Evaluation of a Targeted Next-Generation Sequencing Panel for the Non-Invasive Detection of Variants in Circulating DNA of Colorectal Cancer.

Molecular profiling of circulating cell-free DNA (cfDNA) has shown utility for the management of colorectal cancer (CRC). TruSight Tumor 170 (TST170) is a next-generation sequencing (NGS) panel that covers 170 cancer-related genes, including , which is a key driver gene in CRC. We evaluated the capacity of TST170 to detect gene variants in cfDNA from a retrospective cohort of 20 metastatic CRC patients with known variants in tumor tissue and in cfDNA previously analyzed by pyrosequencing and BEAMing, respectively.

Association between cardiovascular mortality and STOP-Bang questionnaire scores in a cohort of hospitalized patients: a prospective study.

Objective: Obstructive sleep apnea (OSA) is associated with an increased risk of mortality and cardiometabolic diseases. The STOP-Bang questionnaire is a tool to screen populations at risk of OSA and prioritize complementary studies. Our objective was to evaluate the clinical utility of this questionnaire in identifying patients at an increased risk of mortality after discharge in a cohort of hospitalized patients.

Risk of mortality among patients with moderate to severe obstructive sleep apnea and diabetes mellitus: results from the SantOSA cohort.

Introduction: Patients with obstructive sleep apnea (OSA) and comorbid diabetes mellitus (DM) are reported to have an increased risk of cardiovascular (CV) outcomes; however, data on CV mortality are scant.

Aim: This study aimed to evaluate if patients with comorbid OSA and DM have an increased risk of CV mortality that is higher than the two diseases in isolation.

Methods: In this prospective cohort study, we included patients referred for a sleep study with and without DM at baseline.

Clinical utility of oximetric parameters to identify a high-risk phenotype of moderate-severe Obstructive Sleep Apnea (OSA).

Unlabelled: It is unclear if oximetric parameters, such as total time of SpO < 90%, (T90), oxygen desaturation index-3% (ODI), minimum SpO , are able to describe a high-risk subtype of cardiovascular (CV) comorbidities in patients with Obstructive sleep apnea (OSA) beyond the apnea-hypopnea index.

Objective: To analyzed oximetric variables in patients with moderate-severe OSA to assess their predictive value regarding as hypertension, type 2 diabetes mellitus (T2DM), coronary heart disease (CHD) and CV mortality.

Methods: Using data from SantOSA cohort, we develop receiver operating characteristic curve and area under the curve (AUC) for each parameter, defining the proposed cutoff point in a training set.

A clinic-based cluster analysis in patients with moderate-severe obstructive sleep apnea (OSA) in Chile.

Rationale: Patients commonly report differences in either clinical or symptomatic profiles, despite having the same severity of obstructive sleep apnea (OSA).

Objective: To identify clinical and symptomatic phenotypes and to evaluate cardiovascular mortality in each phenotype.

Methods: Data from 1370 participants (788 with moderate-severe OSA and 582 controls as a reference group) were extracted using the SantOSA database.

Predicting Outcome and Therapy Response in mCRC Patients Using an Indirect Method for CTCs Detection by a Multigene Expression Panel: A Multicentric Prospective Validation Study.

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths. Early detection of tumor relapse is crucial for determining the most appropriate therapeutic management. In clinical practice, computed tomography (CT) is routinely used, but small tumor changes are difficult to visualize, and reliable blood-based prognostic and monitoring biomarkers are urgently needed.

Home intervention improves cognitive and social-emotional scores in iron-deficient anemic infants.

Background: Iron-deficiency anemia (IDA) is associated with alterations in infant behavior and development that may not be corrected with iron therapy.

Objective: To determine if a home-based intervention to foster child development improves behavior and development of infants with IDA.

Methods: Infants with IDA and nonanemic infants aged 6 and 12 months were treated with oral iron and randomly assigned to a year of surveillance or intervention.

Identification of a novel modulator of thyroid hormone receptor-mediated action.

Background: Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle.

Methodology/principal Findings: We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats.

Short-term transdermal estradiol enhances nitric oxide synthase III and estrogen receptor mRNA expression in arteries of women with coronary artery disease.

Objective: To analyze the short-term effects of estradiol (E2) on the expression of nitric oxide synthase (NOS III) and estrogen receptors (ER) alpha and beta.

Methods: We studied 20 post-menopausal women with coronary artery disease (CAD) undergoing CABG surgery with left internal mammary artery (LIMA) grafting. Ten women received treatment with transdermal E2 prior to surgery (48-72 h) and 10 did not.

The selective cyclooxygenase-2 inhibitor celecoxib modulates the formation of vasoconstrictor eicosanoids and activates PPARgamma. Influence of albumin.

Background/aims: Selective cyclooxygenase (COX)-2 inhibitors do not adversely affect renal function in experimental cirrhosis. In the current study, we investigated the molecular mechanisms underlying the effects of the selective COX-2 inhibitor, celecoxib, and assessed the influence of albumin on its actions.

Methods: Rat mesangial cells (RMC) were incubated with celecoxib in the absence or presence of albumin, and levels of selected vasoconstrictor eicosanoids, renin release and alpha-smooth muscle actin (alpha-SMA) expression were determined.

Inhibition of 5-lipoxygenase induces cell growth arrest and apoptosis in rat Kupffer cells: implications for liver fibrosis.

The existence of an increased number of Kupffer cells is recognized as critical in the initiation of the inflammatory cascade leading to liver fibrosis. Because 5-lipoxygenase (5-LO) is a key regulator of cell growth and survival, in the current investigation we assessed whether inhibition of the 5-LO pathway would reduce the excessive number of Kupffer cells and attenuate inflammation and fibrosis in experimental liver disease. Kupffer cells were the only liver cell type endowed with a metabolically active 5-LO pathway (i.

Transduction of the liver with activated Akt normalizes portal pressure in cirrhotic rats.

Background & Aims: Portal hypertension in cirrhosis is secondary to an increase in hepatic resistance that occurs mainly through collagen deposition. However, recent evidence points to a major contribution by other factors, such as an intrahepatic reduction in nitric oxide production. Akt is a major activator of the endothelial nitric oxide synthase (eNOS) enzyme, but its potential role in intrahepatic resistance in cirrhosis is unknown.

Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites.

Background: Selective V(2)-AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V(1a)/V(2)-AVP antagonists are also efficacious as aquaretic agents under these conditions. This is important, particularly considering that blockade of V(1a)-AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis.

Nitric oxide synthase 3-dependent vascular remodeling and circulatory dysfunction in cirrhosis.

Vascular remodeling is an active process that consists in important modifications in the vessel wall. Endothelium-derived nitric oxide (NO) plays a major role in this phenomenon. We assessed wall thickness (WT), total wall area (TWA), lumen diameter, and total nuclei number/cross-section (TN) in cirrhotic rats with ascites and in control rats.

Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity.

In many cells and specially in muscle, mitochondria form elongated filaments or a branched reticulum. We show that Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, is induced during myogenesis and contributes to the maintenance and operation of the mitochondrial network. Repression of Mfn2 caused morphological and functional fragmentation of the mitochondrial network into independent clusters.

Effects of hypoxia and thyroid hormone on mRNA levels and activity of phosphoglycerate mutase in rabbit tissues.

Aim: In the present work, we studied the effects of hypoxia and triiodothyronine (T(3)) on phosphoglycerate mutase (PGAM) activity and expression in rabbit liver, brain, and skeletal muscle under in vivo conditions.

Methods: Hypoxia was induced in a methacrylate cage with a mixture of 90% nitrogen and 10% oxygen. Hyperthyroidism was induced daily by T(3) injection (250 microg/kg).

Hypoxia is an inducer of vasodilator agents in peritoneal macrophages of cirrhotic patients.

The aim of the investigation was to assess whether hypoxia induces the production of endogenous vasoactive peptides in macrophages of cirrhotic patients with ascites because low tissue oxygenation is a relatively frequent event in these patients. Peritoneal macrophages were isolated from ascites, seeded on well plates, and cultured at different times under hypoxic (5% O(2)) or normoxic conditions (21% O(2)). Then, accumulation of vasoactive peptides sensitive to hypoxia including endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and adrenomedullin (ADM) was measured.

Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function.

Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. More recent data demonstrates that HNF-4alpha expression is dependent on HNF-1alpha in mouse pancreatic islets and exocrine cells.

Increased plasma levels of neuropeptide Y in hepatorenal syndrome.

Background/aims: To investigate the relationship between neuropeptide Y (NPY), a potent renal vasoconstrictor peptide released upon marked stimulations of sympathetic nervous system (SNS), and renal and circulatory function in cirrhosis.

Methods: Plasma levels of NPY (radioimmunoassay) and norepinephrine and renal function parameters were determined in 17 healthy controls, nine patients with cirrhosis without ascites, and 37 patients with cirrhosis and ascites, of whom 12 had hepatorenal syndrome (HRS).

Results: Patients with ascites showed circulating levels of NPY similar to those of patients without ascites and controls (73+/-4, +/-4 and 68+/-4 pmol/l, respectively; NS).

Cyclooxygenase-1 derived prostaglandins are involved in the maintenance of renal function in rats with cirrhosis and ascites.

1. The maintenance of renal function in decompensated cirrhosis is highly dependent on prostaglandins (PGs). Since PG synthesis is mediated by cyclooxygenase-1 and -2 (COX-1 and COX-2), the present study was designed to examine which COX isoform is involved in this phenomenon.

Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat.

Background & Aims: Recent studies have described the existence of endogenous cannabinoids with vasodilator activity because of their interaction with peripheral CB1 receptors, anandamide being the most extensively investigated. The study investigated whether endogenous cannabinoids are involved in the pathogenesis of the cardiovascular disturbances in experimental cirrhosis.

Methods: Arterial pressure, cardiac output, and total peripheral resistance were measured before and after the administration of a cannabinoid CB1 receptor antagonist to cirrhotic rats with ascites and to control rats.

Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-beta(1) plasma levels in a crossover trial in renal transplant recipients.

Hypertension and hyperfiltration are two important risk factors for the development of chronic allograft nephropathy. Transforming growth factor-beta(1) (TGF-beta(1)) is the main cytokine involved in the fibrotic process that is involved in chronic rejection. Angiotensin II upregulates TGF-beta(1) production.