Metabolic Changes Induced by Bariatric Surgery May be Mediated by PAI-1 and PCSK9 Crosstalk.

BACKGROUND: Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers. METHODS: Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA). RESULTS: PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1. CONCLUSIONS: After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.

OBJECTIVE: To assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. METHODS: A cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. RESULTS: The mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8-315.9) vs 158.1 (113.4-201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. CONCLUSION: Patients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Leptin/adiponectin ratio as a prognostic factor for increased weight gain in girls with central precocious puberty.

Objective: To determine if the leptin, adiponectin, and leptin/adiponectin ratio (LAR) can predict weight gain at the end of GnRH analogs (GnRHa) treatment in girls with central precocious puberty (CPP). Material and methods: Study design: prospective cohort. Serum levels of leptin and adiponectin were determined at diagnosis of CPP. Anthropometry was performed at diagnosis of CPP and every six-months, until treatment with GnRHa was discontinued and they presented menarche. Patients were divided according to BMI<94 and BMI>95 percentile at diagnosis of CPP. The outcome was the increased in weight gain (e.g., from normal weight to overweight) at the end of follow-up. Statistical analysis: repeated measures ANOVA test and Student's t-test were used to compare groups. Logistic regression analysis was used to evaluate the association of leptin and adiponectin levels, as well as LAR values with increased weight gain. Results: Fifty-six CPP patients were studied, 18 had BMI >95 percentile and 38 BMI <94 percentile. Of the 18 patients who initially had BMI >95th, two patients went from obesity to overweight, while among the 38 patients who started with BMI <94th, 21 (55.2%) increased their weight gain at the end of follow-up. This last group had higher leptin levels (8.99 ± 0.6 vs 6.14 ± 0.8, p=0.005) and higher LAR values compared to those who remained in the same weight (1.3 ± 0.5 vs 0.96 ± 0.56, p=0.01). In the logistic regression analysis, it was found that higher leptin levels and higher LAR values were associated with increased weight gain (RR 1.31, 95%CI 1.03-1.66, RR 4.86, 95%CI 1.10-21.51, respectively), regardless of birth weight, pubertal stage, age, and bone/chronological age ratio. Conclusions: In patients with CPP, leptin levels and higher LAR values appear to be associated with significantly greater weight gain during GhRHa treatment, particularly in girls starting with BMI < 94 percentile.

[Vitamin D and its positive effect on the PTH/vitamin D/calcium-FGF23/klotho/phosphorus axis in kidney transplant recipients]. / Vitamina D y su efecto positivo sobre el eje PTH/vitamina D/calcio-FGF23/klotho/fósforo en pacientes con trasplante renal.

Introduction: Background: hypovitaminosis D is frequent in kidney transplant recipient (KTR) patients and is associated with deleterious effects both at the bone and extraosseous levels. Treatment with cholecalciferol is effective for the normalization of 25(OH)D, demonstrating a beneficial effect on the calcium-tropic axis in other populations; however, its effect on the PTH/vitamin D/calcium and FGF23/klotho/phosphorus axis in RTR has not been reported. The aim of this study was to evaluate the effect of normalization of serum 25(OH)D concentrations on the PTH/vitamin D/calcium-FGF23/klotho/phosphorus axis in KTR treated with cholecalciferol, as well as the association between the components of this axis. Methods: a prospective study in 23 KTR with hypovitaminosis D, with evolution from 1 to 12 months post-transplantation, an estimated glomerular filtration rate > 60 mL/min/1.73 m2 and a history of primary nephropathy treated with cholecalciferol, in whom the PTH/vitamin D/calcium and FGF23/klotho/phosphorus axis was evaluated during the state of hypovitaminosis D and at normalization of 25(OH)D. Results: at the normalization of 25(OH)D, a reduction in PTH [103 (58.5-123.9) vs 45.6 (30.1-65.1) pg/mL; p = 0.002] and an increase in serum phosphorus [3.1 (2.3-3.5) vs 3.3 (3-3.6) mg/dL; p = 0.01] were evident, with no differences in calcium, klotho and FGF23 concentrations. The time to achieve normalization of 25(OH)D was 12 weeks (RIC, 4-12), with a dose of 5000 IU/day (RIC, 4000-6000). A positive association between klotho and PTH was corroborated (r = 0.54; p = 0.008; linear regression, ß = 0.421; B = 0.004; 95 % CI, 0.003-0.007; p = 0.045). Conclusions: treatment with cholecalciferol is effective for the normalization of 25(OH)D, with a beneficial effect on calcium-phosphotropic metabolism characterized by a reduction in PTH concentration, without significant changes in calcemia or calciuria, as well as an increase in phosphatemia, without modifications in FGF23 or klotho concentrations.

Introducción: Introducción: la hipovitaminosis D es frecuente en los receptores de trasplante renal (RTR) y se asocia con efectos deletéreos tanto a nivel óseo como extraóseo. El tratamiento con colecalciferol es eficaz para la normalización de la 25(OH)D, demostrándose un efecto benéfico sobre el eje calciotrópico; sin embargo, su efecto sobre el eje fosfotrópico no se ha reportado. El objetivo de este estudio fue evaluar el efecto de la normalización de las concentraciones séricas de 25(OH)D sobre el eje PTH/vitamina D/calcio-FGF23/klotho/fósforo en RTR tratados con colecalciferol, así como la asociación entre sus componentes. Métodos: estudio prospectivo en 23 RTR con hipovitaminosis D y antecedente de nefropatía primaria tratados con colecalciferol, en quienes se evaluó el eje PTH/vitamina D/calcio y FGF23/klotho/fósforo durante el estado de hipovitaminosis D y a la normalización de la 25(OH)D. Resultados: a la normalización de la 25(OH)D se evidenció una reducción de la PTH [103 (58,5-123,9) vs. 45,6 (30,1-65,1) pg/mL; p = 0,002] y un aumento del fósforo sérico [3,1 (2,3-3,5) vs. 3,3 (3-3,6) mg/dL; p = 0,01], sin diferencias en las concentraciones de calcio, klotho y FGF23. El tiempo para lograr la normalización de la 25(OH)D fue de 12 semanas (4-12), con una dosis de 5000 UI/día (4000-6000). Se corroboró una asociación positiva entre klotho y PTH (r = 0,54; p = 0,008; regresión lineal, ß = 0,421; IC 95 %: 0,003-0,007; p = 0,045). Conclusiones: el tratamiento con colecalciferol es eficaz para la normalización de la 25(OH)D con un efecto benéfico sobre el metabolismo calcio-fosfotrópico caracterizado por una reducción de la PTH y un incremento de la fosfatemia, sin modificaciones de calcemia, calciuria, FGF23 o klotho.

Short-term administration of tibolone reduces inflammation and oxidative stress in the hippocampus of ovariectomized rats fed high-fat and high-fructose.

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD-consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water-and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.

Leptin receptor and prolactin in pubertal disorders and chronic kidney disease.

BACKGROUND: Knowledge of chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys is limited as few studies have explored this disorder. This study aimed to identify the usefulness of assessing hormonal parameters in male adolescents with CKD and their correlation with PD in a 12-month follow-up period. METHODS: A prospective cohort study was conducted among male adolescents with CKD (stages IV and V). Data regarding the age at puberty onset were collected from the patients' clinical records and through interview. The patients were followed up for 12 months during their pubertal development. At the beginning, routine hormonal profile tests were performed to examine the patients' thyroid profile, prolactin levels, luteinizing hormone, follicle-stimulating hormone, testosterone, leptin, and receptor leptin. The hormonal profiles of patients with and without PD were compared. Comparisons between the groups were performed using the Student t-test and Fisher's exact tests. Logistic regression analysis was also performed. RESULTS: Data of 64 patients (26/64 with PD) were analyzed. The median age was 15 years and the median time for CKD evolution was 11 months. No differences between groups were noted in the general or biochemical characteristics of the patients. The hormonal parameters, prolactin levels were higher and the free leptin and free thyroxine levels were lower in patients with PD. Leptin receptor levels of >0.90 ng/mL (risk ratio [RR], 8.6; P = 0.004) and hyperprolactinemia (RR, 21.3; P = 0.049) were the risk factors for PD. CONCLUSIONS: Leptin receptor levels of >0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.

The leptin/adiponectin ratio as prognostic marker for dyslipidemia during 1 year of follow-up in pediatric patients receiving kidney replacement therapy.

Introduction: Background: leptin and adiponectin are associated with cardiovascular disease in chronic kidney disease (CKD) patients and could be useful prognostic factors. Objectives. to explore the usefulness of the leptin/adiponectin ratio (LAR) to predict the presence or worsening of dyslipidemia during 1 year of follow-up in children receiving kidney replacement therapy (KRT). Material and methods: a prospective cohort study was performed. Pediatric KRT patients aged between 8 and 17 years who were undergoing hemodialysis or peritoneal dialysis were included. At enrollment, the lipid profile, adiponectin and leptin levels, and somatometric measurements, including body fat percentage, were determined. At the one-year follow-up, the lipid profile was reassessed. Results: of the 70 patients included, the median age was 13 years, and there was no sex predominance (52.8 % males). At the end of follow-up, the patients were divided into three groups: those without dyslipidemia (WOD), those who developed or experienced worsening of their dyslipidemia (DWD) and those with persistent dyslipidemia (PD). A LAR > 0.85 (OR, 16.7) and body fat percentage (OR, 1.46) were associated with an increased risk of PD and DWD at 12 months, independently of urea level, BMI Z-score, benzafibrate treatment, CKD progression time, and replacement treatment. Conclusions: a LAR > 0.85 and fat body percentage at the beginning of follow-up were strongly associated with the presence, persistence or worsening of dyslipidemia at the 12-month follow-up in children with KRT.

Introducción: Antecedentes: la leptina y la adiponectina se asocian con enfermedad cardiovascular en los pacientes con enfermedad renal crónica (ERC) y podrían ser factores pronósticos útiles. Objetivos: explorar la utilidad del cociente leptina/adiponectina (LAR) para predecir la presencia o empeoramiento de la dislipidemia durante 1 año de seguimiento en niños que reciben terapia de reemplazo renal (TRR). Material y métodos: se realizó un estudio de cohortes prospectivo. Se incluyeron pacientes pediátricos con TRR de entre 8 y 17 años que estaban en hemodiálisis o diálisis peritoneal. Al inicio del estudio se determinaron el perfil lipídico, los niveles de adiponectina y leptina, y las mediciones somatométricas, incluido el porcentaje de grasa corporal. En el seguimiento de un año, se reevaluó el perfil de lípidos. Resultados: de los 70 pacientes incluidos, la mediana de edad fue de 13 años y no hubo predominio de sexo (52,8 % de varones). Al final del seguimiento, los pacientes se dividieron en tres grupos: aquellos sin dislipidemia (SD), aquellos que desarrollaron o experimentaron un empeoramiento de su dislipidemia (ED) y aquellos con dislipidemia persistente (PD). Un LAR > 0,85 (OR: 16,7) y el porcentaje de grasa corporal (OR: 1,46) se asociaron con un mayor riesgo de ED y PD a los 12 meses, independientemente del nivel de urea, la puntuación Z del IMC, el tratamiento con benzafibrato, el tiempo de progresión de la ERC y el tratamiento de reemplazo. Conclusiones: un LAR > 0,85 y el porcentaje de grasa corporal al inicio del seguimiento se asociaron fuertemente con la presencia, persistencia o empeoramiento de la dislipidemia a los 12 meses de seguimiento en niños con TRR.

[Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19]. / Activación de sensores del estrés del retículo endoplásmico por dietas asociadas a enfermedades metabólicas y COVID-19.

The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store. Caloric overload and glycolipotoxicity generated by hypercaloric diets cause alteration of the endoplasmic reticulum, activating the Unfolded Protein Response (UPR) as a reaction to cellular stress related to the endoplasmic reticulum and whose objective is to restore the homeostasis of the organelle by decreasing oxidative stress, protein synthesis and Ca2+ leakage. However, during chronic stress, the UPR induces reactive oxygen species formation, inflammation and apoptosis, exacerbating the state of the endoplasmic reticulum and propagating a deleterious effect on the other organelles. This is why endoplasmic reticulum stress has been considered an inducer of the onset and development of metabolic diseases, including the aggravation of COVID-19. So far, few strategies exist to reestablish endoplasmic reticulum homeostasis, which are targeted to sensors that trigger UPR. Therefore, the identification of new mechanisms and novel therapies related to mitigating the impact of endoplasmic reticulum stress and associated complications is urgently warranted.

El retículo endoplásmico es un organelo abundante, dinámico y sensor de energía. Sus abundantes membranas, rugosa y lisa, se encuentran distribuidas en diferentes proporciones dependiendo del linaje y requerimiento celular. Su función es llevar a cabo la síntesis de proteínas y lípidos, y es el almacén principal de Ca2+ intracelular. La sobrecarga calórica y la glucolipotoxicidad generada por dietas hipercalóricas provoca la alteración del retículo endoplásmico, activando la respuesta a proteínas mal plegadas (UPR, Unfolded Protein Response, por sus siglas en inglés) como reacción al estrés celular relacionado con el retículo endoplásmico y cuyo objetivo es restablecer la homeostasis del organelo al disminuir el estrés oxidante, la síntesis de proteínas y la fuga de Ca2+. Sin embargo, durante un estrés crónico, la UPR induce formación de especies reactivas de oxígeno, inflamación y apoptosis, exacerbando el estado del retículo endoplásmico y propagando un efecto nocivo para los demás organelos. Es por ello que el estrés del retículo endoplásmico se ha considerado un inductor del inicio y desarrollo de enfermedades metabólicas, incluido el agravamiento de COVID-19. Hasta el momento, existen pocas estrategias para reestablecer la homeostasis del retículo endoplásmico, las cuales son dirigidas a los sensores que desencadenan la UPR. Por tanto, se justifica con urgencia la identificación de nuevos mecanismos y terapias novedosas relacionadas con mitigar el impacto del estrés del retículo endoplásmico y las complicaciones asociadas.

Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism.

BACKGROUND: The estimation of left ventricular ejection fraction (LVEF) by 2D echocardiography (2D-ECHO) is the most used tool to assess LV systolic function (LVSF). Global longitudinal strain (GLS) has recently been suggested as a superior method for several evaluations. This study explored the association and prevalence of LV systolic dysfunction (LVSD) by using these methods in patients with end-stage renal disease (ESRD) and severe hyperparathyroidism (SHPTH); both associated with cardiovascular events (CEs). AIM: To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional 2D-ECHO. METHODS: In 62 patients with ESRD and SHPTH, asymptomatic, and without a history of CEs, LVSF was evaluated by 2D-ECHO, obtaining the EF, by the Simpson biplane method, and GLS by speckle tracking. RESULTS: The total patients with ESRD had a preserved LVEF (> 50%) but abnormal GLS (< 13.55%). Additionally, multivariate analysis showed an independent association of GLS and serum parathyroid hormone (PTH), LV mass index, and hemoglobin. Also, PTH was independently associated with lateral e' wave and tricuspid regurgitation velocity. CONCLUSION: In patients with SHPTH linked to ESRD, the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.

Activación de sensores del estrés del retículo endoplásmico por dietas asociadas a enfermedades metabólicas y COVID-19 / Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19

El retículo endoplásmico es un organelo abundante, dinámico y sensor de energía. Sus abundantes membranas, rugosa y lisa, se encuentran distribuidas en diferentes proporciones dependiendo del linaje y requerimiento celular. Su función es llevar a cabo la síntesis de proteínas y lípidos, y es el almacén principal de Ca2+ intracelular. La sobrecarga calórica y la glucolipotoxicidad generada por dietas hipercalóricas provoca la alteración del retículo endoplásmico, activando la respuesta a proteínas mal plegadas (UPR, Unfolded Protein Response, por sus siglas en inglés) como reacción al estrés celular relacionado con el retículo endoplásmico y cuyo objetivo es restablecer la homeostasis del organelo al disminuir el estrés oxidante, la síntesis de proteínas y la fuga de Ca2+. Sin embargo, durante un estrés crónico, la UPR induce formación de especies reactivas de oxígeno, inflamación y apoptosis, exacerbando el estado del retículo endoplásmico y propagando un efecto nocivo para los demás organelos. Es por ello que el estrés del retículo endoplásmico se ha considerado un inductor del inicio y desarrollo de enfermedades metabólicas, incluido el agravamiento de COVID-19. Hasta el momento, existen pocas estrategias para reestablecer la homeostasis del retículo endoplásmico, las cuales son dirigidas a los sensores que desencadenan la UPR. Por tanto, se justifica con urgencia la identificación de nuevos mecanismos y terapias novedosas relacionadas con mitigar el impacto del estrés del retículo endoplásmico y las complicaciones asociadas.

The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store. Caloric overload and glycolipotoxicity generated by hypercaloric diets cause alteration of the endoplasmic reticulum, activating the Unfolded Protein Response (UPR) as a reaction to cellular stress related to the endoplasmic reticulum and whose objective is to restore the homeostasis of the organelle by decreasing oxidative stress, protein synthesis and Ca2+ leakage. However, during chronic stress, the UPR induces reactive oxygen species formation, inflammation and apoptosis, exacerbating the state of the endoplasmic reticulum and propagating a deleterious effect on the other organelles. This is why endoplasmic reticulum stress has been considered an inducer of the onset and development of metabolic diseases, including the aggravation of COVID-19. So far, few strategies exist to reestablish endoplasmic reticulum homeostasis, which are targeted to sensors that trigger UPR. Therefore, the identif ication of new mechanisms and novel therapies related to mitigating the impact of endoplasmic reticulum stress and associated complications is urgently warranted.

Pattern of Adiponectin, Osteocalcin, Irisin, FGF-21, and MCP-1 According to the Body Size Phenotype: Could They Be Markers of Metabolic Health in Mexican-Mestizo Middle-Aged Women?

Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics were evaluated in metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy obese, and metabolically unhealthy obese women. There was an association of OCN with BMI (r = -0.107; p = 0.047); adiponectin with BMI (r = -0.217; p = 0.001), insulin (r = -0.415; p = 0.0001), HOMA-IR (r = -0.429; p = 0.0001), and VAT (r = -0.134; p = 0.025); irisin with BMI (r = 0.604; p = 0.001), insulin (r = 0.446; p = 0.0001), HOMA-IR (r = 0.452; p = 0.0001), and VAT (r = 0.645; p = 0.0001); FGF-21 with insulin (r = -0.337; p= 0.030) and HOMA-IR (r = -0.341; p = 0.03); and MCP-1 with BMI (r = 0.481; p = 0.0001), VAT (r = 0.497; p = 0.001), insulin (r = 0.298; p= 0.001), and HOMA-IR (r = 0.255; p = 0.004). A multivariate analysis showed that an elevation of OCN (OR 1.4 (95%CI 1.06-1.81)) and a reduction of adiponectin (OR 0.9 (0.84-0.96)) were associated factors for a metabolic unhealthy phenotype in normal weight participants. Likewise, higher irisin (OR 1.007 (1.003-1.011)) and MCP-1 (1.044 (1.008-1.083)) were risk factors for a metabolic unhealthy phenotype in woman with obesity. OCN, adiponectin, irisin, FGF-21, and MCP-1 are associated with some metabolic parameters such as BMI, HOMA-IR, and VAT, and could be possible biomarkers of an unhealthy metabolic phenotype in middle-aged women.

Increase of 5-HT levels is induced both in mouse brain and HEK-293 cells following their exposure to a non-viral tryptophan hydroxylase construct.

Tryptophan hydroxylase type 2 (Tph2) is the rate-limiting enzyme for serotonin (5-HT) biosynthesis in the brain. Dysfunctional Tph2 alters 5-HT biosynthesis, leading to a deficiency of 5-HT, which could have repercussions on human behavior. In the last decade, several studies have associated polymorphisms of the TPH2 gene with suicidal behavior. Additionally, a 5-HT deficiency has been implicated in various psychiatric pathologies, including alcoholism, impulsive behavior, anxiety, and depression. Therefore, the TPH2 gene could be an ideal target for analyzing the effects of a 5-HT deficiency on brain function. The aim of this study was to use the construct pIRES-hrGFP-1a-Tph2-FLAG to treat CD1-male mice and to transfect HEK-293-cells and then to evaluate whether this treatment increases 5-HT production. 5-HT levels were enhanced 48 h post-transfection, in HEK-293 cells. Three days after the ocular administration of pIRES-hrGFP-1a-Tph2-FLAG to mice, putative 5-HT production was significantly higher than in the control in both hypothalamus and amygdala, but not in the brainstem. Further research will be needed on the possible application of this treatment for psychiatric diseases involving a Tph2 dysfunction or serotonin deficiency.

Altered cardiometabolic profile in girls with central precocious puberty and adipokines: A propensity score matching analysis.

OBJECTIVE: To compare cardiometabolic factors and adipokines between patients with recently diagnosed CPP and controls without CPP, paired by BMI Z scores (BMIz) and classified into girls with adequate nutritional status and girls who are overweight or obese. METHODS: This cross-sectional study was performed from January 2012 to May 2015 at two tertiary care pediatric centers in Mexico City. We included female patients with idiopathic CPP without other chronic pathology and healthy controls. Patients were divided into groups, BMI < 85th and BMI ≥ 85th percentile, according to 2000 CDC Growth Charts. Anthropometric data and fasting plasma concentrations of lipids, glucose, insulin, and leptin were assessed. RESULTS: There were 73 patients with CPP and 82 without CPP. Sixty-six patients were matched between the groups; no significant difference was noted between the groups according to zBMI. However, differences in the bone/chronological age relationship, birth weight and proportions in different Tanner stages were observed. Among girls with normal BMI, the percentage of body fat (24.6% vs 18.9%, p < 0.001), serum triglycerides (102.9 vs 54.3 mg/dl, p < 0.001), leptin (7.46 vs 5.4 ng/ml, p = 0.010) and free leptin (0.44 vs 0.29 ng/ml, p = 0.044) were higher in those with CPP; additionally, girls with CPP presented a higher proportion of hypertriglyceridemia. In the overweight/obese group, adiponectin levels were lower in girls with CPP (6.23 vs 7.28 pg/ml, p = 0.011). CONCLUSIONS: Girls with CPP and normal BMI at diagnosis had a worse cardiometabolic profile, as reflected by higher levels of free leptin, and higher proportion of hypertriglyceridemia than girls without CPP.

Comparación del tipo de cirugía bariátrica sobre la reducción de peso corporal y su relación con la ghrelina / Comparison between type of bariatric surgery on reduction of body weight and its ghrelin relationship

Resumen Objetivo: La cirugía bariátrica es un procedimiento para disminuir de peso a largo plazo en pacientes con obesidad. El objetivo de este estudio fue evaluar los niveles de ghrelina y la reducción del peso de acuerdo al tipo de cirugía bariátrica, comparando el bypass de una sola anastomosis y la gastrectomía formadora de manga. Materiales y Métodos: Estudio de cohorte que incluyó a 50 pacientes con obesidad, 22 mini-bypass y 28 mangas gástricas. Se evaluó el peso corporal y las concentraciones de ghrelina en la etapa prequirúrgica, en el día 7 y en los meses 1, 3 y 6 después de la cirugía. Resultados: Del total de pacientes, el 86% presentaron > 50% pérdida del exceso de peso (PEPP) a los 6 meses. La concentración de ghrelina disminuyó desde la primera semana en el grupo total de participantes. A los 6 meses, se observó mayor reducción de ghrelina en los pacientes con la manga gástrica (4.636 ± 2.535 vs 1.340 ± 1.001 pg/mL, p < 0,0001). El PEPP en pacientes con mini-bypass fue superior, en comparación con manga gástrica. Conclusiones: La comparación entre las técnicas indicó que, a los 6 meses de evolución posquirúrgica, los pacientes con mini-bypass presentaron mayor reducción de peso corporal y del nivel de ghrelina, en comparación con el grupo de manga gástrica. La concentración de ghrelina es una variable que participa en el control de peso; sin embargo, el tipo de abordaje quirúrgico probablemente tiene mayor relación con la pérdida de peso en estos pacientes.

Introduction: Bariatric surgery is a procedure to reduce weight in the long term in patients with obesity. The objective of this study was to evaluate ghrelin levels and weight reduction according to the type of bariatric surgery, comparing the single anastomosis bypass and the sleeve-forming gastrectomy. Materials and Method: Cohort study that included 50 patients with obesity, 22 Mini-Bypass and 28 gastric sleeve. Body weight and ghrelin concentrations were evaluated in the presurgical stage, on day 7 and in months 1, 3 and 6 after surgery. Results: Of the total of patients, 86% had > 50% excess weight loss (PEPP) at 6 months. The concentration of ghrelin decreased within the first week of the intervention. At 6 months, greater reduction of ghrelin was observed in patients with gastric sleeve (4636 ± 2535 vs 1340 ± 1001 pg/mL, p < 0.0001). The PEPP in patients with Mini-Bypass was superior, compared to gastric sleeve. Conclusion: The comparison between the techniques indicated that, after 6 months of post-surgical evolution, patients with Mini-Bypass had a greater reduction in body weight and ghrelin levels, compared to the gastric sleeve group. Ghrelin concentration is a variable that participates in weight control; however, the type of surgical approach is probably more related to weight loss in these patients.

Dímeros D e hiperglucemia y mortalidad en COVID-19 en un centro hospitalario de México / D-dimers, hyperglycemia and mortality in COVID-19 in a hospital in Mexico

Resumen Objetivo: Evaluar la asociación entre la concentración de glucosa al ingreso y los niveles circulantes de dímeros D en pacientes hospitalizados por enfermedad por coronavirus 2019 (COVID-19). Pacientes y métodos: Se estudiaron 187 pacientes hospitalizados por COVID-19. Se evaluaron las características bioquímicas, la concentración de glucosa y dímeros D, la gravedad de la enfermedad definida por la presencia de neumonía y/o insuficiencia respiratoria que ameritó ventilación mecánica invasiva (VMI) y la causa del egreso hospitalario. Resultados: La edad promedio de los pacientes fue 52 años, el 68% eran hombres, un 40.8% con obesidad y un 23.5% con hipertensión. Del total de pacientes hospitalizados, el 45.5% presentaba diabetes o hiperglucemia a la admisión. La concentración de proteína C reactiva y de dímeros D (1,134 [646.5-4,135.0] vs. 755 [548.7-1,780.0] ng/ml; p = 0.04] fue superior en pacientes con diabetes e hiperglucemia, en comparación con los pacientes con glucosa normal. Los pacientes que requirieron VMI presentaron también mayor concentración de dímeros D. Se observó una correlación directa entre las concentraciones de glucosa inicial y dímeros D (r: 0.239; p = 0.003). Conclusión: En los pacientes con COVID-19 el estado hiperglucémico se asocia directamente con un incremento de la concentración de dímeros D. Los resultados de este estudio deben conducir a insistir en el control glucémico como estrategia fundamental en los pacientes con COVID-19.

Abstract Objective: To evaluate the association between glucose level at admission and circulating levels of D-dimers in patients hospitalized for coronavirus disease 2019 (COVID-19). Methods: 187 patients hospitalized for COVID-19 were studied. Biochemical characteristics, glucose and D-dimers levels, severity of disease, defined by the presence of pneumonia and/or respiratory failure that required invasive mechanical ventilation (IVM) and the cause of hospital discharge were evaluated. Results: Age was 52 years, 68% were male, 40.8% with obesity and 23.5% with hypertension. Of the total of hospitalized patients, 45.5% had diabetes or hyperglycemia upon admission. Patients with diabetes and/or admission hyperglycemia had higher levels of protein C-reactive and D-dimers [(1134 (646.5-4135.0) vs. 755 (548.7-1780.0) ng/ml, p = 0.04], compared to patients with normal glucose level. Patients who required IMV also had a higher concentration of D-dimers. A correlation between glucose and D-dimers levels was evidenced (r=0.239, p=0.003). Conclusions: In patients with COVID-19, the hyperglycemic state is directly associated with an increase in the concentration of D-dimers and severity of disease. The results of this study should lead to insisting on glycemic control as a fundamental strategy in patients with COVID-19.

Double-task exercise programmes to strengthen cognitive and vascular health in older adults at risk of cognitive decline: protocol for a randomised clinical trial.

INTRODUCTION: Cognitive and physical declines are frequent causes of disability among older adults (OAs) in Mexico that imposes significant burden on the health system and OAs' families. Programmes to prevent or delay OAs' cognitive and physical decline are scarce. METHODS AND ANALYSIS: A double-blind randomised clinical trial will be conducted. The study will aim to evaluate two 24-week double-task (aerobic and cognitive) square-stepping exercise programmes for OAs at risk of cognitive decline-one programme with and another without caregiver participation-and to compare these with an aerobic-balance-stretching exercise programme (control group). 300 OAs (100 per group) affiliated with the Mexican Institute of Social Security (IMSS) between 60 and 65 years of age with self-reported cognitive concerns will participate. They will be stratified by education level and randomly allocated to the groups. The intervention will last 24 weeks, and the effect of each programme will be evaluated 12, 24 and 52 weeks after the intervention. Participants' demographic and clinical characteristics will be collected at baseline. The outcomes will include: (1) general cognitive function; (2) specific cognitive functions; (3) dual-task gait; (4) blood pressure; (5) carotid intima-media thickness; (6) OAs' health-related quality of life; and (7) caregiver burden. The effects of the interventions on each outcome variable will be examined using a repeated-measures analysis of variance (ANOVA), with study groups as the between-subjects variable and time as the within-subject variable. ETHICS AND DISSEMINATION: The study was approved by the IMSS Ethics and Research Committees (registration number: 2018-785-095). All participants will sign a consent form prior to their participation. The study results will be disseminated to the IMSS authorities, healthcare providers and the research community. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04068376).

The Impact of a History of Pre-maturity on Viral Respiratory Infections in Children Under 2 Years of Age: A Propensity Score-Matching Analysis of in-hospital Complications and Mortality.

Introduction: A history of pre-maturity may be a risk factor for complications in patients under 24 months of age hospitalized for viral respiratory infections (VRIs). Objective: To identify the impact of a history of pre-maturity on in-hospital complications and mortality in patients under 24 months of age who were hospitalized for VRIs over a period of 5 years. Material and Methods: This was a propensity score-matched study. The database was compiled by physicians, electronically validated by engineers, and analyzed by statisticians. Patients diagnosed with VRIs (based on International Classification of Diseases [ICD-10]) codes B974, J12, J120-J129X, J168, J17, J171, J178, J20, J203-J209, J21, J210, J211, J218, J219, J22X, and J189) from 2013 to 2017 were enrolled in the study. The subjects were classified into two groups according to the absence or presence of a history of pre-maturity (P070, P072, P073). Patients with congenital heart disease (CHD) (Q20-Q26) were excluded. Length of hospital stay, in-hospital complications, surgical procedures, and mortality were analyzed. Statistical Analysis: Patients were matched according to age. For comparisons between groups, Student's t-tests and chi2 tests were applied. A logistic regression model was constructed to identify factors related to in-hospital complications and mortality. Results: In total, 5,880 patients were eligible for inclusion in the analysis. The average patient age was 14.25 weeks. The presence of pre-maturity (coefficient = 1.16), male sex, bronchopulmonary dysplasia (BPD), in-hospital infectious complications (coefficient = 11.31), and invasive medical procedures (coefficient = 18.4) increased the number of days of hospitalization. Invasive medical procedures (OR = 6.13), a history of pre-maturity (OR = 2.54), and male sex (OR = 1.78) increased the risk for in-hospital complications. In-hospital infectious complications (OR = 84.2) and invasive medical procedures (OR = 58.4) were risk factors for mortality. Conclusions: A history of pre-maturity increased the length of hospital stay and the rate of in-hospital complications but did not increase mortality in patients under 24 months of age hospitalized for VRIs.

Echography analysis of musculoskeletal, heart and liver alterations associated with endothelial dysfunction in obese rats.

BACKGROUND: Modern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats. METHODS: Sprague Dawley rats (250 ± 5 g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities. RESULTS: The body weight in the Ob group was increased compared to that in the control group, (p < 0.001); in addition, increased glucose, cholesterol and triglyceride concentrations (p < 0.05) as well as increased levels of the adhesion molecules ICAM-1 and, VCAM-1 (p < 0.01) were found in the Ob group vs the C group. On ultrasound, 75% of the Ob group presented fatty liver and distal joint abnormalities. CONCLUSION: Obese rats exhibit endothelial dysfunction and musculoskeletal changes, also, fatty liver and articular cysts in the posterior region of the distal lower- extremity joints.

The gonadal expression pattern of lipocalin­2 and 24p3 receptor is modified in the gonads of the offspring of obese rats.

Obesity represents a global health and economic burden, affecting millions of individuals worldwide. This pathology is associated with a chronic low­grade inflammatory state that is partially responsible for the development of other cardiometabolic complications. Clinical studies have reported an association between high circulating levels of lipocalin­2 (Lcn2) and increased body weight. Additionally, there is scientific evidence demonstrating the impact of maternal obesity on fetal programming. The latter and the fact that the authors previously found that Lcn2 and its receptor (24p3R) are expressed in the gonads of wild­type rats, led to the analysis of their mRNA profile and cellular localization in gonads collected from the offspring of obese rats at 21 days postconception (dpc), and 0, 2, 4, 6, 12, 20 and 30 days postnatal (dpn) in the present study. Semi­quantitative PCR revealed a statistically significant downregulation of Lcn2 and 24p3R mRNA at 21 dpc in the ovaries (P<0.01) and testicles (P<0.001) of the offspring of obese mothers. At 30 dpn, the relative expression of Lcn2 mRNA decreased significantly in the ovaries of the experimental group (P<0.05), while Lcn2 mRNA expression was not detectable in testicles. Regarding 24p3R, its mRNA was only significantly decreased at 21 dpc in ovaries of pups of obese mothers. At 30 dpn, the change in females was not significant. Conversely, in testicles, 24p3R mRNA levels increased slightly in the experimental group at 30 dpn. The Lcn2 protein signal was less intense in gonadal tissue sections from 30 dpn offspring of obese rats (P<0.001), whereas the 24p3R signal was downregulated in ovaries (P<0.001) and slightly upregulated in testicles. It was concluded that maternal obesity changes the expression of Lcn2 and 24p3R in the gonads of the offspring of obese rats, possibly through fetal programming. The consequences of this dysregulation for the offspring's gonadal function remains to be determined.

Hospitalizations for viral respiratory infections in children under 2 years of age: epidemiology and in-hospital complications.

BACKGROUND: Viral respiratory infections (VRIs) are a frequent cause of hospitalization in children under 24 months of age. A history of prematurity or heart disease may be a risk factor for complications in patients hospitalized for VRI. The objective was to describe epidemiological data for children hospitalized for IRV and aged 1 to 24 months and to identify risk factors for the presence of in-hospital complications and mortality over a period of 5 years. METHODS: This was a cross-sectional study. Patients registered with VRI codes B974, J12, J120-J129X, J168, J17, J171, J178, J20, J203-J209, J21, J210, J211, J218, J219 (based on International Classification of Diseases [ICD-10]) from 2013 to 2017 were included. Three subanalyses were performed to compare [1] patients with pathological history (prematurity, bronchopulmonary dysplasia [BPD] and congenital heart disease [CHD]), [2] diagnoses (pneumonia, acute bronchitis, and acute bronchiolitis), and [3] admission to the pediatric intensive care unit. Days of hospital stay, in-hospital complications, invasive medical procedure and mortality were analyzed. STATISTICAL ANALYSIS: VRI hospitalization prevalence was described. For comparison between groups, Student's t-test, ANOVA and the Chi2 test were applied. To identify factors related to days of hospital stay, in-hospital complications and mortality, a linear and logistic regression model was performed. RESULTS: A total of 66,304 hospitalizations were reported. The average age was 14.7 weeks; hospitalization events were higher in winter (39%), followed by autumn (27.3%). A total of 371 (0.56%) patients died. A total of 7068 (10.6%) hospitalized patients with pathological histories were identified. The presence of BPD (coefficient = 1.6), CHD (coefficient = 1.2), diagnosis of pneumonia (coefficient = 1.2), in-hospital complications (coefficient = 2.1) and invasive medical procedures (coefficient = 15.7) were the most common factors that increased the length of hospital stay. Risk factors for in-hospital complications and mortality were invasive medical procedure (OR = 3.3 & 11.7), BPD (OR = 1.8 & 1.6), CHD (OR = 4.6 & 3.4) and diagnosis of pneumonia (OR = 1.8 & 4.2). CONCLUSIONS: Risk factors for morbidity and mortality in patients hospitalized for VRIs are BPD and CHD, diagnosis of pneumonia and invasive medical procedure.