Surrogate indices of insulin resistance using the Matsuda index as reference in adult men-a computational approach.

Background: Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men. Methods: A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust. Results: The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01). Conclusions: The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

Lactate: an alternative pathway for the immunosuppressive properties of mesenchymal stem/stromal cells.

BACKGROUND: The metabolic reprogramming of mesenchymal stem/stromal cells (MSC) favoring glycolysis has recently emerged as a new approach to improve their immunotherapeutic abilities. This strategy is associated with greater lactate release, and interestingly, recent studies have proposed lactate as a functional suppressive molecule, changing the old paradigm of lactate as a waste product. Therefore, we evaluated the role of lactate as an alternative mediator of MSC immunosuppressive properties and its contribution to the enhanced immunoregulatory activity of glycolytic MSCs. MATERIALS AND METHODS: Murine CD4+ T cells from C57BL/6 male mice were differentiated into proinflammatory Th1 or Th17 cells and cultured with either L-lactate, MSCs pretreated or not with the glycolytic inductor, oligomycin, and MSCs pretreated or not with a chemical inhibitor of lactate dehydrogenase A (LDHA), galloflavin or LDH siRNA to prevent lactate production. Additionally, we validated our results using human umbilical cord-derived MSCs (UC-MSCs) in a murine model of delayed type 1 hypersensitivity (DTH). RESULTS: Our results showed that 50 mM of exogenous L-lactate inhibited the proliferation rate and phenotype of CD4+ T cell-derived Th1 or Th17 by 40% and 60%, respectively. Moreover, the suppressive activity of both glycolytic and basal MSCs was impaired when LDH activity was reduced. Likewise, in the DTH inflammation model, lactate production was required for MSC anti-inflammatory activity. This lactate dependent-immunosuppressive mechanism was confirmed in UC-MSCs through the inhibition of LDH, which significantly decreased their capacity to control proliferation of activated CD4+ and CD8+ human T cells by 30%. CONCLUSION: These findings identify a new MSC immunosuppressive pathway that is independent of the classical suppressive mechanism and demonstrated that the enhanced suppressive and therapeutic abilities of glycolytic MSCs depend at least in part on lactate production.

Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.

Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington's disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.

Current Research on Molecular Biomarkers for Colorectal Cancer in Stool Samples.

Colorectal cancer (CRC) is one of the most diagnosed cancers worldwide, with a high incidence and mortality rate when diagnosed late. Currently, the methods used in healthcare to diagnose CRC are the fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. However, the lack of sensitivity and specificity and low population adherence are driving the need to implement other technologies that can identify biomarkers that not only help with early CRC detection but allow for the selection of more personalized treatment options. In this regard, the implementation of omics technologies, which can screen large pools of biological molecules, coupled with molecular validation, stands out as a promising tool for the discovery of new biomarkers from biopsied tissues or body fluids. This review delves into the current state of the art in the identification of novel CRC biomarkers that can distinguish cancerous tissue, specifically from fecal samples, as this could be the least invasive approach.

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy.

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.

Neuroprotective and Neurotoxic Effects of Glial-Derived Exosomes.

Exosomes derived from glial cells such as astrocytes, microglia, and oligodendrocytes can modulate cell communication in the brain and exert protective or neurotoxic effects on neurons, depending on the environmental context upon their release. Their isolation, characterization, and analysis under different conditions in vitro, in animal models and samples derived from patients has allowed to define the participation of other molecular mechanisms behind neuroinflammation and neurodegeneration spreading, and to propose their use as a potential diagnostic tool. Moreover, the discovery of specific molecular cargos, such as cytokines, membrane-bound and soluble proteins (neurotrophic factors, growth factors, misfolded proteins), miRNA and long-non-coding RNA, that are enriched in glial-derived exosomes with neuroprotective or damaging effects, or their inhibitors can now be tested as therapeutic tools. In this review we summarize the state of the art on how exosomes secretion by glia can affect neurons and other glia from the central nervous system in the context of neurodegeneration and neuroinflammation, but also, on how specific stress stimuli and pathological conditions can change the levels of exosome secretion and their properties.

A Short-Term Sucrose Diet Impacts Cell Proliferation of Neural Precursors in the Adult Hypothalamus.

Radial glia-like cells in the hypothalamus and dorsal vagal complex are neural precursors (NPs) located near subventricular organs: median eminence and area postrema, respectively. Their strategic position can detect blood-borne nutrients, hormones, and mitogenic signals. Hypothalamic NPs increase their proliferation with a mechanism that involves hemichannel (HC) activity. NPs can originate new neurons in response to a short-term high-fat diet as a compensatory mechanism. The effects of high carbohydrate Western diets on adult neurogenesis are unknown. Although sugars are usually consumed as sucrose, more free fructose is now incorporated into food items. Here, we studied the proliferation of both types of NPs in Sprague Dawley rats exposed to a short-term high sucrose diet (HSD) and a control diet. In tanycyte cultures, we evaluated the effects of glucose and fructose and a mix of both hexoses on HC activity. In rats fed an HSD, we observed an increase in the proliferative state of both precursors. Glucose, either in the presence or absence of fructose, but not fructose alone, induced in vitro HC activity. These results should broaden the understanding of the nutrient monitoring capacity of NPs in reacting to changes in feeding behavior, specifically to high sugar western diets.

GKRP-dependent modulation of feeding behavior by tanycyte-released monocarboxylates.

Objectives: Glucokinase Regulatory Protein (GKRP) is the only known endogenous modulator of glucokinase (GK) localization and activity to date, and both proteins are localized in tanycytes, radial glia-like cells involved in metabolic and endocrine functions in the hypothalamus. However, the role of tanycytic GKRP and its impact on the regulation of feeding behavior has not been investigated. Here, we hypothesize that GKRP regulates feeding behavior by modulating tanycyte-neuron metabolic communication in the arcuate nucleus. Methods: We used primary cultures of tanycytes to evaluate the production of lactate and ß-hydroxybutyrate (ßHB). Similarly, we examined the electrophysiological responses to these metabolites in pro-opiomelanocortin (POMC) neurons in hypothalamic slices. To evaluate the role of GKRP in feeding behavior, we generated tanycyte-selective GKRP-overexpressing and GKRP-knock down mice (GKRPt-OE and GKRPt-KD respectively) using adenovirus-mediated transduction. Results: We demonstrated that lactate release induced by glucose uptake is favored in GKRP-KD tanycytes. Conversely, tanycytes overexpressing GKRP showed an increase in ßHB efflux induced by low glucose concentration. In line with these findings, the excitability of POMC neurons was enhanced by lactate and decreased in the presence of ßHB. In GKRPt-OE rats, we found an increase in post-fasting food avidity, whereas GKRPt-KD caused a significant decrease in feeding and body weight, which is reverted when MCT1 is silenced. Conclusion: Our study highlights the role of tanycytic GKRP in metabolic regulation and positions this regulator of GK as a therapeutic target for boosting satiety in patients with obesity problems.

Myristic acid reduces skin inflammation and nociception.

This study evaluated the inhibitory effect of myristic acid (MA) on models of inflammation and nociception. The in vitro anti-inflammatory activities of MA were assessed on LPS-stimulated macrophages, membrane stabilization assay, and inhibition of protein denaturation, whereas the inhibitory activity of MA on in vivo inflammation was assessed on TPA-induced ear edema using acute and chronic assays in mice. The inhibitory effect of MA on nociception was assessed using three in vivo models. MA exerted in vitro anti-inflammatory activity by the increase (58%) in the production of IL-10 in LPS-stimulated macrophages. In the in vivo assay, MA showed good anti-inflammatory effects on the acute (ED50 = 62 mg/kg) and chronic (ED50 = 77 mg/kg) TPA-induced ear edema. The antinociceptive activity of MA was related to the participation of the nitrergic system in the formalin-induced paw licking test. PRACTICAL APPLICATIONS: Previous studies with different plant extracts containing MA, as one of their major components, have demonstrated anti-inflammatory and antinociceptive actions. However, the anti-inflammatory and antinociceptive actions of myristic acid have not been previously reported. The results suggest that MA induced anti-inflammatory effects in LPS-stimulated macrophages through the participation of IL-10. The antinociceptive effects of MA are attributed to the participation of the nitrergic system.

Integrating User-Input into Deep Convolutional Neural Networks for Thyroid Nodule Segmentation.

Delineation of thyroid nodule boundaries is necessary for cancer risk assessment and accurate categorization of nodules. Clinicians often use manual or bounding-box approach for nodule assessment which leads to subjective results. Consequently, agreement in thyroid nodule categorization is poor even among experts. Computer-aided diagnosis systems could reduce this variability by minimizing the extent of user interaction and by providing precise nodule segmentations. In this study, we present a novel approach for effective thyroid nodule segmentation and tracking using a single user click on the region of interest. When a user clicks on an ultrasound sweep, our proposed model can predict nodule segmentation over the entire sequence of frames. Quantitative evaluations show that the proposed method out-performs the bounding box approach in terms of the dice score on a large dataset of 372 ultrasound images. The proposed approach saves expert time and reduces the potential variability in thyroid nodule assessment. The proposed one-click approach can save clinicians time required for annotating thyroid nodules within ultrasound images/sweeps. With minimal user interaction we would be able to identify the nodule boundary which can further be used for volumetric measurement and characterization of the nodule. This approach can also be extended for fast labeling of large thyroid imaging datasets suitable for training machine-learning based algorithms.

Thyroid Nodule Segmentation and Classification Using Deep Convolutional Neural Network and Rule-based Classifiers.

Thyroid cancer has a high prevalence all over the world. Accurate thyroid nodule diagnosis can lead to effective treatment and decrease the mortality rate. Ultrasound imaging is a safe, portable, and inexpensive tool for thyroid nodule monitoring. However, the widespread use of ultrasound has also resulted in over-diagnosis and over-treatment of nodules. There is also large variability in the assessment and characterization of nodules. Thyroid nodule classification requires precise delineation of the nodule boundary which is tedious and time- consuming. Automatic segmentation of nodule boundaries is highly desirable, however, it is challenging due to the wide range of nodule appearances, shapes, and sizes. In this study, we propose an end-to-end pipeline for nodule segmentation and classification. A residual dilated UNet (resDUnet) model is proposed for nodule segmentation. The output of resDUnet is fed to two rule-based classifiers to categorize the composition and echogenicity of the segmented nodule. We evaluate our segmentation method on a large dataset of 352 ultrasound images reviewed by a certified radiologist. When compared with ground-truth, resDUnet gives a higher Dice score than the standard UNet (82% vs. 81%). Our method requires minimal user interaction and it is robust to reasonable variations in the user-specified region-of-interest. We expect the proposed method to reduce variability in thyroid nodule assessment which results in more efficient and cost-effective monitoring of thyroid cancer.

Role of microRNA Shuttled in Small Extracellular Vesicles Derived From Mesenchymal Stem/Stromal Cells for Osteoarticular Disease Treatment.

Osteoarticular diseases (OD), such as rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic autoimmune/inflammatory and age-related diseases that affect the joints and other organs for which the current therapies are not effective. Cell therapy using mesenchymal stem/stromal cells (MSCs) is an alternative treatment due to their immunomodulatory and tissue differentiation capacity. Several experimental studies in numerous diseases have demonstrated the MSCs' therapeutic effects. However, MSCs have shown heterogeneity, instability of stemness and differentiation capacities, limited homing ability, and various adverse responses such as abnormal differentiation and tumor formation. Recently, acellular therapy based on MSC secreted factors has raised the attention of several studies. It has been shown that molecules embedded in extracellular vesicles (EVs) derived from MSCs, particularly those from the small fraction enriched in exosomes (sEVs), effectively mimic their impact in target cells. The biological effects of sEVs critically depend on their cargo, where sEVs-embedded microRNAs (miRNAs) are particularly relevant due to their crucial role in gene expression regulation. Therefore, in this review, we will focus on the effect of sEVs derived from MSCs and their miRNA cargo on target cells associated with the pathology of RA and OA and their potential therapeutic impact.

Accurate long-range forecasting of COVID-19 mortality in the USA.

The need for improved models that can accurately predict COVID-19 dynamics is vital to managing the pandemic and its consequences. We use machine learning techniques to design an adaptive learner that, based on epidemiological data available at any given time, produces a model that accurately forecasts the number of reported COVID-19 deaths and cases in the United States, up to 10 weeks into the future with a mean absolute percentage error of 9%. In addition to being the most accurate long-range COVID predictor so far developed, it captures the observed periodicity in daily reported numbers. Its effectiveness is based on three design features: (1) producing different model parameters to predict the number of COVID deaths (and cases) from each time and for a given number of weeks into the future, (2) systematically searching over the available covariates and their historical values to find an effective combination, and (3) training the model using "last-fold partitioning", where each proposed model is validated on only the last instance of the training dataset, rather than being cross-validated. Assessments against many other published COVID predictors show that this predictor is 19-48% more accurate.

The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming.

Mesenchymal stem cells (MSCs) are multipotent adult stromal cells widely studied for their regenerative and immunomodulatory properties. They are capable of modulating macrophage plasticity depending on various microenvironmental signals. Current studies have shown that metabolic changes can also affect macrophage fate and function. Indeed, changes in the environment prompt phenotype change. Therefore, in this review, we will discuss how MSCs orchestrate macrophage's metabolic plasticity and the impact on their function. An improved understanding of the crosstalk between macrophages and MSCs will improve our knowledge of MSC's therapeutic potential in the context of inflammatory diseases, cancer, and tissue repair processes in which macrophages are pivotal.

Maternal Serum Angiopoietin-Like 3 Levels in Healthy and Mild Preeclamptic Pregnant Women.

Objective: Angiopoietin-like protein 3(ANGPTL3) is an important regulator of lipoprotein metabolism in the fed state by inhibiting the enzyme lipoprotein lipase in oxidative tissues. However, the possible role of ANGPTL3 throughout gestation and its relationship with hormonal and biochemical variables are still unknown. The aim of this study was to determinate serum ANGPTL3 level in healthy non-pregnant women, during healthy and preeclamptic pregnancy and postpartum. Methods: Serum ANGPTL3 was analyzed by enzyme-linked immunosorbent assay (ELISA), in a prospective cohort of healthy pregnant women (n = 52) and women with mild preeclampsia (n = 21), and women at three months postpartum (n = 20) and healthy non-pregnant women (n = 20). The results obtained were correlated with biochemical, hormonal and anthropometric variables and insulin resistance indices. Results: Levels of ANGPTL3 were not different between the follicular and the luteal phases of the cycle in healthy non-pregnant women. There was a significant reduction in serum ANGPTL3 levels from the first to the third trimester in healthy pregnant women compared with healthy non-pregnant and postpartum women (p <0.01). ANGPTL3 levels do not differ significantly during the three trimesters of pregnancy neither in healthy women nor in preeclamptic women. The serum levels of ANGPTL3 in women who developed preeclampsia are not statistically different from those observed in healthy pregnant women in each trimester of pregnancy. A significant lineal positive correlation was observed between serum ANGPTL3 levels and triglyceride (P =0.0186, r =0.52), very low-density lipoprotein cholesterol (P =0.0224, r =0.50), and total cholesterol levels (P =0.0220, r =0.50) in healthy non-pregnant women (P 0.05). Besides, there were no significant correlations between serum ANGPTL3 and body mass index (BMI), high-density lipoprotein cholesterol, glucose, insulin, leptin, or HOMA-IR (P >0.05). Conclusions: We describe for the first time the profile of ANGPTL3 throughout pregnancy and postpartum as well as and discussed about explore their potential contribution interactions with lipoprotein metabolism throughout pregnancy and postpartum. Thus, low levels of ANGPTL3 during pregnancy might favor lipid uptake in oxidative tissues as the main maternal energy source, while may helping to preserve glucose for use by the fetus and placenta.

The ATP synthase inhibition induces an AMPK-dependent glycolytic switch of mesenchymal stem cells that enhances their immunotherapeutic potential.

Objectives: Mesenchymal Stem/Stromal Cells (MSC) are promising therapeutic tools for inflammatory diseases due to their potent immunoregulatory capacities. Their suppressive activity mainly depends on inflammatory cues that have been recently associated with changes in MSC bioenergetic status towards a glycolytic metabolism. However, the molecular mechanisms behind this metabolic reprogramming and its impact on MSC therapeutic properties have not been investigated. Methods: Human and murine-derived MSC were metabolically reprogramed using pro-inflammatory cytokines, an inhibitor of ATP synthase (oligomycin), or 2-deoxy-D-glucose (2DG). The immunosuppressive activity of these cells was tested in vitro using co-culture experiments with pro-inflammatory T cells and in vivo with the Delayed-Type Hypersensitivity (DTH) and the Graph versus Host Disease (GVHD) murine models. Results: We found that the oligomycin-mediated pro-glycolytic switch of MSC significantly enhanced their immunosuppressive properties in vitro. Conversely, glycolysis inhibition using 2DG significantly reduced MSC immunoregulatory effects. Moreover, in vivo, MSC glycolytic reprogramming significantly increased their therapeutic benefit in the DTH and GVHD mouse models. Finally, we demonstrated that the MSC glycolytic switch effect partly depends on the activation of the AMPK signaling pathway. Conclusion: Altogether, our findings show that AMPK-dependent glycolytic reprogramming of MSC using an ATP synthase inhibitor contributes to their immunosuppressive and therapeutic functions, and suggest that pro-glycolytic drugs might be used to improve MSC-based therapy.

The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway.

In the adult hypothalamus, the neuronal precursor role is attributed to the radial glia-like cells that line the third-ventricle (3V) wall called tanycytes. Under nutritional cues, including hypercaloric diets, tanycytes proliferate and differentiate into mature neurons that moderate body weight, suggesting that hypothalamic neurogenesis is an adaptive mechanism in response to metabolic changes. Previous studies have shown that the tanycyte glucosensing mechanism depends on connexin-43 hemichannels (Cx43 HCs), purine release, and increased intracellular free calcium ion concentration [(Ca2+ )i ] mediated by purinergic P2Y receptors. Since, Fibroblast Growth Factor 2 (FGF2) causes similar purinergic events in other cell types, we hypothesize that this pathway can be also activated by FGF2 in tanycytes to promote their proliferation. Here, we used bromodeoxyuridine (BrdU) incorporation to evaluate if FGF2-induced tanycyte cell division is sensitive to Cx43 HC inhibition in vitro and in vivo. Immunocytochemical analyses showed that cultured tanycytes maintain the expression of in situ markers. After FGF2 exposure, tanycytic Cx43 HCs opened, enabling release of ATP to the extracellular milieu. Moreover, application of external ATP was enough to induce their cell division, which could be suppressed by Cx43 HC or P2Y1-receptor inhibitors. Similarly, in vivo experiments performed on rats by continuous infusion of FGF2 and a Cx43 HC inhibitor into the 3V, demonstrated that FGF2-induced ß-tanycyte proliferation is sensitive to Cx43 HC blockade. Thus, FGF2 induced Cx43 HC opening, triggered purinergic signaling, and increased ß-tanycytes proliferation, highlighting some of the molecular mechanisms involved in the cell division response of tanycyte. This article has an Editorial Highlight see https://doi.org/10.1111/jnc.15218.

Serum angiopoietin-like 3 levels are elevated in obese non diabetic men but are unaffected during an oral glucose tolerance test.

This study aimed to determine ANGPTL3 serum levels in healthy young lean and obese non-diabetic men during an oral glucose tolerance test (OGTT) and correlate them with anthropometric, biochemical and hormonal parameters. A case-control study was carried out and 30 young obese non-diabetic (23.90 ± 3.84 years and BMI 37.92 ± 4.85 kg/m2) and 28 age-matched healthy lean (24.56 ± 3.50 years and BMI of 22.10 ± 1.72 kg/m2) men were included in this study. The primary outcome measures were serum basal ANGPTL3 and ANGPTL3-area under the curve (AUC) levels. The percentage of body fat was measured by dual-energy X-ray absorptiometry and biochemical, hormonal and insulin resistance indices were determined. Basal ANGPTL3 and ANGPTL3-AUC levels were significantly elevated (p < 0.05) in young obese subjects compared with lean subjects and were positively and significantly associated with different anthropometric measurements. Fasting ANGPTL3 serum levels were positively correlated with fasting insulin, leptin, Leptin/Adiponectin index and triglyceride-glucose index. Moreover, ANGPTL3-AUC was negatively correlated with Matsuda index. In this regard, chronically high ANGPTL3 levels in young obese subjects might favor triglyceride-rich lipoprotein clearance to replenish triglyceride stores by white adipose tissue rather than oxidative tissues.

Late metastasis of right breast cancer to renal pelvis and right ureter. A case report.

ANTECEDENTES: Las metástasis de mama a uréter son extremadamente raras y la mayoría son asintomáticas. CASO CLÍNICO: Mujer de 67 años, con cáncer de mama derecha EC IA luminal A de 5 años de evolución. Presentó infección de vías urinarias de repetición, hematuria macroscópica total y dolor renal derecho. La tomografía abdominopélvica mostró dilatación del cáliz superior y defecto de llenado en la pelvis renal derechos. Se le realizó nefroureterectomía radical derecha, rodete vesical. El reporte histopatológico fue metástasis de carcinoma infiltrante con afectación de pelvis renal y uréter. CONCLUSIONES: La metástasis tardía del cáncer de mama al uréter y la pelvis es rara. BACKGROUND: Breast metastases to ureter are extremely rare. Most are asymptomatic. CASE REPORT: A 67-year-old woman with 5 years of evolution, with right breast cancer stage IA luminal A. She presented repeated urinary tract infection, total macroscopic hematuria and pain in the right renal fossa. The computed tomography showed dilation of the upper calyx and filling defect in the renal pelvis. A right laparoscopic radical nephroureterectomy was realized; the histopathological report was metastasis of infiltrating carcinoma without specific pattern involving renal pelvis and ureter. CONCLUSIONS: Late metastasis of breast cancer to ureter and pelvis are rare.

Niveles séricos de 25-hidroxivitamina D y su relación con síndrome metabólico en una población de hombres jóvenes no diabéticos / Serum levels of 25-hydroxy vitamin D and their relationship to metabolic syndrome in a population of young nondiabetic men

Resumen Introducción: los niveles no suficientes de vitamina D (VD) se han asociado a varias patologías no osteomusculares; sin embargo, es motivo de controversia si éstos se asocian a mayor prevalencia de síndrome metabólico (SM). Objetivo: determinar y comparar la frecuencia de insuficiencia y deficiencia de 25-hidroxivitamina D (25(OH)D) entre hombres jóvenes obesos no diabéticos y controles con peso normal, y su correlación con el estado de SM. Material y métodos: estudio de corte transversal, que incluyó 62 individuos con peso normal y 47 en obesidad, se determinaron los niveles séricos de 25(OH)D y se midieron parámetros antropométricos y bioquímicos para establecer criterios de SM. Resultados: de los 47 sujetos con obesidad, 25 tenían SM, mientas que ninguno de los sujetos de peso normal cumplía con dichos criterios. No se encontraron diferencias estadísticamente significativas en cuanto a la presencia de síndrome en correlación con los niveles de vitamina D (p=0.94). La media de los niveles séricos de 25(OH)D para la población total fue 30.6±8.3 ng/ mL; en sujetos normopeso 30.8±8.5 ng/mL y entre los obesos con SM fue 30.1±9.2 ng/mL y sin SM de 30.6±7.5 ng/mL. Por otro lado no hubo una correlación significativa entre los parámetros individuales de síndrome metabólico y los niveles séricos de VD, tanto de manera global, como en el análisis por subgrupos. Conclusión: no hubo una correlación significativa entre los niveles séricos de 25(OH)D con el estado de SM, tampoco se identificó ningún tipo de correlación significativa entre éstos y los parámetros antropométricos y bioquímicos estudiados.(Acta Med Colomb 2020; 45. DOI:doi.org/10.36104/amc.2020.1323).

Abstract Introduction: insufficient levels of vitamin D (VD) have been associated with several non-musculoskeletal diseases. However, whether they are associated with a greater prevalence of metabolic syndrome (MS) is a matter of controversy. Objective: to determine and compare the frequency of 25-hydroxy vitamin D (25(OH)D) insufficiency and deficiency in young, obese nondiabetic men and normal weight controls, and its correlation with metabolic syndrome. Material and methods: a cross-sectional study which included 62 normal weight and 47 obese individuals. Serum levels of 25(OH)D were ascertained and anthropometric and biochemical parameters were measured to establish MS criteria. Results: of the 47 obese subjects, 25 had MS, while none of the normal weight subjects met the criteria. There were no statistically significant differences in the presence of the syndrome related to the vitamin D levels (p=0.94). The mean serum 25(OH)D level for the total population was 30.6±8.3 ng/mL; in normal weight subjects it was 30.8±8.5 ng/mL, in obese subjects with MS it was 30.1±9.2 ng/mL, and in obese subjects without MS it was 30.6±7.5 ng/mL. Furthermore, there was no significant correlation between the individual MS parameters and serum VD, either globally or on subgroup analysis. Conclusion: there was no significant correlation between serum 25(OH)D levels and MS, nor was any significant correlation found between these and the anthropometric and biochemical parameters studied.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1323).