GLP-1 Receptor Agonists Promote Weight Loss Among People with HIV.

BACKGROUND: Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited. METHODS: A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss. RESULTS: A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss. CONCLUSIONS: Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.

Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS: We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS: Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.

Exploring Attentional Bias toward Alcohol Content: Insights from Eye-Movement Activity.

INTRODUCTION: Attentional bias (AB) is an implicit selective attention toward processing disorder-significant information while neglecting other environmental cues. Considerable empirical evidence highlights the clinical implication of AB in the onset and maintenance of substance use disorder. An innovative method to explore direct measures of AB relies on the eye-movement activity using technologies like eye-tracking (ET). Despite the growing interest regarding the clinical relevance of AB in the spectrum of alcohol consumption, more research is needed to fully determine the AB patterns and its transfer from experimental to clinical applications. The current study consisted of three consecutive experiments. The first experiment aimed to design an ad-hoc visual attention task (VAT) consisting of alcohol-related and neutral images using a nonclinical sample (n = 15). The objective of the second and third experiments was to analyze whether the effect of type of image (alcohol-related vs. neutral images) on AB toward alcohol content using the VAT developed in the first experiment was different for type of drinker (light vs. heavy drinker in the second experiment [n = 30], and occasional social drinkers versus alcohol use disorder (AUD) patients in the third experiment [n = 48]). METHODS: Areas of interest (AOIs) within each type of image (neutral and alcohol-related) were designed and raw ET-based data were subsequently extracted through specific software analyses. For experiment 1, attention maps were created and processed for each image. For experiments 2 and 3, data on ET variables were gathered and subsequently analyzed through a two-way ANOVA with the aim of examining the effects of the type of image and drinker on eye-movement activity. RESULTS: There was a statistically significant interaction effect between type of image and type of drinker (light vs. heavy drinker in experiment 2, F(1, 56) = 13.578, p < 0.001, partial η2 = 0.195, and occasional social drinker versus AUD patients in the experiment 3, F(1, 92) = 35.806, p < 0.001, partial η2 = 0.280) for "first fixation" with large effect sizes, but not for "number of fixations" and "dwell time." The simple main effect of type of image on mean "first fixation" score for AUD patients was not statistically significant. CONCLUSION: The data derived from the experiments indicated the importance of AB in sub-clinical populations: heavy drinkers displayed an implicit preference for alcohol-related images compared to light drinkers. Nevertheless, AB fluctuations in patients with AUD compared to the control group were found. AUD patients displayed an early interest in alcohol images, followed by an avoidance attentional processing of alcohol-related images. The results are discussed in light of recent literature in the field.

Kir2.1-NaV1.5 channelosome and its role in arrhythmias in inheritable cardiac diseases.

Sudden cardiac death in children and young adults is a relatively rare but tragic event whose pathophysiology is unknown at the molecular level. Evidence indicates that the main cardiac sodium channel (NaV1.5) and the strong inward rectifier potassium channel (Kir2.1) physically interact and form macromolecular complexes (channelosomes) with common partners, including adapter, scaffolding, and regulatory proteins that help them traffic together to their eventual membrane microdomains. Most important, dysfunction of either or both ion channels has direct links to hereditary human diseases. For example, certain mutations in the KCNJ2 gene encoding the Kir2.1 protein result in Andersen-Tawil syndrome type 1 and alter both inward rectifier potassium and sodium inward currents. Similarly, trafficking-deficient mutations in the gene encoding the NaV1.5 protein (SCN5A) result in Brugada syndrome and may also disturb both inward rectifier potassium and sodium inward currents. Moreover, gain-of-function mutations in KCNJ2 result in short QT syndrome type 3, which is extremely rare but highly arrhythmogenic, and can modify Kir2.1-NaV1.5 interactions in a mutation-specific way, further highlighting the relevance of channelosomes in ion channel diseases. By expressing mutant proteins that interrupt or modify Kir2.1 or NaV1.5 function in animal models and patient-specific pluripotent stem cell-derived cardiomyocytes, investigators are defining for the first time the mechanistic framework of how mutation-induced dysregulation of the Kir2.1-NaV1.5 channelosome affects cardiac excitability, resulting in arrhythmias and sudden death in different cardiac diseases.

The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of Short QT Syndrome type 3.

AIMS: Short QT Syndrome Type 3 (SQTS3) is a rare arrhythmogenic disease caused by gain-of-function mutations in KCNJ2, the gene coding the inward rectifier potassium channel Kir2.1. We used a multidisciplinary approach and investigated arrhythmogenic mechanisms in an in-vivo model of de-novo mutation Kir2.1E299V identified in a patient presenting an extremely abbreviated QT interval and paroxysmal atrial fibrillation. METHODS AND RESULTS: We used intravenous adeno-associated virus-mediated gene transfer to generate mouse models, and confirmed cardiac-specific expression of Kir2.1WT or Kir2.1E299V. On ECG, the Kir2.1E299V mouse recapitulated the QT interval shortening and the atrial-specific arrhythmia of the patient. The PR interval was also significantly shorter in Kir2.1E299V mice. Patch-clamping showed extremely abbreviated action potentials in both atrial and ventricular Kir2.1E299V cardiomyocytes due to lack of inward-going rectification and increased IK1 at voltages positive to -80 mV. Relative to Kir2.1WT, atrial Kir2.1E299V cardiomyocytes had a significantly reduced slope conductance at voltages negative to -80 mV. After confirming a higher proportion of heterotetrameric Kir2.x channels containing Kir2.2 subunits in the atria, in-silico 3D simulations predicted an atrial-specific impairment of polyamine block and reduced pore diameter in the Kir2.1E299V-Kir2.2WT channel. In ventricular cardiomyocytes, the mutation increased excitability by shifting INa activation and inactivation in the hyperpolarizing direction, which protected the ventricle against arrhythmia. Moreover, Purkinje myocytes from Kir2.1E299V mice manifested substantially higher INa density than Kir2.1WT, explaining the abbreviation in the PR interval. CONCLUSIONS: The first in-vivo mouse model of cardiac-specific SQTS3 recapitulates the electrophysiological phenotype of a patient with the Kir2.1E299V mutation. Kir2.1E299V eliminates rectification in both cardiac chambers but protects against ventricular arrhythmias by increasing excitability in both Purkinje-fiber network and ventricles. Consequently, the predominant arrhythmias are supraventricular likely due to the lack of inward rectification and atrial-specific reduced pore diameter of the Kir2.1E299V-Kir2.2WT heterotetramer.

Soluble galectin-3 as a microenvironment-relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma.

Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin-3 (GAL-3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non-small cell lung cancer patients. For in vitro studies, lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) primary cultures from early-stage patients and commercial cell lines were cultured, using tumorsphere-forming assays and adherent conditions for the control counterparts. We analyzed the pattern of secretion and expression of GAL-3 using reverse transcription-quantitative real-time PCR (RTqPCR), immunoblot, immunofluorescence, flow cytometry, and immunoassay analysis. Our results using three-dimensional (3D) models of lung tumor cells revealed that soluble GAL-3 (sGAL-3) is highly expressed and secreted. To more accurately mimic the TME, a co-culture of tumorspheres and fibroblasts was used, revealing that GAL-3 could be important as an immunomodulatory molecule expressed and secreted in the TME, modulating immunosuppression through regulatory T cells (TREGS ). In the translational phase, we confirmed that patients with high expression levels of GAL-3 had more TREGS , which suggests that tumors may be recruiting this population through GAL-3. Next, we evaluated levels of sGAL-3 before surgery in LUAD and LUSC patients, hypothesizing that sGAL-3 could be used as an independent prognostic biomarker for overall survival and relapse-free survival in early-stage LUAD patients. Additionally, levels of sGAL-3 at pretreatment and first response assessment from plasma to predict clinical outcomes in advanced LUAD and LUSC patients treated with first-line pembrolizumab were evaluated, further supporting that sGAL-3 has a high efficiency in predicting durable clinical response to pembrolizumab with an area under curve of 0.801 (P = 0.011). Moreover, high levels might predict decreased progression-free survival and OS to anti-PD-1 therapy, with sGAL-3 being a prognosis-independent biomarker for advanced LUAD.

Influence of Nutritional Status and Physical Fitness on Cognitive Domains among Older Adults: A Cross-Sectional Study.

BACKGROUND: The health issues presented by the aging population can result in reduced muscle mass, poorer physical function, and cognitive impairment. The goal of this study was to determine how nutritional status and physical fitness relate to cognitive impairment in older adults. METHODS: A cross-sectional descriptive and analytical study involving 100 participants was carried out to analyze the impact of nutritional status and physical fitness on cognitive impairment. Nutritional status was assessed with the Eating Assessment Tool (EAT-10) and The Mini Nutritional Assessment-Short Form (MNA-SF); physical fitness via the implementation of manual grip evaluation, the 4-m walking test (4-MWT), and the Timed Up and Go (TUG) test; and cognitive impairment evaluation was conducted using the Mini-Mental State Examination (MMSE), the Boston Naming Test (BNT) and the Controlled Oral Word Association Test (COWAT). RESULTS: Data analysis revealed that higher malnutrition status was associated with fewer correct responses in the COWAT (R2 = 0.421), while a correlation between higher MMSE and BNT scores, faster completion times for the 4-m walking and TUG tests, and an increase in handgrip strength load was also observed. CONCLUSION: The analysis of the data revealed that those individuals with superior nutritional status and greater levels of physical fitness outperformed others on the cognitive evaluation.

Extracellular cysteine disulfide bond break at Cys122 disrupts PIP2-dependent Kir2.1 channel function and leads to arrhythmias in Andersen-Tawil Syndrome.

Background: Andersen-Tawil Syndrome Type 1 (ATS1) is a rare heritable disease caused by mutations in the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys122-to-Cys154 disulfide bond in the Kir2.1 channel structure is crucial for proper folding, but has not been associated with correct channel function at the membrane. We tested whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing the open state of the channel. Methods and Results: We identified a Kir2.1 loss-of-function mutation in Cys122 (c.366 A>T; p.Cys122Tyr) in a family with ATS1. To study the consequences of this mutation on Kir2.1 function we generated a cardiac specific mouse model expressing the Kir2.1C122Y mutation. Kir2.1C122Y animals recapitulated the abnormal ECG features of ATS1, like QT prolongation, conduction defects, and increased arrhythmia susceptibility. Kir2.1C122Y mouse cardiomyocytes showed significantly reduced inward rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking ability and localization at the sarcolemma and the sarcoplasmic reticulum. Kir2.1C122Y formed heterotetramers with wildtype (WT) subunits. However, molecular dynamic modeling predicted that the Cys122-to-Cys154 disulfide-bond break induced by the C122Y mutation provoked a conformational change over the 2000 ns simulation, characterized by larger loss of the hydrogen bonds between Kir2.1 and phosphatidylinositol-4,5-bisphosphate (PIP2) than WT. Therefore, consistent with the inability of Kir2.1C122Y channels to bind directly to PIP2 in bioluminescence resonance energy transfer experiments, the PIP2 binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch-clamping the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing PIP2 concentrations. Conclusion: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential to channel function. We demonstrated that ATS1 mutations that break disulfide bonds in the extracellular domain disrupt PIP2-dependent regulation, leading to channel dysfunction and life-threatening arrhythmias.

In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study.

AIMS: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays. METHODS: A total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen's (dual) and Fleiss (triple) κ coefficients. RESULTS: In-house BRCA1/2 molecular testing yielded a concordance rate >90.0% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0% to 90.0% with a positive percentage agreement ranging from 75.0% to 80.0% and a negative percentage agreement ranging from 80.0% to 100%. CONCLUSIONS: In-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays.

An approach to the evaluation of the potency of cannabis resin in Madrid: A health hazard? / Aproximación a la evaluación de la potencia de la resina de cannabis en Madrid: ¿Un riesgo para la salud?

The present study investigates the concentration of Delta (9)-tetrahidrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in 60 samples of cannabis resin acquired on the streets of Madrid region and its potential danger to consumers' health. Additionally, we study the possible correlation between the potency of samples and their organoleptic characteristics. The analysis of cannabinoids was carried out using a high performance liquid chromatography (RP-HPLC-UV). To classify samples, a strength scale based on THC content was established. THC content in 76.7% of the samples was higher than 15%. This potency allows these samples to be classified as Schedule I or drugs with "unacceptable risk" for human health. THC content in 36.7% of the samples was 28.8% on average, which means very high potency. The mean CBD content was 5%, while the correlation between the CBD/THC ratio and potency was negative. The mean content of CBN was 1.74% and the CBN/THC ratio also showed a negative correlation in respect to potency. When investigating the possible correlation between sample potency and organoleptic characteristics, those samples which simultaneously presented sticky texture, high elasticity and light brown colour had very high potency, with an average THC content of 28.7%. Our study shows that the THC content of most of the cannabis that can be purchased in Madrid region is over 15% and poses a health hazard. Additionally, we demonstrate for the first time that only those samples with very high potency can be directly associated with certain organoleptic characteristics.

El presente estudio investiga la concentración de Delta(9)-tetrahidrocannabinol (THC), cannabidiol (CBD) y cannabinol (CBN) en 60 muestras de resina de cannabis adquiridas en las calles de Madrid y su potencial riesgo para la salud del consumidor. Adicionalmente, estudiamos la posible asociación entre la potencia de las muestras y sus características organolépticas. El análisis de cannabinoides se llevó a cabo mediante cromatografía líquida de alta resolución (RP-HPLC-UV). Atendiendo al contenido en THC se estableció una escala de potencia para clasificar las muestras. El 76,7% de las muestras tenía un contenido en THC superior al 15%, esta potencia las cataloga como drogas de Grado I con "riesgo inaceptable" para la salud. El 36,7% de las muestras presentaron un contenido medio en THC del 28,8% (potencia muy alta). El contenido medio en CBD fue del 5% y el de CBN 1,74%; ambas ratios, CBD/THC y CBN/THC, mostraron una correlación negativa con la potencia. Al investigar la posible asociación entra potencia y características organolépticas, se observó que las muestras que presentaban a la vez una textura pegajosa, una elasticidad alta y un color marrón claro, tenían una potencia muy alta, con un contenido medio en THC del 28.7%. Nuestro estudio muestra que el contenido en THC de la mayoría de la resina de cannabis que puede adquirirse en Madrid es superior al 15% y supone un elevado riesgo para la salud. Adicionalmente, demostramos por primera vez que solo aquellas muestras con una potencia muy alta pueden asociarse directamente con ciertas características organolépticas.

Molecular stratification of arrhythmogenic mechanisms in the Andersen Tawil syndrome.

Andersen-Tawil syndrome (ATS) is a rare inheritable disease associated with loss-of-function mutations in KCNJ2, the gene coding the strong inward rectifier potassium channel Kir2.1, which forms an essential membrane protein controlling cardiac excitability. ATS is usually marked by a triad of periodic paralysis, life-threatening cardiac arrhythmias and dysmorphic features, but its expression is variable and not all patients with a phenotype linked to ATS have a known genetic alteration. The mechanisms underlying this arrhythmogenic syndrome are poorly understood. Knowing such mechanisms would be essential to distinguish ATS from other channelopathies with overlapping phenotypes and to develop individualized therapies. For example, the recently suggested role of Kir2.1 as a countercurrent to sarcoplasmic calcium reuptake might explain the arrhythmogenic mechanisms of ATS and its overlap with catecholaminergic polymorphic ventricular tachycardia. Here we summarize current knowledge on the mechanisms of arrhythmias leading to sudden cardiac death in ATS. We first provide an overview of the syndrome and its pathophysiology, from the patient's bedside to the protein and discuss the role of essential regulators and interactors that could play a role in cases of ATS. The review highlights novel ideas related to some post-translational channel interactions with partner proteins that might help define the molecular bases of the arrhythmia phenotype. We then propose a new all-embracing classification of the currently known ATS loss-of-function mutations according to their position in the Kir2.1 channel structure and their functional implications. We also discuss specific ATS pathogenic variants, their clinical manifestations, and treatment stratification. The goal is to provide a deeper mechanistic understanding of the syndrome toward the development of novel targets and personalized treatment strategies.

Clinical and technical insights of tumour mutational burden in non-small cell lung cancer.

Despite the durable responses provided by the introduction of checkpoint inhibitors in advanced Non-Small Cell Lung Cancer (NSCLC) without actionable targets in a subset of patients, a large proportion of them will progress after immunotherapy. Programmed Death Ligand 1 (PD-L1) was the first biomarker approved for immunotherapy, although it has multiple limitations, thus the development of novel biomarkers is an urgent need. Tumour Mutational Burden (TMB) is an emerging biomarker defined as the total number of mutations per coding area of tumour genome. Targeted gene panels have emerged as a cost-effective approach to estimate TMB. However, there is still an unmet need to fully standardize sample requirements, panel size, and bioinformatic pipelines to ensure that TMB is calculated appropriately. In addition, researchers are also evaluating TMB calculation in liquid biopsy. In this work, we summarize the relevant advances and the clinical utility of TMB in NSCLC.

Sleep quality and sleep deprivation: relationship with academic performance in university students during examination period.

The beginning of the university brings together maturational, psychosocial and academic changes that make university students more prone to suffer from insufficient or poor quality sleep, which can negatively influence their academic performance. The period of taking exams is a key part of the academic year. However, there are few studies that analyze sleep during this period of time. Our aim is to study the association of sleep quality and sleep deprivation with academic performance during the examination period. A descriptive, cross-sectional and correlational study was carried out with the participation of 640 subjects in the first three years of five faculties belonging to the Universidad Autónoma de Madrid. The instrument used consisted of a questionnaire that included sociodemographic and academic data, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and information about the academic performance. During the examination period, a positive association was found between sleep quality and academic performance. University students slept less than desired, both on weekdays and weekends, and the sleep debt during the week was associated with a worse students' perception of their academic performance. In total, 61.3% of the students believed that their performance would improve by getting more sleep. In addition, low drowsiness and napping were also found. In conclusion, during periods of greater academic demand, an insufficient sleep and poor quality is commonly observed, affecting negatively to their academic performance. Actually, about 2/3 of our subjects believed that their performance would improve by getting more sleep.

Aproximación a la evaluación de la potencia de la resina de cannabis en Madrid: ¿Un riesgo para la salud? / An approach to the evaluation of the potency of cannabis resin in Madrid: A health hazard?

El presente estudio investiga la concentración de Delta(9)-tetrahidrocannabinol (THC), cannabidiol (CBD) y cannabinol (CBN) en 60 muestras de resina de cannabis adquiridas en las calles de Madrid y su potencial riesgo para la salud del consumidor. Adicionalmente, estudiamos la posible asociación entre la potencia de las muestras y sus características organolépticas. El análisis de cannabinoides se llevó a cabo mediante cromatografía líquida de alta resolución (RP-HPLC-UV). Atendiendo al contenido en THC se estableció una escala de potencia para clasificar las muestras. El 76,7% de las muestras tenía un contenido en THC superior al 15%, esta potencia las cataloga como drogas de Grado I con “riesgo inaceptable” para la salud. El 36,7% de las muestras presentaron un contenido medio en THC del 28,8% (potencia muy alta). El contenido medio en CBD fue del 5% y el de CBN 1,74%; ambas ratios, CBD/THC y CBN/THC, mostraron una correlación negativa con la potencia. Al investigar la posible asociación entra potencia y características organolépticas, se observó que las muestras que presentaban a la vez una textura pegajosa, una elasticidad alta y un color marrón claro, tenían una potencia muy alta, con un contenido medio en THC del 28.7%. Nuestro estudio muestra que el contenido en THC de la mayoría de la resina de cannabis que puede adquirirse en Madrid es superior al 15% y supone un elevado riesgo para la salud. Adicionalmente, demostramos por primera vez que solo aquellas muestras con una potencia muy alta pueden asociarse directamente con ciertas características organolépticas. (AU)

The present study investigates the concentration of Delta (9)-tetrahidrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in 60 samples of cannabis resin acquired on the streets of Madrid region and its potential danger to consumers’ health. Additionally, we study the possible correlation between the potency of samples and their organoleptic characteristics. The analysis of cannabinoids was carried out using a high performance liquid chromatography (RP-HPLC-UV). To classify samples, a strength scale based on THC content was established. THC content in 76.7% of the samples was higher than 15%. This potency allows these samples to be classified as Schedule I or drugs with “unacceptable risk” for human health. THC content in 36.7% of the samples was 28.8% on average, which means very high potency. The mean CBD content was 5%, while the correlation between the CBD/THC ratio and potency was negative. The mean content of CBN was 1.74% and the CBN/THC ratio also showed a negative correlation in respect to potency. When investigating the possible correlation between sample potency and organoleptic characteristics, those samples which simultaneously presented sticky texture, high elasticity and light brown colour had very high potency, with an average THC content of 28.7%. Our study shows that the THC content of most of the cannabis that can be purchased in Madrid region is over 15% and poses a health hazard. Additionally, we demonstrate for the first time that only those samples with very high potency can be directly associated with certain organoleptic characteristics. (AU)

Evaluación de una nueva formulación de compuestos naturales sobre la modificación de los componentes del síndrome metabólico en adultos con sobrepeso

El sobrepeso y la obesidad, condiciones cada vez más frecuentes en Chile y el Mundo, se definen como una enfermedad crónica caracterizada por la acumulación excesiva de grasa corporal que puede ser perjudicial para la salud. El exceso de grasa corporal es el principal factor patogénico para el desarrollo de resistencia a la insulina y síndrome metabólico (SM), este último caracterizado por la agrupación de una serie de anormalidades metabólicas que determinan un mayor riesgo de padecer enfermedades metabólicas y mortalidad cardiovascular. El objetivo de este estudio piloto transversal y observacional fue evaluar una nueva formulación de compuestos naturales, Delphinol®, resveratrol y ácido oleanólico, frente a parámetros asociados al SM en una población joven con exceso de peso, al ingerir durante 22 semanas la nueva formulación. La evaluación fue realizada en base al estado clínico y antropométrico de 20 sujetos voluntarios (ambos sexos, 18 a 30 años e IMC 26 a 42), mediante valoración médica y exámenes de laboratorio clínico para cada componente del SM (obesidad abdominal, triglicéridos, HDL, presión arterial y glicemia en ayunas). De esta manera, se observó que con la ingesta diaria de esta formulación existe una reducción significativa de los niveles de glicemia, índice HOMA-IR, triglicéridos y aumento de HDL-colesterol. Estos resultados preliminares se traducirían en un beneficio sobre el estado de salud de los individuos con sobrepeso y obesidad, lo cual impactaría en reducir los índices de SM y de esta manera enlentecer la progresión hacia enfermedades crónicas como diabetes y dislipidemia, y contribuir también a disminuir el riesgo cardiometabólico asociado.

Overweight and obesity, increasingly frequent conditions in Chile and the world, are defined as chronic diseases characterized by the excessive accumulation of body fat, that can be detrimental to health. Excess body fat is the main pathogenic factor for the development of insulin resistance and metabolic syndrome, the latter characterized by a cluster of metabolic abnormalities that increase risk of metabolic diseases and cardiovascular mortality. The objective of this preliminary cross-sectional, observational study was to evaluate a new formulation of natural compounds, Delphinol®, resveratrol and oleanolic acid, against metabolic syndrome components in a young population with excess weight, through the intake during 22 weeks of the new formulation. The evaluation was carried out based on the clinical and anthropometric status of 20 volunteer subjects (both gender, 18 to 30 years and BMI 26 to 42), medical evaluation and laboratory tests using each metabolic syndrome component (abdominal obesity, triglycerides, HDL, blood pressure y fasting glicaemia). It was observed that with the daily intake of this formulation there was a significant reduction in blood glucose levels, HOMA-IR index, triglycerides and an increase in HDL-cholesterol. These preliminary results would translate into a benefit in the health status of overweight and obese individuals, which would impact on reducing rates of metabolic syndrome. Thus, slowing down the progression of chronic diseases such as diabetes and dyslipidemia, and also contributing to decreasing the associated cardiometabolic risk.

Proteomic Changes in Paspalum fasciculatum Leaves Exposed to Cd Stress.

(1) Background: Cadmium is a toxic heavy metal that is widely distributed in water, soil, and air. It is present in agrochemicals, wastewater, battery waste, and volcanic eruptions. Thus, it can be absorbed by plants and enter the trophic chain. P. fasciculatum is a plant with phytoremediation capacity that can tolerate Cd stress, but changes in its proteome related to this tolerance have not yet been identified. (2) Methods: We conducted a quantitative analysis of the proteins present in P. fasciculatum leaves cultivated under greenhouse conditions in mining soils doped with 0 mg kg-1 (control), 30 mg kg-1, or 50 mg kg-1. This was carried out using the label-free shotgun proteomics technique. In this way, we determined the changes in the proteomes of the leaves of these plants, which allowed us to propose some tolerance mechanisms involved in the response to Cd stress. (3) Results: In total, 329 variable proteins were identified between treatments, which were classified into those associated with carbohydrate and energy metabolism; photosynthesis; structure, transport, and metabolism of proteins; antioxidant stress and defense; RNA and DNA processing; and signal transduction. (4) Conclusions: Based on changes in the differences in the leaf protein profiles between treatments, we hypothesize that some proteins associated with signal transduction (Ras-related protein RABA1e), HSPs (heat shock cognate 70 kDa protein 2), growth (actin-7), and cellular development (actin-1) are part of the tolerance response to Cd stress.