Miracle-dz/UniFAR-FTUs huggingface dataset:
Norepinephrine-Induced Stimulation of p38 Mitogen-Activated Protein Kinase Is Mediated by Arachidonic Acid Metabolites Generated by Activation of Cytosolic Phospholipase A2 in Vascular Smooth Muscle Cells

p38 mitogen-activated protein kinase (MAPK) is activated by norepinephrine (NE) in the vasculature and is implicated in vascular smooth muscle hypertrophy, contraction, and cell migration. NE promotes influx of Ca2+ and activates cytosolic phospholipase A2 (cPLA2) in vascular smooth muscle cells (VSMC). The purpose of this study was to determine the contribution of cPLA2-generated arachidonic acid (AA) and its metabolites to the activation of p38 MAPK measured by its phosphorylation, in response to NE in rabbit VSMC. NE-induced p38 MAPK activation was found to be mediated through the stimulation of α-1 and α-2 adrenergic receptors, was dependent on extracellular Ca2+, and was attenuated by an inhibitor of cPLA2 (pyrrolidine-1). Moreover, the cPLA2 product, AA, activated p38 MAPK in VSMC. p38 MAPK activation elicited by NE was decreased significantly by the lipoxygenase (LO) inhibitor baicalein, and to a lesser extent by the cytochrome P450 inhibitor 17-octadecynoic acid, but was not affected by the cyclooxygenase inhibitor indomethacin. The LO metabolites of AA, namely 5(S)-hydroxyeicosatetraenoic acid (HETE), 12(S)-HETE, and 15(S)-HETE and the cytochrome P450 metabolite 20-HETE, activated p38 MAPK. NE-induced p38 MAPK stimulation was found to be independent of phospholipase D (PLD) activation in rabbit VSMC. Transactivation of the epidermal growth factor receptor (EGFR) by NE also did not contribute to p38 MAPK activation. These data suggest that cPLA2-generated AA and its LO metabolites mediate NE-induced p38 MAPK stimulation in rabbit VSMC by a mechanism that is independent of PLD and EGFR activation.
Cytokines in periodontal disease: where to from here?

Numerous studies have attempted to elucidate the cytokine networks involved in chronic periodontitis, often with conflicting results. A variety of techniques were used to study cells in situ, cells extracted from gingival tissues, peripheral blood mononuclear cells, purified cell populations, and T cell lines and clones. Bacterial components, including sonicates, killed cells, outer membrane components, and purified antigens, have all been used to stimulate cells in vitro, making comparisons of cytokine profiles difficult. As it is likely that different cells are present at different disease stages, the inability to determine disease activity clinically is a major limitation of all these studies. In the context of tissue destruction, cytokines such as IL-1, IL-6 and IL-18 are likely to be important, as are their regulating cytokines IL-10 and IL-11. In terms of the nature of the inflammatory infiltrate, two apparently conflicting hypotheses have emerged: one based on direct observations of human lesions, the other based on animal experimentation and the inability to demonstrate IL-4 mRNA in gingival extracts. In the first of these, Th1 responses are responsible for the stable lesion, while in the second Th2 responses are considered protective. Using Porphyromonas gingivalis-specific T cell lines we have shown a tendency for IFN-γ production rather than IL-4 or IL-10 when antigen is presented with peripheral blood mononuclear cells which may contain dendritic cells. It is likely that the nature of the antigen-presenting cell is fundamental in determining the nature of the cytokine profile, which may in turn open up possibilities for new therapeutic modalities.
Government R&D funding: new approaches in the allocation policies for public and private beneficiaries

The objective of this paper is to perform a first experiment of quantitative assessment on changes in allocation mechanisms and in their underlying delegation models, using the quantitative information and the descriptions of national funding systems produced in the PRIME project funding activity. Delegation has been explored through changes in instrument portfolios and in evaluation modes, as proofs of an evolution in research governance. Some common trends can be identified: the reinforcing of both priority setting and peer review processes. The general result of our analysis is that some change in delegation modes took place, but there is not a simple transition from one delegation regime to another, while a "contract" delegation model (the NPM reform) is not detectable through project funding analysis.
The Impact of Dividend Policy on Share Price Volatility: Empirical Evidence with Colombo Stock Exchange in Sri Lanka

: Dividend policy comprises the decisions, whether to retain earnings for capital investment and other purposes orto distribute earnings as dividend among shareholders. In advance effect on market prices deemed to be a main determinant of dividend policy. On that concern, the main purpose of this study would be to examine the relationship between dividend policy and share price volatility in Sri Lankan context. Dividend payout ratio and dividend yield deliberated as independent variables after controlling with growth in assets, firm size and debt while share price volatility considered as a proxy of dependent variable. Data were collected through annual reports of 30 selected companies listed in Colombo Stock Exchange for four-year time period from 2014 to 2017 according to the market capitalization on the date of 31 st December 2017. Descriptive analysis and correlation analysis were used to perform the data analysis while regression model was expanded by adding control variables. While confirming the empirical results; findings of this study showed a negative insignificant relationship between dividend yields with share price volatility. Moreover, price volatility has negative correlation with firm size and positive correlation with growth in assets and debt. Based on the findings of this study, dividend payout ratio and dividend yield have negative impact on share price volatility. yield, payout ratio, debt, growth in assets and firm size.
The Consumption of Conventional and Nonconventional Medicines in an Italian Province: The Influence of Sociodemographic Factors and Health Beliefs

Many studies have investigated the factors that influence the consumption of medicines. This article aims to compare how these factors affect both conventional medicines (prescription and over-the-counter (OTC) medicines) and nonconventional ones, also named as complementary and alternative medicines (CAM). A questionnaire was administered to a purposive sample of 4,074 inhabitants of the province of Mantua, Italy. Logical regressions were used to identify the variables influencing frequency of use. The consumption frequency of various types of medicines was associated not only with demographic aspects (such as gender, age, and education level) but also with everyday treatment strategies (such as self-medication habits and use of the Internet for medical aims) and health beliefs. From this last point of view, the use of conventional and nonconventional medicines is guided by 2 principal therapeutic attitudes, one aimed at removing all pathological aspects from everyday life and the other at contextualizing health problems within a broader philosophical search.
Ultrastructural Changes during the Life Cycle of Mycoplasma salivarium in Oral Biopsies from Patients with Oral Leukoplakia

Bacteria in genus Mycoplasma spp. are the smallest and simplest form of freely replicating bacteria, with 16 species known to infect humans. In the mouth, M. salivarium is the most frequently identified species. Mycoplasma spp. are parasites with small genomes. Although most of the Mycoplasma spp. that infect humans remain attached to the host cell surface throughout their life cycle, we have previously reported the presence of Mycoplasma salivarium in the epithelial cells of oral leukoplakia and oral lichen planus. However, the mechanism underlying the pathogenicity of M. salivarium has remained unclear. Further studies are needed to identify the process of infection of human cells and the stages in the life cycle of M. salivarium. Electron microscopy (EM) is the method of choice for morphological investigation of Mycoplasma spp. in cells or tissues. This study was performed to clarify and detail the ultrastructure of M. salivarium in tissue biopsies of oral mucosal leukoplakia, using three EM methods: (1) a standard EM processing method; (2) an ultracryotomy and immunolabeling method; and (3) the LR White resin post-embedding and immunolabeling method. This study included five oral leukoplakia tissue samples showing hyperplasia and hyperkeratosis. Although there was some variation in ultrastructural appearances between the three EM methods used, there were four ultrastructural appearances that are believed to reflect the stages of the M. salivarium life cycle in the epithelial cells of the oral mucosa: (1) small, electron-dense cellular-like structures or elementary bodies of M. salivarium; (2) large structures of M. salivarium; (3) M. salivarium organisms in cell division; (4) the sequence of events in the life cycle of M. salivarium that includes: (a) elementary bodies of M. salivarium deep in the oral mucosal epithelium; (b) replication by binary fission and daughter cell division from the elementary bodies; (c) maturation or degeneration of M. salivarium in the epithelial cells mainly in the upper part of the epithelium; and (d) death of the organisms in the granular and/or keratinized layer. These ultrastructural images may provide a useful reference for the identification of M. salivarium in diagnostic cytology or biopsy material.
Growth inhibition of colon cancer cells by polyisoprenylated benzophenones is associated with induction of the endoplasmic reticulum response

Polyisoprenylated benzophenones derived from Garcinia xanthochymus have cytotoxic activity in vitro and antitumor activity in rodent models, but the mechanism is unknown. The purpose of our study was to examine in parallel molecular pathways that are targeted by 3 Garcinia‐derived benzophenones‐xanthochymol (X), guttiferone E (GE) and guttiferone H (GH), in 3 human colon cancer cell lines, HCT116, HT29 and SW480. The IC50 concentrations were determined and the cells were then treated with X, GE or GH at their respective IC50 or IC50x2 concentrations. Effects on the cell cycle, mitochondrial membrane potential and apoptosis were assessed by flow cytometry and caspase activation. Changes in gene expression were assessed with Illumina 24 K gene arrays. We found that X, GE and GH induced loss of mitochondrial membrane potential and G1 arrest at their IC50 concentrations and induced caspase activation at IC50 × 2 concentrations. An analysis of the changes in gene expression revealed that with all 3 compounds and all 3 cell lines there was a marked increase in expression of several genes, including XBP1, ATF4 and DDIT3/CHOP, which are components of the endoplasmic reticulum stress response. The DDIT4/REDD1 gene, an inhibitor of the mTOR survival pathway, was also up‐regulated. Therefore, X, GE and GH appear to inhibit the growth of human colon cancer cells, at least in part, by activating the endoplasmic reticulum stress response and inhibiting the mTOR cell survival pathway. These combined effects may contribute to the anticancer activity of these novel compounds. © 2008 Wiley‐Liss, Inc.
Right ventricular longitudinal strain for risk stratification in low-flow, low-gradient aortic stenosis with low ejection fraction

Background Left ventricular global longitudinal strain (LVLS) is a powerful predictor of outcome in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) and low LV ejection fraction (LVEF). However, the impact of right ventricular (RV) function on the outcome of these patients remains unknown. Objectives The aim of this study was to examine the impact of RV function as evaluated by RV free wall longitudinal strain (RVLS) on mortality in patients with LF-LG AS and low LVEF. Methods 211 patients with LF-LG AS (mean gradient <40 mm Hg and indexed aortic valve area (AVA) ≤0.6 cm2/m2) and low LVEF (≤40%)) were prospectively recruited in the True or Pseudo-severe Aortic Stenosis study. AS severity was assessed using the projected AVA (AVAproj) at normal flow rate. Among the 211 patients, 128 had RVLS measurement available at rest and were included in this analysis. RVLS measurement at dobutamine stress echocardiography (DSE) was available in 58 of the 128 patients. Results Two-year survival was lower in patients with RVLS<|13|% (53%±9%) compared with those with RVLS>|13|% (69%±5%) (p=0.04). In multivariable Cox analysis stratified for the type of treatment (aortic valve replacement vs conservative) and adjusted for age, AS severity, previous myocardial infarction and LVLS, rest RVLS<|13|% (HR=2.70; 95% CI 1.19 to 6.11; p=0.018) was independently associated with all-cause mortality. RVLS had incremental prognostic value over baseline risk factors and LVLS (χ2=20.13 vs 13.56; p=0.01). Reduced stress RVLS was also associated with increased risk of mortality (stress RVLS<|14|%: HR=2.98; 95% CI 1.30 to 6.52; p=0.01). In multivariable Cox analysis, stress RVLS<|14|% remained independently associated with mortality (HR=2.94; 95% CI 1.23 to 7.02; p=0.015). After further adjustment for rest RVLS, stress RVLS<|14|% remained independently associated with mortality (HR=3.29; 95% CI 1.17 to 9.25; p=0.024), whereas rest RVLS was not (p>0.05). Conclusions In this series of patients with LF-LG AS and low LVEF, reduced RVLS was independently associated with increased risk of mortality. Furthermore, stress RVLS provided incremental prognostic value beyond that obtained from rest RVLS. Thus, RVLS measurement at rest and at DSE may be helpful to enhance risk stratification in this high-risk population. Trial registration number NCT01835028; Results.
Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation

Objectives: To assess the acceptability of the delivery of an isoflavone supplementation in the form of a powdered drink, and whether the supplementation of dietary isoflavones in this manner decreased the incidence of menopausal flushes. The secondary aims included assessment of other symptoms or parameters of estrogen deficiency and responses to isoflavones. Methods: A randomized, double-blind, placebo-controlled, parallel-group trial comprising 24 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period. The women were randomized to receive a dietary beverage containing isoflavones or an isoflavone-free, isocaloric placebo preparation. Results: Although there was a high compliance rate among individual patients, there was a 25% withdrawal rate from the study in the active group. The incidence of complaints of bad taste tended to be higher in the active group (p = 0.07), and the total number of adverse events was significantly higher in this group (p < 0.001). There was no statistically significant difference in the incidence of flushes between the groups. There was no difference between the groups in Greene Menopause Symptom Scores, vaginal maturation value, levels of follicle stimulating hormone (FSH) or sex hormone-binding globulin (SHBG), or bone turnover markers. Conclusions: Powdered energy drinks are not commonly consumed in Australia and were poorly tolerated in this study. The high withdrawal rate and reporting of side-effects suggests that other methods of isoflavone delivery may be more appropriate in this culture, in future trials. At the dose used no benefit was seen in relief from menopausal symptoms, although for the sample size, the study could only have been expected to detect major differences between the groups.
The Nodulus and Uvula: Source of Cerebellar Control of Spatial Orientation of the Angular Vestibulo‐Ocular Reflex

Abstract: The nodulus and rostral‐ventral uvula of the vestibulo‐cerebellum play a critical role in orienting eye velocity of the slow component of the angular vestibulo‐ocular reflex (aVOR) to gravito‐inertial acceleration (GIA). This is done by altering the time constants of “velocity storage” in the vestibular system and by generating “cross‐coupled” eye velocities that shift the eye velocity vector from along the body yaw axis to the yaw axis in a spatial frame. In this report, we show that eye velocity generated through the aVOR by constant velocity centrifugation in the monkey orients to the GIA in space, regardless of the position of the head with respect to the axis of rotation. We also show that, after removal of the nodulus and rostral‐ventral uvula, the spatial orientation of eye velocity to the GIA is lost and that eye velocity is then purely driven by the semicircular canals in a body frame of reference. These findings are further confirmation that these regions of the vestibulo‐cerebellum control spatial orientation of the aVOR.
Effects of inter-industry and spatial spillovers on regional productivity: Evidence from Spanish panel data

This paper examines the role of both intra and inter-industry spillovers when estimating regional aggregate production functions. To our knowledge, this is the first paper that examines technological and spatial externalities simultaneously using sector-level data. The proposed model also extends the standard spatial econometric models by modeling interregional (spatial) dependence through the economic criteria of migration flows. We apply our methodology to the Spanish provinces over the 2001-2013 period. Our results reveal the simultaneous presence of both Marshallian and Jacobian externalities. The spillovers of private production factors are negative in most of the sectors, indicating the presence of inter-regional and inter-sectoral competition for skilled labor and private capital. Our results also indicate that the core-periphery theory can be applied to both fully efficient and inefficient sectors, a finding that should be examined more deeply in the future.
Pharmacological Immunomodulation of Surgical Trauma

Surgery and accidental trauma induce changes in the immune response, showing a predominant pattern of activation through the Th2 cell pathway to the detriment of Th1 cell pathway activation. Anapsos is a hydrosoluble extract obtained from Polypodium leucotomos. Anapsos has shown immunomodulating effects in vitro. On a rat experimental model (tibia and fibula fracture), cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, and IL-12) (enzyme-linked immunosorbent assay, ELISA) and cell percentages of CD4, CD8 CD25, CD122, and CD132 (monoclonal antibodies, MoAb) were determined in peripheral blood 7 days before surgery (PRE), 1 day after surgery (1PO), and 7 days after surgery (7PO). On postoperative day 1, rats undergoing fracture show an increase of CD8 percent expression and IL-6 and IL-10 levels, in contrast to rats undergoing fracture plus anapsos treatment. On postoperative day 7, rats undergoing fracture show an increase of IL-6 levels, whereas rats undergoing fracture plus anapsos do not. The IL-12 level decreases on postoperative day 7 in the group with fracture but not in the fracture plus anapsos group. Thus, we conclude that anapsos is able to modulate the immune response after trauma, inhibiting Th2 pathway activation with no effect on Th1 pathway activation. In trauma, Anapsos could prevent the shifting Th1/Th2 balance.
Changes in Electrical Perception Threshold Within the First 6 Months After Traumatic Spinal Cord Injury

Objective. To assess the reliability of the electrical perception threshold (EPT) in healthy participants and its responsiveness in patients for 6 months after traumatic spinal cord injury (SCI). Methods. The reliability of EPT measures was assessed in 15 healthy volunteers (from C3 to S2). EPT measures were assessed in 37 patients at 1, 3, and 6 months after SCI. EPT was determined in dermatomes at, above, and below the neurological level of lesion. Reliability was quantified with an intraclass correlation coefficient (ICC) and responsiveness with the standardized response mean (SRM). Dermatomes were classified as having normal or pathological sensory perception, based on both light touch (LT) and EPT testing. The percentage of agreement between LT and EPT classifications was determined. Results. The ICCs varied considerably between dermatomes (0.00 ≤ ICC ≤ 0.86). Overall, EPTs changed little within the first 6 months after SCI, resulting in small SRM values. Agreement between classifications according to EPT or LT testing varied from 30% to 100%. The least agreement was observed in the first segment below the lesion. Conclusion. Future studies must note that the reliability of EPT differs between dermatomes in healthy participants. Furthermore, at and below the level of the lesion, spontaneous recovery of sensory perception is poor within the first 6 months after SCI. Based on subgroup analyses, if a translational trial aims to improve sensory perception around the level of the lesion, sensory-incomplete tetraplegic patients could be included. These patients show poor spontaneous recovery, and the EPT may detect subtle changes in perception.
Commentary: Childbirth Education in Iran

With regard to childbirth, the role of every health-care system is to improve maternity care as well as the birth experience of women and their family members. Despite many efforts to improve maternity care in the Islamic Republic of Iran, the nation’s childbirth care still faces a tremendous amount of unnecessary intervention and, consequently, a high rate of cesarean births. This article describes the strengths and weaknesses of Iran’s maternity-care system and childbirth education in light of evidence-based practice.
An Inducible Cytochrome P450 3A4-Dependent Vitamin D Catabolic Pathway

Vitamin D3 is critical for the regulation of calcium and phosphate homeostasis. In some individuals, mineral homeostasis can be disrupted by long-term therapy with certain antiepileptic drugs and the antimicrobial agent rifampin, resulting in drug-induced osteomalacia, which is attributed to vitamin D deficiency. We now report a novel CYP3A4-dependent pathway, the 4-hydroxylation of 25-hydroxyvitamin D3 (25OHD3), the induction of which may contribute to drug-induced vitamin D deficiency. The metabolism of 25OHD3 was fully characterized in vitro. CYP3A4 was the predominant source of 25OHD3 hydroxylation by human liver microsomes, with the formation of 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] dominating (Vmax/Km = 0.85 ml · min−1 · nmol enzyme−1). 4β,25(OH)2D3 was found in human plasma at concentrations comparable to that of 1α,25-dihydroxyvitamin D3, and its formation rate in a panel of human liver microsomes was strongly correlated with CYP3A4 content and midazolam hydroxylation activity. Formation of 4β,25(OH)2D3 in primary human hepatocytes was induced by rifampin and inhibited by CYP3A4-specific inhibitors. Short-term treatment of healthy volunteers (n = 6) with rifampin selectively induced CYP3A4-dependent 4β,25(OH)2D3, but not CYP24A1-dependent 24R,25-dihydroxyvitamin D3 formation, and altered systemic mineral homeostasis. Our results suggest that CYP3A4-dependent 25OHD3 metabolism may play an important role in the regulation of vitamin D3 in vivo and in the etiology of drug-induced osteomalacia.
Methyl 3-oxo-2,3-dihydro-1,2-benzothiazole-2-acetate 1,1-dioxide

The title molecule, C10H9NO5S, is composed of two essentially planar units with a dihedral angle of 89.16 (6)° between them. In the crystal structure, there are weak intermolecular C—H⋯O interactions resulting in dimeric pairs of molecules about inversion centres and chains of molecules extended along the a and c axes, thus stabilizing the structure. In addition, benzothiazole rings lying parallel to each other with centroid–centroid distances of 3.679 (2) and 3.999 (2) Å indicate the existence of π–π stacking interactions.