Adipose Tissue Dysfunction and the Role of Adipocyte-Derived Extracellular Vesicles in Obesity and Metabolic Syndrome.

Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.

The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor.

Blood pressure (BP) regulation is a complex process involving various hormones, including aldosterone and its mineralocorticoid receptor. Mineralocorticoid receptor is expressed in several tissues, including the kidney, and plays a crucial role in regulating BP by controlling the sodium and water balance. During different stages of life, hormonal changes can affect mineralocorticoid receptor activity and aldosterone levels, leading to changes in BP. Increasing evidence suggests that sex steroids modulate aldosterone levels. Estrogens, particularly estradiol, mediate aldosterone biosynthesis by activating classical estrogen receptors and the G protein-coupled receptor. Progesterone acts as an anti-mineralocorticoid by inhibiting the binding of aldosterone to the mineralocorticoid receptor. Moreover, progesterone inhibits aldosterone synthase enzymes. The effect of testosterone on aldosterone synthesis is still a subject of debate. However, certain studies show that testosterone downregulates the mRNA levels of aldosterone synthase, leading to decreased plasma aldosterone levels.

Low Cortisone as a Novel Predictor of the Low-Renin Phenotype.

A large proportion of patients with low-renin hypertension (LRH) correspond to primary aldosteronism (PA). However, some of these subjects have low to normal aldosterone. Since low renin is driven by excessive mineralocorticoids or glucocorticoids acting on mineralocorticoid receptors (MRs), we hypothesize that a low-cortisone condition, associated classically with 11ßHSD2 deficiency, is a proxy of chronic MR activation by cortisol, which can also lead to low renin, elevated blood pressure, and renal and vascular alterations. Objective: To evaluate low cortisone as a predictor of low renin activity and its association with parameters of kidney and vascular damage. Methods: A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low plasma renin activity (<1 ng/mL × hours) and low cortisone (<25th percentile). Results: Plasma renin activity was associated with aldosterone (r = 0.36; P < .001) and cortisone (r = 0.22; P = .001). A binary logistic regression analysis showed that serum cortisone per ug/dL increase predicted the low-renin phenotype (OR 0.4, 95% CI 0.21-0.78). The receiver operating characteristic curves for cortisone showed an area under the curve of 0.6 to discriminate subjects with low renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium (P < .05). Conclusion: This is the first study showing that low cortisone is a predictor of a low-renin condition. Low cortisone also predicted surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the aldosterone-renin ratio calculation.

Academic stress in college students: descriptive analyses and scoring of the SISCO-II inventory.

In a competitive and demanding world, academic stress is of increasing concern to students. This systemic, adaptive, and psychological process is composed of stressful stimuli, imbalance symptoms, and coping strategies. The SISCO-II Academic Stress Inventory (SISCO-II-AS) is a psychometric instrument validated in Chile. It evaluates stressors, symptoms, and coping, both individually and globally. For its practical interpretation, a scale is required. Therefore, this study aims to descriptively analyze the SISCO-II-AS and to obtain its corresponding scales. Employing a non-experimental quantitative approach, we administered the SISCO-II-AS to 1,049 second and third-year students from three Chilean universities, with a disproportionate gender representation of 75.21% female to 24.79% male participants. Through descriptive and bivariate analysis, we established norms based on percentiles. For the complete instrument and its subscales, significant differences by sex were identified, with magnitudes varying from small to moderate. For the full instrument and its subscales, bar scale norms by percentile and sex are presented. Each subscale (stressors, physical and psychological reactions, social behavioural reactions, total reaction, and coping) has score ranges defined for low, medium, and high levels. These ranges vary according to the sex of the respondent, with notable differences in stressors and physical, psychological, and social behavioural reactions. This study stands out for its broad and heterogeneous sample, which enriches the representativeness of the data. It offers a comprehensive view of academic stress in college students, identifying distinctive factors and highlighting the importance of gender-sensitive approaches. Its findings contribute to understanding and guide future interventions. By offering a descriptive analysis of the SISCO-II-AS inventory and establishing bar norms, this research aids health professionals and educators in better assessing and addressing academic stress in the student population.

Yeast diversity in open agave fermentations across Mexico.

Yeasts are a diverse group of fungal microorganisms that are widely used to produce fermented foods and beverages. In Mexico, open fermentations are used to obtain spirits from agave plants. Despite the prevalence of this traditional practice throughout the country, yeasts have only been isolated and studied from a limited number of distilleries. To systematically describe the diversity of yeast species from open agave fermentations, here we generate the YMX-1.0 culture collection by isolating 4524 strains from 68 sites with diverse climatic, geographical, and biological contexts. We used MALDI-TOF mass spectrometry for taxonomic classification and validated a subset of the strains by ITS and D1/D2 sequencing, which also revealed two potential novel species of Saccharomycetales. Overall, the composition of yeast communities was weakly associated with local variables and types of climate, yet a core set of six species was consistently isolated from most producing regions. To explore the intraspecific variation of the yeasts from agave fermentations, we sequenced the genomes of four isolates of the nonconventional yeast Kazachstania humilis. The genomes of these four strains were substantially distinct from a European isolate of the same species, suggesting that they may belong to different populations. Our work contributes to the understanding and conservation of an open fermentation system of great cultural and economic importance, providing a valuable resource to study the biology and genetic diversity of microorganisms living at the interface of natural and human-associated environments.

Increased academic stress is associated with decreased plasma BDNF in Chilean college students.

Introduction: Academic stress (AS) is a prevalent challenge faced by university students, potentially affecting molecular indicators such as brain-derived neurotrophic factor (BDNF) and global DNA methylation (G-DNA-M). These indicators could illuminate the physiological ramifications of academic stress. Study Design and Methods: This research followed a quantitative, non-experimental, longitudinal panel design spanning two academic semesters, observing phenomena in their natural context. Students from the Medical Technology program at Universidad de Concepción, Chile were involved, with assessments at the beginning and during heightened academic stress periods. Sample: Of the total participants, 63.0% were females, with an average age of 21.14 years at baseline, and 36.92% were males, averaging 21.36 years. By the study's conclusion, female participants averaged 21.95 years, and males 22.13 years. Results: Significant differences were observed between initial and final assessments for the SISCO-II Inventory of Academic Stress and Beck Depression Inventory-II, notably in stressor scores, and physical, and psychological reactions. Gender differences emerged in the final physical and psychological reactions. No significant changes were detected between the two assessments in plasma BDNF or G-DNA-M values. A refined predictive model showcased that, on average, there was a 3.56% decrease in females' plasma BDNF at the final assessment and a 17.14% decrease in males. In the sample, the G-DNA-M percentage at the final assessment increased by 15.06% from the baseline for females and 18.96% for males. Conclusions: The study underscores the physiological impact of academic stress on university students, evidenced by changes in markers like BDNF and G-DNA-M. These findings offer an in-depth understanding of the intricate mechanisms regulating academic stress responses and highlight the need for interventions tailored to mitigate its physiological and psychological effects.

Interaction of Val66Met BDNF and 5-HTTLPR polymorphisms with prevalence of post-earthquake 27-F PTSD in Chilean population.

Post-traumatic stress (PTSD) disorder is a mental health condition that can occur after experiencing or witnessing a traumatic event. The 27-F earthquake that struck Chile in 2010 was one such event that had a significant impact on the mental health of the population. A study was conducted to investigate the prevalence of PTSD and its associated factors among survivors of this earthquake. The study was a longitudinal design, involving a sample of 913 patients aged 18 to 75 years who attended 10 Primary Care Centers in Concepción, Chile. The Composite International Diagnostic Interview (CIDI) was used to assess both depressive episodes (DE) and PTSD before and after the earthquake. The study also involved genotyping studies using saliva samples from the participants, specifically focusing on the Val66Met and 5-HTTLPR polymorphisms. Statistical analysis was performed to examine the association between different variables and the presence of PTSD. These variables included demographic factors, family history of psychiatric disorders, DE, childhood maltreatment experiences, and critical traumatic events related to the earthquake. The results showed that the incidence of post-earthquake PTSD was 11.06%. No significant differences were found between the groups of participants who developed post-earthquake PTSD regarding the Val66Met or 5-HTTLPR polymorphisms. However, a significant association was found between the concomitant diagnosis of DE and the development of post-earthquake PTSD. The presence of DE doubled the risk of developing post-earthquake PTSD. The number of traumatic events experienced also had a statistically significant association with an increased risk of developing post-earthquake PTSD. The study's limitations include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. In conclusion, the study found that PTSD following the 27-F earthquake in Chile was associated with a concomitant diagnosis of DE and the number of traumatic events experienced. The study did not find a significant association between PTSD and the Val66Met or 5-HTTLPR polymorphisms. The researchers recommend that mental health professionals should prioritize the detection and treatment of concomitant depressive episodes and exposure to critical traumatic events in survivors of disasters. They also suggest that further research is needed to better understand the relationship between genetic factors and post-disaster PTSD.

mHealth Monitoring of Treatment of Cutaneous Leishmaniasis Patients: A Community-Based Implementation Study.

Cutaneous leishmaniasis (CL) remains a global health problem. Compelled by the protracted healing process, initial and final outcomes of treatment are determined at 90 and 180 days, respectively, after initiation of treatment. Loss to follow-up during these intervals is substantial. Consequently, the effectiveness of treatment is largely unknown. We conducted an effectiveness-implementation hybrid design study of a community-based mobile health (mHealth) strategy to monitor adherence to anti-leishmanial treatment, adverse drug reactions, and therapeutic response compared with standard of care in two rural communities of Colombia. Three implementation outcomes were evaluated: usability and acceptability by qualitative methods and fidelity using quantitative methods. Fifty-seven patients were prospectively included in the mHealth intervention and 48 in the standard-of-care group. In addition, 24 community health leaders (CHLs), health workers, and patients participated in qualitative evaluations. The intervention significantly increased the proportion of patients having follow-up of therapeutic outcomes 90 and 180 days after initiating treatment from 4.2% (standard of care) to 82.5% (intervention), P < 0.001. The proportion of patients having records of treatment adherence, adverse drug reactions, and therapeutic response also increased significantly (P < 0.001). Fidelity to the intervention (recording of treatment adherence, adverse drug reactions, lesion photographs, and evaluation of therapeutic response) was 70-100%. The app was highly accepted by CHLs, health workers, and patients, who perceived that the app improved case identification and follow-up and met a public health need. Although usability was high, low connectivity affected real-time transmission of data. This community-based mHealth strategy facilitated access to health care for CL in rural areas and knowledge of treatment effectiveness.

Osteopathic Manipulation as a Method of Cortisol Modification: A Systematic Review.

The effectiveness of osteopathic manipulative treatment (OMT) in the modification of various hormones has been studied; however, there is still a need for quantitative measurements to determine how large of an influence exists. The goal of this meta-analysis is to investigate the implications OMT has on cortisol levels. A systematic literature search restricted to English was performed from October 2022 to November 2022 using Google Scholar, OSTMED.DR, and PubMed and included articles from 2000 onward. Articles were excluded if they did not include a measurement for the control group in their study. We identified 4120 studies for potential inclusion. Of these, a total of four studies met the inclusion criteria, with a total of 135 participants (N= 68 OMT, N= 67 control). Out of the 135 participants, 126 participants (N= 62 OMT, N= 64 control) made up the salivary cortisol studies, and the remaining nine participants made up the serum cortisol studies (OMT N= 6, control N= 3). The National Institutes of Health (NIH) bias assessment tool was utilized to measure the risk of bias. Standard mean differences were calculated for effect size. A mean difference in cortisol of 0.10µg/dl (-10µg/dl, 95%CI -0.15, -0.04) was found when comparing all pre- versus post-cortisol levels with OMT versus sham control groups. OMT demonstrated a 0.10µg/dl larger decrease in cortisol than sham control treatments. The standard mean difference was found to be -0.46 (95%CI -1.40, 0.48) making this finding a medium effect size without significance. Heterogeneity for the salivary analysis measured by I2 was 0% indicating no significant heterogeneity across studies. When serum cortisol was included, heterogeneity stayed at 0%. A larger number of high-quality studies, especially those specific to serum cortisol, are recommended, to elucidate the relationship between OMT and cortisol. This research suggests OMT reduces cortisol more than sham treatment before versus after OMT treatment, and though the change is small when comparing after one treatment, it may have clinical usage if multiple OMT sessions are performed.

Peripheral brain-derived neurotrophic factor (BDNF) and salivary cortisol levels in college students with different levels of academic stress. Study protocol.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) is essential for brain physiological processes influencing memory and learning. BDNF levels can be affected by many factors, including stress. Stress increase serum and salivary cortisol levels. Academic stress is of the chronic type. BDNF levels can be measure from serum, plasma or platelets, and there is still no standard methodology, which is relevant to ensure reproducibility and comparability between studies. HYPOTHESIS: (i) BDNF concentrations in serum show greater variability than in plasma. (ii) In college students with academic stress, peripheral BDNF decreases and salivary cortisol increases. GENERAL OBJECTIVE: To standardize plasma and serum collection for BDNF levels and to determine whether academic stress affects peripheral BDNF and salivary cortisol levels. DESIGN: Quantitative research, with a non-experimental cross-sectional descriptive design. PARTICIPANTS: Student volunteers. Under convenience sampling, 20 individuals will be included for standardization of plasma and serum collection and between 70 and 80 individuals to determine the effect of academic stress on BDNF and salivary cortisol. PERIPHERAL BLOOD AND SALIVARY CORTISOL SAMPLING, MEASUREMENTS: 12 mL of peripheral blood (with and without anticoagulant) will be drawn per participant, separated from plasma or serum and cryopreserved at -80°C. Additionally, they will be instructed in the collection of 1 mL of saliva samples, which will be centrifuged. Val66Met polymorphism will be performed by allele-specific PCR, while BDNF and salivary cortisol levels will be determined by ELISA. STATISTICAL ANALYSIS: (i) descriptive analysis of the variables, through measures of central tendency and dispersion, and the categorical variables through their frequency and percentage. (ii) Then a bivariate analysis will be performed comparing groups using each variable separately. EXPECTED RESULTS: We expect to (i) determine the analytical factors that allow a better reproducibility in the measurement of peripheral BDNF, and (ii) the effect of academic stress on BDNF and salivary cortisol levels.

Aging in nucleus accumbens and its impact on alcohol use disorders.

Ethanol is one of the most widely consumed drugs in the world and prolonged excessive ethanol intake might lead to alcohol use disorders (AUDs), which are characterized by neuroadaptations in different brain regions, such as in the reward circuitry. In addition, the global population is aging, and it appears that they are increasing their ethanol consumption. Although research involving the effects of alcohol in aging subjects is limited, differential effects have been described. For example, studies in human subjects show that older adults perform worse in tests assessing working memory, attention, and cognition as compared to younger adults. Interestingly, in the field of the neurobiological basis of ethanol actions, there is a significant dichotomy between what we know about the effects of ethanol on neurochemical targets in young animals and how it might affect them in the aging brain. To be able to understand the distinct effects of ethanol in the aging brain, the following questions need to be answered: (1) How does physiological aging impact the function of an ethanol-relevant region (e.g., the nucleus accumbens)? and (2) How does ethanol affect these neurobiological systems in the aged brain? This review discusses the available data to try to understand how aging affects the nucleus accumbens (nAc) and its neurochemical response to alcohol. The data show that there is little information on the effects of ethanol in aged mice and rats, and that many studies had considered 2-3-month-old mice as adults, which needs to be reconsidered since more recent literature defines 6 months as young adults and >18 months as an older mouse. Considering the actual relevance of an aged worldwide population and that this segment is drinking more frequently, it appears at least reasonable to explore how ethanol affects the brain in adult and aged models.

Inguinal Intranodal Lymphangioma in an Adult: A Clinical Case Report.

Lymphangiomas are benign deformities of the lymphatic system that are most common in pediatric populations and are usually found in the neck, axilla, chest wall, cervicofacial, and pelvic regions, as they are areas with more lymphatic activity. Herein, we report the case of a 43-year-old African-American male who presented with bilateral inguinal lymphangiomas, the first documented incidence of its kind. This patient presented with several months of bilateral swellings in his groin area, accompanied by increased tenderness and discomfort. A physical exam revealed that the left groin swelling was larger than the right groin swelling and that the left lymph node was about < 2 cm in size. Bilaterally, there was no tenderness of the lymph nodes in the area and no skin changes, ulceration, induration, discharge, or bleeding from the site. The diagnostic assessment included ultrasound, a left inguinal lymphadenectomy, and a frozen section biopsy to provide a definitive diagnosis. The pathology report described the lesion as a benign lymphangioma and was negative for lymphoproliferative lesions.

Sensitivity and Specificity of the Remote Evaluation of Therapeutic Response in Cutaneous Leishmaniasis Using Photographs from a Mobile Application.

Cutaneous leishmaniasis (CL) primarily affects people in remote settings with limited access to health services. mHealth tools offer an opportunity to overcome knowledge gaps about clinical response to treatment. We evaluated the validity of the Guaral+ST mobile application for the remote assessment of therapeutic response in patients with CL, through photographs of lesions captured with the app by community health volunteers. Patients with confirmed CL were followed at weeks 13 and 26 after completion of treatment to assess therapeutic response in two clinical settings in southwest Colombia. Direct evaluation of lesions performed by an experienced physician was considered the reference standard. Photographs of lesions taken by CHV or nurse assistants with the mobile app, were independently evaluated by three physicians to define clinical response. A summary measure of clinical outcome defined by the three physicians was considered the index test. Sensitivity, specificity, and positive and negative predictive values were estimated. Interrater reliability (kappa) was calculated. Among 53 participants with CL who had at least one follow-up visit, the sensitivity of therapeutic response evaluation through photographs taken with the Guaral+ST app, compared with direct evaluation by an expert physician, had high validity with sensitivity of 100% (95% confidence interval: 80.5-100%) and specificity of 97.2% (95% confidence interval: 85.5-99.9%). The chance-adjusted agreement (κ) was > 0.8, which is conventionally characterized as almost perfect. The high accuracy of the remote evaluation of photographs for the assessment of therapeutic response supports the use of mHealth tools for improving access to treatment follow-up for CL.

Inventario SISCO del estrés académico: revisión de sus propiedades psicométricas en estudiantes universitarios / SISCO inventory of academic stress: review of its psychometric properties in university students

Resumen: Los estudios superiores representan el punto culminante del estrés académico, proceso multifactorial complejo, con alta carga de trabajo. El inventario SISCO del estrés académico posee buenas propiedades psicométricas para sus subescalas de Estresores, Sintomatología y para la puntuación media total, no así para la subescala de Afrontamiento. El objetivo de este artículo es corroborar lo reportado previamente en base a un análisis psicométrico completo. En 1126 estudiantes universitarios, se obtuvieron buenas propiedades psicométricas para las subescalas de Estresores y Sintomatología, con un buen ajuste en el análisis factorial confirmatorio, en base a una estructura de cuatro factores. La subescala de Sintomatología quedó conformada por las subescalas Reacciones físicas y psicológicas y por Reacciones del comportamiento social. La subescala de Afrontamiento mantiene propiedades psicométricas deficientes. La puntuación para el total de los ítems del instrumento muestra buenas propiedades psicométricas (alfa de Cronbach y omega de 0.820 y 0.860, respectivamente). Se corrobora lo reportado previamente, avalándose la necesidad de más estudios, y la modificación del instrumento, en especial la subescala de Afrontamiento.

Abstract: Higher education represents the peak of academic stress, a complex multifactorial process with a high workload. The SISCO academic stress inventory has good psychometric properties for its subscales Stressors, Symptomatology and for the whole instrument, but not for the Coping subscale. The aim of this paper is to corroborate previous reports based on a full psychometric analysis. In 1,126 university students, good psychometric properties were obtained for the Stressors and Symptomatology subscales, with a good fit in the confirmatory factor analysis, based on a four-factor structure. The Symptomatology subscale consisted of the subscales Physical and Psychological Reactions and Social Behavioural Reactions. The Coping subscale maintains poor psychometric properties. The complete scale score shows good psychometric properties (Cronbach's alpha and omega of 0.820 and 0.860, respectively). This corroborates previous reports and supports the need for further study and modification of the instrument, especially the Coping subscale.

Clinical, biochemical, and miRNA profile of subjects with positive screening of primary aldosteronism and nonclassic apparent mineralocorticoid excess.

Primary aldosteronism (PA) and nonclassic apparent mineralocorticoid excess (NCAME) have been recognized as endocrine-related conditions having a broad clinical-biochemical spectrum, spanning from normotension to severe arterial hypertension (AHT). However, the coexistence of both phenotypes have not been reported to date. AIM: To identify and characterize clinical and biochemical parameters of subjects with both PA and NCAME conditions (NCAME&PA) and study the miRNA cargo in their urinary extracellular vesicles as potential biomarkers for this novel condition. METHODS: We performed a cross-sectional study of 206 Chilean adult subjects from a primary care cohort. We measured blood pressure (BP), cortisol (F), cortisone (E), aldosterone, plasma renin activity (PRA), microalbuminuria (MAC), plasma NGAL, MMP9, fractional-potassium-excretion (FEK). Subjects were classified as NCAME&PA, PA, NCAME, essential hypertensives (EH), or healthy controls (CTL). EV-miRNAs were quantified by Taqman-qPCR. RESULTS: We found that 30.6% subjects had an abnormal endocrine phenotype: NCAME&PA (6.8%), PA (11.2%) or NCAME (12.6%), and the prevalence of AHT was 92.9%, 82.6%, and 65%, respectively. NCAME&PA subjects had both lower cortisone (p < 0.05) and lower PRA (p < 0.0001), higher FEK (p = 0.02) and higher MAC (p = 0.01) than EH or CTL. NCAME&PA subjects had also higher NGAL levels than CTL and PA (p < 0.05). Exosome miR-192, miR-133a and miR-21 expression decreased with phenotype severity and correlated with BP and PRA (p < 0.05). CONCLUSION: We identified adult subjects with a combined condition of NCAME and PA associated with higher BP, increased renal and endothelial damage markers than control and EH. Additionally, we observed a differential expression of a specific miRNAs, suggesting a potential role of these miRNAs associated to this novel combined phenotype.

Modeling the interaction of polymeric nanoparticles functionalized with cell penetrating peptides at the nano-bio interface.

The interaction of nanoparticles with Caco-2 monolayers in cell culture underpins our predictions of the uptake of nanoformulations in vivo for drug delivery. Cell-penetrating peptides (CPP), such as oligoarginine, are currently of interest to enhance cellular uptake of bioactives and nanoparticles. This paper assesses the cellular association of poly(ethyl-cyanoacrylate) nanoparticles functionalized with di-arginine-histidine (RRH) in a Caco-2 cell model. We applied a computational model of particokinetics, In vitro Sedimentation, Diffusion and Dosimetry (ISDD) to predict the accumulation of nanoparticles on the cell surface. An important finding is that the proportion of nanoparticles associated with cells was less than 5 %. This has important implications for interpreting nanoparticle uptake in vitro. RRH-decoration does not appear to alter nanoparticle deposition, but increases association of nanoparticles with Caco-2 cells. Immediate deposition of nanoparticles on the cell surface was apparent and similar between formulations, but underestimated by the ISDD model. Key to understanding the nano-bio interface for drug delivery, nanoparticles that reach the cells were not necessarily absorbed by them, but can become detached. This variable of nanoparticle release from cells was incorporated into a new mathematical model presented here.

Cortisol resistance in the degu (Octodon degus).

Cortisol resistance has also been reported in the degu, Octodon degus, a New World hystricomorph endemic to central Chile. The degu is used as a model for studies of stress and diurnal rhythms, parental behaviour and female masculinization. Another New World hystricomorph, the guinea pig, also exhibits glucocorticoid resistance, a result of amino acid sequences that differ from other mammalian glucocorticoid receptors (GR). Mutations in the ligand-binding domain of the human GR have been identified in familial or sporadic generalised cortisol resistance as have variants in the guinea pig. To address the possibility that the high levels of cortisol observed in the degu are a result of the same or similar sequence variations observed in the guinea pig GR, we have cloned, expressed and characterised the ligand-binding domain (LBD) of the degu GR. Somewhat unexpectedly, neither the amino acids nor the region involved in the resistance observed in the guinea pig GR are relevant in the degu GR. The relative resistance to cortisol observed in the degu GR is conferred by the substitution of two isoleucine residues, which are highly conserved in the GR across species, with a valine doublet. These amino acids lie in the region between helices 5 and 6 of the GR LBD, a region known to be important in determining the affinity of ligand-binding in steroid receptors.

Plasminogen Activator Inhibitor-1 and Adiponectin Are Associated With Metabolic Syndrome Components.

BACKGROUND: We aimed to study the associations of adipocytokines, endothelial damage markers, and high-sensitivity C-reactive protein (hs-CRP) with metabolic syndrome (MetS) components. METHODS: This cross-sectional study included 202 subjects categorized into MetS and No-MetS according to Harmonizing Adult Treatment Panel III. RESULTS: Subjects with MetS showed higher levels of proinflammatory molecules but significantly lower adiponectin levels than subjects with No-MetS. Among the studied adipocytokines, plasminogen activator inhibitor-1 (PAI-1) and adiponectin showed the strongest associations with most MetS components. PAI-1 was associated with MetS (odds ratio (OR) 1.107 (1.065-1.151), P < 0.0001), whereas adiponectin was inversely associated with MetS (OR 0.710 (0.610-0.825), P < 0.0001). Following adjustment by sex, age, body mass index, and 24-hour urinary sodium excretion in a multivariate analysis, the association of PAI-1 (OR 1.090 (1.044-1.137), P < 0.0001) and adiponectin (OR 0.634 (0.519-0.775), P < 0.0001) with MetS remained significant. Multivariate analyses supported a model in which systolic blood pressure (BP) could be predicted by PAI-1, hs-CRP, and matrix metalloproteinase 2 (R2 = 0.125; P = 0.04); diastolic BP (R2 = 0.218; P = 0.0001) and glucose (R2 = 0.074; P = 0.0001) could be predicted by PAI-1; waist circumference could be predicted by PAI-1 and hs-CRP (R2 = 0.28; P = 0.016). Receiver operating characteristic curve analysis showed that a PAI-1 concentration had the best sensitivity and specificity for discriminating subjects with MetS. CONCLUSION: PAI-1 and adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk.

Primary Aldosteronism, Aldosterone, and Extracellular Vesicles.

Primary aldosteronism (PA) is an endocrine related condition leading to arterial hypertension due to inappropriately high and unregulated aldosterone concentration. Recently, a broad spectrum of PA has been recognized, which brings new challenges associated with early identification of this condition that affect renal epithelial and extrarenal tissues. Reports have shown the potential role of extracellular vesicles (EVs) and EV cargo as novel and complementary biomarkers in diagnosis and prognosis of PA. In vivo and in vitro studies have identified specific EV surface antigens, EV-proteins, and EV microRNAs that can be useful to develop novel diagnostic algorithms to detect, confirm, or follow up the PA. Moreover, the study of EVs in the field of PA provides further insight in the pathophysiological mechanism of the PA disease.