IJRTP Volume 10(iv) Table of Contents

Special Issue : Pilgrimage as a Multi-Faceted Diamond, containing papers from Sacred Journeys 9th Global Conference at the University of Primorska’s Department of Tourism, in Portoroz and Piran, Slovenia, from July 6-8, 202

Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis.

Transient receptor potential canonical 5 (TRPC5), a calcium-permeable, non-selective cation channel is expressed in the periphery, but there is limited knowledge of its regulatory roles in vivo. Endogenous modulators of TRPC5 include a range of phospholipids that have an established role in liver disease, including lysophosphatidylcholine (LPC). Cholestasis is characterized by impairment of excretion of bile acids, leading to elevation of hepatic bile acids. We investigated the contribution of TRPC5 in a murine model of cholestasis. Wild-type (WT) and TRPC5 knock-out (KO) mice were fed a diet supplemented with 0.5% cholic acid (CA) for 21 days. CA-diet supplementation resulted in enlargement of the liver in WT mice, which was ameliorated in TRPC5 KO mice. Hepatic bile acid and lipid content was elevated in WT mice, with a reduction observed in TRPC5 KO mice. Consistently, liver enzymes were significantly increased in cholestatic WT mice and significantly blunted in TRPC5 KO mice. Localized dyslipidaemia, secondary to cholestasis, was investigated utilizing a selected lipid analysis. This revealed significant perturbations in the lipid profile following CA-diet feeding, with increased cholesterol, triglycerides and phospholipids, in WT, but not TRPC5 KO mice. Our results suggest that activation of TRPC5 contributes to the development of cholestasis and associated dyslipidemia. Modulation of TRPC5 activity may present as a novel therapeutic target for liver disease

Blurred vision due to choroidal metastasis as the first manifestation of lung cancer: A case report

<p>Abstract</p> <p>Background</p> <p>Reduction in visual acuity combined with blurred vision is rarely the first sign of lung cancer and very few cases have been announced globally.</p> <p>Case presentation</p> <p>A case of a 46-year-old man who admitted with blurred vision is presented. His medical history, apart from a mild gastritis under treatment was negative. Ocular examination revealed a decrease in visual acuity due to a choroidal tumor. Further image body scans demonstrated a right lung lesion with dissemination to other organs. Diagnosis of a non-small cell lung cancer established after a VATS biopsy carried out.</p> <p>Conclusion</p> <p>Blurred vision due to choroidal metastasis as the primary symptom of lung cancer is very uncommon. A great index of suspicion is essential when a choroidal lesion appears.</p

Determinants for the success of software startups: Insights from a regional cluster

In recent years, we have seen a growing interest in technology-based companies and intensive knowledge. Several regional clusters have appeared supported in dynamic entrepreneurial ecosystems which, alongside intrinsic aspects of the business, are important determinants of the success of new companies. However, most startups created in these innovation-oriented spaces do not survive the first years of life, due to the high competitiveness of the technological market, due to deficiencies in the business model, due to the support conditions provided by the surrounding ecosystem, and finally due to a weak adjustment between all these dimensions. Among several models available, the Early-Life Decision Model (ELDM) presents itself as an interesting framework for studying the development and success conditions of software companies. This article discusses the application of the ELDM based on a series of interviews conducted to 15 Portuguese software startups installed in a technological cluster located in the northeast of Portugal. Based on the results obtained, it was appropriate to add a new dimension to the ELDM model (learning) and complementing it with the perspectives of the business type and internal versus external determinants.This work was supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT (Fundação para a Ciência e a Tecnologia) within the Project Scope: UID/CEC/00319/2013

Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner

BACKGROUND: The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. METHODS: Mono-arthritis was induced by unilateral intra-articular injection of complete Freund’s adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK(1)) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP(8–37)). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. RESULTS: Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. CONCLUSIONS: We provide evidence that environmental cold exposure enhances pain and increases blood flow in a mono-arthritis model. These changes are dependent on TRPA1. Thus, TRPA1 may act locally within the joint to influence blood flow via sensory nerves, in addition to its established nociceptive actions

Imaging shear stress distribution and evaluating the stress concentration factor of the human eye.

Healthy eyes are vital for a better quality of human life. Historically, for man-made materials, scientists and engineers use stress concentration factors to characterise the effects of structural non-homogeneities on their mechanical strength. However, such information is scarce for the human eye. Here we present the shear stress distribution profiles of a healthy human cornea surface in vivo using photo-stress analysis tomography, which is a non-intrusive and non-X-ray based method. The corneal birefringent retardation measured here is comparable to that of previous studies. Using this, we derive eye stress concentration factors and the directional alignment of major principal stress on the surface of the cornea. Similar to thermometers being used for monitoring the general health in humans, this report provides a foundation to characterise the shear stress carrying capacity of the cornea, and a potential bench mark for validating theoretical modelling of stresses in the human eye in future

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A resolved, au-scale gas disk around the B[e] star HD 50138

articleHD 50138 is a B[e] star surrounded by a large amount of circumstellar gas and dust. Its spectrum shows characteristics which may indicate either a pre- or a post-main-sequence system. Mapping the kinematics of the gas in the inner few au of the system contributes to a better understanding of its physical nature. We present the first high spatial and spectral resolution interferometric observations of the Brγ line of HD 50138, obtained with VLTI/AMBER. The line emission originates in a region more compact (up to 3 au) than the continuum-emitting region. Blue- and red-shifted emission originates from the two different hemispheres of an elongated structure perpendicular to the polarization angle. The velocity of the emitting medium decreases radially. An overall offset along the NW direction between the line- and continuum-emitting regions is observed. We compare the data with a geometric model of a thin Keplerian disk and a spherical halo on top of a Gaussian continuum. Most of the data are well reproduced by this model, except for the variability, the global offset and the visibility at the systemic velocity. The evolutionary state of the system is discussed; most diagnostics are ambiguous and may point either to a post-main-sequence or a pre-main-sequence nature.National Science FoundationGeorgia State UniversityW.M. Keck FoundationDavid and Lucile Packard FoundationFizeau ProgramCNRS-PICS progra