Simulación clínica: metodología didáctica en la formación de competencia inherentes a la seguridad del paciente / Clinical simulation: didactic methodology in the training of competencies inherent to patient safety

Con el objetivo de establecer la correlación entre la seguridad del paciente y los elementos del aprendizaje en la simulación clínica relativos a la presencia de un EA, en estudiantes de la carre-ra de Enfermería de la Universidad Juárez del Estado de Durango, durante el período compren-dido entre agosto de 2018 y diciembre de 2019. Se desarrolló un estudio cuantitativo, no experi-mental correlacional y longitudinal prospectivo. Se trabajó con la totalidad de la población de estudio, la que estuvo constituida por los 98 alumnos de ese contexto de investigación. La media de la edad de los participantes fue de 19,35 (σ=1.30), predominando el género femenino con 63,3%. Los elementos autovalorativos del aprendizaje relativos al temor a generar un EA predo-minaron (75,50%); mientras que, un 74,5% consideró que dominaba cómo actuar ante una situa-ción de emergencia. La mayoría manejó bien la tecnología durante el cuidado (87,80%) y mane-jaba adecuadamente los protocolos de seguridad del paciente (74,5%), se detectaron dificultades relativas a las competencias básicas en el cuidado de enfermería (67,3%). El mayor acierto con respecto a la seguridad del paciente resultó el cumplimiento de los protocolos de comunicación efectiva; mientras que, la más afectada fue la toma de medidas adecuadas durante la administra-ción de medicamentos. Los valores de Rho de Spearman permitieron establecer una correlación significativa, positiva moderada entre la seguridad del paciente y el temor a cometer un EA durante el ejercicio práctico; la que resultó significativa, moderada y negativa con respecto a la manifestación de agotamiento emocional.

This research aimed to establish the correlation between patient safety and the elements of learning in clinical simulation related to the presence of an AE, in students of the Nursing career of the Juárez University of the State of Durango, during the period between August 2018 and December 2019. A prospective longitudinal, correlational, and quantitative non-experimental study was developed. The entire study population was considered, which was made up of the 98 students from that research context. The mean age of the participants was 19.35 (σ = 1.30), predominantly female with 63.3%. The self-evaluating elements of learning related to the fear of generating an AE predominated (75.50%); while 74.5% considered that they mastered how to act in an emergency situation. Most of them handled technology well during care (87.80%) and mastered patient safety protocols (74.5%), difficulties related to basic skills in nursing care were detected (67.3%). The greatest success with respect to patient safety resulted in compliance with effective communication protocols, while the most affected was the taking of adequate measures during the administration of medications. Spearman's Rho values allowed to establish a modera-te positive correlation significance between patient safety and fear of committing an AE during practical exercise; this one showed a moderate and negative significance with respect to the manifestation of emotional exhaustion.

Spray Drying of Blueberry Juice-Maltodextrin Mixtures: Evaluation of Processing Conditions on Content of Resveratrol.

Resveratrol is an antioxidant abundant in red fruits, and one of the most powerful inhibiting reactive oxygen species (ROS) and oxidative stress (OS) produced by human metabolism. The effect of the spray drying processing conditions of blueberry juice (BJ) and maltodextrin (MX) mixtures was studied on content and retention of resveratrol. Quantitatively, analysis of variance (ANOVA) showed that concentration of MX was the main variable influencing content of resveratrol. Response surface plots (RSP) confirmed the application limits of maltodextrins based on their molecular weight, where low molecular weight MXs showed a better performance as carrying agents. After qualitatively comparing results for resveratrol against those reported for a larger antioxidant molecule (quercetin 3-D-galactoside), it was observed a higher influence of the number of active sites available for the chemical interactions, instead of stearic hindrance effects.

Evaluation of cardiovascular responses to silver nanoparticles (AgNPs) in spontaneously hypertensive rats.

Silver nanoparticles (AgNPs) are used in the medical, pharmaceutical and food industry. Adverse effects and toxicity induced by AgNPs upon cardiac function related to nitric oxide (NO) and oxidative stress (OS) are described. AgNPs-toxicity may be influenced by cardiovascular pathologies such as hypertension. However, the molecules involved under pathophysiological conditions are not well studied. The aim of this work was to evaluate perfusion pressure (PP) and left ventricle pressure (LVP) as physiological parameters of cardiovascular function in response to AgNPs, using isolated perfused hearts from spontaneously hypertensive rats (SHR), and identify the role of NO and OS. The results suggest that AgNPs reduced NO derived from endothelial/inducible NO-synthase and increased OS, leading to increased and sustained vasoconstriction and myocardial contractility. Additionally, the hypertension condition alters phenylephrine (Phe) and acetylcholine (ACh) classic effects. These data suggest that hypertension intensified AgNPs-cardiotoxicity. Nevertheless, the precise mechanism of action is still under elucidation.

Bioactivity of an antihypertensive peptide expressed in Chlamydomonas reinhardtii.

In this study, we developed a transplastomic C. reinhardtii strain that accumulates anti-hypertensive peptides. Tandem repeats of VLPVP peptide were included. PCR analysis confirmed the presence of the transgene in the modified strains. After in vitro digestion of biomass of a recombinant C. reinhardtii strain the VLVPV peptide was identified and quantified by HPLC. The highest expression line produced 0.292mg of recombinant protein per mg of freeze-dried biomass. Intragastric administration of the genetically modified strain to spontaneous hypertensive rats at a dose of 30mg/kg of body weight of recombinant protein significantly reduced systolic blood pressure. At the same dose, the recombinant protein exerts an ACE-inhibitory effect. This is the first study that indicates the potential of this microalga producing an antihypertensive peptide as a dietary supplement for hypertension patients.

(1R)-(+)-camphor and acetone derived alpha'-hydroxy enones in asymmetric Diels-Alder reaction: catalytic activation by Lewis and Brønsted acids, substrate scope, applications in syntheses, and mechanistic studies.

The Diels-Alder reaction constitutes one of the most powerful and convergent C-C bond-forming transformations and continues to be the privileged route to access cyclohexene substructures, which are widespread within natural products and bioactive constituents. Over the recent years, asymmetric catalytic Diels-Alder methodologies have experienced a tremendous advance, but still inherently difficult diene-dienophile combinations prevail, such as those involving dienes less reactive than cyclopentadiene or dienophiles like beta-substituted acrylates and equivalents. Here the main features of alpha'-hydroxy enones as reaction partners of the Diels-Alder reaction are shown, with especial focus on their potentials and limitations in solving the above difficult cases. Alpha'-hydroxy enones are able to bind reversibly to both Lewis acids and Brønsted acids, forming 1,4-coordinated species that are shown to efficiently engage in these inherently difficult Diels-Alder reactions. On these bases, a convenient control of the reaction stereocontrol can be achieved using a camphor-derived chiral alpha'-hydroxy enone model (substrate-controlled asymmetric induction) and either Lewis acid or Brønsted acid catalysis. Complementing this approach, highly enantio- and diastereoselective Diels-Alder reactions can also be carried out by using simple achiral alpha'-hydroxy enones in combination with Evans' chiral Cu(II)-BOX complexes (catalyst-controlled asymmetric induction). Of importance, alpha'-hydroxy enones showed improved reactivity profiles and levels of stereoselectivity (endo/exo and facial selectivity) as compared with other prototypical dienophiles in the reactions involving dienes less reactive than cyclopentadiene. A rationale of some of these results is provided based on both kinetic experiments and quantum calculations. Thus, kinetic measurements of Brønsted acid promoted Diels-Alder reactions of alpha'-hydroxy enones show a first-order rate with respect to both enone and Brønsted acid promoter. Quantum calculations also support this trend and provide a rational explanation of the observed stereochemical outcome of the reactions. Finally, these fundamental studies are complemented with applications in natural products synthesis. More specifically, a nonracemic synthesis of (-)-nicolaioidesin C is described wherein a Brønsted acid catalyzed Diels-Alder reaction involving a alpha'-hydroxy enone substrate is the key step toward the hitherto challenging trisubstituted cyclohexene subunit.

Catalytic Michael reactions of ketoesters with a camphor-derived acrylate equivalent: stereoselective access to all-carbon quaternary centers.

A camphor-based alpha'-hydroxy enone reagent acts as a chiral acrylate equivalent in copper-catalyzed Michael reactions of beta-keto esters and affords products that possess all-carbon quaternary stereocenters of high enantiomeric purity.

Inorganic arsenic exposure affects pain behavior and inflammatory response in rat.

Inorganic arsenic (iAs) contamination of drinking water is a worldwide problem associated with an increased risk for the development of various types of cancer and noncancerous damage. In vitro studies have suggested that iAs can modulate the activity of macrophages producing an over-expression of cyclooxygenase-2 (COX-2) and resulting in an increase in prostaglandin E(2) (PGE(2)) concentrations in endothelial cells. These effects may lead to an in vivo enhancement of inflammatory and pain responses. Our aim was to determine the effect of a single dose of arsenic or subchronic exposure to arsenic on pain behavior and tissue inflammation in rats. Rats were given a single dose of sodium arsenite (0.1, 1 and 10 mg/kg i.p.) or submitted to subchronic exposure to arsenic added to the drinking water for 4 weeks (0.1, 1, 10 and 100 ppm). Inflammatory pain was assessed by using the formalin and tail-flick tests, while inflammation was evaluated with the carrageenan model. Arsenite did not induce pain or significant inflammation by itself. In contrast, arsenite in both single dose administration and subchronic exposure increased not only the inflammatory process and the underlying hyperalgesic pain, but also induced a decrease in the pain threshold. Alterations in pain processing were dependent on the arsenic dose and the length of exposure, and the underlying mechanism involved an increased release of local PGE(2). These results suggest that inorganic arsenic exposure enhances pain perception and exacerbates the pathological state of inflammatory diseases.

Pre-emptive analgesic effect of tramadol after mandibular third molar extraction: a pilot study.

PURPOSE: We compared the efficacy of tramadol given before or immediately after surgical extraction of an impacted mandibular third molar under local anesthesia. MATERIALS AND METHODS: In this prospective, randomized, controlled, double-blind pilot study, 3 groups of 20 patients each were included: tramadol preoperative, 100 mg intramuscularly (IM) 1 hour before surgery (group A); tramadol postoperative, 100 mg IM immediately after surgery (group B); and saline (group C). We evaluated intensity of pain and analgesic consumption as was requested. RESULTS: The analgesic efficacy measured as complete relief of pain at 24 hours was 86% in the preemptive tramadol compared with 70% and 36% for postoperative tramadol administration and control group. A significant reduction in the consumption of analgesics was seen in preoperative group as compared with the postoperative and control groups. Adverse events were minimal and similar in all groups. CONCLUSIONS: This study suggests the preemptive use of tramadol as an alternative for the acute pain treatment after the removal of an impacted mandibular third molar carried out under local anesthesia.

Isobolographic analysis of the dual-site synergism in the antinociceptive response of tramadol in the formalin test in rats.

Tramadol is an atypical opioid with a complex mechanism of action including a synergistic interaction between the parent drug and an active metabolite. The local action of the parent drug is poorly documented. This study was designed to evaluate the site-site interaction of the antinociception produced by tramadol given by two different routes. The effects of individual and fixed-ratio combinations of intraplantar (i.pl.) and intraperitoneal (i.p.) tramadol were evaluated using the formalin test in rats. Isobolographic analysis was employed to identify the synergy produced by combinations. In both first and second phases of the formalin test, tramadol was active not only by the systemic (ED50 10.2+/-2.1 and 7.1+/-0.5 mg/kg i.p.) but also by the local route (ED50 171.0+/-44.8 and 134.6 microg/paw i.pl.). The isobolographic analysis revealed a "self-synergism" in the antinociceptive effect between the two routes of administration, as the experimental ED50 (211.1+/-13.6 and 45.9+/-3.9 "dose units" phase 1 and 2, respectively) of the combination was significantly lower than the theoretical ED50 (422.2+/-50.5 and 138.5+/-9.2 "dose units"). The mechanism underlying this self-synergism appears to be partially opioid since systemic but not local naloxone reversed the potentiation. The observed dual-site interaction in the antinociceptive action of tramadol provides insights for alternatives in the management of pain.

Analgesic efficacy of tramadol by route of administration in a clinical model of pain.

The objective of this study was to evaluate the analgesic efficacy produced by tramadol given by two different routes of administration in patients experiencing pain after removal of an impacted mandibular third molar under local anesthesia. A double-blind, randomized, placebo-controlled clinical trial was conducted. Patients were assigned into four groups of treatment, twelve subjects per group: Group A, tramadol 50 mg IM one hr before surgery; group B, tramadol 50 mg into the surgical site; group C, tramadol by both routes of administration, 50 mg IM one hr before surgery plus 50 mg into the surgical site; and group D, control. We evaluated intensity of pain and analgesic consumption as was requested. Demographic characteristics and variables describing the difficulty of the surgical procedure were similar between groups. The duration of the anesthetic effect was significantly longer in the groups where tramadol was injected into the surgical site (215 and 252 min). Administration of systemic and local tramadol (50 mg) suppressed the pain intensity values in comparison to the control group (p < 0.05). Also, tramadol in both routes of administration suppressed the pain intensity values in comparison to all groups (p < 0.05). A significant reduction in the consumption of ketorolac was seen in all treatments as compared to the control group. However, only in the route combination group was a significant reduction in the requirement of acetaminophen observed. Nine patients requiring additional medication were treated with ketorolac 30 mg injected intramuscularly; 2 in the systemic group, 2 in the local group, 4 in the control group and only 1 in the combination group. Adverse events were minimal and similar in all groups.

A practical total synthesis of hapalosin, a 12-membered cyclic depsipeptide with multidrug resistance-reversing activity, by employing improved segment coupling and macrolactonization.

A practical total synthesis of hapalosin, a compound with multidrug resistance-reversing activity, has been carried out using an unprecedented macrolactonization strategy. One of the features of the new approach is the straightforward and fully stereocontrolled access to the key gamma-amino beta-hydroxy carboxylic acid subunit via an efficient acetate aldol addition reaction with N-methyl alpha-aminoaldehydes, which relies on a camphor-derived chiral lithium acetate enolate reagent. The scope of this aldol reaction is investigated and its potential application to the synthesis of other structurally related, biologically relevant compounds illustrated. Remarkably, the chiral tether in the resulting gamma-amino aldol adducts sterically protect the carbonyl group, thus avoiding intramolecular cyclization during the amino group deprotection and the subsequent segment coupling event. After successful segment coupling and smooth, clean release of the chiral auxiliary, a new macrolactonization protocol, based on the principle of double activation of both reactive sites, is applied, which leads to the 12-membered macrolactone hapalosin in unprecedented chemical efficiency.

Effect of acute exposure to arsenic on formalin-induced nociception and tramadol-mediated antinociception in mice.

In vitro studies have suggested that arsenic can modify the activity of macrophages in the mouse producing an over-regulation of the COX-2 and increased concentrations of PGE2 in endothelial cells. These effects may lead in vivo to enhancement of inflammatory and painful responses. In this study we studied the effect of an acute intoxication with sodium arsenite (1, 5, 10, 36 and 100 nmol/kg s.c.) on the nociceptive response of mice in the formalin test. On the other hand, the effect of arsenic on the antinociceptive response mediated by tramadol was evaluated in mice administered with a single dose of the analgesic agent (10 mg/kg s.c.). Arsenic levels in the liver were measured as a marker of the intoxication degree. Our results indicated that the arsenic acute exposure increases the nociceptive behavior in mice in a dose-dependent manner. Accordingly, the exposure to arsenic partially blocked the analgesic effect of tramadol although no statistical differences were reached. These results support the previous in vitro evidences regarding the alterations in the inflammatory-painful processes produced by the acute exposure to arsenic. Moreover, our results suggest that the intoxication with arsenic might exacerbate the pathological state in inflammatory diseases.

Evidence of self-synergism in the antinociceptive effect of tramadol in rats.

Tramadol is an atypical opioid with a complex mechanism of action including the synergistic interaction between the parent drug and an active metabolite. However, the local action of the parent drug is poorly documented. This study was designed to evaluate the site-site interaction of the antinociception produced by tramadol given by two different routes. The effects of individual and fixed-ratio combinations of locally (subcutaneous) and systemically (intraperitoneal) dosed tramadol were evaluated using the formalin test in rats. Isobolographic analysis was employed to identify the synergy produced by combinations. In the second phase of the formalin test, tramadol was active not only by the systemic (ED50 7.15+/-0.46 mg/kg i.p.) but also by the local route (ED50 134.6+/-25.1 microg/paw). The isobolographic analysis evidenced a "self-synergism" in the antinociceptive effect between the two routes of administration since the experimental ED50 (30.8+/-0.1 "dose units") of the combination was significantly lower than the theoretical ED50 (70.9+/-12.6 "dose units"). The mechanism underlying this self-synergism appears to be partially opioid since naloxone reversed the potentiation. The observed site-site interaction in the antinociceptive action of tramadol provides insights for alternatives in the management of pain.

Synergistic effects between codeine and diclofenac after local, spinal and systemic administration.

This study was designed to evaluate the extent of the antinociceptive interaction between codeine and diclofenac at the local, spinal and systemic level. The effects of individual and fixed-ratio combinations of locally, spinally or orally given codeine and diclofenac were assayed using the formalin test in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Codeine, diclofenac and fixed-ratio codeine-diclofenac combinations produced a dose-dependent antinociceptive effect when administered locally, spinally or systemically. ED(30) values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED(30) values for the combination estimated from the isobolograms were 422.2+/-50.5 microg/paw, 138.5+/-9.2 microg/rat, and 9.3+/-1.1 mg/kg for the local, spinal and oral routes, respectively. These values were significantly higher than the actually observed ED(30) values which were 211.1+/-13.6 microg/paw, 45.9+/-3.9 microg/rat, and 2.5+/-0.2 mg/kg, indicating a synergistic interaction. Systemic administration resulted in the highest increase in potency, being about fourfold, while spinal and local administration increased potency in two- and threefold, respectively. The fact that the highest synergism was observed after systemic administration suggests that the interaction is occurring at several anatomical sites. The results support the clinical use of this combination in pain management.