Summary
Obesity‐related glomerulopathy (ORG) is a silent comorbidity which is increasing in incidence as the obesity epidemic escalates. ORG is associated with serious health consequences including ...chronic kidney disease, end‐stage renal disease (ESRD), and increased mortality. Although the pathogenic mechanisms involved in the development of ORG are not fully understood, glomerular hemodynamic changes, renin‐angiotensin‐aldosterone system (RAAS) overactivation, insulin‐resistance, inflammation and ectopic lipid accumulation seem to play a major role. Despite albuminuria being commonly used for the non‐invasive evaluation of ORG, promising biomarkers of early kidney injury that are emerging, as well as new approaches with proteomics and metabolomics, might permit an earlier diagnosis of this disease. In addition, the assessment of ectopic kidney fat by renal imaging could be a useful tool to detect and evaluate the progression of ORG. Weight loss interventions appear to be effective in ORG, although large‐scale trials are needed. RAAS blockade has a renoprotective effect in patients with ORG, but even so, a significant proportion of patients with ORG will eventually progress to ESRD despite therapeutic efforts. It is noteworthy that certain antidiabetic agents such as sodium‐glucose cotransporter 2 inhibitors (SGLT2i) or glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) could be useful in the treatment of ORG through different pleiotropic effects. In this article, we review current approaches and future perspectives in the care and treatment of ORG.
Type 2 diabetes guidelines recommend glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and/or sodium-glucose co-transporter-2 inhibitors for people living with type 2 diabetes (PLWT2D) with an ...established or high risk of cardiovascular disease and/or renal disease, regardless of glycated haemoglobin (HbA1c) levels.1-3 Semaglutide is the first and only GLP-1 RA available for oral use. Despite its proven safety and efficacy in randomized clinical trials,4, 5 insights into its real-world use in clinical settings are needed.6We designed the ENDOcrinology Oral Sema Real-World Data (ENDO2S-RWD) study to evaluate the effectiveness, safety and tolerability of oral semaglutide in a large cohort of PLWT2D in Spain. We assessed the factors associated with the clinical response and drug persistence.
Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human ...studies have examined the health benefits of olive oils rich in these biophenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity.
Randomised, double-blind, crossover trial done in people aged 40–65 years with obesity (BMI 30–40 kg/m2) and prediabetes (HbA1c 5.7–6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No changes in diet or physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, glucose handling and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis.
A total of 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P = 0.041). Total antioxidant status increased and lipid and organic peroxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P < 0.05). Decreases in weight, BMI and blood glucose (p < 0.05) were found after treatment with EVOO and not with OO.
Treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes.
Summary
Nonalcoholic fatty liver disease (NAFLD) is increasing in parallel with the rising prevalence of obesity, leading to major health and socioeconomic consequences. To date, the most effective ...therapeutic approach for NAFLD is weight loss. Accordingly, bariatric surgery (BS), which produces marked reductions in body weight, is associated with significant histopathological improvements in advanced stages of NAFLD, such as nonalcoholic steatohepatitis (NASH) and liver fibrosis. BS is also associated with substantial taxonomical and functional alterations in gut microbiota, which are believed to play a significant role in metabolic improvement after BS. Interestingly, gut microbiota and related metabolites may be implicated in the pathogenesis of NAFLD through diverse mechanisms, including specific microbiome signatures, short chain fatty acid production or the modulation of one‐carbon metabolism. Moreover, emerging evidence highlights the potential association between gut microbiota changes after BS and NASH resolution. In this review, we summarize the current knowledge on the relationship between NAFLD severity and gut microbiota, as well as the role of the gut microbiome and related metabolites in NAFLD improvement after BS.
We demonstrate how resonant planar coils may be used as sensors to detect and quantify magnetic nanoparticles reliably. A coil's resonant frequency depends on the adjacent materials' magnetic ...permeability and electric permittivity. A small number of nanoparticles dispersed on a supporting matrix on top of a planar coil circuit may thus be quantified. Such nanoparticle detection has application detection to create new devices to assess biomedicine, food quality assurance, and environmental control challenges. We developed a mathematical model for the inductive sensor response at radio frequencies to obtain the nanoparticles' mass from the self-resonance frequency of the coil. In the model, the calibration parameters only depend on the refraction index of the material around the coil, not on the separate magnetic permeability and electric permittivity. The model compares favourably with three-dimensional electromagnetic simulations and independent experimental measurements. The sensor can be scaled and automated in portable devices to measure small quantities of nanoparticles at a low cost. The resonant sensor combined with the mathematical model is a significant improvement over simple inductive sensors, which operate at smaller frequencies and do not have the required sensitivity, and oscillator-based inductive sensors, which focus on just magnetic permeability.
Sensory factors may play an important role in the determination of appetite and food choices. Also, some adipokines may alter or predict the perception and pleasantness of specific odors. We aimed to ...analyze differences in smell-taste capacity between females with different weights and relate them with fat and fat-free mass, visceral fat, and several adipokines.
179 females with different weights (from low weight to morbid obesity) were studied. We analyzed the relation between fat, fat-free mass, visceral fat (indirectly estimated by bioelectrical impedance analysis with visceral fat rating (VFR)), leptin, adiponectin and visfatin. The smell and taste assessments were performed through the "Sniffin' Sticks" and "Taste Strips" respectively.
We found a lower score in the measurement of smell (TDI-score (Threshold, Discrimination and Identification)) in obese subjects. All the olfactory functions measured, such as threshold, discrimination, identification and the TDI-score, correlated negatively with age, body mass index (BMI), leptin, fat mass, fat-free mass and VFR. In a multiple linear regression model, VFR mainly predicted the TDI-score. With regard to the taste function measurements, the normal weight subjects showed a higher score of taste functions. However a tendency to decrease was observed in the groups with greater or lesser BMI. In a multiple linear regression model VFR and age mainly predicted the total taste scores.
We show for the first time that a reverse relationship exists between visceral fat and sensory signals, such as smell and taste, across a population with different body weight conditions.
Despite the abundance of registered clinical trials worldwide, the availability of effective drugs for obesity treatment is limited due to their associated side effects. Thus, there is growing ...interest in therapies that stimulate energy expenditure in white adipose tissue. Recently, we demonstrated that the delivery of a miR-21 mimic using JetPEI effectively inhibits weight gain in an obese mouse model by promoting metabolism, browning, and thermogenesis, suggesting the potential of miR-21 mimic as a treatment for obesity. Despite these promising results, the implementation of more advanced delivery system techniques for miR-21 mimic would greatly enhance the advancement of safe and efficient treatment approaches for individuals with obesity in the future. Our objective is to explore whether a new delivery system based on gold nanoparticles and Gemini surfactants (Au@16-ph-16) can replicate the favorable effects of the miR-21 mimic on weight gain, browning, and thermogenesis. We found that dosages as low as 0.2 μg miR-21 mimic /animal significantly inhibited weight gain and induced browning and thermogenic parameters. This was evidenced by the upregulation of specific genes and proteins associated with these processes, as well as the biogenesis of beige adipocytes and mitochondria. Significant increases in miR-21 levels were observed in adipose tissue but not in other tissue types. Our data indicates that Au@16-ph-16 could serve as an effective delivery system for miRNA mimics, suggesting its potential suitability for the development of future clinical treatments against obesity.
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•Au@16-ph-16 nanosystem conserved miR-21 mimic beneficial effects previously obtained with the JetPEI vehicle.•Au@16-ph-16/miR21 mimic resulted in approximately 7% reduction in body weight gain in a murine model of diet-induced obesity.•Au@16-ph-16/miR21 mimic induced browning and thermogenesis in inguinal and interscapular adipose tissues.•Au@16-ph-16 allowed a significant reduced dosage of the synthetic miR-21 mimic at a range of 0.2-0.3μg.•Au@16-ph-16/miR21 mimic increased significantly miR-21 levels in adipose tissues, without affecting non-adipose tissues.
The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included ...patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice.
We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group.
Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively).
FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.
The use of social assistive robots for interactive stimulation has strong potential in neurorehabilitation therapies. It is of particular interest in the case of pediatric patients to promote ...children’s motivation and adherence, specially when those robots are able of guide gamified activities, as it is the case of NAOTherapist. NAOTherapist is a Social Assistive Robotics (SAR) platform for hands-off rehabilitation based on upper-limb activities, that was originally designed for pediatric patients with Cerebral Palsy (CP) or Obstetric Braxial Plexus Palsy (OBPP). Formerly, it endowed the therapists with tools to perform rehabilitation exercises. This paper proposes the gamification of NAOTherapist in order to incorporate additional characteristics which allow its intensive use in new rehabilitation procedures, such as the Hand-Arm Bimanual Intensive Therapy (HABIT). This intensive therapy setting involves daily activities in several consecutive days, which require a strong engagement of the patients with the therapeutic methods and the acceptation of the NAOTherapist as a rehabilitation system. The gamified system shows very accurate results considering the different aspects defined in the USUS methodology; namely Usability, Social acceptance, User experience and Societal impact.
The productive application of motile microorganisms for degrading hydrophobic contaminants in soil is one of the most promising processes in modern remediation due to its sustainability and low cost. ...However, the incomplete biodegradation of the contaminants and the formation of the intermediary metabolites in the process may increase the toxicity in soil during bioremediation, and motile inoculants may mobilize the pollutants through biosorption. Therefore, controlling these factors should be a fundamental part of soil remediation approaches. The aim of this study was to evaluate the sources of risk associated with the cometabolism-based transformation of 14C-labeled pyrene by inoculated Pseudomonas putida G7 and identify ways to minimize risk. Our model scenario examined the increase in bioaccessibility to a distant source of contamination facilitated by sunflower (Helianthus annuus L.) roots. A biochar trap for mobilized pollutant metabolites and bacteria has also been employed. The experimental design consisted of pots filled with a layer of sand with 14C-labeled pyrene (88 mg kg−1) as a contamination focus located several centimeters from the inoculation point. Half of the pots included a biochar layer at the bottom. The pots were incubated in a greenhouse with sunflower plants and P. putida G7 bacteria. Pots with sunflower plants showed a higher biodegradation of pyrene, its mobilization as metabolites through the percolate and the roots, and bacterial mobilization toward the source of contamination, also resulting in increased pyrene transformation. In addition, the biochar layer efficiently reduced the concentrations of pyrene metabolites collected in the leachates. Therefore, the combination of plants, motile bacteria and biochar safely reduced the risk caused by the biological transformation of pyrene.
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•Sunflowers transform distantly located 14C-pyrene in soil.•Root-mediated bacterial mobilization facilitates cometabolism of this PAH.•Pyrene metabolites appeared in leachates and in plant tissues.•Biochar retained metabolites and reduced biotransformation risks.•This new scenario has implications for risk reduction during bioremediation.
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