Search

The relationship between tourists’ emotional experience and perception of destination brand personality, has not been empirically explored before. Moreover, there is a literature gap in understanding how emotional experience, destination personality, destination satisfaction, and behavioral intentions, interact together in one model. Based on this, the principal aim of this study is to analyze how tourists’ emotional experience affects the perception of destination personality traits, as well as how these two constructs relate to tourists’ satisfaction and behavioral intentions. In order to explore this, the survey was conducted on a sample of 203 domestic and international tourists, who have visited the city of Novi Sad, while Structural Equation Modeling (SEM) was applied to test the hypothesized model. The results confirmed the positive role of emotional experience in shaping destination personality and destination satisfaction. Destination satisfaction and certain personality traits positively predicted behavioral intentions. Theoretical and managerial implications are discussed in the paper.

Introduction: Thyroid hormones affect the cardiovascular system, but the precise mechanisms of their effects on the development of atherosclerosis are not entirely clear. The relationship between subclinical hypothyroidism, dyslipidemia and carotid atherosclerosis has been widely investigated, but the findings were controversial. The aim of the present study was to determine whether female subjects with subclinical hypothyroidism (SHypo) have increased carotid intima-media thickness (IMT) compared with euthyroid subjects, as well as to examine the association of SHypo, carotid atherosclerosis and dyslipidemia.

There is a global danger that hides in the shadows and is changing the way continuing care operators care for residents. Today, to provide that same historical level of resident care, a group of techno-soldiers are not just a nice-to-have, but are a must, to protect our critical Information Technology (IT) infrastructure. There is little doubt that technology has enabled us to provide better care. Electronic medical records, human resources information systems, and voice over Internet communications systems have created great efficiencies in operations. However, global cybercriminals lurk in the same technologies that support us. Continuously attempting to rob our private information and hold us ransom, or play havoc with our IT systems impeding our provision of care. How can a continuing care operator, an already funding-challenged industry balance the costs of protecting their IT infrastructure against this growing massive threat? Compounding the issue, rising insurance expectations for continuing care operators to continuously enhance their IT safety controls against evolving cyberterrorism. This is the story of the Good Samaritan Society/Canada (Good Samaritan) digital transformation journey. Our digital roadmap sets Good Samaritan up to rise above the ongoing barrage of cyberattacks and loss of insurance. This is a digital divide story of David vs. Goliath., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Antivirals with broad coronavirus activity are important for treating high-risk individuals exposed to the constantly evolving SARS-CoV-2 variants of concern (VOCs) as well as emerging drug-resistant variants. We developed and characterized a novel class of active-site-directed 3-chymotrypsin-like protease (3CLpro) inhibitors ( C2-C5a ). Our lead direct-acting antiviral (DAA), C5a , is a non-covalent, non-peptide with a dissociation constant of 170 nM against recombinant SARS-CoV-2 3CLpro. The compounds C2-C5a exhibit broad-spectrum activity against Omicron subvariants (BA.5, BQ.1.1, and XBB.1.5) and seasonal human coronavirus-229E infection in human cells. Notably, C5a has median effective concentrations of 30-50 nM against BQ.1.1 and XBB.1.5 in two different human cell lines. X-ray crystallography has confirmed the unique binding modes of C2-C5a to the 3CLpro, which can limit virus cross-resistance to emerging Paxlovid-resistant variants. We tested the effect of C5a with two of our newly discovered host-directed antivirals (HDAs): N-0385, a TMPRSS2 inhibitor, and bafilomycin D (BafD), a human vacuolar H + -ATPase [V-ATPase] inhibitor. We demonstrated a synergistic action of C5a in combination with N-0385 and BafD against Omicron BA.5 infection in human Calu-3 lung cells. Our findings underscore that a SARS-CoV-2 multi-targeted treatment for circulating Omicron subvariants based on DAAs ( C5a ) and HDAs (N-0385 or BafD) can lead to therapeutic benefits by enhancing treatment efficacy. Furthermore, the high-resolution structures of SARS-CoV-2 3CLpro in complex with C2-C5a will facilitate future rational optimization of our novel broad-spectrum active-site-directed 3C-like protease inhibitors.

The rapid global spread of the SARS-CoV-2 virus facilitated the development of novel direct-acting antiviral agents (DAAs). The papain-like protease (PLpro) has been proposed as one of the major SARS-CoV-2 targets for DAAs due to its dual role in processing viral proteins and facilitating the host's immune suppression. This dual role makes identifying small molecules that can effectively neutralize SARS-CoV-2 PLpro activity a high-priority task. However, PLpro drug discovery faces a significant challenge due to the high mobility and induced-fit effects in the protease's active site. Herein, we virtually screened the ZINC20 database with Deep Docking (DD) to identify prospective noncovalent PLpro binders and combined ultra-large consensus docking with two pharmacophore (ph4)-filtering strategies. The analysis of active compounds revealed their somewhat-limited diversity, likely attributed to the induced-fit nature of PLpro's active site in the crystal structures, and therefore, the use of rigid docking protocols poses inherited limitations. The top hits were assessed against recombinant viral proteins and live viruses, demonstrating desirable inhibitory activities. The best compound VPC-300195 (IC 50 : 15 μM) ranks among the top noncovalent PLpro inhibitors discovered through in silico methodologies. In the search for novel SARS-CoV-2 PLpro-specific chemotypes, the identified inhibitors could serve as diverse templates for the development of effective noncovalent PLpro inhibitors.

The indole moiety is one of the most widespread heterocycles found in both natural products and biological systems. Indoles have important biological activities including anticancer, antioxidant, anti-inflammatory, antifungal, anticholinesterase, and antibacterial properties. Scientists are therefore interested in the synthesis of biologically active indole-based hybrids such as indole-coumarin, indole-chalcone, indole-isatin, indole-pyrimidine and so on, with the aim of improving activity, selectivity, and mitigating side effects. This review will discuss the newly synthesized indole-based hybrids along with their biological activity which will be useful in drug discovery and development., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Background: Acute ischemic stroke (AIS) has a high risk of recurrence, particularly in the early stage. Recurrent ischemic stroke (RIS) is associated with adverse neurological outcomes but the phenomenon of early RIS in the endovascular thrombectomy era has not been frequently discussed. We report a case addressing this issue., Case Presentation: We present a patient who was successfully treated by mechanical thrombectomy (MT) for middle cerebral artery occlusion. Due to an early stroke recurrence, within 72 h after the first MT, he received systemic thrombolysis and repeated MT was performed with excellent clinical outcome., Discussion: We discuss the aspects of reperfusion therapy for patients experiencing early stroke recurrence. Consideration was given to stroke etiology and off-label use of thrombolytic therapy. Also, effectiveness of repeated MT for early re-occlusion of initially reanalyzed vessel was evaluated in order to allow more patients with RIS to benefit from reperfusion therapy., (© 2021. Fondazione Società Italiana di Neurologia.)

Components of carotid atherosclerotic plaque can be analysed preoperatively by non-invasive advanced imaging modalities such as magnetic resonance imaging (MRI). The expression of matrix metalloproteinase-9 protein (MMP-9), which has a potential role in remodelling of atherosclerotic plaques, can be analysed immunohistochemically. The aim of the present prospective pilot study is to analyse histological characteristics and expression of MMP-9 in carotid plaques of patients undergoing carotid endarterectomy (CEA) and to investigate the correlation with preoperative clinical symptoms and MRI features. Preoperative clinical assessment, MRI imaging, postoperative histological and immunohistochemical analyses were performed. Fifteen patients with symptomatic (7/15; 47%) and asymptomatic carotid artery stenosis undergoing CEA were included. Among symptomatic patients, 5 (71%) had recent stroke and 2 (29%) had recent transient ischaemic attack with a median timing of 6 weeks (IQR: 1, 18) before the surgery. Both groups did not significantly differ in respect to preoperative characteristics. Prevalence of unstable plaque was higher in symptomatic than asymptomatic patients, although it was not significant (63% vs. 37%, p = 0.077). The expression of MMP-9 in CD68 cells within the plaque by semiquantitative analysis was found to be significantly higher in symptomatic as compared to asymptomatic patients (86% vs. 25% with the highest expression, p = 0.014). The average microvascular density was found to be higher and lipid core area larger among both symptomatic patients and unstable carotid plaque specimens, although this did not reach statistical significance ( p = 0.064 and p = 0.132, p = 0.360 and p = 0.569, respectively). Our results demonstrate that MRI is reliable in classifying carotid lesions and differentiating unstable from stable plaques. We have also shown that the expression of MMP-9 is significantly higher among symptomatic patients undergoing CEA., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)