Beneficial effects of physical exercise on the osteo-renal Klotho-FGF-23 axis in Chronic Kidney Disease: A systematic review with meta-analysis.

The aim of this study was to investigate the efficacy of physical exercise in chronic kidney disease, describing its impact on the Klotho-FGF23 axis. PubMed, Web of Science and Scopus databases, updated to January 2023, were searched. The present study employed mean difference and a 95% confidence interval (CI) to examine the efficacy of the intervention. Heterogeneity was assessed through inconsistency statistics (I2). Out of the 299 studies identified, a total of 4 randomized controlled trials (RCTs), comprising 272 participants, met the eligibility criteria. Compared with the control group, physical exercise significantly decreased the concentrations of FGF23 (MD: -102.07 Pg/mL, 95% CI: -176.23.47, -27.91 I2= 97%, p = 0.001), and a significantly increased the concentrations of Klotho protein: (MD: 158.82 Pg/mL, 95% CI: 123.33, -194.31, I2 = 0%, p = 0.001). The results of our study indicated that the exercise has a direct relationship with Klotho-FGF23 axis. We can conclude that physical exercise in patients with CKD produces beneficial effects on the pathophysiological components related to this disease, including cardiorespiratory fitness and vascular functions. As observed, both endurance and aerobic physical exercise increase Klotho production and decrease FGF23 levels. Evidence indicates that exercise attenuates the progression of CKD, improves uremic parameters and down-regulates inflammation-related markers.

Mindfulness Practice Reduces Hair Cortisol, Anxiety and Perceived Stress in University Workers: Randomized Clinical Trial.

BACKGROUND: Anxiety and stress are common mental health conditions reported by university workers. Practices of mindfulness represent one promising approach as an effective and feasible means to reduce stress, improve mental health and promote well-being; however, there are no clinical trials that have combined long-term stress biomarkers (hair cortisol) and psychometric assessments in a sample of university workers. OBJECTIVE: This study investigated the effectiveness of a mindfulness-based program on long-term stress, by measuring hair cortisol concentration and perceived stress and anxiety among workers who were undergoing high levels of stress. METHOD: We conducted a randomized clinical trial at work among the employees of a public university. We compared a group that received the eight-week mindfulness intervention with the wait list group who received no intervention. RESULTS: A total of 30 participants were included in the study, with n = 15 subjects in the intervention group and n = 15 in the control group. Hair cortisol, perceived stress and anxiety significantly reduced after the intervention compared to the control group, which had no appreciable decline in the measured variables. CONCLUSION: This clinical trial showed the effectiveness of a mindfulness program on mental health psychometric measures (perceived stress and anxiety) and on a long-term stress biomarker (hair cortisol). It can be concluded that an eight-week mindfulness program could be implemented as an effective strategy to reduce stress biomarkers (hair cortisol) as well as perceived stress and anxiety, improving the mental health of university workers.

Longitudinal study of the body mass index and biochemical nutritional parameters of patients in dialysis / Estudio longitudinal del índice de masa corporal y parámetros bioquímicos nutricionales en pacientes en diálisis

ABSTRACT Background/Aim: Chronic kidney failure is frequently related to malnutrition. This research aimed to assess the nutritional status of hemodialysis patients by assessing their biochemical and anthropometric parameters and determining whether the disorders suffered stemmed from nutritional deterioration directly related to time on dialysis. Materials and Methods: This research monitored 90 patients of both genders with chronic kidney failure who regularly received hemodialysis at the kidney unit of our Hospital in Granada (Spain) over five years. The patient's blood was tested quarterly for plasma albumin (Alb), total cholesterol (TC), and total proteins (TP) and monthly for transferrin (Tr). Anthropometric measurements were taken of the patient's weight, height, and body mass index (BMI) and, based on the patient's BMI, classified as established by the World Health Organization. Results: During the five years of our study, patients experienced a statistically significant decrease in total protein (0.941g/dl), plasma albumin (0.9382g/dl), total cholesterol (23.77mg/dl), and transferrin (78.17. g/dl) p < 0.0001. On the contrary, the mean BMI values did not show statistically relevant differences (p < 0.805). However, all patients remained in the WHO category of overweight. The body volume values did not show statistically significant differences either. Conclusions: In conclusion, the nutritional deterioration of these patients was not reflected in their BMI but mainly in their serum chemistry.

RESUMEN Antecedentes/Objetivo: La insuficiencia renal crónica está relacionada frecuentemente con la malnutrición, afectando aproximadamente a un tercio de los pacientes con enfermedad renal avanzada, lo que contribuye a su morbilidad y mortalidad. El objetivo de esta investigación fue evaluar el estado nutricional de los pacientes en hemodiálisis valorando sus parámetros bioquímicos y antropométricos y determinar si los trastornos que padecían se debían al deterioro nutricional directamente relacionado con el tiempo en diálisis. Materiales y Métodos: Es esta investigación realizó un seguimiento de 90 pacientes de ambos sexos con insuficiencia renal crónica, que recibían hemodiálisis periódicamente en la unidad renal de nuestro Hospital en Granada (España) durante un período de cinco años. La sangre de los pacientes se analizó trimestralmente para albúmina plasmática (Alb), colesterol total (TC) y proteínas totales (TP), y mensualmente para transferrina (Tr). Se tomaron medidas antropométricas de peso, talla e índice de masa corporal (IMC) de los pacientes y se les efectuaron mediciones antropométricas de peso, altura e índice de masa corporal calculado mediante la formula peso/talla², y agrupada según la clasificación de la OMS en IMC < 18.50 infrapeso, 18.50 a 24,99 normal, 25 a 29,99 sobrepeso y >30 del IMC s/OMS y se consideró para el estudio como desnutrición un en IMC < 23 kg/m2 y niveles de albumina <3,8 g/dl según el consenso del panel de expertos de la International Society for Renal Nutrition and Metabolism. Resultados: Durante los cinco años de nuestro estudio, los pacientes experimentaron una disminución estadísticamente significativa de proteínas totales (0,941 g/dl), albúmina plasmática (0,9382 g/dl), colesterol total (23,77 mg/dl) y transferrina (78,17. g /dl) p < 0,0001. Por el contrario, los valores medios del IMC no mostraron diferencias estadísticamente relevantes (p < 0,805). Sin embargo, todos los pacientes permanecieron en la categoría de sobrepeso de la OMS. Los valores de volumen corporal tampoco mostraron diferencias estadísticamente significativas. Conclusiones: La desnutrición de los pacientes en diálisis es un hecho patente, el IMC no se corresponde con los parámetros bioquímicos observados, por lo que el deterioro nutricional de estos pacientes se manifiesta principalmente mediante los parámetros bioquímicos estudiados.

Validation of nasospheroids to assay CFTR functionality and modulator responses in cystic fibrosis.

The availability of a simple, robust and non-invasive in vitro airway model would be useful to study the functionality of the cystic fibrosis transmembrane regulator (CFTR) protein and to personalize modulator therapy for cystic fibrosis (CF) patients. Our aim was to validate a CFTR functional study using nasospheroids, a patient-derived nasal cell 3D-culture. We performed live-cell experiments in nasospheroids obtained from wild-type individuals and CF patients with different genotypes and phenotypes. We extended the existing method and expanded the analysis to upgrade measurements of CFTR activity using forskolin-induced shrinking. We also tested modulator drugs in CF samples. Immobilizing suspended-nasospheroids provided a high number of samples for live-cell imaging. The diversity observed in basal sizes of nasospheroids did not affect the functional analysis of CFTR. Statistical analysis with our method was simple, making this protocol easy to reproduce. Moreover, we implemented the measurement of inner fluid reservoir areas to further differentiate CFTR functionality. In summary, this rapid methodology is helpful to analyse response to modulators in CF samples to allow individualized treatment for CF patients.

Study of weight and body mass index on graft loss after transplant over 5 years of evolution.

Patients frequently experience a weight gain after organ transplantation. This increase in weight is the result of multiple factors, and is usually intensified by glucocorticoids and immunosuppressive drugs. It can also delay graft function and cause serious health problems. The objective of this study was to study the obesity as well as its causes and consequences in kidney transplant patients. The sample population consisted of 282 renal transplant patients, 170 men and 112 women, 18-74 years of age, who were monitored over a period of five years. For the purposes of our research, the patients were divided into two groups: (1) normal weight 18.5 ≤ BMI <25; (2) overweight 25 ≤ BMI ≤30. The association between BMI as an independent variable and graft survival was determined by means of a Cox regression analysis. Overweight patients were characterized by a higher comorbidity prevalence. In the Cox multivariate analysis, the initial BMI, evaluated as a continuous variable continued to be an independent predictor of delayed graft function and chronic nephropathy. This study evaluated the BMI as a continuous value instead of a categorical value. In conclusion, our results suggest that an increase in BMI without categorical variation can be an independent risk factor for graft loss. Consequently, obesity prevention for renal transplant patients should include dietary counseling and management, moderate physical activity, and steroid minimization.

A comparison of gene expression and DNA methylation patterns across tissues and species.

Previously published comparative functional genomic data sets from primates using frozen tissue samples, including many data sets from our own group, were often collected and analyzed using nonoptimal study designs and analysis approaches. In addition, when samples from multiple tissues were studied in a comparative framework, individuals and tissues were confounded. We designed a multitissue comparative study of gene expression and DNA methylation in primates that minimizes confounding effects by using a balanced design with respect to species, tissues, and individuals. We also developed a comparative analysis pipeline that minimizes biases attributable to sequence divergence. Thus, we present the most comprehensive catalog of similarities and differences in gene expression and DNA methylation levels between livers, kidneys, hearts, and lungs, in humans, chimpanzees, and rhesus macaques. We estimate that overall, interspecies and inter-tissue differences in gene expression levels can only modestly be accounted for by corresponding differences in promoter DNA methylation. However, the expression pattern of genes with conserved inter-tissue expression differences can be explained by corresponding interspecies methylation changes more often. Finally, we show that genes whose tissue-specific regulatory patterns are consistent with the action of natural selection are highly connected in both gene regulatory and protein-protein interaction networks.

Molecular and cellular reorganization of neural circuits in the human lineage.

To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease.