Calcium-sensing receptor activation increases cell-cell adhesion and ß-cell function

Background/Aims: The extracellular calcium-sensing receptor (CaR) is expressed in pancreatic β-cells where it is thought to facilitate cell-to-cell communication and augment insulin secretion. However, it is unknown how CaR activation improves β-cell function. Methods: Immunocytochemistry and western blotting confirmed the expression of CaR in MIN6 β-cell line. The calcimimetic R568 (1µM) was used to increase the affinity of the CaR and specifically activate the receptor at a physiologically appropriate extracellular calcium concentration. Incorporation of 5-bromo-2’-deoxyuridine (BrdU) was used to measure cell proliferation, whilst changes in non-nutrient-evoked cytosolic calcium were assessed using fura-2-microfluorimetry. AFM-single-cell-force spectroscopy related CaR-evoked changes in epithelial (E)-cadherin expression to improved functional tethering between coupled cells. Results: Activation of the CaR over 48hr doubled the expression of E-cadherin (206±41%) and increased L-type voltage-dependent calcium channel expression by 70% compared to control. These changes produced a 30% increase in cell-cell tethering and elevated the basal-to-peak amplitude of ATP (50µM) and tolbutamide (100µM)-evoked changes in cytosolic calcium. Activation of the receptor also increased PD98059 (1-100µM) and SU1498 (1-100µM)-dependent β-cell proliferation. Conclusion: Our data suggest that activation of the CaR increases E-cadherin mediated functional tethering between β-cells and increases expression of L-type VDCC and secretagogue-evoked changes in [Ca2+]i. These findings could explain how local changes in calcium, co-released with insulin, activate the CaR on neighbouring cells to help ensure efficient and appropriate secretory function

Factors influencing public attitudes toward paid online newspaper subscriptions- a field study

Despite the implementation of new business models in several Western media organizations, most Arab newspapers have not yet explored these models, and little is known about public attitudes towards their willingness to pay for online news. The study sought to identify factors that encourage the public to pay. It was applied to a sample of 530 newspaper consumers in the UAE, Saudi Arabia, and Oman. The study concluded that there are unfavorable trends in the public regarding their interest in following up on the news and did not show willingness for paying for online news. Most of them prefer to pay for entertainment materials. The study found that demographic variables such as age and income were important indicators of the public’s willingness to pay. Most respondents were not yet exposed to the paywall and anticipated difficulty in implementing the culture of paying for online news in Arab societies. They also expected that many print newspapers will disappear in the near future, and the idea of paying for online news was not seen favorably

Trapping cold atoms using surface-grown carbon nanotubes

We present a feasibility study for loading cold atomic clouds into magnetic traps created by single-wall carbon nanotubes grown directly onto dielectric surfaces. We show that atoms may be captured for experimentally sustainable nanotube currents, generating trapped clouds whose densities and lifetimes are sufficient to enable detection by simple imaging methods. This opens the way for a novel type of conductor to be used in atomchips, enabling atom trapping at sub-micron distances, with implications for both fundamental studies and for technological applications

CHOLESTATIC LIVER FIBROSIS IN A RAT MODEL OF BILE DUCT LIGATION: EVALUATING BIOCHEMICAL VERSUS HISTOPATHOLOGICAL CHANGES

Objective: Bile duct ligation (BDL), chronic liver injury model, was extensively used in studying mechanisms of fibrogenesis and antifibrotic agents. Considering the liver regenerative capacity and the diverse results from BDL, the present study aimed to evaluate the biochemical and histopathological changes over 10 weeks following BDL assessing if BDL-induced changes remain in a deterioration state or improve at a certain stage.Methods: Sham operation and BDL were conducted in Male Wistar rats. Serum AST, ALT, total bilirubin and albumin and hepatic hydroxyproline (HYP), reduced glutathione (GSH) and malondialdehyde (MDA) were measured in sham-operated (n=3) and BDL-rats (n=6) at 0, 1, 2, 4, 6, 8 and 10 weeks following operation. Liver tissue was also processed for histopathological analysis (H&E and Sirus red staining).Results: Progressive liver injury (H&E) and collagen deposition (Sirus red and HYP) in BDL-rats were observed starting from the first week post-operation and reached their maximum with early signs of cirrhosis on the 10th week of BDL. Severe and sustained cholestatic injury appeared in 2 weeks (increased ALT, AST, bilirubin along with decreased albumin (P<0.001) compared to sham-operated rats). AST peaked on first week, however, bilirubin, ALT and MDA peaked on the 4th week (P<0.001) then gradually decreased compared to their peaks.Conclusion: The relative improvement in liver function/cholestasis following their peaks in BDL model despite progression of fibrosis and hepatic injury require investigators using this model to consider not only biochemical, but also histopathological findings to guarantee an accurate interpretation of their results.Â

Safety Performance Of Subcontractors In The Palestinian Construction Industry

Subcontractors perform most of the construction works and their effect on industry are apparent in different activities of construction. Therefore, subcontractors need more attention from government and contractors union. The aim of this paper is to identify, evaluate, and rank factors that influence safety performance of subcontractors in the Gaza Strip (Palestine) according to their relative importance. The study concluded that reported accident rates will decrease among subcontractors and their workers if new workers are trained well in the work site and they are informed about dangerous places, and if a workable safety plan is well preplanned. The results also showed that reported accident rates increased among subcontractors when using old, unsafe equipment and due to the complexity or difficulty in the construction sites features. Owners and general contractors need to stipulate strict clauses for safety in the contract for improving safety record of subcontractors. Construction workers must receive proper job related safety and health training with a safety logbook. It is recommended that the subcontractors and workers should attend continuing safety programs on regular basis as part of their perquisite to work in construction sites

Racial and Ethnic Distribution of ABO and Rh (D) blood groups in Thi-Qar, Iraq

Most data in the literature include frequencies of these antigens in European and American countries. In this study for the first time we have reported frequencies of these antigens in the Thi-Qar of Iraq. The aim of the present study was to record the various blood groups among the population of Thi-Qar and to compare it with other populations. To determine the prevalence of different blood groups and Rh factors in a random population sample from urban and rural areas of Thi-qar of Iraq. Blood group and Rh factor determination was carried out by the antigen-antibody agglutination test. The frequency of each type was calculated. Out of 2841 subjects 4804 (59.1%) were male subjects and 1963 (40.9%) were female. The overall phenotypic frequencies of ABO blood in three groups in the total sample was O>A>B>AB. The frequencies of ABO and Rh phenotypes in Thi-Qar are similar to those reported from most areas in the Arabian regio

Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review

The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its “value for money”. This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim “F” = 4; pegfilgrastim “P” = 4) with varying baseline FN—risk (range 22–32 %), mortality (range 1.4–6.0 %) and utility (range 0.33–0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold

Histological pattern of tumor inflammation and stromal density correlate with patient demographics and immuno-oncologic transcriptional profile in oral squamous cell carcinoma

IntroductionOral squamous cell carcinoma (OSCC) is the most prevalent oral malignancy, with emerging interest in the characterization of its tumor microenvironment. Herein, we present a comprehensive histological analysis of OSCC stromal density and inflammation and their relationship with patient demographics, clinicopathologic features and immuno-oncologic signatures.Materials-methodsEighty-seven completely excised OSCC tissues were prospectively collected and scored for histopathologic inflammatory subtypes [HIS]—inflamed (INF), immune-excluded (IE) and immune-desert (ID), peritumoral stromal inflammation (PTSI), and peritumoral stromal fibrosis (PTSF). Scoring of inflammation was complemented by Semaphorin 4D immunohistochemistry. NanoString differential gene expression (DGE) analysis was conducted for eight OSCC cases representative of the inflammatory and stromal subtypes and the demographic groups.ResultsPTSF correlated with male gender (p = 0.0043), smoking (p = 0.0455), alcohol consumption (p = 0.0044), increased tumor size (p = 0.0054), and advanced stage (p = 0.002). On the contrary, PTSI occurred predominantly in females (p = 0.0105), non-drinkers (p = 0.0329), and small tumors (p = 0.0044). Transcriptionally, decreased cytokine signaling, and oncogenic pathway activation were observed in HIS-IE. Smokers and males displayed decreased global immune-cell levels and myeloid-cell predominance.ConclusionOur work describes OSCC stromal and inflammatory phenotypes in correlation with distinct patient groups and DGE, highlighting the translational potential of characterizing the tumor microenvironment for optimal patient stratification