Miracle-dz/UniFAR-FTUs huggingface dataset:
The Application of Youth Substance Use Media Campaigns to Problem Gambling: A Critical Evaluation

ABSTRACT Despite the negative impact that problem gambling poses on individuals and society there have been few gambling prevention campaigns specifically targeting youth. The authors review the literature on past and current drug, alcohol, and tobacco use prevention media campaigns, examining the similarities across 25 health communication programs with the aim of viewing their applicability for the prevention of youth problem gambling. Critical features of effective campaigns are identified and assessed in terms of their applicability for youth problem gambling. Recommendations for the design, implementation, and evaluation of a youth gambling media campaign are discussed.
Airway isocyanate-adducts in asthma induced by exposure to hexamethylene diisocyanate.

OBJECTIVES The clinical features, airway histology, and detection of hexamethylene diisocyanate (HDI) protein adducts in endobronchial biopsies from a patient with HDI asthma are described. METHODS Isocyanate asthma was diagnosed by history, methacholine challenge, and workplace HDI challenge. Bronchoscopy was performed 24 h after challenge and immunohistochemical staining was performed. RESULTS Airway biopsies obtained at bronchoscopy demonstrated inflammatory changes typical for asthma, including increased airway eosinophils and T cells. Immunohistochemical staining with specific anti-HDI antibodies demonstrated the presence and localization of HDI adducts in human bronchial biopsies. CONCLUSIONS These studies confirm epithelial exposure to HDI following workplace challenge and demonstrate the feasibility of detecting and localizing isocyanate adducts in human lung tissue. Identifying and characterizing the airway macromolecules to which isocyanates bind in vivo are probably crucial to the understanding of how isocyanates cause sensitization and asthma. The ability to detect isocyanate adducts may also help characterize isocyanate exposure patterns and exposure-disease relationships.
Patent-related survey on new monoamine oxidase inhibitors and their therapeutic potential

Introduction: Monoamine oxidase (MAO) plays an important role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critical for the regulation of several mental and cognitive functions. The by-products of MAO-mediated reactions comprehend reactive and toxic chemical species. As a consequence of this, the development of human MAO inhibitors led to important discoveries in the treatment of several neuropsychiatric and neurodegenerative disorders. Areas covered: This review highlights the recent MAO inhibitors-related patents (2010–2012) and reports on new associations of already known MAO inhibitors with other drugs, innovative therapeutic targets, MAO inhibitors obtained by plants extraction, alternative administration routes and synthetic processes. Expert opinion: MAO inhibitors appear promising for further clinical development being often endowed with other pharmacological functions (iron-chelating property, cholinesterase inhibition). A new ‘golden age' of MAO inhibitors recently started from (i) the discovery of new therapeutic targets (prostate cancer, diabetes, ischemia/reperfusion injury, tobacco dependence, transmissible spongiform encephalopathy); (ii) the recognized role of MAO as biomolecular markers (insomnia, chronic alcoholism, obsessive-compulsive behavior); (iii) the activity of these enzymes in other tissues (platelets, prostate cells).
Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells

Embryonic stem cells sustain a microenvironment that facilitates a balance of self-renewal and differentiation. Aggressive cancer cells, expressing a multipotent, embryonic cell-like phenotype, engage in a dynamic reciprocity with a microenvironment that promotes plasticity and tumorigenicity. However, the cancer-associated milieu lacks the appropriate regulatory mechanisms to maintain a normal cellular phenotype. Previous work from our laboratory reported that aggressive melanoma and breast carcinoma express the embryonic morphogen Nodal, which is essential for human embryonic stem cell (hESC) pluripotency. Based on the aberrant expression of this embryonic plasticity gene by tumor cells, this current study tested whether these cells could respond to regulatory cues controlling the Nodal signaling pathway, which might be sequestered within the microenvironment of hESCs, resulting in the suppression of the tumorigenic phenotype. Specifically, we discovered that metastatic tumor cells do not express the inhibitor to Nodal, Lefty, allowing them to overexpress this embryonic morphogen in an unregulated manner. However, exposure of the tumor cells to a hESC microenvironment (containing Lefty) leads to a dramatic down-regulation in their Nodal expression concomitant with a reduction in clonogenicity and tumorigenesis accompanied by an increase in apoptosis. Furthermore, this ability to suppress the tumorigenic phenotype is directly associated with the secretion of Lefty, exclusive to hESCs, because it is not detected in other stem cell types, normal cell types, or trophoblasts. The tumor-suppressive effects of the hESC microenvironment, by neutralizing the expression of Nodal in aggressive tumor cells, provide previously unexplored therapeutic modalities for cancer treatment.
Activity of Antibiotics in Chronic Granulomatous Disease Leukocytes

Summary: Patients with chronic granulomatous disease (CGD) have recurrent infections with catalase-producing organisms, particularly staphylococci, that survive within their leukocytes. To be most effective, antibiotics used to treat infections in CGD patients may need to kill both intracellular and extracellular organisms. We studied the ability of certain antibiotics to penetrate normal and CGD neutrophils and to kill intracellular staphylococci. Trimethoprim and clindamycin were concentrated in normal and in CGD neutrophils; maximum cellular-to-extracellular concentration ratios of clindamycin and of trimethoprim were ∼30 and ∼4, respectively. In contrast, penicillin was excluded from normal neutrophils. Clindamycin, trimethoprim/sulfamethoxazole, rifampin, and trimethoprim/rifampin significantly reduced the number of viable intracellular staphylococci in normal and CGD neutrophils. After 24 h of incubation in the presence of these antibiotics, the number of viable intracellular staphylococci in normal and CGD neutrophils was similar. In contrast, dicloxacillin, gentamicin, and cephalothin had no significant effect on the number of intracellular staphylococci in normal or CGD neutrophils.
Fibre Optic Communication Systems

The basic requirements for practical optical communication systems are reviewed. The construction and performance of some of the key constituents such as the fibre, cable, sources, connectors and splices are discussed. Particular emphasis is placed on the special properties of optical communication systems such as the economic advantage of wideband trunk communication, the immunity to electrical interference, and the high strength to weight ratio of the transmission medium. Details of a repeated 140 Mbit/s field demonstration over a 9 km route between Hitchin and Stevenage are given to illustrate the features of a comprehensive optical communication system.
Prediction of the Physiological Dead Space /Tidal Volume Ratio during Anaesthesia/IPPV from Simple Pre‐operative Tests

It can be shown that the assumption of an arbitrary value for VDphys/VT during IPPV can lead to unacceptable degrees of hypo‐ or hyperventilation. We investigated 33 adult patients scheduled for major non‐thoracic surgery, to see if any simple tests could be used to predict VDphys/VT during anaesthesia/IPPV. Fifteen were smokers and 18 non‐ or ex‐smokers. The tests were spirometry, and the single breath tests for CO2 and for N2 (SBT‐CO2: SBT‐N2). Patients were ventilated during anaesthesia with a Servo Ventilator 900 B, and SBT‐CO2 was recorded from a CO2 Analyzer 930. During anaesthesia/IPPV, smokers had significantly greater VDphys/VT (0.40±0.10 vs. 0.31 ±0.07 [P<0.01]), and they had more steeply sloping phase IIIs of SBT‐CO2 (P<0.01) than non‐ and ex‐smokers. For smokers, VDphys/VT was correlated to age (r = 0.75, P<0.01), to the slope of phase III of both SBT‐CO2 and SBT‐N2, and to the ratio of FEV% to its predicted value. For non‐ and ex‐smokers, only one variable, efficiency, describing the shape of SBT‐CO2, was correlated to VDphys/VT (r = 0.53, P<0.05). Pre‐operative prediction of VDphys/VT based on age, smoking history, and SBT‐CO2 can reduce the uncertainty in estimating VDphys/VT and therefore ventilatory requirements. It appears to offer the greatest benefits amongst smokers, who show a large variation in VDphys/VT.
Pulsatile urea excretion in gulf toadfish (Opsanus beta): evidence for activation of a specific facilitated diffusion transport system.

When toadfish are made ureotelic by a crowding/confinement protocol, they excrete approximately 90 % of their urea nitrogen (urea-N) production in large, irregular pulses (1-2 pulses per day) from the gill region. We investigated three hypotheses as to the mechanism of pulsatile excretion: (i) the presence of an active reabsorptive 'back-transport' mechanism that is periodically inhibited to allow urea-N excretion to occur; (ii) the periodic occurrence of a generalized, non-specific increase in gill permeability; and (iii) the presence of a specific facilitated diffusion transport system that is periodically activated. Exposure of toadfish during non-pulse periods to treatments designed to block a 'back-transport' mechanism (Na+-free sea water or the urea analogues 30 mmol l-1 thiourea or 30 mmol l-1 acetamide in the external water) did not stimulate a leakage of urea-N, thereby opposing the first hypothesis. The second hypothesis was opposed by several results. Neither injection of the potent branchial vasodilator L-isoprenaline (10(-5) mol l-1) nor infusion of NH4Cl, the latter at levels known to stimulate urea-N efflux in perfused gills, had any effect on urea-N excretion. Furthermore, during natural pulse events, when the normally very low gill permeability to urea (3x10(-7) cm s-1) increased at least 35-fold, there was no accompanying increase in permeability to either 3H2O (1.5x10(-5) cm s-1) or the paracellular marker [14C]PEG-4000 (10(-8) cm s-1). However [14C]thiourea permeability (1.5x10(-7) cm s-1) increased approximately fivefold, in support of the third hypothesis. Furthermore, when 30 mmol l-1 urea was placed in the external water, a concentration (60 000 micromol-N l-1) approximately three times that of blood (20 000 micromol-N l-1), each efflux pulse event (measured with [14C]urea) was accompanied by a net uptake, such that blood urea-N levels rose rather than fell. A proportional 1:1 relationship between influx per unit external concentration and efflux per unit internal (i.e. plasma) concentration indicated a fully bidirectional transport system. The simultaneous presence of 60 mmol l-1 thiourea in the external water inhibited the influx component by 73 %, further supporting this conclusion. These data, together with recent molecular, morphological and endocrinological evidence, strongly suggest that pulsatile urea-N excretion is caused by the periodic activation of a facilitated urea transporter in the gills, similar to the vasopressin-regulated urea transporter in the mammalian kidney.
Molecular Isolation and Characterization of a Soluble Isoform of Activated Leukocyte Cell Adhesion Molecule That Modulates Endothelial Cell Function*

Cell adhesion molecules regulate a variety of endothelial cell functions such as migration, response to inflammation, and angiogenesis. Recently, activated leukocyte cell adhesion molecule (ALCAM), a member of the Ig superfamily, has been detected in the primitive subsets of hematopoietic cells and endothelial cells during embryogenesis. ALCAM supports the development of hematopoietic cells as well as enhancing capillary tube formation in vitro. Here, we isolated a novel soluble isoform of ALCAM (sALCAM) that is produced via alternative splicing. sALCAM contains the single amino-terminal Ig-like domain of ALCAM and lacks a transmembrane domain. When expressed in cultured cells, sALCAM was properly secreted into the media. Both ALCAM and sALCAM are expressed in a variety of cultured human endothelial cells. Notably, their transcripts were differentially regulated in human microvascular endothelial cells (HMVEC) upon tumor necrosis factor-α stimulation. ALCAM significantly enhanced tube formation of endothelial-like yolk sac cells on Matrigel, whereas it inhibited their migration in vitro. sALCAM completely abolished these effects of ALCAM. Furthermore, sALCAM enhanced migration of mock-transfected endothelial-like yolk sac cells that do not express ALCAM, indicating that sALCAM has an independent effect on cell migration in addition to modulating ALCAM function. In addition, sALCAM significantly enhanced migration of HMVEC, whereas it inhibited tube formation of HMVEC on Matrigel. sALCAM demonstrated an ability to bind ALCAM and partially inhibited ALCAM-ALCAM homophilic interactions. Taken together, these data characterize a novel soluble isoform of ALCAM that may have ALCAM-dependent and ALCAM-independent functions, providing further insights regarding the role of this adhesion molecule in the regulation of endothelial cell function.
Associations between γ-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort： A possible implication for oxidative stress

AIM: To examine the relationships between γ -glutamyl-transferase (GGT), alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample. METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1 339 subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy). RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference, hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders. In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06; 95%CI 0.67-1.45), but not with the AST and ALT tertiles. In a multiple regression model, after adjusting for age, sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β = 0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia. CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.
A gene delivery system with a human artificial chromosome vector based on migration of mesenchymal stem cells towards human glioblastoma HTB14 cells

Abstract Mesenchymal stem cells (MSCs) have been expected to become useful gene delivery vehicles against human malignant gliomas when coupled with an appropriate vector system, because they migrate towards the lesion. Human artificial chromosomes (HACs) are non-integrating vectors with several advantages for gene therapy, namely, no limitations on the size and number of genes that can be inserted. We investigated the migration of human immortalized MSCs bearing a HAC vector containing the herpes simplex virus thymidine kinase gene (HAC-tk-hiMSCs) towards malignant gliomas in vivo. Red fluorescence protein-labeled human glioblastoma HTB14 cells were implanted into a subcortical region in nude mice. Four days later, green fluorescence protein-labeled HAC-tk-hiMSCs were injected into a contralateral subcortical region (the HTB14/HAC-tk-hiMSC injection model). Tropism to the glioma mass and the route of migration were visualized by fluorescence microscopy and immunohistochemical staining. HAC-tk-hiMSCs began to migrate toward the HTB14 glioma area via the corpus callosum on day 4, and gathered around the HTB14 glioma mass on day 7. To test whether the delivered gene could effectively treat glioblastoma in vivo, HTB14/HAC-tk-hiMSC injected mice were treated with ganciclovir (GCV) or PBS. The HTB14 glioma mass was significantly reduced by GCV treatment in mice injected with HAC-tk-hiMSCs. It was confirmed that gene delivery by our HAC-hiMSC system was effective after migration of MSCs to the glioma mass in vivo. Therefore, MSCs containing HACs carrying an anticancer gene or genes may provide a new tool for the treatment of malignant gliomas and possibly of other tumor types.
College-Aged Young Consumers' Perceptions of Social Media Marketing: The Story of Instagram

ABSTRACT A qualitative study was conducted to explore college-aged young consumers' interpretation of Instagram and marketing via Instagram. The themes that emerged regarding those young consumers' understanding of the photo-sharing social medium are picture me, tech-a-break, and mirror of celebrity, and the themes regarding the participants' interpretation of marketing information on Instagram include subtleness, privileged and new information, and social and celebrity endorsement. Theoretical and practical implications are offered.
GENOMIC BASIS OF AGING AND LIFE‐HISTORY EVOLUTION IN DROSOPHILA MELANOGASTER

Natural diversity in aging and other life‐history patterns is a hallmark of organismal variation. Related species, populations, and individuals within populations show genetically based variation in life span and other aspects of age‐related performance. Population differences are especially informative because these differences can be large relative to within‐population variation and because they occur in organisms with otherwise similar genomes. We used experimental evolution to produce populations divergent for life span and late‐age fertility and then used deep genome sequencing to detect sequence variants with nucleotide‐level resolution. Several genes and genome regions showed strong signatures of selection, and the same regions were implicated in independent comparisons, suggesting that the same alleles were selected in replicate lines. Genes related to oogenesis, immunity, and protein degradation were implicated as important modifiers of late‐life performance. Expression profiling and functional annotation narrowed the list of strong candidate genes to 38, most of which are novel candidates for regulating aging. Life span and early age fecundity were negatively correlated among populations; therefore, the alleles we identified also are candidate regulators of a major life‐history trade‐off. More generally, we argue that hitchhiking mapping can be a powerful tool for uncovering the molecular bases of quantitative genetic variation.
The prevalence of celiac disease in children with iron-deficiency anemia.

BACKGROUND/AIMS Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. Iron-deficiency anemia is the most commonly encountered anemia in humans. Iron-deficiency anemia also is a common extraintestinal manifestation of celiac disease. To determine the celiac disease prevalence in children with iron-deficiency anemia and to compare the hematologic parameters in iron-deficiency anemia patients with and without celiac disease. MATERIALS AND METHODS A total of 61 patients aged 2-16 years who presented with iron-deficiency anemia were included in this study. Hemoglobin, red cell indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width), serum iron, and serum ferritin were determined. Venous blood samples for anti-tissue transglutaminase antibody immunoglobuline A were obtained from these patients. Upper gastrointestinal endoscopy was recommended to patients who had positive serology. RESULTS Of 61 patients with iron-deficiency anemia, 13 (21,3%) had positive serology for celiac disease. The small intestine biopsy of all patients with positive serology showed villous atrophy (Marsh 3). The mean hemoglobin level was significantly lower in iron-deficiency anemia patients with celiac disease when compared to those without celiac disease (7,8±2,6 vs. 11,3±0,9 g/dL, p>0,05). There was a statistically significant negative correlation of tissue transglutaminase titers with hemoglobin, red cell indices, serum iron, and serum ferritin levels. CONCLUSIONS Screening of celiac disease by anti-tissue transglutaminase antibody should be done as a routine investigation in children with iron-deficiency anemia. Biopsy should be recommended in patients with iron-deficiency anemia who have positive celiac disease serology.
“Stiffness Has Different Meanings, I Think, to Everyone”: Examining Stiffness From the Perspective of People Living With Rheumatoid Arthritis

Stiffness is a well‐recognized symptom of rheumatoid arthritis (RA). It is frequently queried during clinic visits as an indicator of disease activity and was included in the 1961 and 1987 RA classification criteria. Little is known about how people with RA experience stiffness and its impact on their lives.