Catch-up growth in juvenile rats, fat expansion, and dysregulation of visceral adipose tissue

BACKGROUND: Accelerated catch-up growth following intrauterine restriction increases the risk of developing visceral adiposity and metabolic abnormalities. However, the underlying molecular mechanisms of such metabolic programming are still poorly understood. METHODS: A Wistar rat model of catch-up growth following intrauterine restriction was used. A gene expression array was performed in the retroperitoneal adipose tissue sampled at postnatal day (PD) 42. RESULTS: Five hundred and forty-six differentially expressed genes (DEGs) were identified (adjusted p value < 0.05). Gene ontology enrichment analysis identified pathways related to immune and lipid metabolic processes, brown fat cell differentiation, and regulation of PI3K. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups (all p < 0.01) and related to several fat expansion and metabolic parameters, including body weight at PD42, postnatal body weight gain, white and brown adipose tissue mass, plasma triglycerides, and insulin resistance index (all p < 0.05). CONCLUSIONS: Genes related to immune and metabolic processes were upregulated in retroperitoneal adipose tissue following catch-up growth in juvenile rats and were found to be associated with fat expansion and metabolic parameters. Our results provide evidence for several dysregulated genes in white adipose tissue that could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth

The correlation of RNase A enzymatic activity with the changes in the distance between Nepsilon2-His12 and N delta1-His119 upon addition of stabilizing and destabilizing salts.

The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25 degrees C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N(epsilon2) of His(12) and N(delta1) of His(119) at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2', 3'-cyclic monophosphate as a substrate. The results from the measurements of distances between N(epsilon2) of His(12) and N(delta1) of His(119) and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements

ENVEJECIMIENTO Y SOLEDAD

Objective: The aim of this study is to analyze whether elderly people in a state of fragility, visited by the Emergency Domiciliary Care service, have received a follow-up program by the nursing staff and whether they were labeled as “Elderly people in state of fragility.” Material and method: A two-phase observational study. Firstly, in phase I, a population comprising people older than 64 and visited by the emergency domiciliary service from the Raval Nord Primary Care Centre was selected. Whether they had received nursing follow-up and whether they had been diagnosed as elderly people in a frail state was analyzed. In phase II, a simple random sample from this population was chosen. Here, it was analyzed whether there had been changes in the nursing diagnosis and follow-up. Results: Of a total was seen that of 776 medical emergency domiciliary visits, 568 (73.19%) were people belonging to the over 64 group. Out of the total, 57 cases (10%) belonged to the age group between 75 and 85 years old (80%). Out of this group, 77.26% were women; 94% were diagnosed with a chronic condition (diabetes, hypertension, chronic obstructive pulmonary disease, etc); and 77.2% were polymedicated. In addition, 66.7% were not included in the Domiciliary Care Program and were not diagnosed as frail elderly people. In phase II, an increase in nursing care, as well as in the “frail elderly people” diagnosis were found. Conclusions: The use of nursing diagnosis for elderly people in a frail state is an indispensable tool for the monitoring and follow-up of that population.Objetivo: Analizar si en las personas mayores en situación de fragilidad que han sido atendidas por el servicio de urgencias domiciliarias, constaba el seguimiento por el personal de enfermería del centro y  si constaba  el diagnóstico de “Personas mayores en situación de fragilidad”. Material y método: Se realizó un estudio observacional en dos fases: 1ª se analizaron todas las personas mayores de 64 años que fueron atendidas en el servicio de urgencias domiciliarias del centro de Atención Primaría de Raval Nord, se analizó si en dicha población constaba el seguimiento de enfermería y el diagnóstico de personas mayores en situación de fragilidad ; 2ª fase, se realizó un muestreo simple  de la población analizada y se evaluó si se produjeron cambios en  los diagnósticos de enfermería y seguimiento de dicha población. Resultados: De un total de 776 visitas domiciliarias de urgencias médicas, se observó que 568 (73,19%) eran mayores de 64 años. Del total, se estudiaron 57 (10%) casos y se observó que el 80% pertenecían al grupo de edad comprendido entre 75 y 85 años; el 77,26% eran mujeres; el 94% con diagnóstico crónico (Diabetes, Hipertensión Epoc...); el 77,2% eran personas polimedicadas y el 66,7% del total no estaban incluidas en el programa de Atención Domiciliaria y no constaba ningún diagnóstico de “personas mayores frágiles”. En la segunda fase se observa un incremento  en la atención por parte de los profesionales de enfermería y un aumento en el diagnóstico de “Personas mayores frágiles”. Conclusiones: La utilización del diagnóstico de enfermería en las personas en situación de fragilidad es una herramienta imprescindible para el seguimiento y control de dicha población.  

A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA

\ua9 2021 European Association for the Study of the Liver. Background &amp; Aims: Patients with primary biliary cholangitis (PBC) who have an incomplete response to ursodeoxycholic acid remain at risk of disease progression. We investigated the safety and efficacy of elafibranor, a dual PPARα/δ agonist, in patients with PBC. Methods: This 12-week, double-blind phase II trial enrolled 45 adults with PBC who had incomplete response to ursodeoxycholic acid (alkaline phosphatase levels ≥1.67-fold the upper limit of normal (ULN). Patients were randomly assigned to elafibranor 80 mg, elafibranor 120 mg or placebo. The primary endpoint was the relative change of ALP at 12 weeks (NCT03124108). Results: At 12 weeks, ALP was reduced by -48.3\ub114.8% in the elafibranor 80 mg group (p &lt;0.001 vs. placebo) and by -40.6\ub117.4% in the elafibranor 120 mg group (p &lt;0.001) compared to a +3.2\ub114.8% increase in the placebo group. The composite endpoint of ALP ≤1.67-fold the ULN, decrease of ALP &gt;15% and total bilirubin below the ULN was achieved in 67% patients in the elafibranor 80 mg group and 79% patients in the elafibranor 120 mg group, vs. 6.7% patients in the placebo group. Levels of gamma-glutamyltransferase decreased by 37.0\ub125.5% in the elafibranor 80 mg group (p &lt;0.001) and 40.0\ub124.1% in the elafibranor 120 mg group (p &lt;0.01) compared to no change (+0.2\ub126.0%) in the placebo group. Levels of disease markers such as IgM, 5’-nucleotidase or high-sensitivity C-reactive protein were likewise reduced by elafibranor. Pruritus was not induced or exacerbated by elafibranor and patients with pruritus at baseline reported less pruritic symptoms at the end of treatment. All possibly drug-related non-serious adverse events were mild to moderate. Conclusion: In this randomized phase II trial, elafibranor was generally safe and well tolerated and significantly reduced levels of ALP, composite endpoints of bilirubin and ALP, as well as other markers of disease activity in patients with PBC and an incomplete response to ursodeoxycholic acid. Lay summary: Patients with primary biliary cholangitis (a rare chronic liver disease) that do not respond to standard therapy remain at risk of disease progression toward cirrhosis and impaired quality of life. Elafibranor is a nuclear receptor agonist that we tested in a randomized clinical trial over 12 weeks. It successfully decreased levels of disease activity markers, including alkaline phosphatase. Thus, this study is the foundation for a larger prospective study that will determine the efficacy and safety of this drug as a second-line therapy. Clinical trial registration number: Clinical Trials.gov NCT0312410

Trends in liver transplantation for primary biliary cirrhosis in the Netherlands 1988-2008

Background: A decrease in the need for liver transplantations (LTX) in Primary Biliary Cirrhosis (PBC), possibly related to treatment with ursodeoxycholic acid (UDCA), has been reported in the USA and UK. The aim of this study was to assess LTX require

High‐resolution rock magnetic cyclostratigraphy in an Eocene flysch, Spanish Pyrenees

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95346/1/ggge1746.pd

Fibrates for the treatment of cholestatic itch (FITCH): study protocol for a randomized controlled trial

Cellular mechanisms in basic and clinical gastroenterology and hepatolog