Boosting intracellular sodium selectively kills hepatocarcinoma cells and induces hepatocellular carcinoma tumor shrinkage in mice.

Pharmacological treatments for advanced hepatocellular carcinoma (HCC) have a partial efficacy. Augmented Na content and water retention are observed in human cancers and offer unexplored targets for anticancer therapies. Na levels are evaluated upon treatments with the antibiotic cation ionophore Monensin by fluorimetry, ICP-MS, Na-MRI, NMR relaxometry, confocal or time-lapse analysis related to energy production, water fluxes and cell death, employing both murine and human HCC cell lines, primary murine hepatocytes, or HCC allografts in NSG mice.

Factor VIII as a potential player in cancer pathophysiology.

Background: Trousseau sign was the first demonstration of a close relationship between cancer and thrombosis. Currently, venous thromboembolism (VTE) is five to six times more likely to occur in cancer patients, whereas there is a greater risk of cancer diagnoses following thromboses. In considering novel players, factor VIII (FVIII), an essential coagulation cofactor with emerging extracoagulative functions, has been identified as an independent VTE risk factor in cancer; however, the basis of this increase is unknown.

Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial.

Background & Aims: Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality.

Methods: Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466).

Large-scale evaluation of ion mobility spectrometry for the rapid detection of synthetic cannabinoid receptor agonists in infused papers in prisons.

Synthetic cannabinoid receptor agonists (SCRAs), colloquially known as "spice," are commonly used in prisons and enter establishments via the mail in the form of infused papers. Many prisons use benchtop ion mobility spectroscopy (IMS) instruments to screen mail and seized materials for the presence of SCRAs and other controlled substances. The selectivity and sensitivity of Rapiscan Itemiser 3E and Itemiser 4DN Ion Trap Mobility Spectroscopy™ (ITMS™) systems were evaluated using 21 SCRA reference standards.

Deciphering the Ets-1/2-mediated transcriptional regulation of F8 gene identifies a minimal F8 promoter for hemophilia A gene therapy.

A major challenge in the development of a gene therapy for hemophilia A (HA) is the selection of cell type- or tissue-specific promoters to ensure factor VIII (FVIII) expression without eliciting an immune response. As liver sinusoidal endothelial cells (LSECs) are the major FVIII source, understanding the transcriptional F8 regulation in these cells would help optimize the minimal F8 promoter (pF8) to efficiently drive FVIII expression. In silico analyses predicted several binding sites (BS) for the E26 transformation-specific (Ets) transcription factors Ets-1 and Ets-2 in the pF8.

Identification and functional characterization of a novel splicing variant in the F8 coagulation gene causing severe hemophilia A.

Background: We have identified a synonymous F8 variation in a severe hemophilia A (HA) patient who developed inhibitors following factor VIII (FVIII) prophylaxis. The unreported c.6273 G > A variant targets the consensus splicing site of exon 21.

Detection and quantitation of synthetic cannabinoid receptor agonists in infused papers from prisons in a constantly evolving illicit market.

Drug misuse in prisons contributes to increased disruption and violence and negatively impacts prisoner safety, rehabilitation, and recovery. Synthetic cannabinoid receptor agonists (SCRAs), colloquially known as "spice", are infused into papers and are of particular concern in a prison setting where they are commonly vaped. Methods for the qualitative and quantitative analysis of SCRA infused papers, including impurity profiling, were developed using gas chromatography-mass spectrometry (GC-MS) with qualitative confirmation by ultra high pressure liquid chromatography with photodiode array and quadrupole time of flight mass spectrometry detection (UPLC-PDA-QToF-MS) and applied to 354 individual seized paper samples originating from 168 seizures from three Scottish prisons.

Circulating adipokines and metabolic setting in differentiated thyroid cancer.

The associative link relating insulin resistance (IR) and adipokines to the occurrence and phenotype of differentiated thyroid cancer (DTC) is unknown. The aim of this study was to evaluate the relationship between IR and adipokines in DTC patients, as compared with carriers of benign thyroid diseases (BTD) and healthy controls. This observational study enrolled 77 subjects phenotyped as DTC (N = 30), BTD (N = 27) and healthy subjects (N = 20).

Identification of Haptoglobin as a Readout of rhGH Therapy in GH Deficiency.

Background: GH deficiency (GHD) is characterized by a cluster of cardiovascular risk factors and subtle inflammation. We aimed to demonstrate, through a proteomic approach, molecules directly modulated by GHD and involved in the inflammatory state.

Methods: Ten children with isolated GHD were studied before and after 1 year of treatment with rhGH and compared with 14 matched controls.

Fetuin B links vitamin D deficiency and pediatric obesity: Direct negative regulation by vitamin D.

Vitamin D (VD) deficiency (VDD) correlates to obesity, with VD a recognized mediator of metabolic diseases. From a previous proteomic study identifying adiponectin as a link between VDD and pediatric obesity, herein we analysed another protein (SSP2301) increased with VDD. A focused 2D-electrophoretic analysis identified 4 corresponding plasma proteins, with one predicted to be fetuin B (FETUB).

Terahertz frequency-wavelet domain deconvolution for stratigraphic and subsurface investigation of art painting.

Terahertz frequency-wavelet deconvolution is utilized specifically for the stratigraphic and subsurface investigation of art paintings with terahertz reflective imaging. In order to resolve the optically thin paint layers, a deconvolution technique is enhanced by the combination of frequency-domain filtering and stationary wavelet shrinkage, and applied to investigate a mid-20th century Italian oil painting on paperboard, After Fishing, by Ausonio Tanda. Based on the deconvolved terahertz data, the stratigraphy of the painting including the paint layers is reconstructed and subsurface features are clearly revealed, demonstrating that terahertz frequency-wavelet deconvolution can be an effective tool to characterize stratified systems with optically thin layers.

Intracoronary Des-Acyl Ghrelin Acutely Increases Cardiac Perfusion Through a Nitric Oxide-Related Mechanism in Female Anesthetized Pigs.

Des-acyl ghrelin (DAG), the most abundant form of ghrelin in humans, has been found to reduce arterial blood pressure and prevent cardiac and endothelial cell apoptosis. Despite this, data regarding its direct effect on cardiac function and coronary blood flow, as well as the related involvement of autonomic nervous system and nitric oxide (NO), are scarce. We therefore examined these issues using both in vivo and in vitro studies.

Influence of Ultraviolet Radiation on the Association between 25-Hydroxy Vitamin D Levels and Cardiovascular Risk Factors in Obesity.

Objective: To establish if the correction with estimates of ultraviolet (UV) exposure influences the association between 25-OH-vitamin D (25OHD) levels and metabolic variables.

Study Design: A cross-sectional study was performed in 575 obese children and adolescents (>6 years of age) in a tertiary referral center. Cardiovascular risk factors were measured.

Adiponectin oligomers are similarly distributed in adequate-for-gestational-age obese children irrespective of feeding in their first year.

Background: Nutrition and growth in early postnatal life have a role in future diseases. Our aim was to investigate adiponectin oligomers in adequate-for-gestational-age obese children with respect to type and duration of feeding in the first year of life.

Methods: Adiponectin oligomers and cardiometabolic risk factors were measured in 113 adequate-for-gestational-age obese children, divided into group A (prolonged breast feeding, >6 mo), group B (short breast feeding, 1-6 mo), and group C (formula feeding from birth).

The pathophysiology of abdominal adipose tissue depots in health and disease.

Obesity is currently the most important contributor to ill health and expenditure worldwide. More alarming is the fact that the pediatric population parallels adults, with obesity closely associated to type 2 diabetes mellitus (T2D), cardiovascular disease, hypertension, non-alcoholic fatty liver disease, vitamin D deficiency (VDD) and certain types of cancer. The observation in the early 1950s that android or truncal adipose tissue (AT) distribution compared to gynoid had a greater association with metabolic dysfunction, in particular T2D and cardiovascular disease risk, led to the hypothesis that obesity-associated complications are not associated with fat mass per se, but the pattern of fat distribution.

Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity.

High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m(2)), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.

Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized pig.

Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature and myocardial systo-diastolic function, as well as on parasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, we planned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO.

Novel mutations in the GH gene (GH1) uncover putative splicing regulatory elements.

Mutations affecting exon 3 splicing are the main cause of autosomal dominant Isolated GH Deficiency II (IGHDII) by increasing the level of exon 3-skipped mRNA encoding the functionally inactive dominant-negative 17.5-kDa isoform. The exons and introns of the gene encoding GH (GH1) were screened for the presence of mutations in 103 sporadic isolated GH deficiency cases.

Pediatric obesity and vitamin D deficiency: a proteomic approach identifies multimeric adiponectin as a key link between these conditions.

Key circulating molecules that link vitamin D (VD) to pediatric obesity and its co-morbidities remain unclear. Using a proteomic approach, our objective was to identify key molecules in obese children dichotomized according to 25OH-vitamin D (25OHD) levels. A total of 42 obese children (M/F = 18/24) were divided according to their 25OHD3 levels into 25OHD3 deficient (VDD; n = 18; 25OHD<15 ng/ml) or normal subjects (NVD; n = 24; >30 ng/ml).

Obesity modifies expression profiles of metabolic markers in superficial and deep subcutaneous abdominal adipose tissue depots.

While visceral adipose tissue (VAT) associates to obesity, there is debate for subcutaneous adipose tissue (SAT). One explanation may be SAT subcompartments, superficial-SAT (sSAT) and deep-SAT (dSAT), recently recognized as independent depots. Our aim was to establish roles for sSAT/dSAT with obesity by examining the expression of proteins key to adipocyte metabolism.

Lymphocytes and immunoglobulin patterns across the threshold of severe obesity.

The proinflammatory state of metabolic disorders encompasses the alterations in leukocyte counts and acute-phase reactants, and thus, predisposes to acute and chronic cardiovascular events linked to fat accumulation. Leptin is a marker of adiposity and also yields regulatory effects on innate and adaptive immunity; however, its role on the immune function of obese subjects remains to be elucidated. The aim of this study is to determine the influence of obesity and the role of leptin concentrations on lymphocyte counts and immunoglobulin levels as broad markers of immune function.

Control of growth hormone and IGF1 in patients with acromegaly in the UK: responses to medical treatment with somatostatin analogues and dopamine agonists.

Objective: We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment.

Design: The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y.

Patients: We identified 2572 patients.

Sub-surface terahertz imaging through uneven surfaces: visualizing Neolithic wall paintings in Çatalhöyük.

Pulsed terahertz imaging is being developed as a technique to image obscured mural paintings. Due to significant advances in terahertz technology, portable systems are now capable of operating in unregulated environments and this has prompted their use on archaeological excavations. August 2011 saw the first use of pulsed terahertz imaging at the archaeological site of Çatalhöyük, Turkey, where mural paintings dating from the Neolithic period are continuously being uncovered by archaeologists.