Intelligent Recommendation Systems Powered by Consensus Neural Networks: The Ultimate Solution for Finding Suitable Chiral Chromatographic Systems?

The selection of suitable combinations of chiral stationary phases (CSPs) and mobile phases (MPs) for the enantioresolution of chiral compounds is a complex issue that often requires considerable experimental effort and can lead to significant waste. Linking the structure of a chiral compound to a CSP/MP system suitable for its enantioseparation can be an effective solution to this problem. In this study, we evaluate algorithmic tools for this purpose. Our proposed consensus model, which uses multiple optimized artificial neural networks (ANNs), shows potential as an intelligent recommendation system (IRS) for ranking chromatographic systems suitable for the enantioresolution of chiral compounds with different molecular structures. To evaluate the IRS potential in a proof-of-concept stage, 56 structural descriptors for 56 structurally unrelated chiral compounds across 14 different families are considered. Chromatographic systems under study comprise 7 cellulose and amylose derivative CSPs and acetonitrile or methanol aqueous MPs (14 chromatographic systems in all). The ANNs are optimized using a fit-for-purpose version of the chaotic neural network algorithm with competitive learning (CCLNNA), a novel approach not previously applied in the chemical domain. CCLNNA is adapted to define the inner ANN complexity and perform feature selection of the structural descriptors. A customized target function evaluates the correctness of recommending the appropriate CSP/MP system. The ANN-consensus model exhibits no advisory failures and requires only an experimental attempt to verify the IRS recommendation for complete enantioresolution. This outstanding performance highlights its potential to effectively resolve this problem.

Gender inequalities in secondary prevention of cardiovascular disease: a scoping review.

BACKGROUND: Despite significant progress in cardiovascular disease (CVD) management, it remains a public health priority and a global challenge. Within the disease process, health care after a cardiovascular event (secondary prevention) is essential to prevent recurrences. Nonetheless, evidence has suggested the existence of gender disparities in CVD management, leaving women in a vulnerable situation. The objective of this study is to identify all available evidence on the existence of gender differences in health care attention after a major adverse cardiovascular event. METHODS: A scoping review following the structure of PRISMA-ScR was conducted. To define the inclusion criteria, we used Joanna Briggs Institute (JBI) population, concept, context framework for scoping reviews. A systematic search was performed in MEDLINE (PubMed), EMBASE and Cochrane. The methods of this review are registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) (INPLASY202350084). RESULTS: The initial search retrieved 3,322 studies. 26 articles were identified manually. After the reviewing process, 93 articles were finally included. The main intervention studied was the pharmacological treatment received (n = 61, 66%), distantly followed by guideline-recommended care (n = 26, 28%) and cardiac rehabilitation (CR) referral (n = 16)". Literature described gender differences in care and management of secondary prevention of CVD. Women were less frequently treated with guideline-recommended medications and seem more likely to be non-adherent. When analysing guideline recommendations, women were more likely to make dietary changes, however, men were more likely to increase physical activity. Studies also showed that women had lower rates of risk factor testing and cholesterol goals attainment. Female sex was associated with lower rates of cardiac rehabilitation referral and participation. CONCLUSIONS: This review allowed us to compile knowledge on the existence of gender inequalities on the secondary prevention of CVD. Additional research is required to delve into various factors influencing therapeutic disparities, referral and non-participation in CR programs, among other aspects, in order to improve existing knowledge about the management and treatment of CVD in men and women. This approach is crucial to ensure the most equitable and effective attention to this issue.

Factors influencing the perception of feeling safe in pre-hospital emergency care: A mixed-methods systematic review.

AIMS: To systematically describe the factors influencing the perception of feeling safe among patients receiving pre-hospital emergency care. BACKGROUND: Patient safety is a top priority worldwide. Little is known about how patients perceive safety during emergency health care and what the related factors are. DESIGN: A mixed-methods systematic review. METHODS: Six databases were searched to December 2021. Inclusion criteria were as follows: studies with patients of any age, framed in pre-hospital emergency care settings, referring to patient safety, addressing the perception of safety, and with a quantitative or qualitative research design. Exclusion criteria were as follows: conference records, abstracts, supplements, letters, editorials and reviews. The quality of the evidence was assessed with the Joanna Briggs Institute (JBI) checklists. A convergent integrated approach was followed according to the JBI methodology. The protocol was registered on PROSPERO (CRD42022306337). PRISMA 2020 guidelines were followed in reporting this review. RESULTS: Among the 5223 records identified, the whole texts of 35 articles were reviewed. Ten studies were relevant to the research question. Seven followed a qualitative methodology, with interviews or focus group. Three involved a quantitative methodology, with questionnaires or validated measures. The 74 findings were organised into 11 categories and then grouped into four dimensions: 'receiving a satisfying response from healthcare professionals when I need it', 'EMS personnel's professional competence', 'the variable and unfamiliar settings of pre-hospital emergencies', and 'patients' personal characteristics'. CONCLUSIONS: The perception of safety is influenced by many factors, which can be grouped into four independent dimensions. Quantitative and qualitative studies can provide us with complementary findings. RELEVANCE TO CLINICAL PRACTICE: Awareness of these factors enables us to act upon them. When patients feel safe their health outcomes improve, their anxiety decreases and they collaborate more actively. NO PATIENT OR PUBLIC CONTRIBUTION: Patients and caregivers shared their experiences in the articles included.

Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity.

Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan® Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. Results: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. Conclusions: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.

Comparison of Carotid Intima-Media Thickness in Children and Adults With and Without Obesity: A Hysteresis Model.

OBJECTIVE: To describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups. METHODS: A quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling. RESULTS: The additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P < .0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as R2, and the cubic function estimated parameters like a polynomial model. CONCLUSION: This practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood.

Lung Ultrasound Integration in Assessment of Patients with Noncritical COVID-19.

OBJECTIVES: Performing lung ultrasound during the clinical assessment of patients with suspicion of noncritical COVID-19 may increase the diagnostic rate of pulmonary involvement over other diagnostic techniques used in routine clinical practice. This study aims to compare complications (readmissions, emergency department [ED] visits, and length of outpatient follow-up) in the first 30 days after ED discharge in patients with confirmed COVID-19 who were managed with versus without lung ultrasound. MATERIALS AND METHODS: Prospective, observational, analytical study in noncritical patients with confirmed respiratory disease due to SARS-CoV-2, assessed in the ED of a tertiary Spanish hospital in March and April 2020. We compared 2 cohorts, differentiated by the use of lung ultrasound as a diagnostic tool. Complications were assessed (hospital admissions, ED revisits and days of outpatient follow-up) at 30 days postdischarge. RESULTS: Of the 88 included patients, 31% (n = 27) underwent an initial lung ultrasound, while 61 (68%) did not. In 82.5% of the patients evaluated with ultrasound, the most predominant areas affected were the posterobasal regions, in the form of focalized and confluent B-lines; 70.4% showed pleural irregularity in these same areas. Use of the lung ultrasound was associated with a greater probability of hospital admission (odds ratio 5.63, 95% confidence interval 3.31 to 9.57; p < 0.001). However, it was not significantly associated with mortality or short-term complications. CONCLUSIONS: Lung ultrasound could identify noncritical patients with lung impairment due to SARS-CoV-2, in whom other tests used routinely show no abnormalities. However, it has not shown a prognostic value in these patients and could generate a higher percentage of hospital admissions. More studies are still needed to demonstrate the clear benefit of this use.

Clinical performance evaluation of the Idylla™ EGFR Mutation Test on formalin-fixed paraffin-embedded tissue of non-small cell lung cancer.

BACKGROUND: Detection of epidermal growth factor receptor (EGFR) mutations in exons 18-21 is recommended in all patients with advanced Non-small-cell lung carcinoma due to the demonstrated efficiency of the standard therapy with tyrosine kinase inhibitors in EGFR-mutated patients. Therefore, choosing a suitable technique to test EGFR mutational status is crucial to warrant a valid result in a short turnaround time using the lowest possible amount of tissue material. The Idylla™ EGFR Mutation Test is a simple, fast and reliable method designed for the detection of EGFR mutations from formalin-fixed paraffin-embedded samples. The aim of this study was the Clinical Performace Evaluation of the Idylla™ EGFR Mutation Test on the Idylla™ System. METHODS: EGFR mutational status was determined on 132 archived formalin-fixed paraffin-embedded tissue sections with Idylla™ technology. Results were compared with the results previously obtained by routine method in the reference lab (Therascreen® EGFR RGQ PCR v2, Qiagen in Molecular Pathology lab, Hospital Universitario Virgen del Rocío de Sevilla). RESULTS: The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and the Comparator test method was 95.38% (with 1-sided 95% lower limit of 91.7%) showing Positive Diagnostic Agreement of 93.22% and Negative Diagnostic Agreement of 97.18%, with a Limit Of Detection ≤5%. CONCLUSIONS: The Idylla™ EGFR Mutation Test passed its clinical validity performance characteristics for accuracy.

Gender-specific differences in clinical and metabolic variables associated with NAFLD in a Mexican pediatric population.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD. METHODS: We included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender. RESULTS: The mean age was 10.64±2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR=2.39; 95%CI=1.10-5.19; p=0.025). For girls, NAFLD was significantly associated with triglycerides (p=0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p=0.048), and the visceral adiposity index (VAI) (p=0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p=0.001), waist circumference (WC) (p<0.001), HDL cholesterol (p=0.021), alanine aminotransferase (ALT) (p<0.001), and aspartate aminotransferase (AST) (p=0.002). CONCLUSIONS: In our study NAFLD is more frequent in boys, only ALT, and no other clinical or metabolic variables, were associated with NAFLD in these patients. HOMA-IR, VAI, triglyceride levels, and ALT were associated with NAFLD only in girls. The ALT cut-off points for the development of NAFLD in our study were 28.5U/L in females and 27.5U/L in males. Our findings showed that NAFLD should be intentionally screened in patients with obesity, particularly in boys.

Involvement of stanniocalcins in the deregulation of glycaemia in obese mice and type 2 diabetic patients.

Stanniocalcins are expressed in the pancreas tissue, and it was suggested a direct correlation between circulating insulin and STC2 concentrations in human. Here, we show a significant correlation between STC1 and both glycaemia and glycosylated haemoglobin among DM2 patients, while DM2 patients who present the greatest glycosylated haemoglobin values exhibited the lowest STC2 expression. However, treatment of patients with antiglycaemic drugs does not significantly modify the expression of both STCs. On the other hand, STC2-/- mice that exhibited neonatal and adult overweight further presented deregulated glycaemia when they were feed with a hypercaloric diet (breeding pellet, BP). This alteration is more evident at the early stages of the animal life. Deregulated glycaemia in these mice was confirmed using glucose oral test. In addition, STC2-/- mice present enhanced pancreas size; thus, the histological analysis reveals that WT mice respond to BP diet by increasing the size of the pancreatic islets through inducing cell division, and STC2-/- mice lack this compensatory mechanism. Contrary, BP fed STC2-/- mice show enhanced number of islets but of similar size than those fed with regular pellet. Histopathological analysis demonstrates tissue structure disruption and erythrocytes infiltrations in STC2-/- mice, possibly due to the stress evoked by the BP diet. Finally, enhanced glucagon immunostaining was observed in the islet of STC2-/- mice, and the glucagon ELISA assay confirmed the increase in the circulating glucagon. Summarizing, we present evidence of the role of STCs, mainly STC2, as a possible early marker during development of diabetes mellitus.

PEDIATRIC VISCERAL ADIPOSITY INDEX ADAPTATION CORRELATES WITH HOMA-IR, MATSUDA, AND TRANSAMINASES.

OBJECTIVE: Visceral adiposity index (VAI) is a mathematical model associated with cardiometabolic risk in adults, but studies on children failed to support this association. Our group has proposed a pediatric VAI model using pediatric ranges, but it has not yet been evaluated and needs further adjustments. The objective of this study was to further adjust the proposed pediatric VAI by age, creating a new pediatric metabolic index (PMI), and assess the correlation of the PMI with insulin resistance indexes and hepatic enzymes. METHODS: A cross-sectional design with data from 396 children (age 5 to 17 years) was analyzed with a generalized linear model to find the coefficients for triglycerides, high-density-lipoprotein cholesterol, and waist circumference-body mass index quotient. The model was constructed according to sex and age and designated PMI. A cross-validation analysis was performed and a receiver operating characteristic curve was used to determine cut-off points. RESULTS: Significant moderate correlation was found between PMI and homeostatic model assessment of insulin resistance (HOMA-IR) ( r = 0.452; P = .003), Matsuda ( r = -0.366; P = .019), alanine aminotransferase ( r = 0.315, P = .045), and γ-glutamyltransferase ( r = 0.397; P = .010). A PMI score >1.7 was considered as risk. CONCLUSION: PMI correlates with HOMA-IR, Matsuda, and hepatic enzymes. It could be helpful for identifying children at risk for cardiometabolic diseases. ABBREVIATIONS: ALT = alanine transaminase BMI = body mass index GGT = γ-glutamyltransferase HDL-C = high-density-lipoprotein cholesterol HOMA-IR = homeostatic model assessment of insulin resistance hs-CRP = high sensitivity C-reactive protein ISI = insulin sensitivity index NAFLD = nonalcoholic fatty liver disease PMI = pediatric metabolic index QUICKI = quantitative insulin sensitivity check index ROC = receiver operating characteristic TG = triglyceride TNF-α = tumor necrosis factor-alpha VAI = visceral adiposity index VAT = visceral adipose tissue WC = waist circumference.

[Decisional conflict among people with diabetes mellitus or hypertension attending primary care]. / Conflicto decisional en personas con diabetes mellitus e hipertensión arterial usuarias del nivel primario de atención de salud de Chile.

BACKGROUND: Decisional conflict refers to the personal uncertainty about which course of action to take when the choice involves risk, regret, or challenge to personal life values. AIM: To determine the level of decisional conflict (DC) of people with Diabetes Mellitus (DM) or High Blood Pressure (HBP) attending primary care centers (PCC) in Chile. PATIENTS AND METHODS: A Spanish version of the Decisional Conflict Scale (DCS) was applied to patients who were recruited if they had DM or HBP, were 18 years old or older, and had an appointment at the PCC the day of the recruitment. The scale was self-administered. Analysis of covariance (ANCOVA) was used to determine association between DC and other variables of interest while controlling confounding variables. RESULTS: The scale was answered by 1075 participants from 24 PCC aged 62 ± 14 years (74% female). Average score for the DCS scale was 16.8 ± 12.9 of a maximum of 100 points indicating a higher DC. The sub-scale "information" had the highest score (19.9 ± 20.0). Low educational level and older age were significantly associated with higher DCS scores (p < 0.05). Having a bad health perception, deciding to initiate a medical treatment and being attended by a doctor were significantly associated with higher DC. These associations persisted when confounding variables such as sex, age and education were controlled. CONCLUSIONS: People with DM or HBP who have a poor health perception, who initiated their treatment and were attended by a doctor had higher levels of DC, independent of their age and educational level.

The effect of vapour pressure deficit on stomatal conductance, sap pH and leaf-specific hydraulic conductance in Eucalyptus globulus clones grown under two watering regimes.

BACKGROUND AND AIMS: Stomatal conductance has long been considered of key interest in the study of plant adaptation to water stress. The expected increase in extreme meteorological events under a climate change scenario may compromise survival in Eucalyptus globulus plantations established in south-western Spain. We investigated to what extent changes in stomatal conductance in response to high vapour pressure deficits and water shortage are mediated by hydraulic and chemical signals in greenhouse-grown E. globulus clones. METHODS: Rooted cuttings were grown in pots and submitted to two watering regimes. Stomatal conductance, shoot water potential, sap pH and hydraulic conductance were measured consecutively in each plant over 4 weeks under vapour pressure deficits ranging 0·42 to 2·25 kPa. Evapotranspiration, growth in leaf area and shoot biomass were also determined. KEY RESULTS: There was a significant effect of both clone and watering regime in stomatal conductance and leaf-specific hydraulic conductance, but not in sap pH. Sap pH decreased as water potential and stomatal conductance decreased under increasing vapour pressure deficit. There was no significant relationship between stomatal conductance and leaf-specific hydraulic conductance. Stomata closure precluded shoot water potential from falling below -1·8 MPa. The percentage loss of hydraulic conductance ranged from 40 to 85 %. The highest and lowest leaf-specific hydraulic conductances were measured in clones from the same half-sib families. Water shortage reduced growth and evapotranspiration, decreases in evapotranspiration ranging from 14 to 32 % in the five clones tested. CONCLUSIONS: Changes in sap pH seemed to be a response to changes in atmospheric conditions rather than soil water in the species. Stomata closed after a considerable amount of hydraulic conductance was lost, although intraspecific differences in leaf-specific hydraulic conductance suggest the possibility of selection for improved productivity under water-limiting conditions combined with high temperatures in the early stages of growth.

Intravehicular, Short- and Long-Range Communication Information Fusion for Providing Safe Speed Warnings.

Inappropriate speed is a relevant concurrent factor in many traffic accidents. Moreover, in recent years, traffic accidents numbers in Spain have fallen sharply, but this reduction has not been so significant on single carriageway roads. These infrastructures have less equipment than high-capacity roads, therefore measures to reduce accidents on them should be implemented in vehicles. This article describes the development and analysis of the impact on the driver of a warning system for the safe speed on each road section in terms of geometry, the presence of traffic jams, weather conditions, type of vehicle and actual driving conditions. This system is based on an application for smartphones and includes knowledge of the vehicle position via Ground Positioning System (GPS), access to intravehicular information from onboard sensors through the Controller Area Network (CAN) bus, vehicle data entry by the driver, access to roadside information (short-range communications) and access to a centralized server with information about the road in the current and following sections of the route (long-range communications). Using this information, the system calculates the safe speed, recommends the appropriate speed in advance in the following sections and provides warnings to the driver. Finally, data are sent from vehicles to a server to generate new information to disseminate to other users or to supervise drivers' behaviour. Tests in a driving simulator have been used to define the system warnings and Human Machine Interface (HMI) and final tests have been performed on real roads in order to analyze the effect of the system on driver behavior.

[Perceptions of patients and health professionals about the quality of care provided to chronic obstructive pulmonary disease patients]. / Percepciones de pacientes y profesionales sobre la calidad de la atención a personas con enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To explore the understanding and knowledge of patients and health professionals about factors that influence the quality of care provided in Primary Care to people with Chronic Obstructive Pulmonary Disease (COPD). DESIGN: Qualitative study performed between February and March 2010. LOCATION: Primary Care Centers. PARTICIPANTS: Medical and nursing professionals and patients with COPD. METHODS: Non-probabilistic intentional sampling with representation criterion of the discourse. Two group (focus group) and 6 individual interviews were performed. The interviews were recorded, literally transcribed and interpreted by social discourse analysis. RESULTS: Patients neither identify properly the symptomatology nor they assume the COPD importance until advanced states. The lacks of knowledge about the evolution of the disease and the impact on quality of life hinders the necessary changes. Professionals reports problems with performing spirometry. Among doctors, scepticism regarding to the effectiveness of the interventions aimed at change of behaviour is identified. The existence of Clinical Guides, the improvement of the coordination between professionals and the alignment of priorities between managers and professionals stand out as organizational factors. CONCLUSIONS: The identified factors suggest the possibility of improving the health care through improved communication to motivate them to take the recommended changes and to increase the adherence to treatments. To this effect, the awareness and training of professionals, the healthcare coordination, the implementation of Clinical Guides and the use of indicators in a process of quality assessment.

Prevalence of concomitant medications in older HIV+ patients and comparison with general population.

OBJECTIVE: The increasing population of human immunodeficiency virus (HIV)-infected elderly patients results in a higher number of comorbidities and greater incidence of polypharmacy in addition to antiretroviral therapy (ART). The aim of this study is to describe the use of concomitant medication in older HIV-infected patients and to compare it with older general population. METHODS: The study included HIV-positive outpatients (>49 years) who received ART in 2011. Co-medication dispensed by pharmacies in that year was collected. Defined daily dose (DDD) for each drug was calculated by patient. A comparison was made between the use of co-medication among men between 50 and 64 years old in general population against the HIV-infected population. RESULTS: The study was based on 118 patients (77% men), of which 82% took at least one co-medication and 58% at least five. The commonest co-medications used by HIV-positive patients were antibiotics (44%); analgesics (44%); anti-inflammatories (39%); antacids (38%); and psycholeptics (38%). The medicines used for the greatest number of days per HIV-positive patient were those related to the renin-angiotensin system; anti-diabetics; lipid modifying agents; antithrombotics; and calcium channel blockers. In comparison with the general male population, a higher proportion of HIV-infected patients used antibiotics (42 vs 30%, P = 0.018), antiepileptics (16 vs 5%, P = 0.000), psycholeptics (35 vs 17%, P = 0.000) and COPD medications (14 vs 7%, P = 0.008). The duration of antibiotics and psycholeptic use in HIV-infected patients was longer compared to the general population (P < 0.05). CONCLUSIONS: Older HIV-positive patients frequently take a higher number of co-medication, which increases the risk of adverse events, interactions with other medication, and may lead to poorer treatment adherence.

Evaluation of the enantioselective binding of imazalil to human serum albumin by capillary electrophoresis.

In this work, a methodology for the evaluation of enantioselective binding of imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the separation of free and bound to HSA fractions is developed. This methodology comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the capillary electrophoresis system and the subsequent direct injection and chiral separation of IMA employing highly sulfated ß-cyclodextrin as chiral selector and the complete filling technique. Two mathematical approaches were used to estimate apparent affinity constants (K1), protein binding and enantioselectivity (ES) for both enantiomers of IMA. Moderate enantioselective binding of IMA enantiomers to HSA (ES = 2.0) was shown by the 1:1 stoichiometry and log K1 values of 3.4 ± 0.4 and 3.1 ± 0.3 for the first and second eluted enantiomers, respectively.

Morphological and thermodynamic comparison of the lesions created by 4 open-irrigated catheters in 2 experimental models.

INTRODUCTION: New generation open-irrigated catheters aim to improve irrigation efficiency. This may change lesion patterns, challenging operators. Indeed, safety issues have recently arisen. We aimed to experimentally assess 4 open-irrigated catheters, comparing lesion size, safety, and heat transfer. METHODS: The thigh lesion model was employed in 6 anesthetized pigs to assess the morphology of perpendicular and tangential lesions (n = 140) created by the newer catheters ThermoCool® SF, CoolFlex™, and Blazer™ Open-Irrigated, and the standard ThermoCool®, at a constant power of 30 W (60 seconds). To evaluate the propensity for deep-tissue overheating, a set of 120 applications were performed at 50 W (180 seconds) comparing pop rates. Thermal assessment of the lesion generation process (20 W, 60 seconds, n = 32) was performed with an infrared camera on bovine ventricular tissue. RESULTS: At 30 W, the newer catheters showed lower temperature readings compared with the ThermoCool®. No major efficacy or safety differences were found at tangential applications; however, at perpendicular applications: (1) the SF at 17 mL/min better preserved the superficial layers and focused its maximum thermal effect deeper, but at recommended flow rates (8 mL/min) it generated the largest superficial lesions; (2) CoolFlex™ created smaller lesions than SF and readily induced steam pops at 50 W without temperature control; and (3) no major differences were found comparing Blazer™ Open-Irrigated and ThermoCool®. CONCLUSIONS: The lower temperature readings in the newer catheters make them more prone to deliver the maximum programmed power. Under experimental conditions, the SF catheter focuses its maximum effect deeper and the CoolFlex™ can be more prone to induce steam pops at high power settings.

The quality of outpatient antimicrobial prescribing: a comparison between two areas of northern and southern Europe.

PURPOSE: The aim of the study was to analyse and compare the quality of outpatient antimicrobial prescribing in Denmark and Aragón (in northeastern Spain), with the objective of assessing inappropriate prescribing. METHODS: Outpatient antimicrobial prescription data were obtained from the National Institute for Health Data and Disease Control in Denmark, and from the Aragón Information System of Drug Consumption. The number of Defined Daily Doses (DDD) of the different substances were calculated, and the quality of the antimicrobial prescription was analysed using the 'Drug Utilization 90 %' method and the European Surveillance of Antimicrobial Consumption (ESAC) quality indicators for outpatient antimicrobial use. RESULTS: The majority of the prescriptions (90 % of total DDD) were comprised of 14 (of 39) different antimicrobials in Denmark, based mainly on narrow spectrum penicillin, and 11 (of 59) antimicrobials in Aragón, principally broad spectrum penicillins. The quality indicators described an elevated consumption of antimicrobials and an important seasonal variation in Aragón. In Denmark, the values obtained reflected a more moderate use with minor seasonal variation. CONCLUSIONS: The results showed important differences between the two study areas in relation to quantity and quality of outpatient antimicrobial prescription. The data indicate an overuse (and/or misuse) of antimicrobials in the Spanish region, despite national and local guidelines. The pattern of prescription in Denmark reflects a better adherence to recommendations.

Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated-ß-cyclodextrin by counter-current capillary electrophoresis.

The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated ß-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complete filling technique (CFT) in counter-current mode. The enantiomers of eight psychoactive drugs, four antihistamines (dimethindene, promethazine, orphenadrine and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine and viloxazine) were separated for the first time for this cyclodextrin (CD). Estimations of thermodynamic and electrophoretic enantioselectivies were also performed. Results indicate that, in general, thermodynamic enantioselectivity is the main component explaining the high resolution found, but also one case suggests that electrophoretic enantioselectivity itself is enough to obtain a satisfactory resolution. CFT results advantageous compared with conventional capillary electrophoresis (CE) and partial filling technique (PFT) for the study of the interaction between drugs and chiral selectors. It combines the use of a simple fitting model (as in CE), when the enantiomers do not exit the chiral selector plug during the separation (i.e. mobility of electroosmotic flow larger than mobility of CD), and drastic reduction of the consumption (and cost; ~99.7%) of the CD reagent (as in PFT) compared with the conventional CE.

Differences in outpatient antibiotic use between a Spanish region and a Nordic country.

INTRODUCTION: Antibiotic use and misuse are linked to pathogen resistance and, as such, both constitute a public health issue with local, national, and global dimensions. Early studies have shown striking variations in the use of these drugs between Nordic and Mediterranean countries. The aim of the present study was to describe and compare antibiotic prescribing in Primary Care in Denmark and Aragón (a North-eastern Spanish region). METHODS: Outpatient antibiotic prescription data (2010) were obtained from the National Institute for Health Data and Disease Control (Denmark), and the Information System on Medication Consumption in Aragón. The consumption of antibiotics (ATC J01) was analyzed from the prescription rates and the number of defined daily dose (DDD) per 1000 inhabitants/day (DID). RESULTS: The rate of antibiotic prescription in 2010 in Aragón was greater than in Denmark (407 compared to 315 exposed individuals/1000 inhabitants). There were significant differences as regards overall consumption of antibiotics (23.2 DID in Aragón and 17.0 DID in Denmark), as well as the therapeutic group selection. There was an elevated use of broad spectrum penicillins, quinolones and cephalosporins in the Spanish region while, in Denmark, the most-consumed antibiotic was narrow spectrum penicillin. CONCLUSION: The use of antibiotics in the Spanish region is very high, and there are marked differences in the choice of drug between this region and Denmark. Interventions are needed that promote the rational use of these drugs to reduce potential bacterial resistance, and to avoid unnecessary risks to patients.