Advances in the phytochemical screening and biological potential of propolis.

Propolis is a natural resinous product collected from different parts of plants by bees and mixed with their salivary secretions. The occurrence of more than 180 different chemotypes has flavonoids, phenolic acids, esters, and phenolic aldehydes, as well as balsamic resins, beeswax, pollen, and essential and aromatic oils, among others. Its biological potential documented throughout the world justifies the need, from time to time, to organize reviews on the subject, with the intention of gathering and informing about the update on propolis. In this review (CRD42020212971), phytochemical advances, in vitro, in vivo, and clinical biological assays of pharmacological interest are showcased. The focus of this work is to present propolis clinical safety assays, antitumor, analgesic, antioxidant, anti-inflammatory, and antimicrobial activities. This literature review highlights propolis' promising biological activity, as it also suggests that studies associating propolis with nanotechnology should be further explored for enhanced bioprocessing applications.

Pre-clinical safety of topically administered sunitinib-loaded lipid and polymeric nanocarriers targeting corneal neovascularization.

Three different types of sunitinib-loaded (SUN-loaded) nanocarriers were compared, aiming at the topical treatment of corneal neovascularization (CNV): polymeric nanospheres (NS), liposomes (LIP), and solid lipid nanoparticles (SLN). Three out of eleven formulations prepared for an optimization study - the best SUN-loaded nanocarrier of each assessed type (NS, LIP, and SLN) - were selected, based on their size, polydispersity index (PdI), drug load (DL), and encapsulation efficiency (EE). These three optimal formulations were further characterized by nanoparticle tracking analysis (NTA), electron paramagnetic resonance (EPR) spectroscopy, and zeta potential. In vitro SUN release profiles were obtained for the optimal formulations, along with ex vivo corneal permeability/retention studies, and ocular tolerance assays, namely: the bovine corneal opacity and permeability (BCOP) assay, the HET-CAM test (hen's egg test - chorioallantoic membrane), and hemolytic potential (HP) assay. None of the optimal formulations exhibited toxicity or potential for ocular irritation. SLN showed higher surface fluidity, drug release more suitable for topical ocular applications, besides greater SUN corneal retention. Our results suggest that SLN are the best CNV-targeting SUN-loaded nanocarriers for clinical translation when compared to their NS and LIP analogues.

Device implant based on poly (lactic acid) with vitamin E for vaccine delivery system in Tilapia: Study for biocompatibility and biodegradation.

The use of Poly (lactic acid) (PLA) as a slow-release vehicle for vaccines has attracted the attention of researchers, since its insertion improves the uptake of them, and reduces side effects or by stimulating recruited defense cells, assisting immunity without the need for booster vaccine doses. Seeking to develop new strategies for the administration of drugs and vaccines in aquaculture, we evaluated the biocompatibility and biodegradation of polymeric PLA devices and PLA plus vitamin E devices, implanted through subcutaneous (SC) and intraperitoneal (IP) routes in Nile tilapia. To carry out this study, 84 male tilapia (initial 243.82 ± 56.74 g; final 400.71 ± 100.54 g) were randomly distributed in 3 tanks (n = 28 fish per treatment/tank). The devices were prepared in two formulations: neat PLA (containing 100% PLA) and PLAVE (PLA plus vitamin E) implanted using a commercial AnimalTag® applicator, and non-implanted fish (control). Fish were sampled 15, 30, 60, and 120 days post-implantation (DPI). Blood analysis was used to access blood cells and blood smear for differential leucocytes count. Serum biochemistry to evaluated changes in serum proteins and glycemia. Histopathological investigation using hematoxylin-eosin (H&E) was used to assess polymer-tissue interaction. Histochemistry and immunohistochemistry was used to detection immune cells and phagocytes in capsule, and analyses of melanomacrophage centers (MMCs) to morphometric evaluation and percentage amount of melanin, hemosiderin and lipofucsin pigments. Histopathological study revealed an increase of capsular formation and inflammatory cell infiltration in PLAVE-implanted tilapia through SC route (15 DPI). Tilapia implanted with PLAVE and PLA (SC) presented mast cells and eosinophilic granular cells during 15, 30, and 60 DPI, with a decrease in these cells in the fibrous capsule around the polymer at 120 DPI. PLAVE implanted tilapia SC at 60 DPI showed significantly phagocytosis points than other groups. Phagocytic cells (F4/80+) were observed near to biopolymers in phagocytosis sites. Lipofuscin at 120 DPI in spleen melanomacrophage centers were significantly high in PLAVE implanted tilapias when compared to fish with PLA implants and control. The serum biochemical study of tilapia did not reveal changes in cytotoxicity and liver function in implanted fish. The absence of side effects in hematological and biochemical findings, including the absence of mortality after device implantation, proves its clinical safety. PLA implants in tilapia have demonstrated biocompatibility, biodegradation, clinical safety, and excellent evolution of foreign body inflammatory responses.

Preclinical and clinical studies to evaluate cutaneous biodistribution, safety and efficacy of UV filters encapsulated in mesoporous silica SBA-15.

Innovative technologies have been designed to improve efficacy and safety of chemical UV filters. Encapsulation can enhance efficacy and reduce transdermal permeation and systemic exposure. The aims of this work were (i) to determine the cutaneous biodistribution of avobenzone (AVO), oxybenzone (OXY), and octyl methoxycinnamate (OMC) incorporated in mesoporous silica SBA-15 and (ii) to perform preclinical (in vitro) and (iii) clinical safety studies to demonstrate their innocuity and to evaluate sun protection factor (SPF) in humans. Skin penetration studies showed that deposition of OXY and AVO in porcine and human skin after application of stick formulation with incorporated filters (stick incorporated filters) was significantly lower than from a marketed (non-encapsulated) stick. Cutaneous deposition and transdermal permeation of OXY in and across human skin were 3.8-and 13.4- fold lower, respectively, after application of stick entrapped filters. Biodistribution results showed that encapsulation in SBA-15 decreased AVO and OXY penetration reaching porcine and human dermis. Greater deposition (and permeation) of OXY in porcine skin than in human skin, pointed to the role of follicular transport. Stick incorporated filters had good biocompatibility in vivo and safety profiles, even under sun-exposed conditions. Entrapment of UV filters improved the SPF by 26% and produced the same SPF profile as a marketed stick. Overall, the results showed that SBA-15 enabled safety and efficacy of UV filters to be increased.

Risk Analysis for Patient Safety in Surgical Departments: Cross-Sectional Design Usefulness.

(1) Background: Identifying and measuring adverse events (AE) is a priority for patient safety, which allows us to define and prioritise areas for improvement and evaluate and develop solutions to improve health care quality. The aim of this work was to determine the prevalence of AEs in surgical and medical-surgical departments and to know the health impact of these AEs. (2) Methods: A cross-sectional study determining the prevalence of AEs in surgical and medical-surgical departments was conducted and a comparison was made among both clinical areas. A total of 5228 patients were admitted in 58 hospitals in Argentina, Colombia, Costa Rica, Mexico, and Peru, within the Latin American Study of Adverse Events (IBEAS), led by the Spanish Ministry of Health, the Pan American Health Organization, and the WHO Patient Safety programme. (3) Results: The global prevalence of AEs was 10.7%. However, the prevalence of AEs in surgical departments was 11.9%, while in medical-surgical departments it was 8.9%. The causes of these AEs were associated with surgical procedures (38.6%) and nosocomial infections (35.4%). About 60.6% of the AEs extended hospital stays by 30.7 days on average and 25.8% led to readmission with an average hospitalisation of 15 days. About 22.4% resulted in death, disability, or surgical reintervention. (4) Conclusions: Surgical departments were associated with a higher risk of experiencing AEs.

Seguridad y destreza autoreportadas en la formación de competencias clínicas obstétricas en estudiantes de obstetricia / Self-reported confidence and skills in training for clinical-obstetric competences on Obstetrics students

Introducción: la educación en ciencias de la salud ha requerido adaptaciones de acuerdo a necesidades de la población, y así muchos programas de estudios han adoptado el modelo de competencias. Se hace necesario demostrar la adquisición del conocimiento práctico desarrollándose actividades con seguridad y destreza que permita la atención clínica efectiva. Objetivo: analizar niveles de destreza y seguridad autoreportados y rendimiento obtenido por estudiantes de la carrera de Obstetricia y Puericultura de la Universidad de Concepción, Chile, que entrenan competencias obstétricas, además con simulación clínica. Métodos: se realizó estudio no experimental, analítico y relacional, en 127 estudiantes de la carrera de Obstetricia y Puericultura de la Universidad de Concepción, en el año 2014. Se aplicó encuesta para medir destreza con escala tipo Likert posterior al entrenamiento de competencias obstétricas en modalidad preclínica, y la seguridad en modalidad clínica y se relacionó con el rendimiento obtenido. Se realizó análisis descriptivo y relacional. Resultados: 119 estudiantes respondieron las encuestas para destreza y 115 para seguridad. Las competencias obstétricas fueron 30, de complejidad variable, con resultados diversos. Las destrezas altas se relacionan con seguridad alta, sin embargo no todas las competencias siguen este curso. La destreza no se relaciona con rendimiento. Conclusiones: las competencias obstétricas son diversas en complejidad, con diferentes niveles de destreza y seguridad, algunas muy altas y otras más bajas, sin embargo algunas importantes presentan niveles más bajos que los esperados. Es necesario ordenar los niveles de complejidades. La evaluación de los estudiantes no se relaciona con el logro de competencias, se hace necesario establecer instrumentos adecuados(AU)

Introduction: The education of health sciences has required adjustments according to the needs of the general population and therefore most programs have adopted models based on competencies. It is necessary to demonstrate the acquisition of practical knowledge developed with regards to safety and skill that allows for more effective clinical care. Objective: To analyze the self-reported levels of skill and safety and the assessments obtained by students of midwifery at University of Concepcion, Chile. They train in obstetric skills mainly via clinical simulation. Method: Analytical and relational, non-experimental study with non-probabilistic by 119 volunteer midwifery students at the university at the University of Concepcion in 2014. A Likert type scale survey was administered post practical trainings in preclinical and clinical settings which was correlated with the student's performances. A descriptive and relational analysis was executed. Results: 119 students completed the surveys for skill level and 115 for security of procedures. There were 30 obstetric skills practical trainings, all of varying degrees of complexity with mixed results. High levels of skill are related to high levels of security but not all of their competencies follow this pattern. The level of skill does not relate to performance. Conclusions: Obstetric skills are diverse in terms of complexity, with diferent levels of skill and safety, mostly high for both, but some are not important. It is necessary to sort the levels of complexity. The evaluation of students is not related to the achievement of competencies. It is necessary to establish appropriate measuring instruments(AU)

Clinical safety of dichlorvos (45%), cypermethrin (5%) and piperonyl butoxide (25%) administered by spray on the skin of cattle / Seguridad clínica del diclorvos (45%), cipermetrina (5%) y butóxido de piperonilo (25%) administrado por aspersión sobre la piel de bovinos

Objective. Due to the importance of controlling ectoparasites, associated with the necessity of technical knowledge on the safety of topical treatment with organophosphates, pyrethroids and piperonyl butoxide to the animal organism, this bioassay was carried out to evaluate the clinical safety of the association of dichlorvos (45%) + cypermethrin (5%) + piperonyl butoxide (25%) administered by spray on the skin of cattle, through the study of clinical parameters, biochemical, haematological and behavioral changes. Materials and methods. Sixteen crossbred animals with a mean age of 18 months, males and females grouped into two treatments with eight animals each: T1 (1:800 v/v) and T2 (1:200 v/v). Were collected blood samples at six different times: before treatment (BT), 24, 48, 72, 96 and 192 hours post treatment (HPT). Results. The antiparasitic association administered by spray on the skin did not result in changes in the enzymatic activity of ALT, AST, GGT and ALP, as well as in serum albumin, triglycerides, cholesterol, urea and creatinine, demonstrating the safety of this antiparasitic compound for maintaining hepatic and renal functionality. The erythrocyte, leukocyte and platelet studies showed no changes caused by treatments, and no clinical signs and behavioral changes were observed after treatment. Conclusions. These findings demonstrated good safety margin for spray treatment on the skin with this antiparasitic compound, even when administered at a dilution of 1:200 v/v, which is four times the dose recommended for ectoparasite control.

Objetivo. Debido a la importancia del control de ectoparásitos en bovinos, asociado a la necesidad de conocimientos técnicos sobre la seguridad del tratamiento tópico con organofosforados, piretroides y butóxido de piperonilo, se realizó este bioensayo para la evaluación de la seguridad clínica de la asociación de diclorvos (45%) + cipermetrina (5%) + butóxido de piperonilo (25%), administrado por aspersión en la piel del ganado bovino, a través del estudio de los parámetros clínicos, bioquímicos, hematológicos y comportamentales. Materiales y métodos. Dieciséis animales entre machos y hembras cruzados con edad media de 18 meses, agrupados en dos tratamientos de ocho animales cada uno: T1 (1:800 v/v) y T2 (1:200 v/v). Fueron colectadas muestras de sangre en seis momentos diferentes: antes del tratamiento (BT), 24, 48, 72, 96 y 192 horas post tratamiento (HPT). Resultados. La asociación antiparasitaria administrada por aspersión en la piel no alteró la actividad enzimática de ALT, AST, GGT y FA, así como la albúmina, triglicéridos, colesterol, urea y creatinina, que demuestra la seguridad de este compuesto antiparasitario en la función renal y hepática. El análisis de eritrocitos, leucocitos y plaquetas no mostraron cambios en los tratamientos, tampoco fueron observados signos clínicos y de comportamiento post tratamiento. Conclusiones. Estos resultados demostraron buen margen de seguridad en el tratamiento por aspersión en la piel con este compuesto antiparasitario, incluso cuando se administra en una dilución de 1:200 v/v, que es cuatro veces la dosis recomendada para el control de ectoparásitos.

Evaluation of clinical safety and anthelmintic efficacy of aurixazole administed orally at 24 mg/kg in cattle.

The current study evaluated, in vivo, the clinical safety and the anthelmintic efficacy of 24% aurixazole (24 mg/kg), administered orally, in bovines. Two experiments were conducted: the first one evaluating the clinical safety of 24% aurixazole (24 mg/kg) in cattle, and a second one evaluating the anthelmintic efficacy of aurixazole (24 mg/kg) against gastrointestinal nematodes on naturally infected cattle. Based on the results of clinical safety, no alterations on clinical and haematological signs and on the biochemical values obtained in animals treated orally with aurixazole 24 mg/kg were observed. Regarding the results of reduction or efficacy, obtained by eggs per gram of faeces (EPG) counts, the formulation of aurixazole reached values superior to 99% (arithmetic means) in all post-treatment dates. In two occasions, this formulation reached maximum efficacy (100%). Comparing these results with the reduction percentages obtained by EPG counts, it is possible to verify that the values obtained by all three formulations were compatible with the efficacy results. Aurixazole reached maximum efficacy (100%) against Haemonchus placei, Cooperia spatulata and Oesophagostomum radiatum. Against Cooperia punctata, this formulation reached an efficacy index of 99.99%. Regarding aurixazole, no specific trials were conducted on the field in order to evaluate the behaviour of this molecule against helminths that are resistant to other molecules, specially isolated levamisole and disophenolat. Due to this fact, future studies will be necessary to assess the effectiveness of aurixazole against strains of nematodes that are resistant to levamisole and disophenolat, but the results of clinical safety and efficacy described in this study allow us to conclude that the aurixazole molecule, concomitantly with other measures and orally administered formulations, can be another important tool in the control of nematodes parasitizing bovines.