Enzymatic Reactions Observed with Zero- and Low-Field Nuclear Magnetic Resonance.

We demonstrate that enzyme-catalyzed reactions can be observed in zero- and low-field NMR experiments by combining recent advances in parahydrogen-based hyperpolarization methods with state-of-the-art magnetometry. Specifically, we investigated two model biological processes: the conversion of fumarate into malate, which is used in vivo as a marker of cell necrosis, and the conversion of pyruvate into lactate, which is the most widely studied metabolic process in hyperpolarization-enhanced imaging. In addition to this, we constructed a microfluidic zero-field NMR setup to perform experiments on microliter-scale samples of [1-13C]fumarate in a lab-on-a-chip device. Zero- to ultralow-field (ZULF) NMR has two key advantages over high-field NMR: the signals can pass through conductive materials (e.g., metals), and line broadening from sample heterogeneity is negligible. To date, the use of ZULF NMR for process monitoring has been limited to studying hydrogenation reactions. In this work, we demonstrate this emerging analytical technique for more general reaction monitoring and compare zero- vs low-field detection.

Parallel detection of chemical reactions in a microfluidic platform using hyperpolarized nuclear magnetic resonance.

The sensitivity of NMR may be enhanced by more than four orders of magnitude via dissolution dynamic nuclear polarization (dDNP), potentially allowing real-time, in situ analysis of chemical reactions. However, there has been no widespread use of the technique for this application and the major limitation has been the low experimental throughput caused by the time-consuming polarization build-up process at cryogenic temperatures and fast decay of the hyper-intense signal post dissolution. To overcome this limitation, we have developed a microfluidic device compatible with dDNP-MR spectroscopic imaging methods for detection of reactants and products in chemical reactions in which up to 8 reactions can be measured simultaneously using a single dDNP sample. Multiple MR spectroscopic data sets can be generated under the same exact conditions of hyperpolarized solute polarization, concentration, pH, and temperature. A proof-of-concept for the technology is demonstrated by identifying the reactants in the decarboxylation of pyruvate via hydrogen peroxide (e.g. 2-hydroperoxy-2-hydroxypropanoate, peroxymonocarbonate and CO2). dDNP-MR allows tracing of fast chemical reactions that would be barely detectable at thermal equilibrium by MR. We envisage that dDNP-MR spectroscopic imaging combined with microfluidics will provide a new high-throughput method for dDNP enhanced MR analysis of multiple components in chemical reactions and for non-destructive in situ metabolic analysis of hyperpolarized substrates in biological samples for laboratory and preclinical research.

Encrucijadas sobre ¿qué vender?: máquinas expendedoras en entornos alimentarios universitarios / Crossroads about what to sell?: vending machines in university food environments

Introducción. Las máquinas expendedoras de bebidas y alimentos (MEBA) ganan presencialidad en universidades, lo que potencia aumento de peso en adultos jóvenes. Objetivo. reconocer la configuración de las MEBA para la construcción del ambiente alimentario saludable en una universidad de Colombia. Materiales y métodos. Diseño descriptivo multimodos, con aproximación empírica de: entrevista a tomadores de decisión (n=6) de la institución educativa; análisis de ventas durante un año (n=12.955) en las MEBA (n=12); caracterización por densidad nutricional de la oferta (n=152) y rastreo a comunicaciones circulantes asociadas con alimentación. El análisis consideró cuatro momentos: I-Relaciones; II-Canal MEBA; III-Nutrición y IV-Interacción. Los I y II se enfocaron en los componentes político, sociocultural, físico y económico. El III estudió el aporte nutricional de bebidas y alimentos para integrar resultados en el IV. Resultados. La ausencia de política sobre alimentación institucional como la visibilización comunicativa parecen potenciar condiciones sociales que refuerzan lógicas de: "mal necesario", "perfil de consumo ya existente", "ausencia de ejercicios académicos" y "experiencias negativas con alimentación saludable". Cimientos para ofertar con mayor demanda bebidas como refrescos y agua y, en alimentos, chocolate en diferentes formulaciones. En la clasificación por densidad nutricional se encontró que las bebidas fueron clasificadas como "no saludable" (51,6%); "algo saludable" (28,1%) y "saludable" (20,3%). Los alimentos "algo saludable" (44,9%); "no saludable" (32,2%) y "saludable" (22,9%). Conclusiones. la universidad, espacio de formación, requiere realizar esfuerzos de comprensión sociocultural, gerencia alineada a normativas de promoción de salud para incidir en la calidad nutricional ofertada a la comunidad universitaria(AU)

Introduction. Food and beverage vending machines (MEBA) are gaining presence in universities, which promotes weight gain in young adults. Objective. to recognize the configuration of the MEBA for the construction of a healthy food environment in a university in Colombia. Materials and methods. multimodal descriptive design, with an empirical approach of: interview with decision makers of the educational institution (n=6); analysis of sales during one year (n=12,955) in the MEBAs (n=12); characterization by nutritional density of the offer (n=152) and tracking of circulating communications associated with food. The analysis considered four moments: I-Relationships; II-MEBA Channel; III-Nutrition and IV-Interaction. I and II focused on the political, sociocultural, physical and economic components. The III studied the nutritional contribution of drinks and foods to integrate results in the IV. Results. the absence of a policy on institutional food such as communicative visibility seems to enhance social conditions that reinforce logics of: "necessary evil", "already existing consumption profile", "absence of academic exercises" and "negative experiences with healthy eating". Foundations to offer with greater demand drinks such as soft drinks and water and, in food, chocolate in different formulations. In the classification by nutritional density, it was found that the drinks were classified as "unhealthy" (51.6%); "something healthy" (28.1%) and "healthy" (20.3%). "Somewhat healthy" foods (44.9%); "unhealthy" (32.2%) and "healthy" (22.9%). Conclusions. the university, a training space, requires efforts at sociocultural understanding, management aligned with health promotion regulations to influence the nutritional quality offered to the university community(AU)

Genetic variants of antioxidant and xenobiotic metabolizing enzymes and their association with prostate cancer: A meta-analysis and functional in silico analysis.

The development and progression of prostate cancer (PCa) depends on complex interactions between genetic, environmental and dietary factors that modulate the carcinogenesis process. Interactions between chemical exposures and genetic polymorphisms in genes encoding xenobiotic metabolizing enzymes (XME), antioxidant enzymes and DNA repair enzymes have been reported as the main drivers of cancer. Thus, a better understanding of the causal risk factors for PCa will provide avenues to identify men at increased risk and will contribute to develop effective detection and prevention methods. We performed a meta-analysis on 17,518 cases and 42,507 controls obtained from 42 studies to determine whether seven SNPs and one CNV pertaining to oxidative stress, xenobiotic detoxification and DNA repair enzymes are associated with the risk of PCa (GPX1 (rs1050450), XRCC1 (rs25487), PON1 (rs662), SOD2 (rs4880), CAT (rs1001179), GSTP1 (rs1695) and CNV GSTM1). A significant increased risk of PCa was found for SOD2 (rs4880) ORGG+GA vs. AA 1.08; 95%CI 1.01-1.15, CAT (rs1001179) ORTT vs. TC+CC 1.39; 95%CI 1.17-1.66, PON1 (rs662) ORCT vs. CC+TT 1.17; 95%CI 1.01-1.35, GSTP1 (rs1695) ORGG vs. GA+AA 1.20; 95%CI 1.05-1.38 and GSTM1 (dual null vs. functional genotype) ORN vs. NN1+NN2 1.34; 95%CI 1.10-1.64. The meta-analysis showed that the CNV GSTM1, and the SNPs GSTP1 (rs1695) and CAT (rs1001179) are strongly associated with a greater risk of PCa and, to a lesser extent, the genetic variants SOD2 (rs4880) and PON1 (rs662). Although several antioxidant enzymes and XME play an important role in the PCa development, other risk factors such as chemical exposures should also be considered to gain insight on PCa risk. The functional in silico analysis showed that the genetic variants studied had no clinical implication regarding malignancy, except for GPX1 (rs1050450) SNP.

Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study.

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, µ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1-5] vs. 1 [0-2], p < 0.01) and 42% opioid dose (35 [22-61] vs. 60 [40-80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58-0.82] vs. 0.51 [0.13-0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30-34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.

Correlación del ácido úrico con el grosor de la íntima media de la carótida en adolescentes con obesidad / Correlation of uric acid with carotid intima media thickness in obese adolescents

Introducción: la obesidad en la población pediátrica es un problema de salud pública. Se ha demostrado la correlación del ácido úrico y el grosor de la íntima media de la carótida en adultos. Objetivo: identificar la correlación del ácido úrico y el grosor de la íntima media de la carótida en adolescentes con obesidad. Material y métodos: se realizó un estudio observacional, transversal. Se incluyeron pacientes de diez a 16 años con diagnóstico de obesidad. Se determinó ácido úrico, perfil de lípidos y grosor de la íntima media carotidea. En el análisis estadístico, se correlacionó el grosor de la íntima media carotídea con los niveles de ácido úrico a través del coeficiente de correlación de Spearman. Resultados: se incluyeron 169 adolescentes con una mediana para la edad de 13 años, sin predominio de sexo. Se identificó una correlación positiva del ácido úrico con el grosor de la íntima media carotídea (r = 0,242, p = 0,001). Al estratificarse de acuerdo con el sexo, no hubo correlación en las mujeres (r = -0,187, p = 0,074), mientras que en los hombres aumentó (r = 0,36, p = 0,001) y por estadio puberal, los adolescentes varones púberes tuvieron una correlación positiva (p = 0,384, p = 0,002). Conclusión: se identificó una correlación positiva débil entre el grosor de la íntima de la carótida y el ácido úrico en adolescentes con obesidad. (AU)

Introduction: obesity in the pediatric population is a public health problem. The correlation of uric acid and carotid intima media thickness in adults has been demonstrated.Objective: to identify the correlation of uric acid and carotid intima media thickness in adolescents with obesity.Material and methods: an observational, cross-sectional study was carried out. Patients aged ten to 16 years with a diagnosis of obesity were included. Uric acid, lipid profile and carotid intima media thickness were determined. In relation to the statistical analysis, carotid intima media thickness was correlated with uric acid levels through Spearman's correlation coefficient. Results: one hundred and sixty-nine adolescents were included with a median age of 13 years, without predominance of sex. A positive correlation of uric acid with carotid intima media thickness was identified (r = 0.242, p = 0.001). When stratified according to sex, there was no correlation in women (r = -0.187, p = 0.074), while in men it increased (r = 0.36, p = 0.001) and by pubertal stage, pubertal male adolescents had a positive correlation (p = 0.384, p = 0.002).Conclusion: a weak positive correlation was identified between carotid intimal thickness and uric acid in obese adolescents. (AU)

Inhibition of DPP-IV Activity and Stimulation of GLP-1 Release by Gastrointestinally Digested Black Soldier Fly Prepupae.

The beneficial effects of an insect-based diet on human health and, in particular, the regulatory ability of digested insects' proteins on the glycaemic response in humans are topics that need to be investigated deeper. In this work, we performed an in vitro study on the modulatory activity of gastrointestinal digested black soldier fly (BSF) prepupae on the enterohormone GLP-1 and its natural inhibitor, DPP-IV. We verified whether actions intended to valorise the starting insect biomass, i.e., insect-optimised growth substrates and prior fermentation, can positively impact human health. Our results highlight that the digested BSF proteins from all the prepupae samples had a high stimulatory and inhibitory ability on the GLP-1 secretion and the DPP-IV enzyme in the human GLUTag cell line. Gastrointestinal digestion significantly improved the DPP-IV inhibitory capacity of the whole insect protein. Moreover, it was seen that optimised diets or fermentation processes preceding the digestion, in any case, did not positively affect the efficacy of the answer. BSF was already considered one of the edible insects more suitable for human consumption for its optimal nutritional profile. The BSF bioactivity here shown, after simulated digestion, on glycaemic control systems makes this species even more promising.

GSPE Pre-Treatment Exerts Long-Lasting Preventive Effects against Aging-Induced Changes in the Colonic Enterohormone Profile of Female Rats.

The impact that healthy aging can have on society has raised great interest in understanding aging mechanisms. However, the effects this biological process may have on the gastrointestinal tract (GIT) have not yet been fully described. Results in relation to changes observed in the enteroendocrine system along the GIT are controversial. Grape seed proanthocyanidin extracts (GSPE) have been shown to protect against several pathologies associated with aging. Based on previous results, we hypothesized that a GSPE pre-treatment could prevent the aging processes that affect the enteroendocrine system. To test this hypothesis, we treated 21-month-old female rats with GSPE for 10 days. Eleven weeks after the treatment, we analyzed the effects of GSPE by comparing these aged animals with young animals. Aging induced a greater endocrine response to stimulation in the upper GIT segments (cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1)), a decrease in the mRNA abundance of GLP-1, peptide YY (PYY) and chromogranin A (ChgA) in the colon, and an increase in colonic butyrate. GSPE-treated rats were protected against a decrease in enterohormone expression in the colon. This effect is not directly related to the abundance of microbiome or short-chain fatty acids (SCFA) at this location. GSPE may therefore be effective in preventing a decrease in the colonic abundance of enterohormone expression induced by aging.

[Correlation of uric acid with carotid intima media thickness in obese adolescents]. / Correlación del ácido úrico con el grosor de la íntima media de la carótida en adolescentes con obesidad.

Introduction: Introduction: obesity in the pediatric population is a public health problem. The correlation of uric acid and carotid intima media thickness in adults has been demonstrated. Objective: to identify the correlation of uric acid and carotid intima media thickness in adolescents with obesity. Material and methods: an observational, cross-sectional study was carried out. Patients aged ten to 16 years with a diagnosis of obesity were included. Uric acid, lipid profile and carotid intima media thickness were determined. In relation to the statistical analysis, carotid intima media thickness was correlated with uric acid levels through Spearman's correlation coefficient. Results: one hundred and sixty-nine adolescents were included with a median age of 13 years, without predominance of sex. A positive correlation of uric acid with carotid intima media thickness was identified (r = 0.242, p = 0.001). When stratified according to sex, there was no correlation in women (r = -0.187, p = 0.074), while in men it increased (r = 0.36, p = 0.001) and by pubertal stage, pubertal male adolescents had a positive correlation (p = 0.384, p = 0.002). Conclusion: a weak positive correlation was identified between carotid intimal thickness and uric acid in obese adolescents.

Introducción: Introducción: la obesidad en la población pediátrica es un problema de salud pública. Se ha demostrado la correlación del ácido úrico y el grosor de la íntima media de la carótida en adultos. Objetivo: identificar la correlación del ácido úrico y el grosor de la íntima media de la carótida en adolescentes con obesidad. Material y métodos: se realizó un estudio observacional, transversal. Se incluyeron pacientes de diez a 16 años con diagnóstico de obesidad. Se determinó ácido úrico, perfil de lípidos y grosor de la íntima media carotidea. En el análisis estadístico, se correlacionó el grosor de la íntima media carotídea con los niveles de ácido úrico a través del coeficiente de correlación de Spearman. Resultados: se incluyeron 169 adolescentes con una mediana para la edad de 13 años, sin predominio de sexo. Se identificó una correlación positiva del ácido úrico con el grosor de la íntima media carotídea (r = 0,242, p = 0,001). Al estratificarse de acuerdo con el sexo, no hubo correlación en las mujeres (r = -0,187, p = 0,074), mientras que en los hombres aumentó (r = 0,36, p = 0,001) y por estadio puberal, los adolescentes varones púberes tuvieron una correlación positiva (p = 0,384, p = 0,002). Conclusión: se identificó una correlación positiva débil entre el grosor de la íntima de la carótida y el ácido úrico en adolescentes con obesidad.

Bajo riesgo de contagio ambiental por SARS-CoV-2 en espacios no sanitarios / Low risk of environmental contagion by SARS-CoV-2 in non-sanitary spaces

Objetivo: Estudiar la presencia de SARS-CoV-2 en superficies (alto, medio y bajo contacto) y aires de espacios no sanitarios pero de elevada afluencia de público para evaluar el riesgo de contagio ambiental. Método: Se ha realizado el análisis de las superficies y de los aires por RT-qPCR para detectar la presencia de SARS-CoV-2. Resultados: Se obtuvieron 394 superficies y 23 muestras de aire de espacios de alta afluencia de personas, como oficinas, centros comerciales y residencias de ancianos. El virus no fue detectado en ninguna de las muestras analizadas. Conclusión: Aunque no podemos concluir rotundamente que no existe un riesgo de infección ambiental por SARS-CoV-2 en espacios no sanitarios, sí podemos afirmar que el riesgo es casi nulo.(AU)

Objective: To study the presence of SARS-CoV-2 on surfaces (high, medium and low contacts) and airs in non-sanitary spaces with high public influx to evaluate the risk of environmental contagion. Method: Surfaces and airs were analysed by RT-qPCR to detect the presence of SARS-CoV-2. Results: A total of 394 surfaces and air samples were obtained from spaces with high public influx such as offices, shopping centres and nursing homes. The virus was not detected in any of the samples analysed. Conclusion: Although we cannot emphatically conclude that there is no risk of environmental infection by SARS-CoV-2 in non-sanitary spaces, we can affirm that the risk is almost non- existent.(AU)

Compliance to Multidisciplinary Lifestyle Intervention Decreases Blood Pressure in Patients with Resistant Hypertension: A Cross-Sectional Pilot Study.

Hypertension is a common chronic medical condition. Treatment is not satisfactory in a significant proportion of patients with primary hypertension, despite the concurrent use of three or more medications with different mechanisms of action. Such treatment-resistant hypertension is a clinical challenge associated with poor prognosis and needs further investigation. The efficacy of lifestyle changes has not been established yet in patients with resistant hypertension, and educational efforts appear clinically irrelevant in patients who must achieve behavioral changes without supervision. A 6-month multidisciplinary pilot intervention enrolled 50 patients with established resistant hypertension. The aims were: (1) to examine whether intensive and supervised lifestyle changes contribute to decreasing blood pressure in this condition, and (2) to identify which components affect compliance and feasibility. The program provided intensive changes in nutrition, physical exercise, and control of sleep disturbances supervised by nutritionists, physiotherapists, and psychologists. Nurses and pharmacists followed up on adherence to the antihypertensive medication. The primary outcome was 24 h blood pressure control. Data in patients with full compliance (n = 30) indicate that lifestyle modifications in resistant hypertension significantly reduced 24 h both systolic and diastolic blood pressure (p < 0.01), body mass index (p < 0.01), medication burden (p = 0.04), improving physical fitness, and cardiovascular risk markers such as heart rate (p = 0.01) and augmentation index (p = 0.02). The adherence to the intervention was moderate, with an attrition rate of 12%. A modified version reducing visits and explorations will likely improve compliance and can be used to assess the long-term maintenance of these benefits in managing resistant hypertension by diverse healthcare providers.

Administration of Alphitobius diaperinus or Tenebrio molitor before meals transiently increases food intake through enterohormone regulation in female rats.

BACKGROUND: It has been previously shown that acutely administered insect Alphitobius diaperinus protein increases food intake in rats and modifies the ex vivo enterohormone secretory profile differently than beef or almond proteins. In this study, we aimed to evaluate whether these effects could be maintained for a longer period and determine the underlying mechanisms. RESULTS: We administered two different insect species to rats for 26 days and measured food intake at different time points. Both insect species increased food intake in the first week, but the effect was later lost. Glucagon-like peptide 1 (GLP-1) and ghrelin were measured in plasma and ex vivo, and no chronic effects on their secretion or desensitization were found. Nevertheless, digested A. diaperinus acutely modified GLP-1 and ghrelin secretion ex vivo. CONCLUSION: Our results suggest that increases in food intake could be explained by a local ghrelin reduction acting in the small intestine. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Promotion of physical activity after hospitalization for COPD exacerbation: A randomized control trial.

BACKGROUND AND OBJECTIVE: Physical activity worsens during exacerbations of chronic obstructive pulmonary disease (COPD) and notably after hospitalizations. Pedometer-based interventions are useful to increase physical activity in stable patients with COPD. However, there is little information concerning the implementation of such programs following severe exacerbation. This study assessed the efficacy of a physical activity program after hospitalization for a COPD exacerbation. METHODS: We performed a prospective, 12-week, parallel group, assessor-blinded, randomized control trial in COPD patients hospitalized for an exacerbation. After discharge, physical activity and other secondary variables were assessed. Patients were allocated (1:1) to a physical activity promotion program (intervention group, IG) or usual care (control group, CG). Based on a motivational interview and accelerometer physical activity assessment, a patient-tailored, pedometer-based, progressive and target-driven program was designed. Linear mixed effect models were used to analyse between-group differences. RESULTS: Forty-six out of 61 patients recruited were randomized and 43 (IG = 20, CG = 23) completed the study. In-hospital and baseline characteristics were similar in both groups. After 12 weeks of intervention, the mean steps difference between groups was 2093 steps/day, p = 0.018, 95% CI 376-4012, favouring the IG. Only the IG significantly increased the number of steps/day compared to baseline (mean difference [95% CI] 2932 [1069-4795] steps; p = 0.004). There were no other between-group differences. CONCLUSION: After hospitalization for a COPD exacerbation, a patient-tailored physical activity program based on a motivational interview and the use of pedometers, with progressive and customized targets, improved the number of steps/day.

[Low risk of environmental contagion by SARS-CoV-2 in non-sanitary spaces]. / Bajo riesgo de contagio ambiental por SARS-CoV-2 en espacios no sanitarios.

Objective: To study the presence of SARS-CoV-2 on surfaces (high, medium and low contacts) and airs in non-sanitary spaces with high public influx to evaluate the risk of environmental contagion. Method: Surfaces and airs were analysed by RT-qPCR to detect the presence of SARS-CoV-2. Results: A total of 394 surfaces and air samples were obtained from spaces with high public influx such as offices, shopping centres and nursing homes. The virus was not detected in any of the samples analysed. Conclusion: Although we cannot emphatically conclude that there is no risk of environmental infection by SARS-CoV-2 in non-sanitary spaces, we can affirm that the risk is almost non- existent.

Low risk of environmental contagion by SARS-CoV-2 in non-sanitary spaces.

OBJECTIVE: To study the presence of SARS-CoV-2 on surfaces (high, medium and low contact) and airs in non-sanitary spaces with high public influx to evaluate the risk of environmental contagion. METHODS: Surfaces and airs were analysed by RT-qPCR to detect the presence of SARS-CoV-2. RESULTS: 394 surfaces and air samples were obtained from spaces with high public influx such as offices, shopping centres and nursing homes. The virus was not detected in any of the samples analysed. CONCLUSION: Although we cannot emphatically conclude that there is no risk of environmental 27 infection by SARS-CoV-2 in non-sanitary spaces, we can affirm that the risk is almost non- existent.

Comportamiento asertivo en cuidadores familiares de personas con demencia: desarrollo y validación del “Cuestionario de asertividad en el cuidado” (CAQ) / Assertive behavior in family caregivers of people with dementia: development and validation of the “Caregiving Assertiveness Questionnaire” (CAQ)

La asertividad podría tener un papel relevante en el proceso de estrés y afrontamiento del cuidado familiar de personas con demencia. Sin embargo, la investigación sobre esta cuestión es todavía escasa. Este estudio presenta las propiedades psicométricas del “Cuestionario de asertividad en el cuidado” (CAQ), y analiza las asociaciones entre esta variable y otras que presentan un papel importante en el afrontamiento del cuidado. Participaron 147 cuidadores de personas con demencia. Se identificó la estructura factorial del CAQ (expresión del malestar, hacer frente a los conflictos y poner límites), que explicaba el 69,63% de la varianza en asertividad. Se encontraron asociaciones significativas entre las puntuaciones en el CAQ (escala total y subescalas) y otras variables tales como la evitación experiencial, fusión cognitiva y frecuencia de ocio. El CAQ presenta adecuadas propiedades psicométricas y es un instrumento de potencial utilidad a tener en cuenta a la hora de diseñar protocolos de evaluación de los cuidadores familiares y diseñar intervenciones dirigidas a ayudar a estas personas. (AU)

The Impact of Nicotine along with Oral Contraceptive Exposure on Brain Fatty Acid Metabolism in Female Rats.

Smoking-derived nicotine (N) and oral contraceptive (OC) synergistically exacerbate ischemic brain damage in females, and the underlying mechanisms remain elusive. In a previous study, we showed that N + OC exposure altered brain glucose metabolism in females. Since lipid metabolism complements glycolysis, the current study aims to examine the metabolic fingerprint of fatty acids in the brain of female rats exposed to N+/-OC. Adolescent and adult Sprague-Dawley female rats were randomly (n = 8 per group) exposed to either saline or N (4.5 mg/kg) +/-OC (combined OC or placebo delivered via oral gavage) for 16-21 days. Following exposure, brain tissue was harvested for unbiased metabolomic analysis (performed by Metabolon Inc., Morrisville, NC, USA) and the metabolomic profile changes were complemented with Western blot analysis of key enzymes in the lipid pathway. Metabolomic data showed significant accumulation of fatty acids and phosphatidylcholine (PC) metabolites in the brain. Adolescent, more so than adult females, exposed to N + OC showed significant increases in carnitine-conjugated fatty acid metabolites compared to saline control animals. These changes in fatty acyl carnitines were accompanied by an increase in a subset of free fatty acids, suggesting elevated fatty acid ß-oxidation in the mitochondria to meet energy demand. In support, ß-hydroxybutyrate was significantly lower in N + OC exposure groups in adolescent animals, implying a complete shunting of acetyl CoA for energy production via the TCA cycle. The reported changes in fatty acids and PC metabolism due to N + OC could inhibit post-translational palmitoylation of membrane proteins and synaptic vesicle formation, respectively, thus exacerbating ischemic brain damage in female rats.