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In Latin America, obesity rates are among the highest in the world. Currently, people with obesity (PWO) receive suboptimal care due to several challenges and barriers. The international ACTION-IO study aimed to identify perceptions, attitudes and behaviours of PWO and healthcare providers (HCP), and to assess potential barriers to effective obesity care. The aim of this subanalysis of the Chilean cohort was to compare their characteristics, perceptions, attitudes and behaviours according to the percentage of weight loss (lower weight loss [LWL; ≤10%] or higher weight loss [HWL; >10%] of basal weight). The ACTION-IO survey was completed by 1000 Chilean PWO and 200 HCPs. Mean age of PWO was 38 years (range 18-75); 62% were female. The majority had class I obesity. HWL subgroup represented 17.2% of all Chilean subset. Specific characteristics of patients with HWL were identified (higher educational level, lower proportion of class III obesity, preference for consulting obesity specialists, considering conversations with HCP as very helpful). HWL patients reported higher rates of favourable outcomes following HCP advice and a higher probability of attending scheduled follow-up visits. Certain demographic and behavioural variables (educational level, consultation to obesity specialists, adherence to HCP advice, follow-up scheduled visits and becoming aware of the obesity state) may identify PWO with a higher probability of a greater weight loss.

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CONTEXT: Primary aldosteronism (PA) represents 6% to 10% of all essential hypertension patients and is diagnosed using the aldosterone-to-renin ratio (ARR) and confirmatory studies. The complexity of PA diagnosis encourages the identification of novel PA biomarkers. Urinary extracellular vesicles (uEVs) are a potential source of biomarkers, considering that their cargo reflects the content of the parent cell. OBJECTIVE: We aimed to evaluate the proteome of uEVs from PA patients and identify potential biomarker candidates for PA. METHODS: Second morning spot urine was collected from healthy controls (n = 8) and PA patients (n = 7). The uEVs were isolated by ultracentrifugation and characterized. Proteomic analysis on uEVs was performed using LC-MS Orbitrap. RESULTS: Isolated uEVs carried extracellular vesicle markers, showed a round shape and sizes between 50 and 150 nm. The concentration of uEVs showed a direct correlation with urinary creatinine (r = 0.6357; P = 0.0128). The uEV size mean (167 ±â€…6 vs 183 ±â€…4nm) and mode (137 ±â€…7 vs 171 ±â€…11nm) was significantly smaller in PA patients than in control subjects, but similar in concentration. Proteomic analysis of uEVs from PA patients identified an upregulation of alpha-1-acid glycoprotein 1 (AGP1) in PA uEVs, which was confirmed using immunoblot. A receiver operating characteristic curve analysis showed an area under the curve of 0.92 (0.82 to 1; P = 0.0055). CONCLUSION: Proteomic and further immunoblot analyses of uEVs highlights AGP1 as potential biomarker for PA.

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BACKGROUND: The "nonclassic" apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. This phenotype is characterized by low plasma renin activity (PRA), high serum cortisol (F) to cortisone (E) ratio, low cortisone, high Fractional Excretion of potassium (FEK) and normal-elevated systolic blood pressure (SBP). An early detection and/or identification of novel biomarkers of this phenotype could avoid the progression or future complications leading to arterial hypertension. Isolation of extracellular vesicles, such as exosomes, in specific biofluids support the identification of tissue-specific RNA and miRNA, which may be useful as novel biomarkers. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype. METHODS: We perform a cross-sectional study in a primary care cohort of 127 Chilean subjects. We measured BP, serum cortisol, cortisone, aldosterone, PRA. According to the previous reported, a subgroup of subjects was classified as NC-AME (n = 10). Urinary exosomes were isolated and miRNA cargo was sequenced by Illumina-NextSeq-500. RESULTS: We found that NC-AME subjects had lower cortisone (p < 0.0001), higher F/E ratio (p < 0.0001), lower serum potassium (p = 0.009) and higher FEK 24 h (p = 0.03) than controls. We found miR-204-5p (fold-change = 0.115; p 0.001) and miR-192-5p (fold-change = 0.246; p 0.03) are both significantly downregulated in NC-AME. miR-192-5p expression was correlated with PRA (r = 0.45; p 0.028) and miR-204-5p expression with SBP (r = - 0.48, p 0.027) and F/E ratio (r = - 0.48; p 0.026). CONCLUSIONS: These findings could support a potential role of these miRNAs as regulators and novel biomarkers of the NC-AME phenotype.

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Energy advancement and innovation have generated several challenges for large modernized cities, such as the increase in energy demand, causing the appearance of the small power grid with a local source of supply, called the Microgrid. A Microgrid operates either connected to the national centralized power grid or singly, as a power island mode. Microgrids address these challenges using sensing technologies and Fog-Cloudcomputing infrastructures for building smart electrical grids. A smart Microgrid can be used to minimize the power demand problem, but this solution needs to be implemented correctly so as not to increase the amount of data being generated. Thus, this paper proposes the use of Fog computing to help control power demand and manage power production by eliminating the high volume of data being passed to the Cloud and decreasing the requests' response time. The GridLab-d simulator was used to create a Microgrid, where it is possible to exchange information between consumers and generators. Thus, to understand the potential of the Fog in this scenario, a performance evaluation is performed to verify how factors such as residence number, optimization algorithms, appliance shifting, and energy sources may influence the response time and resource usage.

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BACKGROUND: Aldosterone has been linked with obesity, metabolic syndrome (MetS), pro-inflammatory, and prothrombotic states; however, most studies relate these indicators with primary aldosteronism (PA), excluding non-PA patients. OBJECTIVE: To determine whether aldosterone, renin, or the plasma aldosterone/renin ratio (ARR) are associated with metabolic disorders and inflammatory/vascular biomarkers in a non-PA population. METHODS: We studied 275 patients including adolescents and adults of both genders and measured plasma and urinary aldosterone and determined the plasma renin activity. In all subjects, the presence of MetS was determined according to Adult Treatment Panel III. Renal, vascular, inflammatory, and mineralocorticoid activity biomarkers were evaluated. RESULTS: The ARR correlated with the number of variables of MetS (r = 0.191, P = 0.002), body mass index (BMI; r = 0.136, P = 0.026), systolic blood pressure (r = 0.183, P = 0.002), diastolic blood pressure (r = 0.1917, P = 0.0014), potassium excreted fraction (r = 0.174, P = 0.004), low-density lipoprotein (r = 0.156, P = 0.01), plasminogen activator inhibitor type 1 (r = 0.158, P = 0.009), microalbuminuria (r = 0.136, P = 0.029), and leptin (r = 0.142, P = 0.019). In a linear regression model adjusted by age, BMI, and gender, only the ARR was still significant (r = 0.108, P = 0.05). In a logistic regression analysis, the ARR predicted MetS index (odds ratio (OR) = 1.07 [95% confidence interval (CI) = 1.011-1.131], P= 0.02) even after adjusting for age, BMI, and gender. On the other hand, aldosterone showed no association with MetS or inflammatory markers. CONCLUSION: These results suggest a continuum of cardiometabolic risk beyond the classic PA threshold screening. The ARR could be a more sensitive marker of obesity, MetS, and endothelial damage in non-PA patients than aldosterone or renin alone. Prospective studies are needed to develop future screening cutoff values.

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About 15% of the essential hypertensive patients would have a low activity of the 11ßHSD2 enzyme, which inactivates cortisol (F) to cortisone (E). Gene expression can be negatively regulated by miRNA. Urinary exosomes and their specific content (miRNA/proteins) represent a valuable tool as a biomarker for the diagnosis and prognosis of the disease. Aim: To evaluate the expression of miRNA specific for 11ßHSD2 in samples of urinary exosomes and to determine its association with biochemical variables associated with mineralocorticoid metabolism. Subjects and Methods: Cross-sectional study in subjects between 10-60 years. They were classified into subjects with high F/E (> p75) and low cortisone (< p25) and control subjects. The urinary exosomes were isolated with the Invitrogen kit. Bioinformatic analysis was performed with Mir Walk to identify specific miRNAs of HSD11B2. The expression of miRNA was evaluated by qRT PCR. The comparisons were made with the Mann-Whitney test. Results: 7.1% of the subjects are suggestive of a partial deficiency of 11ßHSD2 (NC-AME). The expression of miR-488 was higher in NC-AME than in controls (5839 ± 1719 vs 3,437 ± 2,581; p = 0.01). We found positive associations between mir-615 and ARP; miR-488 and the sodium/potassium ratio; miR-1205 with age and urinary sodium excretion; miR-494 with age, activity MMP9 and NGAL. Conclusion: We identified high expression of miR488 in NC-AME subjects and associations of miRNAs with biochemical variables associated with mineralocorticoid metabolism. Thus, exosomes and their miRNA content could be potential regulators and biomarkers of 11ßHSD2 activity.

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Arterial hypertension (AHT) currently affects approximately 40% of adults worldwide, and its pathological mechanisms are mainly related to renal, vascular, and endocrine systems. Steroid hormones as aldosterone and cortisol are highly relevant to human endocrine physiology, and also to endocrine hypertension. Pathophysiological conditions, such as primary aldosteronism, affect approximately 10% of patients diagnosed with AHT and are secondary to a high production of aldosterone, increasing the risk also for cardiovascular damage and heart diseases. Excess of aldosterone or cortisol increases the activity of the mineralocorticoid receptor (MR) in epithelial and non-epithelial cells. Current research in this field highlights the potential regulatory mechanisms of the MR pathway, including pre-receptor regulation of the MR (action of 11BHSD2), MR activating proteins, and the downstream genes/proteins sensitive to MR (e.g., epithelial sodium channel, NCC, NKCC2). Mineralocorticoid AHT is present in 15-20% of hypertensive subjects, but the mechanisms associated to this condition have been poorly described, due mainly to the absence of reliable biomarkers. In this way, steroids, peptides, and lately urinary exosomes are thought to be potential reporters of biological processes. This review highlight exosomes and their cargo as potential biomarkers of metabolic changes associated to mineralocorticoid AHT. Recent reports have shown the presence of RNA, microRNAs, and proteins in urinary exosomes, which could be used as biomarkers in physiological and pathophysiological conditions. However, more studies are needed in order to benefit from exosomes and the exosomal cargo as a diagnostic tool in mineralocorticoid AHT.

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Nitric oxide plays several roles in cellular physiology, including control of the vascular tone and defence against pathogen infection. Neuronal, inducible and endothelial nitric oxide synthase (NOS) isoforms synthesize nitric oxide. Cells generate acid and base equivalents, whose physiological intracellular concentrations are kept due to membrane transport systems, including Na+ /H+ exchangers and Na+ /HCO3- transporters, thus maintaining a physiological pH at the intracellular (~7.0) and extracellular (~7.4) medium. In several pathologies, including cancer, cells are exposed to an extracellular acidic microenvironment, and the role for these membrane transport mechanisms in this phenomenon is likely. As altered NOS expression and activity is seen in cancer cells and because this gas promotes a glycolytic phenotype leading to extracellular acidosis in gynaecological cancer cells, a pro-inflammatory microenvironment increasing inducible NOS expression in this cell type is feasible. However, whether abnormal control of intracellular and extracellular pH by cancer cells regards with their ability to synthesize or respond to nitric oxide is unknown. We, here, discuss a potential link between pH alterations, pH controlling membrane transport systems and NOS function. We propose a potential association between inducible NOS induction and Na+ /H+ exchanger expression and activity in human ovary cancer. A potentiation between nitric oxide generation and the maintenance of a low extracellular pH (i.e. acidic) is proposed to establish a sequence of events in ovarian cancer cells, thus preserving a pro-proliferative acidic tumour extracellular microenvironment. We suggest that pharmacological therapeutic targeting of Na+ /H+ exchangers and inducible NOS may have benefits in human epithelial ovarian cancer.

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The placenta is a vital organ whose function in diseases of pregnancy is altered, resulting in an abnormal supply of nutrients to the foetus. The lack of placental vasculature homeostasis regulation causes endothelial dysfunction and altered vascular reactivity. The proper distribution of acid- (protons (H(+))) and base-equivalents through the placenta is essential to achieve physiological homeostasis. Several membrane transport mechanisms that control H(+) distribution between the extracellular and intracellular spaces are expressed in the human placenta vascular endothelium and syncytiotrophoblast, including sodium (Na(+))/H(+) exchangers (NHEs). One member of the NHEs family is NHE isoform 1 (NHE1), whose activity results in an alkaline intracellular pH (high intracellular pH (pHi)) and an acidic extracellular pH (pHo). Increased NHE1 expression, maximal transport activity, and turnover are reported in human syncytiotrophoblasts and lymphocytes from patients with diabetes mellitus type I (DMT1), and a positive correlation between NHEs activity and plasma factors, such as that between thrombin and platelet factor 3, has been reported in diabetes mellitus type II (DMT2). However, gestational diabetes mellitus (GDM) could result in a higher sensitivity of the human placenta to acidic pHo. We summarized the findings on pHi and pHo modulation in the human placenta with an emphasis on pregnancies in which the mother diagnosed with diabetes mellitus. A potential role of NHEs, particularly NHE1, is proposed regarding placental dysfunction in DMT1, DMT2, and GDM.

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Preeclampsia (PE), gestational diabetes mellitus (GDM), and maternal supraphysiological hypercholesterolaemia (MSPH) are pregnancy-related conditions that cause metabolic disruptions leading to alterations of the mother, fetus and neonate health. These syndromes result in fetoplacental vascular dysfunction, where nitric oxide (NO) plays a crucial role. PE characterizes by abnormal increase in the placental blood pressure and a negative correlation between NO level and fetal weight, suggesting that increased NO level and oxidative stress could be involved. GDM courses with macrosomia along with altered function of the fetal cardiovascular system and fetoplacental vasculature. Even when NO synthesis in the fetoplacental vasculature is increased, NO bioavailability is reduced due to the higher oxidative stress seen in this disease. In MSPH, there is an early development of atherosclerotic lesions in fetal and newborn arteries, altered function of the fetoplacental vasculature, and higher markers of oxidative stress in fetal blood and placenta, thus, vascular alterations related with NO metabolism occur as a consequence of this syndrome. Potential mechanisms of altered NO synthesis and bioavailability result from transcriptional and post-translational NO synthases (NOS) modulation, including phosphorylation/dephosphorylation cycles, coupling/uncoupling of NOS, tetrahydrobiopterin bioavailability, calcium/calmodulin-NOS and caveolin-1-NOS interaction. Additionally, oxidative stress also plays a role in the reduced NO bioavailability. This review summarizes the available information regarding lower NO bioavailability in these pregnancy pathologies. A common NO-dependent mechanism in PE, GDM and MSPH contributing to fetoplacental endothelial dysfunction is described.

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