Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with ...anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here, we tested the effect of a 2-year resveratrol administration on proinflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Resveratrol supplementation (80 and 480 mg/day for the first and second year, respectively) decreased adipocyte size, increased sirtuin 1 expression, decreased NF-κB activation, and improved insulin sensitivity in visceral, but not subcutaneous, WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS ± resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys.
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•Resveratrol elicits transcriptional changes in visceral and subcutaneous WAT•Resveratrol exerts anti-inflammatory effects in visceral WAT of HFS-fed monkeys•Resveratrol’s anti-inflammatory effect coincides with improved insulin sensitivity•Adipocytes play a key role in the adaptations evoked by resveratrol
Adiponectin is a member of the family of adipose tissue-related hormones known as adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and antiangiogenic properties. Adiponectin ...actions are primarily mediated through binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2. Likewise, adiponectin expression has been detected in adipocytes as well as in a variety of extra-adipose tissues, including the chicken pituitary. Interestingly, adiponectin secretion and adiponectin receptor expression in adipocytes have been shown to be regulated by pituitary hormones. These observations led us to investigate whether adiponectin, like the adipokine leptin, regulates pituitary hormone production. Specifically, we focused our analysis on somatotrophs and gonadotrophs because of the relationship between the control of energy metabolism, growth and reproduction. To this end, the effects of adiponectin on both GH and LH secretion as well as its interaction with major stimulatory regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat pituitary cell cultures. Results show that adiponectin inhibits GH and LH release as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH-R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we demonstrate that the pituitary expresses both adiponectin and adiponectin receptors under the regulation of the adipokine. In sum, our data indicate that adiponectin, either locally produced or from other sources, may play a neuroendocrine role in the control of both somatotrophs and gonadotrophs.
Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an ...awareness of their spatial location, a property termed positional identity. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/Rarres1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting Hoxa13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.
The main limitations of lipidomics analysis are the chemical complexity of the lipids, the range of concentrations at which they exist, and the variety of samples usually analyzed. These limitations ...particularly affect the characterization of polar lipids owing to the interference of neutral lipids, essentially acylglycerides, which are at high concentration and suppress ionization of low concentrated lipids in mass spectrometry detection. The influence of sample preparation on lipidomics analysis of polar lipids in adipose tissue by LC–MS/MS was the aim of this research. Two common extractants used for lipids isolation, methanol:chloroform (MeOH:CHCl3) and methyl tert-butyl ether (MTBE), were qualitatively and quantitatively compared for the extraction of the main families of lipids. The obtained results showed that each family of lipids is influenced differently by the extractant used. However, as a general trend, the use of MTBE as extractant led to higher extraction efficiency for unsaturated fatty acids, glycerophospholipids and ceramides, while MeOH:CHCl3 favored the isolation of saturated fatty acids and plasmalogens. The implementation of a solid-phase extraction (SPE) step for selective isolation of glycerophospholipids prior to LC–MS/MS analysis was assayed to evaluate its influence on lipids detection coverage as compared to direct analysis. This step was critical to enhance the detection coverage of glycerophospholipids by removal of ionization suppression effects caused by acylglycerides.
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•Sample preparation has been studied in the analysis of polar lipids in adipose tissue.•The matrix used in this research was human visceral adipose tissue.•The study was performed by an untargeted LC–QTOF MS/MS approach.
Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and ...therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient’s outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.
•Bone sarcoma (STS) encompass more than 30 different histologic subtypes.•Clinical practice guidelines for bone sarcoma still lack in Latin-American countries.•Tailored clinical guidelines are instrumental to improve outcome in bone sarcoma patients in Latin-American countries.•This is the first review establishing bone sarcoma guidelines for the purpose of Latin-American clinical practices to our knowledge.
ABSTRACT
We study the optical gri photometric variability of a sample of 190 quasars within the SDSS Stripe 82 region that have long-term photometric coverage during ∼1998−2020 with SDSS, ...PanSTARRS-1, the Dark Energy Survey, and dedicated follow-up monitoring with Blanco 4m/DECam. With on average ∼200 nightly epochs per quasar per filter band, we improve the parameter constraints from a Damped Random Walk (DRW) model fit to the light curves over previous studies with 10–15 yr baselines and ≲ 100 epochs. We find that the average damping time-scale τDRW continues to rise with increased baseline, reaching a median value of ∼750 d (g band) in the rest frame of these quasars using the 20-yr light curves. Some quasars may have gradual, long-term trends in their light curves, suggesting that either the DRW fit requires very long baselines to converge, or that the underlying variability is more complex than a single DRW process for these quasars. Using a subset of quasars with better-constrained τDRW (less than 20 per cent of the baseline), we confirm a weak wavelength dependence of τDRW∝λ0.51 ± 0.20. We further quantify optical variability of these quasars over days to decades time-scales using structure function (SF) and power spectrum density (PSD) analyses. The SF and PSD measurements qualitatively confirm the measured (hundreds of days) damping time-scales from the DRW fits. However, the ensemble PSD is steeper than that of a DRW on time-scales less than ∼ a month for these luminous quasars, and this second break point correlates with the longer DRW damping time-scale.
The nuclear protein high-mobility group box 1 (HMGB1) can be passively released by necrotic cells or secreted actively by several cell types to regulate immune and inflammatory responses, as well as ...tissue remodeling. We herein aimed to characterize the effect of insulin resistance on HMGB1 in adipose tissue and to examine its potential role as a metabolic regulator in β-pancreatic cells.
Plasma HMGB1 concentration and adipose HMGB1 expression were assessed in relation to obesity and insulin resistance. Cultured adipocytes from lean and obese patients were used to investigate the intracellular distribution and factors regulating HMGB1 release, as well as to test its effects on adipogenesis and lipid metabolism. A regulatory role for HMGB1 in insulin secretion was also investigated.
Circulating HMGB1 was positively associated with body mass index, while adipose HMGB1 mRNA levels correlated with the expression of inflammatory markers. Insulin resistance modified the intracellular distribution of HMGB1 in human adipocytes, with HMGB1 being predominantly nuclear in lean and obese normoglycemic individuals while localized to the cytosol in obese patients with type 2 diabetes. Adipocytes from lean individuals exposed to conditioned media from lipopolysaccharide-stimulated macrophages induced HMGB1 redistribution to the cytoplasm and release. HMGB1 treatment had no effect on differentiation and lipid metabolism in adipocytes. However, HMGB1, whose circulating levels correlated with postload insulin concentration, increased both insulin release and intracellular Ca(2+) concentration in INS-1 cells.
These findings show, for the first time, that HMGB1 expression and release by human adipocytes is altered by inflammatory conditions as those imposed by obesity and insulin resistance. Our data reveal a novel role for HMGB1 as a stimulatory factor of insulin secretion of β-pancreatic cells.
Summary Many intrinsically related determinants of health and disease exist, including social and economic status, education, employment, housing, and physical and environmental exposures. These ...factors interact to cumulatively affect health and disease burden of individuals and populations, and to establish health inequities and disparities across and within countries. Biomedical models of health care decrease adverse consequences of disease, but are not enough to effectively improve individual and population health and advance health equity. Social determinants of health are especially important in Latin American countries, which are characterised by adverse colonial legacies, tremendous social injustice, huge socioeconomic disparities, and wide health inequities. Poverty and inequality worsened substantially in the 1980s, 1990s, and early 2000s in these countries. Many Latin American countries have introduced public policies that integrate health, social, and economic actions, and have sought to develop health systems that incorporate multisectoral interventions when introducing universal health coverage to improve health and its upstream determinants. We present case studies from four Latin American countries to show the design and implementation of health programmes underpinned by intersectoral action and social participation that have reached national scale to effectively address social determinants of health, improve health outcomes, and reduce health inequities. Investment in managerial and political capacity, strong political and managerial commitment, and state programmes, not just time-limited government actions, have been crucial in underpinning the success of these policies.
Somatostatin receptors (sst1-5) are present in different types of tumors, where they inhibit key cellular processes such as proliferation and invasion. Although ssts are densely expressed in breast ...cancer, especially sst2, their role and therapeutic potential remain uncertain. Recently, we identified a new truncated sst5 variant, sst5TMD4, which is related to the abnormal response of certain pituitary tumors to treatment with somatostatin analogs. Here, we investigated the possible role of sst5TMD4 in breast cancer. This study revealed that sst5TMD4 is absent in normal mammary gland, but is abundant in a subset of poorly differentiated human breast tumors, where its expression correlated to that of sst2. Moreover, in the MCF-7 breast cancer model cell, sst5TMD4 expression increased malignancy features such as invasion and proliferation abilities (both in cell cultures and nude mice). This was likely mediated by sst5TMD4-induced increase in phosphorylated extracellular signal-regulated kinases 1 and 2 and p-Akt levels, and cyclin D3 and Arp2/3 complex expression, which also led to mesenchymal-like phenotype. Interestingly, sst5TMD4 interacts physically with sst2 and thereby alters its signaling, enabling disruption of sst2 inhibitory feedback and providing a plausible basis for our findings. These results suggest that sst5TMD4 could be involved in the pathophysiology of certain types of breast tumors.
Introduction
Home Treatment (HT) teams are among the better-studied options to reduce admission at the hospital, having been described as an alternative to hospitalization in patients with ...schizophrenia. There may be certain risk factors which has already been described such as living alone (Dean and Gadd, BMJ, 1990; 301, 1021–1023; Schnyder et al., Acta Psychiatr. Scand. 1999; 99, 179–187), lack of awareness of the illness, uncooperativeness (Cotton et al., BMC Psychiatry, 2007; 7, 52) and fewer visits carried out (Morgan et al., Aust. New Zeal. J. Psychiatry,2006; 40, 683–690) which together can negatively influence the possibility of conducting intensive home follow-up and, therefore, increase the likelihood of hospitalization.
Objectives
To describe de relative contribution of several risk factors to patient hospitalization related to the possibility of conducting intensive home follow-up of patients diagnosed with Schizophrenia following home treatment. Second, to determine de risk of hospitalization related to the possibility of conducting intensive home follow-up according to the presence of one or more risk factors of patients diagnosed with Schizophrenia following home treatment.
Methods
All patients with schizophrenia who were visited by a home treatment team in Barcelona between January 2017 and December 2021 were included in the study. To assess whether there was an increased risk of hospitalization associated with factors such as living alone, uncooperativeness (PANSS G8 item >= 4) and ≤1 home visit, two bivariate logistic regression analyses were conducted. We studied these factors as independent variables to assess the relative contribution to the risk of hospitalization, and we studied if the presence of 1, 2, 3 or 4 of these risk factors as independent variables worsened the risk of hospitalization.
Results
Uncooperativeness shows the highest contribution to the risk of hospitalization, followed by ≤ 1 home visit, lack of insight and living alone, all results reaching significance (p=0.000).
There is an increase in the risk of hospitalization depending of the presence of 1,2,3 or 4 of these risk factors (1 risk factor (Odds Ratio = 1.21), 2 risk factors (Odds Ratio = 5.28), 3 risk factors (Odds ratio = 13.53), 4 risk factors (Odds ratio = 29.18).
Conclusions
There are a number of factors directly related to the possibility of conducting intensive follow-up that appear relevant in the case of psychotic patients in acute crisis treated at home. This set of variables are the lack of awareness of the illness, lack of collaboration, living alone and the number of visits that have been made, all with statistically significant differences in our study. These factors together also greatly increase the risk of hospitalization, becoming almost 30 times more likely when these 4 factors are present.
Disclosure of Interest
None Declared
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