Metabolic effects of testosterone added to intensive lifestyle intervention in older men with obesity and hypogonadism.

BACKGROUND: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. OBJECTIVE: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty. INTERVENTIONS: LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months. OUTCOME MEASURES: Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score. RESULTS: HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02). CONCLUSION: In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT.

Microplastic and PTFE contamination of food from cookware.

Microplastics are a prolific environmental contaminant that have been evidenced in human tissues. Human uptake of microplastic occurs via inhalation of airborne fibres and ingestion of microplastic-contaminated foods and beverages. Plastic and PTFE-coated cookware and food contact materials may release micro- and nanoplastics into food during food preparation. In this study, the extent to which non-plastic, new plastic and old plastic cookware releases microplastics into prepared food is investigated. Jelly is used as a food simulant, undergoing a series of processing steps including heating, cooling, mixing, slicing and storage to replicate food preparation steps undertaken in home kitchens. Using non-plastic cookware did not introduce microplastics to the food simulant. Conversely, using new and old plastic cookware resulted in significant increases in microplastic contamination. Microplastics comprised PTFE, polyethylene and polypropylene particulates and fibrous particles, ranging 13-318 µm. Assuming a meal was prepared daily per the prescribed methodology, new and old plastic cookware may be contributing 2409-4964 microplastics per annum into homecooked food. The health implications of ingesting microplastics remains unclear.

A Case of Diffuse Thyroid Lipomatosis With Amyloid Deposits Presenting With Thyrotoxicosis.

Diffuse thyroid lipomatosis (DTL) is a rare entity of unknown etiology that can be associated with amyloidosis and rarely, thyrotoxicosis. Here, we present a case of DTL with amyloid deposits and concurrent thyrotoxicosis. A 64-year-old South-Asian woman with a several-year history of an enlarging goiter, unintentional weight loss, and work-up 10 months prior suggestive of thyroiditis presented with a viral syndrome in setting of several weeks of progressive fatigue. Her examination was notable for resting sinus tachycardia and massive painless goiter. Initial work-up revealed nephrotic range proteinuria with hypoalbuminemia, which progressed to end-stage-renal disease, elevated inflammatory markers, and elevated free thyroxine (FT4) with a suppressed thyrotropin. Hemodialysis was initiated. Further testing revealed a negative antithyroid antibody panel, an enlarged fatty thyroid per thyroid ultrasound and neck computed tomography, and normal 24-hour uptake on radioactive iodine uptake scan. Both renal and thyroid core biopsies showed amyloid deposits, with the latter confirming benign adipose tissue with entrapped thyroid follicles. Given her rising FT4 levels and persistent tachycardia, methimazole and atenolol were initiated. FT4 levels nearly normalized after uptitration of methimazole and dosing after dialysis. Although the etiopathogenesis and natural history of DTL remain unclear, we discuss the possible mechanisms of thyrotoxicosis in our patient.

Linking chemical exposure and fish metabolome: Discovering new biomarkers of environmental exposure of Argyrosomus regius to the antidepressant venlafaxine.

In this study, a non-target metabolomic approach was used to investigate changes in the metabolome of juvenile meagre (Argyrosomus regius) exposed to venlafaxine (20 µg/L). A total of 24, 22 and 8 endogenous metabolites tentatively identified in liver, brain and plasma, respectively, were significantly changed in venlafaxine exposed meagre, showing tissue-dependent variations in the metabolic profile. The amino acids tryptophan, tyrosine and phenylalanine, which are related to the synthesis, availability, and expression of neurotransmitters (e.g., serotonin, dopamine, epinephrine), showed to be dysregulated by venlafaxine exposure. A high impact was observed in fish brain metabolome that showed a trend of up-regulation for most of the tentatively identified metabolites. In conclusion, the identification of possible biomarkers of exposure in fish metabolome to environmental stressors such as venlafaxine is crucial to assess early signal changes at molecular level, enabling the prevention of deleterious effects at the organism and population levels.

Incidencia de lesiones deportivas en participantes del torneo de fútbol SECACUP 2022 categoría sub-9 / Incidence of sports injuries in participants of the soccer tournament SECACUP 2022 sub-9 category

El fútbol es un deporte complejo que implica alto riego de lesión, sin embargo, a pesar de su popularidad a nivel juvenil, los datos sobre la presencia de traumatismo en edades menores a 9 años son limitados. El objetivo de este trabajo es determinar la incidencia de lesiones deportivas en participantes del torneo de fútbol SECACUP 2022 categoría sub-9. Se realizó un estudio observacional, no experimental, transversal y exploratorio. Los parámetros de evaluación fueron: ubicación topográfica, mecanismo de lesión, diagnóstico presuntivo, momento del torneo, tipo de atención, superficie de la cancha y limitación para jugar. Se evaluaron 107 jugadores repartidos en 9 equipos, obteniendo un total de 9 lesionados durante 15 juegos. La incidencia de lesiones fue 4,18 lesiones/1000hrs de juego con un promedio de 0,6 lesiones/partido, en su mayoría contusiones en muslo. El 89% de los jugadores lesionados no presentaban una lesión previa al momento del inicio del torneo. La posición con mayor incidencia de lesiones fue el Medio-Campo con 45%. En 89% de los casos, la causa de la lesión fue el traumatismo directo. Está actividad ha llevado a mayor participación de niños, incrementando las lesiones, el conocimiento de la incidencia es importante para desarrollar medidas preventivas apropiadas para la edad(AU)

Soccer is a complex sport that involves a high risk of injury; however, despite its popularity at the youth level, data on the presence of trauma in children under 9 years of age are limited. The objective of this work is to determine the incidence of sports injuries in participants of the SECACUP 2022 soccer tournament under-9 category. An observational, nonexperimental, cross-sectional and exploratory study was made. The evaluation parameters were: topographic location, injury mechanism, presumptive diagnosis, time of the tournament, type of care, court surface and limitation to play. 107 players divided into 9 teams were evaluated, obtaining a total of 9 injured during 15 games. The incidence of injuries was 4, 18 injuries/1000 hours of play with an average of 0,6 injuries/game, mostly thigh contusions. 89% of the injured players had no previous injury at the start of the tournament. The position with the highest incidence of injuries was Midfield with 45%. In 89% of cases, the cause of the injury was direct trauma. This activity has led to a greater participation of children, increasing injuries, knowledge of the incidence is important to develop age-appropriate preventive measures(AU)

Association of irisin levels with cardiac magnetic resonance, inflammatory, and biochemical parameters in patients with chronic heart failure versus controls.

BACKGROUND AND AIMS: Chronic heart failure (CHF) represents a significant cause of morbidity and mortality globally. Metabolic maladaptation has proven to be critical in the progression of this condition. Preclinical studies have shown that irisin, an adipomyokine involved in metabolic regulations, can induce positive cardioprotective effects by improving cardiac remodeling, cardiomyocyte viability, calcium delivery, and reducing inflammatory mediators. However, data on clinical studies identifying the associations between irisin levels and functional imaging parameters are scarce in CHF patients. The objective of this study was to determine the association of irisin levels with cardiac imaging measurements through cardiac magnetic resonance, inflammatory markers, and biochemical parameters in patients with CHF compared with control subjects. METHODS AND RESULTS: Thirty-two subjects diagnosed with CHF and thirty-two healthy controls were evaluated in a cross-sectional study. Serum irisin levels were significantly lower in patients with CHF than in controls. This is the first study to report a significant positive correlation between irisin levels and cardiac magnetic resonance parameters such as left ventricular ejection fraction, fraction shortening, and global radial strain. A negative correlation was demonstrated between irisin levels and brain natriuretic peptide, insulin levels, and Homeostatic model assessment for insulin resistance index. We did not observe significant correlations between irisin levels and inflammatory cytokines. CONCLUSIONS: Given the importance of fraction shortening and global radial strain as accurate markers of ventricular wall motion, these results support the hypothesis that irisin may play an essential role in maintaining an adequate myocardial wall architecture, deformation, and thickness.

Current Insights on the Role of Irisin in Endothelial Dysfunction.

Endothelial dysfunction is a crucial physiopathological mechanism for cardiovascular diseases that results from the harmful impact of metabolic disorders. Irisin, a recently discovered adipomyokine, has been shown to exert beneficial metabolic effects by increasing energy consumption, improving insulin sensitivity, and reducing the proinflammatory milieu. Multiple preclinical models have assessed irisin's possible role in the development of endothelial dysfunction, displaying that treatment with exogenous irisin can decrease the production of oxidative stress mediators by up-regulating Akt/mTOR/Nrf2 pathway, promote endothelial-dependent vasodilatation through the activation of AMPK-PI3K-AkteNOS pathway, and increase the endothelial cell viability by activation of ERK proliferation pathway and downregulation of Bad/Bax/Caspase 3 pro-apoptotic pathway. However, there is scarce evidence of these mechanisms in clinical studies, and available results are controversial. Some have shown negative correlations of irisin levels with the burden of coronary atherosclerosis and leukocyte adhesion molecules' expression. Others have demonstrated associations between irisin levels and increased atherosclerosis risk and higher carotid intima-media thickness. Since the role of irisin in endothelial damage remains unclear, in this review, we compare, contrast, and integrate the current knowledge from preclinical and clinical studies to elucidate the potential preventive role and the underlying mechanisms and pathways of irisin in endothelial dysfunction. This review also comprises original figures to illustrate these mechanisms.

Prospects on coupling UV/H2O2 with activated sludge or a fungal treatment for the removal of pharmaceutically active compounds in real hospital wastewater.

Conventional active sludge (AS) process at municipal centralized wastewater treatment facilities may exhibit little pharmaceuticals (PhACs) removal efficiencies when treating hospital wastewater (HWW). Therefore, a dedicated efficient wastewater treatment at the source point is recommended. In this sense, advanced oxidation processes (AOPs) and fungal treatment (FG) have evidenced promising results in degrading PhACs. The coupling of the AOP based on UV/H2O2 treatment with biological treatment (AS or FG) treating a real non-sterile HWW, was evaluated in this work. In addition, a coagulation-flocculation pretreatment was applied to improve the efficiency of all approaches. Twenty-two PhACs were detected in raw HWW, which were effectively removed (93-95%) with the combination of any of the biological treatment followed by UV/H2O2 treatment. Similar removal results (94%) were obtained when placing UV/H2O2 treatment before FG, while a lower removal (83%) was obtained in the combination of UV/H2O2 followed by AS. However, the latest was the only treatment combination that achieved a decrease in the toxicity of water. Moreover, deconjugation of conjugated PhACs has been suggested for ofloxacin and lorazepam after AS treatment, and for ketoprofen after fungal treatment. Monitoring of carbamazepine and its transformation products along the treatment allowed to identify the same carbamazepine degradation pathway in UV/H2O2 and AS treatments, unlike fungal treatment, which followed another degradation route.

Extended suspect screening to identify contaminants of emerging concern in riverine and coastal ecosystems and assessment of environmental risks.

A suspect screening methodology was developed for the fast and reliable identification of 360 contaminants of emerging concern (CECs) of anthropogenic origin in the vulnerable area of the Ebro Delta (Catalonia, Spain) and to track for potential contamination sources. The suspect screening methodology was combined with a risk assessment approach to prioritize the most ecologically relevant CECs. Out of the 360 suspects, 37 compounds were tentatively identified, 22 of which were fully confirmed using isotopically labelled standards. The detected suspect compounds included pesticides, pharmaceuticals, personal care products, stimulants and their metabolites. Pesticides were more ubiquitous in irrigation and drainage channels, while pharmaceuticals, stimulants, and personal care products were the most common in effluent wastewaters, in the receiving freshwater systems as well as in the marine environment. Ten compounds were found to be of high ecological concern, including the pharmaceuticals telmisartan, venlafaxine, and carbamazepine, the herbicides terbuthylazine, desethylterbuthylazine, and terbutryn, the fungicides azoxystrobin, tebuconazole and prochloraz and the insecticide tebufenozide. These compounds could be used as markers of anthropogenic contamination in riverine and coastal ecosystems.

Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome.

The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the pediatric population. Irisin, an adipomyokine, is involved in white adipose tissue browning, energy expenditure, insulin sensitivity, and anti-inflammatory pathways. Data on the associations among circulating irisin levels, soluble cell adhesion molecules (sCAMs), and inflammatory cytokines is scarce in children and adolescents with MetS and T2DM. Subjects aged 6-16 years were grouped into T2DM, MetS, and healthy controls. Serum irisin levels were significantly lower in the MetS (6.6 [2.8-18.0] ng/mL) and T2DM (6.8 [2.2-23.2] ng/mL) groups compared with controls (30.3 [24.6-57.1] ng/mL). Negative correlations between irisin and the BMI percentile (R = -0.358), WC percentile (R = -0.308), and triglycerides (R = -0.284) were identified, while positive associations with TC (R = 0.287), HDL-c (R = 0.488), and LDL-c (R = 0.414) were observed. Significant negative correlations were found between irisin and sNCAM (R = -0.382), sICAM-2 (R = -0.300), sVCAM-1 (R = -0.292), MCP-1 (R = -0.308), and IFN-α2 (R = -0.406). Of note, lower concentrations of most sCAMs (sICAM-1, sPSGL-1, sP-selectin, sEpCAM, sICAM-2, sALCAM, sPECAM-1, sCD44, sVCAM-1, sICAM-3, sL-selectin, and sNCAM) were shown in T2DM subjects compared with MetS patients. Lower irisin levels induce a lack of inhibition of oxidative stress and inflammation. In T2DM, higher ROS, AGEs, glucotoxicity, and inflammation trigger endothelial cell apoptosis, which downregulates the sCAM expression as a compensatory mechanism to prevent further vascular damage. In opposition, in subjects with MetS that have not yet developed T2DM and its accompanying stressors, the upregulation of the sCAM expression is ensued.

Electrospinning of PCL-Based Blends: Processing Optimization for Their Scalable Production.

In this work poly(ε-caprolactone) (PCL) based electrospun mats were prepared by blending PCL with microcrystalline cellulose (MCC) and poly(3-hydroxybutyrate) (PHB). The electrospinning processing parameters were firstly optimized with the aim to obtain scalable PCL-based electrospun mats to be used in the industrial sector. Neat PCL as well as PCL-MCC and PCL-PHB based mats in different proportions (99:1; 95:5; 90:10) were prepared. A complete morphological, thermal and mechanical characterization of the developed materials was carried out. Scanning electron microscopy (SEM) observations showed that the addition of PHB to the PCL matrix considerably reduced the formation of beads. Both the addition of MCC and PHB reduced the thermal stability of PCL, but obtained materials with enough thermal stability for the intended use. The electrospun PCL fibers show greatly reduced flexibility with respect to the PCL bulk material, however when PCL is blended with PHB their stretchability is increased, changing their elongation at break from 35% to 70% when 10 wt% of PHB is blended with PCL. However, the mechanical response of the different blends increases with respect to the neat electrospun PCL, offering the possibility to modulate their properties according to the required industrial applications.

Sustainable microalgae-based technology for biotransformation of benzalkonium chloride in oil and gas produced water: A laboratory-scale study.

Many countries have implemented stringent regulatory standards for discharging produced water (PW) from the oil and gas extraction process. Among the different chemical pollutants occurring in PW, surfactants are widely applied in the oil and gas industry to provide a barrier from metal corrosion. However, the release of these substances from the shale formation can pose serious hazardous impacts on the aquatic environment. In this study, a low-cost and eco-friendly microalgae laboratory-scale technology has been tested for biotransformation of benzalkonium chloride (BACC12 and BACC14) in seawater and PW during 14-days of treatment (spiked at 5 mg/L). From the eight microalgae strains selected, Tetraselmis suecica showed the highest removal rates of about 100% and 54% in seawater and PW, respectively. Suspect screening analysis using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) allowed the identification of 12 isomeric intermediates generated coming from biotransformation mechanisms. Among them, the intermediate [OH-BACC12] was found as the most intense compound generated from BACC12, while the intermediate [2OH-BACC14] was found as the most intense compound generated from BACC14. The suggested chemical structures demonstrated a high reduction on their amphiphilic properties, and thus, their tendency to be adsorbed into sediments after water discharge. In this study, Tetraselmis suecica was classified as the most successful specie to reduce the surfactant activity of benzalkonium chloride in treated effluents.

The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review.

Exercise is an effective strategy for preventing and treating obesity and its related cardiometabolic disorders, resulting in significant loss of body fat mass, white adipose tissue browning, redistribution of energy substrates, optimization of global energy expenditure, enhancement of hypothalamic circuits that control appetite-satiety and energy expenditure, and decreased systemic inflammation and insulin resistance. Novel exercise-inducible soluble factors, including myokines, hepatokines, and osteokines, and immune cytokines and adipokines are hypothesized to play an important role in the body's response to exercise. To our knowledge, no review has provided a comprehensive integrative overview of these novel molecular players and the mechanisms involved in the redistribution of metabolic fuel during and after exercise, the loss of weight and fat mass, and reduced inflammation. In this review, we explain the potential role of these exercise-inducible factors, namely myokines, such as irisin, IL-6, IL-15, METRNL, BAIBA, and myostatin, and hepatokines, in particular selenoprotein P, fetuin A, FGF21, ANGPTL4, and follistatin. We also describe the function of osteokines, specifically osteocalcin, and of adipokines such as leptin, adiponectin, and resistin. We also emphasize an integrative overview of the pleiotropic mechanisms, the metabolic pathways, and the inter-organ crosstalk involved in energy expenditure, fat mass loss, reduced inflammation, and healthy weight induced by exercise.

Effect-Based Identification of Hazardous Antibiotic Transformation Products after Water Chlorination.

Antibiotic transformation products (TPs) generated during water treatment can be considered as an environmental concern, since they can retain part of the bioactivity of the parent compound. Effect-directed analysis (EDA) was applied for the identification of bioactive intermediates of azithromycin (AZI) and ciprofloxacin (CFC) after water chlorination. Fractionation of samples allowed the identification of bioactive intermediates by measuring the antibiotic activity and acute toxicity, combined with an automated suspect screening approach for chemical analysis. While the removal of AZI was in line with the decrease of bioactivity in chlorinated samples, an increase of bioactivity after complete removal of CFC was observed (at >0.5 mgCl2/L). Principal component analysis (PCA) revealed that some of the CFC intermediates could contribute to the overall toxicity of the chlorinated samples. Fractionation of bioactive samples identified that the chlorinated TP296 (generated from the destruction of the CFC piperazine ring) maintained 41%, 44%, and 30% of the antibiotic activity of the parent compound in chlorinated samples at 2.0, 3.0, and 4.0 mgCl2/L, respectively. These results indicate the spectrum of antibacterial activity can be altered by controlling the chemical substituents and configuration of the CFC structure with chlorine. On the other hand, the potential presence of volatile DBPs and fractionation losses do not allow for tentative confirmation of the main intermediates contributing to the acute toxic effects measured in chlorinated samples. Our results encourage further development of new and advanced methodologies to study the bioactivity of isolated unknown TPs to understand their hazardous effects in treated effluents.

Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach.

Bioaccumulation of pharmaceuticals in fish exposed to contaminated water can be shaped by their capability to metabolize these xenobiotics, affecting their toxicity and animal welfare. In this study the in vivo metabolization of the antidepressant venlafaxine by the juvenile marine fish meagre (Argyrosomus regius) was evaluated using a combined target and suspect screening analytical approach. Thirteen venlafaxine metabolites were identified, namely N-desmethylvenlafaxine and N,N-didesmethylvenlafaxine, which were unequivocally identified using analytical standards, and 11 more tentatively identified by suspect screening analysis, including two Phase II metabolites formed by amino acid conjugation. All of them were detected in the liver, while in plasma and brain only 9 and 6 metabolites, respectively, were detected. Based on these findings, for the first time, a tentative metabolization pathway of venlafaxine by A. regius is proposed. Contrarily to what happen in humans, N-demethylation was identified as the main route of metabolization of venlafaxine by fish. Our findings highlight species-specificity in the metabolization of venlafaxine and allow a better understanding of venlafaxine's toxicokinetic in fish. These results emphasize the need to investigate the biotransformation of xenobiotics by non-target organisms to have an integrated overview of their environmental exposure and to improve future evaluations of environmental risk assessment.

The role of B cells in heart failure and implications for future immunomodulatory treatment strategies.

Despite numerous demonstrations that the immune system is activated in heart failure, negatively affecting patients' outcomes, no definitive treatment strategy exists directed to modulate the immune system. In this review, we present the evidence that B cells contribute to the development of hypertrophy, inflammation, and maladaptive tissue remodelling. B cells produce antibodies that interfere with cardiomyocyte function, which culminates as the result of recruitment and activation of a variety of innate and structural cell populations, including neutrophils, macrophages, fibroblasts, and T cells. As B cells appear as active players in heart failure, we propose here novel immunomodulatory therapeutic strategies that target B cells and their products.

Characterization of organic matter by HRMS in surface waters: Effects of chlorination on molecular fingerprints and correlation with DBP formation potential.

In order to understand and minimize the formation of halogenated disinfection by-products (DBPs), it is important to investigate how dissolved organic matter (DOM) contributes to their generation. In the present study, we analysed the DOM profile of water samples from the Barcelona catchment area by high resolution mass spectrometry (HRMS) and we studied the changes after chlorination. Chlorination produced significant changes in the DOM, decreased the average m/z and Kendrick mass defect (KMD) of their spectra and decreased the number and abundance of lignin-like features. The Van Krevelen (VK) fingerprint exhibited several noticeable changes, including the appearance of highly oxidized peaks in the tannin-like region (average O/C, 0.78 ± 0.08), the appearance of features with low H/C and the disappearance of more than half of the lipids-like features. Up to 657 halogenated peaks were generated during sample chlorination, most of which in the condensed hydrocarbons-like and the lignin-like region of the VK diagram. Around 200 features were found to be strongly correlated (ρ ≥ 0.795) to the formation potential of trihalomethanes (THMs) and 5 were correlated with the formation potential of haloacetonitrile (HANs). They all were plotted in the lignin fraction of the VK diagram, but both groups of features exhibited different nitrogen content: those features related to HANs FP had at least one nitrogen atoms in their structures, whilst those related to THMs did not.

Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study.

Vitamin D deficiency is highly prevalent worldwide. It has been associated with heart failure (HF) given its immunoregulatory functions. In-vitro and animal models have shown protective roles through mechanisms involving procollagen-1, JNK2, calcineurin/NFAT, NF-κB, MAPK, Th1, Th2, Th17, cytokines, cholesterol-efflux, oxLDL, and GLUT4, among others. A 12-month follow-up in HF patients showed a high prevalence of vitamin D deficiency, with no seasonal variation (64.7-82.4%). A positive correlation between serum 25(OH)D concentration and dietary intake of vitamin D-rich foods was found. A significant inverse correlation with IL-1ß (R = -0.78), TNF-α (R = -0.53), IL-6 (R = -0.42), IL-8 (R = -0.41), IL-17A (R = -0.31), LDL-cholesterol (R = -0.51), Apo-B (R = -0.57), total-cholesterol (R = -0.48), and triglycerides (R = -0.32) was shown. Cluster analysis demonstrated that patients from cluster three, with the lowest 25(OH)D levels, presented the lowermost vitamin D intake, IL-10 (1.0 ± 0.9 pg/mL), and IL-12p70 (0.5 ± 0.4 pg/mL), but the highest TNF-α (9.1 ± 3.5 pg/mL), IL-8 (55.6 ± 117.1 pg/mL), IL-17A (3.5 ± 2.0 pg/mL), total-cholesterol (193.9 ± 61.4 mg/dL), LDL-cholesterol (127.7 ± 58.2 mg/dL), and Apo-B (101.4 ± 33.4 mg/dL) levels, compared with patients from cluster one. Although the role of vitamin D in the pathogenesis of HF in humans is still uncertain, we applied the molecular mechanisms of in-vitro and animal models to explain our findings. Vitamin D deficiency might contribute to inflammation, remodeling, fibrosis, and atherosclerosis in patients with HF.

Myokine-adipokine cross-talk: potential mechanisms for the association between plasma irisin and adipokines and cardiometabolic risk factors in Mexican children with obesity and the metabolic syndrome.

BACKGROUND: Adipokines and the myokine irisin, involved in mechanisms associated with obesity and metabolic syndrome (MS), are understudied in the pediatric population. OBJECTIVE: To investigate the relationship between irisin, and leptin, resistin, adiponectin, adipsin, anthropometric and cardiovascular risk factors in Mexican children. METHODS: A cross-sample of 126 Mexican children aged 6-12 years old were classified as normal weight (n = 46), obese (n = 40), and MS (n = 40) according to CDC's and Cook's age-modified criteria for obesity and MS. Anthropometric parameters and blood pressure were determined and percentiles calculated for age and gender. Irisin, leptin, adiponectin, adipsin, resistin, triglycerides, glucose, high-density lipoprotein cholesterol (HDL-c) levels, and physical activity were determined. Statistical tests for differences between groups, correlation, and multiple regression analyses were performed. RESULTS: Irisin plasma levels were significantly lower in the obese (6.08 [4.68-6.65]) and MS groups (6.46 [5.74-7.02]) compared with the normal-weight group (8.05 [7.24-8.94]) (p < 0.001). Irisin levels were not influenced by age or gender, but significant dispersion was observed in obese girls (95% CI median [2.29-6.30]). Leptin, resistin, and adipsin levels were significantly increased in the obese and MS groups. Lean-fat ratio was significantly higher in the NW group. Irisin correlated negatively with leptin (- 0.310), resistin (- 0.389), adipsin (- 0.362), BMI% (-0.472), WC% (- 0.453), BMI z-score (- 0.496), fat free mass (- 0.257), fat percentage (- 0.532), fat mass (- 0.515), triglycerides (- 0.291), the number of cardiometabolic risk factors (- 0.443) (p < 0.001); positively with lean-fat ratio (0.489) and HDL-c (0.328) (p < 0.001) and none with physical activity (p < 0.001). Following stepwise multiple linear regression analysis, the lean-fat ratio was the only determinant of irisin levels (B = 1.168, p < 0.001). CONCLUSIONS: Lean-fat ratio, more than the absolute amount of muscle or fat mass, as well as potential myokine-adipokine cross-talk mechanisms may explain the lower irisin levels in children with obesity and MS, through blunted compensatory responses interfering with tissue-dependent irisin secretion, contributing to a continuous deleterious effect cycle.

Metoprolol and metoprolol acid degradation in UV/H2O2 treated wastewaters: An integrated screening approach for the identification of hazardous transformation products.

Advancements on analytical strategies to determine the chemicals present in treated wastewater are necessary to clearly link their occurrence with the ecotoxicity of such effluents. This study describes the development of an integrated screening approach to determine the highest number of pharmaceutical transformation products (TPs) in a single run. The identification of TPs was based on the comparison of detected features with literature sources, compound prediction tools, in-house libraries and reference standards using high-resolution mass spectrometry (HRMS). This integrated approach allowed a better estimation (in silico) of the ecotoxicological contribution of the individual TPs identified. As a proof of concept, this methodology was applied for identification of the TPs generated from metoprolol and its main human metabolite (metoprolol acid) in pure water, hospital wastewater and industrial wastewater treated by UV/H2O2. Twenty-four TPs with potential ecotoxicological implications were identified and their presence was pinpointed as a function of the treated wastewater. An integrated screening approach has been developed using four different screening methodologies in the same run. Additionally, the metabolite MTPA has been considered as a target pollutant in UV/H2O2 experiments.