability of standard guidelines on tracheostomy management and inadequate training can make this basic practice complex. The nursing staff and doctors play a very important role in bedside management, both in the ward and in the intensive care unit (ICU) setup. Therefore, it is crucial that all healthcare providers directly involved in providing postoperative care to such patients can do this efficiently. OBJECTIVES: The objective of this study is to assess the knowledge regarding identification and management of tracheostomy-related emergencies and early complications among healthcare professionals so as to improve practice and further standardization. METHODS: Cross-sectional observational study included two hundred and fifty-four doctors and nurses from four large tertiary care hospitals. The questions used were simple and straightforward regarding tracheostomy suctioning, cuff care, cuff management, tube blockage, and feeding management in patients with tracheostomy. RESULTS: Based on evidence from our study, knowledge level regarding tracheostomy care ranges from 48% to 52% with knowledge scores above 50% being considered satisfactory. Significant gaps in knowledge exist in various aspects of tracheostomy care and management among healthcare professionals. CONCLUSION: Our findings demonstrated an adequate knowledge level among health care professionals ranging from 48% to 52% with knowledge scores above 50% being considered satisfactory and revealed that gaps in knowledge still exist in various aspects of tracheostomy care and management.

Analysis for the presence of determinants involved in the transport of mercury across bacterial membrane from polluted water bodies of India

Abstract Mercury, which is ubiquitous and recalcitrant to biodegradation processes, threatens human health by escaping to the environment via various natural and anthropogenic activities. Non-biodegradability of mercury pollutants has necessitated the development and implementation of economic alternatives with promising potential to remove metals from the environment. Enhancement of microbial based remediation strategies through genetic engineering approaches provides one such alternative with a promising future. In this study, bacterial isolates inhabiting polluted sites were screened for tolerance to varying concentrations of mercuric chloride. Following identification, several Pseudomonas and Klebsiella species were found to exhibit the highest tolerance to both organic and inorganic mercury. Screened bacterial isolates were examined for their genetic make-up in terms of the presence of genes (merP and merT) involved in the transport of mercury across the membrane either alone or in combination to deal with the toxic mercury. Gene sequence analysis revealed that the merP gene showed 86–99% homology, while the merT gene showed >98% homology with previously reported sequences. By exploring the genes involved in imparting metal resistance to bacteria, this study will serve to highlight the credentials that are particularly advantageous for their practical application to remediation of mercury from the environment.

Analysis for the presence of determinants involved in the transport of mercury across bacterial membrane from polluted water bodies of India.

Mercury, which is ubiquitous and recalcitrant to biodegradation processes, threatens human health by escaping to the environment via various natural and anthropogenic activities. Non-biodegradability of mercury pollutants has necessitated the development and implementation of economic alternatives with promising potential to remove metals from the environment. Enhancement of microbial based remediation strategies through genetic engineering approaches provides one such alternative with a promising future. In this study, bacterial isolates inhabiting polluted sites were screened for tolerance to varying concentrations of mercuric chloride. Following identification, several Pseudomonas and Klebsiella species were found to exhibit the highest tolerance to both organic and inorganic mercury. Screened bacterial isolates were examined for their genetic make-up in terms of the presence of genes (merP and merT) involved in the transport of mercury across the membrane either alone or in combination to deal with the toxic mercury. Gene sequence analysis revealed that the merP gene showed 86-99% homology, while the merT gene showed >98% homology with previously reported sequences. By exploring the genes involved in imparting metal resistance to bacteria, this study will serve to highlight the credentials that are particularly advantageous for their practical application to remediation of mercury from the environment.

Analysis for the presence of determinants involved in the transport of mercury across bacterial membrane from polluted water bodies of India

Mercury, which is ubiquitous and recalcitrant to biodegradation processes, threatens human health by escaping to the environment via various natural and anthropogenic activities. Non-biodegradability of mercury pollutants has necessitated the development and implementation of economic alternatives with promising potential to remove metals from the environment. Enhancement of microbial based remediation strategies through genetic engineering approaches provides one such alternative with a promising future. In this study, bacterial isolates inhabiting polluted sites were screened for tolerance to varying concentrations of mercuric chloride. Following identification, several Pseudomonas and Klebsiella species were found to exhibit the highest tolerance to both organic and inorganic mercury. Screened bacterial isolates were examined for their genetic make-up in terms of the presence of genes (merP and merT) involved in the transport of mercury across the membrane either alone or in combination to deal with the toxic mercury. Gene sequence analysis revealed that the merP gene showed 8699% homology, while the merT gene showed >98% homology with previously reported sequences. By exploring the genes involved in imparting metal resistance to bacteria, this study will serve to highlight the credentials that are particularly advantageous for their practical application to remediation of mercury from the environment. (AU)