In silico and In vitro Assessment of Dimeric Flavonoids (Brachydins) on Rhipicephalus microplus Glutathione S-transferase.

INTRODUCTION: Rhipicephalus microplus, an important cattle ectoparasite, is responsible for a substantial negative impact on the economy due to productivity loss. The emergence of resistance to widely used commercial acaricides has sparked efforts to explore alternative products for tick control. METHOD: To address this challenge, innovative solutions targeting essential tick enzymes, like glutathione S-transferase (GST), have gained attention. Dimeric flavonoids, particularly brachydins (BRAs), have demonstrated various biological activities, including antiparasitic effects. The objectives of this study were to isolate four dimeric flavonoids from Fridericia platyphylla roots and to evaluate their potential as inhibitors of R. microplus GST. RESULTS: In vitro assays confirmed the inhibition of R. microplus GST by BRA-G, BRA-I, BRA-J, and BRA-K with IC50 values of 0.075, 0.079, 0.075, and 0.058 mg/mL, respectively, with minimal hemolytic effects. Molecular docking of BRA-G, BRA-I, BRA-J, and BRA-K in a threedimensional model of R. microplus GST revealed predicted interactions with MolDock Scores of - 142.537, -126.831, -108.571, and -123.041, respectively. Both in silico and in vitro analyses show that brachydins are potential inhibitors of R. microplus GST. CONCLUSION: The findings of this study deepen our understanding of GST inhibition in ticks, affirming its viability as a drug target. This knowledge contributes to the advancement of treatment modalities and strategies for improved tick control.

Contextual incongruency triggers memory reinstatement and the disruption of neural stability.

Schemas, or internal representation models of the environment, are thought to be central in organising our everyday life behaviour by giving stability and predictiveness to the structure of the world. However, when an element from an unfolding event mismatches the schema-derived expectations, the coherent narrative is interrupted and an update to the current event model representation is required. Here, we asked whether the perceived incongruence of an item from an unfolding event and its impact on memory relied on the disruption of neural stability patterns preceded by the neural reactivation of the memory representations of the just-encoded event. Our study includes data from two different experiments whereby human participants (N = 33, 26 females and N = 18, 16 females, respectively) encoded images of objects preceded by trial-unique sequences of events depicting daily routine. We found that neural stability patterns gradually increased throughout the ongoing exposure to a schema-consistent episode, which was corroborated by the re-analysis of data from two other experiments, and that the brain stability pattern was interrupted when the encoding of an object of the event was incongruent with the ongoing schema. We found that the decrease in neural stability for low-congruence items was seen at ∼1000 ms from object encoding onset and that it was preceded by an enhanced N400 ERP and an increased degree of neural reactivation of the just-encoded episode. Current results offer new insights into the neural mechanisms and their temporal orchestration that are engaged during online encoding of schema-consistent episodic narratives and the detection of incongruencies.

First-Principles Density Limit Scaling in Tokamaks Based on Edge Turbulent Transport and Implications for ITER.

A first-principles scaling law, based on turbulent transport considerations, and a multimachine database of density limit discharges from the ASDEX Upgrade, JET, and TCV tokamaks, show that the increase of the boundary turbulent transport with the plasma collisionality sets the maximum density achievable in tokamaks. This scaling law shows a strong dependence on the heating power, therefore predicting for ITER a significantly larger safety margin than the Greenwald empirical scaling [Greenwald et al., Nucl. Fusion, 28, 2199 (1988)NUFUAU0029-551510.1088/0029-5515/28/12/009] in case of unintentional high-to-low confinement transition.

Semantic Congruence Drives Long-Term Memory and Similarly Affects Neural Retrieval Dynamics in Young and Older Adults.

Learning novel information can be promoted if it is congruent with already stored knowledge. This so-called semantic congruence effect has been broadly studied in healthy young adults with a focus on neural encoding mechanisms. However, the impacts on retrieval, and possible impairments during healthy aging, which is typically associated with changes in declarative long-term memory, remain unclear. To investigate these issues, we used a previously established paradigm in healthy young and older humans with a focus on the neural activity at a final retrieval stage as measured with electroencephalography (EEG). In both age groups, semantic congruence at encoding enhanced subsequent long-term recognition memory of words. Compatible with this observation, semantic congruence led to differences in event-related potentials (ERPs) at retrieval, and this effect was not modulated by age. Specifically, congruence modulated old/new ERPs at a fronto-central (Fz) and left parietal (P3) electrode in a late (400-600 ms) time window, which has previously been associated with recognition memory processes. Importantly, ERPs to old items also correlated with the positive effect of semantic congruence on long-term memory independent of age. Together, our findings suggest that semantic congruence drives subsequent recognition memory across the lifespan through changes in neural retrieval processes.

Functional coupling between CA3 and laterobasal amygdala supports schema dependent memory formation.

The medial temporal lobe drives semantic congruence dependent memory formation. However, the exact roles of hippocampal subfields and surrounding brain regions remain unclear. Here, we used an established paradigm and high-resolution functional magnetic resonance imaging of the medial temporal lobe together with cytoarchitectonic probability estimates in healthy humans. Behaviorally, robust congruence effects emerged in young and older adults, indicating that schema dependent learning is unimpaired during healthy aging. Within the medial temporal lobe, semantic congruence was associated with hemodynamic activity in the subiculum, CA1, CA3 and dentate gyrus, as well as the entorhinal cortex and laterobasal amygdala. Importantly, a subsequent memory analysis showed increased activity for later remembered vs. later forgotten congruent items specifically within CA3, and this subfield showed enhanced functional connectivity to the laterobasal amygdala. As such, our findings extend current models on schema dependent learning by pinpointing the functional properties of subregions within the medial temporal lobe.

Neural oscillations and event-related potentials reveal how semantic congruence drives long-term memory in both young and older humans.

Long-term memory can improve when incoming information is congruent with known semantic information. This so-called congruence effect has widely been shown in younger adults, but age-related changes and neural mechanisms remain unclear. Here, congruence improved recognition memory in younger and older adults (i.e. congruence effect), with only weak evidence for age-related decline in one behavioral study. In an EEG study, however, no significant behavioral differences in the congruence effect could be observed between age-groups. In line with this observation, electroencephalography data show that, in both groups, congruence led to widespread differences in Event-Related Potentials (ERPs), starting at around 400 ms after stimulus onset, and theta, alpha and beta oscillations (4-20 Hz). Importantly, these congruence-related ERPs were associated to increases in memory performance for congruent items, in both age groups. Finally, the described ERPs and neural oscillations in the theta-alpha range (5-13 Hz) were less pronounced in the elderly despite a preserved congruence effect. Together, semantic congruence increases long-term memory across the lifespan, and, at the neural level, this could be linked to neural oscillations in the theta, alpha and beta range, as well as ERPs that were previously associated with semantic processing.

[Supply medicinal products improvement in outpatient care in a hospital pharmacy service]. / Mejora de la dispensación a pacientes externos de un servicio de farmacia hospitalaria.

INTRODUCTION: Pharmaceutical care to outpatients is currently one of the main occupations of hospital pharmacy services (PEX). There are several questionnaires to measure the satisfaction of the PEX of a pharmacy service, and the results of these questionnaires can generate improvement actions that result in satisfaction. OBJECTIVES: To verify if a satisfaction questionnaire for outpatients is valid for the generation of improvements in the care provided, and if after its implementation, the same questionnaire is able to detect changes in satisfaction. MATERIAL AND METHOD: Prospective study of a single center carried out in a tertiary hospital in 2015 and 2016. A questionnaire previously validated with 16 Likert-type items was used. Demographic and classification data were collected. A descriptive analysis was performed and the internal consistency was calculated using the Cronbach's α value. RESULTS: A total of 258 questionnaires were collected in 2015 and 493 in 2016. There were no differences in the baseline characteristics of the patients and users of the service. The items with the lowest satisfaction scores in 2015 (comfort of the waiting room, dispensing privacy, drug pick-up time and medication pick-up time) guided the improvement actions to be implemented. In 2016 there was an improvement in the waiting time until collection in 12.3% (p = 0.002); in the comfort of the waiting room 4.9% (p = 0.304); business hours for medication collection, 10.7% (p = 0.013); and in the confidentiality of the dispensation 4% (p = 0.292). The remaining scores fluctuated minimally, with no statistical significance at all. A 5.1% improvement in overall satisfaction was found (p < 0.001). Satisfaction values obtained as a whole were high. CONCLUSIONS: The satisfaction questionnaire is a valid instrument for generating actions to improve the care received in an outpatient unit of a pharmacy service. This same questionnaire is a tool to monitor the changes implemented to improve the care received.

Clinical audit training improves undergraduates' performance in root canal therapy.

AIM: To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates. METHODS: Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test. RESULTS: Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001). CONCLUSION: Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT.

Semantic Congruence Accelerates the Onset of the Neural Signals of Successful Memory Encoding.

As the stream of experience unfolds, our memory system rapidly transforms current inputs into long-lasting meaningful memories. A putative neural mechanism that strongly influences how input elements are transformed into meaningful memory codes relies on the ability to integrate them with existing structures of knowledge or schemas. However, it is not yet clear whether schema-related integration neural mechanisms occur during online encoding. In the current investigation, we examined the encoding-dependent nature of this phenomenon in humans. We showed that actively integrating words with congruent semantic information provided by a category cue enhances memory for words and increases false recall. The memory effect of such active integration with congruent information was robust, even with an interference task occurring right after each encoding word list. In addition, via electroencephalography, we show in 2 separate studies that the onset of the neural signals of successful encoding appeared early (∼400 ms) during the encoding of congruent words. That the neural signals of successful encoding of congruent and incongruent information followed similarly ∼200 ms later suggests that this earlier neural response contributed to memory formation. We propose that the encoding of events that are congruent with readily available contextual semantics can trigger an accelerated onset of the neural mechanisms, supporting the integration of semantic information with the event input. This faster onset would result in a long-lasting and meaningful memory trace for the event but, at the same time, make it difficult to distinguish it from plausible but never encoded events (i.e., related false memories). SIGNIFICANCE STATEMENT: Conceptual or schema congruence has a strong influence on long-term memory. However, the question of whether schema-related integration neural mechanisms occur during online encoding has yet to be clarified. We investigated the neural mechanisms reflecting how the active integration of words with congruent semantic categories enhances memory for words and increases false recall of semantically related words. We analyzed event-related potentials during encoding and showed that the onset of the neural signals of successful encoding appeared early (∼400 ms) during the encoding of congruent words. Our findings indicate that congruent events can trigger an accelerated onset of neural encoding mechanisms supporting the integration of semantic information with the event input.

Motivated encoding selectively promotes memory for future inconsequential semantically-related events.

Neurobiological models of long-term memory explain how memory for inconsequential events fades, unless these happen before or after other relevant (i.e., rewarding or aversive) or novel events. Recently, it has been shown in humans that retrospective and prospective memories are selectively enhanced if semantically related events are paired with aversive stimuli. However, it remains unclear whether motivating stimuli, as opposed to aversive, have the same effect in humans. Here, participants performed a three phase incidental encoding task where one semantic category was rewarded during the second phase. A memory test 24h after, but not immediately after encoding, revealed that memory for inconsequential items was selectively enhanced only if items from the same category had been previously, but not subsequently, paired with rewards. This result suggests that prospective memory enhancement of reward-related information requires, like previously reported for aversive memories, of a period of memory consolidation. The current findings provide the first empirical evidence in humans that the effects of motivated encoding are selectively and prospectively prolonged over time.

Comparative evaluation of the effectiveness of desensitizing agents in dentine tubule occlusion using scanning electron microscopy.

BACKGROUND: Dentine hypersensitivity (DH) occurs on exposed dentine and is dependent on the patency of dentinal tubules. This study compared the effectiveness of red propolis extract (RPE), calcium sodium phosphosilicate (Novamin) and arginine-calcium carbonate (ACC) in occluding dentine tubules. METHODS: Eighty dentine discs from extracted human molars were randomly divided into four groups (n=20): Group 1--RPE; Group 2--Novamin; Group 3--ACC; Group 4--saline. The discs were etched with 37.5% phosphoric acid and treated with the test agents. Ten treated discs from each group were then exposed to 6% citric acid challenge. The extent of tubule occlusion was assessed using scanning electron microscopy (SEM). Three blinded assessors scored each SEM image on the degree of tubule occlusion. Differences in occlusion were tested using ANOVA and Tukey adjustment. RESULTS: Discs treated with ACC demonstrated more tubule occlusion, followed by RPE and Novamin, and were greater in statistical significance when compared to discs treated with saline. Following acid challenge, RPE treated discs maintained more occlusion, followed by ACC and Novamin. CONCLUSIONS: All three agents demonstrated tubule occlusion. Although ACC showed more occlusion following treatment, RPE demonstrated a higher degree of occlusion following acid challenge.

Human hippocampus arbitrates approach-avoidance conflict.

Animal models of human anxiety often invoke a conflict between approach and avoidance. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus. Efforts to translate these approaches to clinical contexts are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.

Reducción del riesgo de complicaciones relacionadas con los catéteres venosos centrales: una propuesta para mejorar la seguridad del paciente / Reduction of the risk of complications related to central venous catheters: a proposal for improving patient safety

Objetivo: Implementar medidas eficaces para disminuir la bacteriemia relacionada con catéter venoso central. Material y método: Se revisó la técnica de inserción y el material necesario, elaborando instrucciones y material gráfico de ayuda. Calculamos la prevalencia de inserción de los catéteres venosos centrales (CVC). Se han analizado todas las listas de verificación realizadas entre 2010 y 2012 en un año y los datos de una encuesta autocumplimentada y anónima para valorar los conocimientos del mantenimiento de la vía central, evaluando el resultado conforme a las nuevas instrucciones. Se elaboró la «Instrucción de seguridad para la prevención de la bacteriemia relacionada con el catéter en pacientes hospitalizados», se organizó un kit de inserción y se formó a 58 médicos y 168 enfermeras. Se revisó a 687 pacientes, encontrando un 6,7% de portadores de un CVC. Resultados: El 21,7% de los pacientes tenían cumplimentada la lista de verificación y un 39,4% necesitó más de un intento. En cuanto a los cuidados, falló el registro de fechas de cambios de apósito y de sistemas de infusión. Conclusiones: Se ha conseguido una máxima difusión del material elaborado. Se deben reforzar aquellos procedimientos donde se han producido un mayor porcentaje de errores (AU)

Objective: To adopt effective measures for reducing bacteremia related to central venous catheters (CVCs). Material and methods: A review was made of the insertion technique and required material, developing instructions and graphic support. The prevalence of CVC insertion was calculated. An analysis was made of all the yearly checklists between 2010 and 2012, along with the data drawn from an anonymous self-administered questionnaire, to assess knowledge of maintenance of central catheterization, and evaluating performance on the basis of the new instructions provided. «Safety instructions for the prevention of catheter-related bacteremia in hospitalized patients» were developed, an insertion kit was produced, and 58 physicians and 168 nurses were trained. A total of 687 patients were reviewed, of which 6.7% were seen to carry a CVC. Results: The checklist was found to be completed in 21.7% of the patients, and 39.4% required more than one catheterization attempt. Regarding care-related aspects, there were deficiencies in the registry of the dates on which the dressings and infusion systems were replaced. Conclusions: Maximum diffusion of the developed material was achieved. Reinforcement is required of those procedures in which a greater percentage of errors were detected (AU)

Predictores de la satisfacción de los pacientes con la alimentación de un hospital público de Madrid / Predictors of patient satisfaction with the food services in a public hospital in Madrid

Objetivo. Conocer el nivel de satisfacción de los pacientes con la alimentación recibida durante su ingreso y qué factores la predicen. Material y métodos. Estudio transversal realizado en el Hospital Clínico San Carlos entre mayo y septiembre de 2010 mediante una encuesta autocumplimentada tras el alta hospitalaria tanto en pacientes con dieta basal como terapéutica. Se recogieron variables sociodemográficas, satisfacción global con la alimentación y con diferentes aspectos y tipos de alimentos. Se realizó un análisis descriptivo y multivariable, siendo la variable dependiente la satisfacción global mediante regresión logística binaria. Resultados. Se obtuvieron 549 encuestas (tasa de respuesta del 29%), de las cuales el 60,7% habían recibido dieta terapéutica. La edad mediana fue de 68 años y el 55,4% eran hombres. El 75% manifestaron estar satisfechos o muy satisfechos. Las variables que influyeron de forma significativa en la satisfacción con la alimentación fueron la condimentación, la temperatura, y la satisfacción con los pescados y sopas/cremas. Conclusiones. A pesar de un elevado nivel de satisfacción con la alimentación existen oportunidades de mejora. Se han identificado algunos factores sobre los cuales podría ser más rentable actuar(AU)

Objective. To describe patients satisfaction with the food services during hospitalisation, and to determine the predictors. Methodology. A cross-sectional study was conducted in the “Clínico San Carlos” Hospital, between May and September 2010. A self-completion questionnaire was given to patients with both regular and therapeutic diets after their hospital discharge. We included socio-demographic variables, overall satisfaction, and satisfaction regarding different aspects and types of food. Descriptive and multivariable analyses were performed, with the overall satisfaction with food as the dependent variable using binary logistic regression. Results. A total of 549 questionnaires were returned (rate 29%), of which 60.7% received a therapeutic diet. 55.4% were men, and the median age was 68 years. Three-quarters (75%) were satisfied or very satisfied. Statistically significant variables associated with patient satisfaction with the food services received were the meal's taste and temperature, as well as being satisfied with the fish and soups on the menu. Conclusions. Despite the high level of satisfaction with food services, there is scope for improvement. We have identified some of the aspects on which action would be more beneficial(AU)

[Predictors of patient satisfaction with the food services in a public hospital in Madrid]. / Predictores de la satisfacción de los pacientes con la alimentación de un hospital público de Madrid.

OBJECTIVE: To describe patients satisfaction with the food services during hospitalisation, and to determine the predictors. METHODOLOGY: A cross-sectional study was conducted in the "Clínico San Carlos" Hospital, between May and September 2010. A self-completion questionnaire was given to patients with both regular and therapeutic diets after their hospital discharge. We included socio-demographic variables, overall satisfaction, and satisfaction regarding different aspects and types of food. Descriptive and multivariable analyses were performed, with the overall satisfaction with food as the dependent variable using binary logistic regression. RESULTS: A total of 549 questionnaires were returned (rate 29%), of which 60.7% received a therapeutic diet. 55.4% were men, and the median age was 68 years. Three-quarters (75%) were satisfied or very satisfied. Statistically significant variables associated with patient satisfaction with the food services received were the meal's taste and temperature, as well as being satisfied with the fish and soups on the menu. CONCLUSIONS: Despite the high level of satisfaction with food services, there is scope for improvement. We have identified some of the aspects on which action would be more beneficial.

CHALLENGES IN MANAGEMENT OF WARFARIN ANTI-COAGULATION IN ADVANCED HIV/AIDS PATIENTS WITH VENOUS THROMBOTIC EVENTS--A CASE SERIES FROM A RESEARCH CLINIC IN RURAL KERICHO, KENYA.

BACKGROUND: Venous thrombotic events (VTE) occur at high ratesin HIV/AIDS patients and are likely under-diagnosed in rural sub-Saharan Africa. OBJECTIVE: To describe clinical presentations and challenges in the management of VTE in patients with advanced HIV/AIDS. DESIGN: Case series from patients enrolled in a prospective observational cohort study. SETTINGS: A clinical research centre in rural Kericho, Kenya. SUBJECTS: Two hundred patients with median age 38 (30-47) years, BMI 16.9 (12.4-20.3) kg/m2, haemoglobin 9.3 (6.8-13.4) g/dL, CD4+ T-cell count 27 (4-77) cells/mm and plasma HIV RNA 5.23 (3.70-5.88) log10 copies/mL. INTERVENTIONS: VTE cases were diagnosed by clinical presentation and Doppler/ radiographic confirmation. Anti-coagulation therapy was managed by a multidisciplinary team; patients were initiated on enoxaparin or heparin followed by warfarin. RESULTS: Over two years,11patients (5.5%) experienced VTE. All but one (10/11,90.9%) case occurred within six months of starting ART. Nine patients had peripheral VTE (five popliteal, four femoral) and two had cerebral sinus thromboses. VTE was diagnosed 52 (1-469) days after ART initiation, and 81.8% of cases were outpatients at presentation. All patients received at least one concomitant medication that could significantly interact with warfarin (efavirenz, nevirapine, lopinavir/ritonavir, rifampicin, trimethoprim-sulfamethoxazole, and fluconazole). A median of 39 (10-180) days and eight (4-22) additional clinic visits were required to achieve/maintain a therapeutic INR of 2-3. Two minor bleeding complications occurred. No recurrent VTE cases were observed. CONCLUSION: Consideration of VTE and preparedness for management in patients with advanced HIV/AIDS starting ART is critical in sub-Saharan Africa. Overcoming challenges in anti-coagulation is possible in rural settings using a multidisciplinary team approach.

Synthesis of biologically active bridged diazabicycloheptanes.

The chemistry underlying how diazabicycloheptanes are assembled is described, subdivided according to chemical structure of two types, the 3,6 diazabicyclo[3.1.1]heptane and the 2,5-diazabicyclo[2.2.1]heptane ring system. Detailed information on myriad of activities of compounds derived from the two scaffolds are reported.