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Byline: Shalesh. Rohatgi, Prajwal. Rao, Satish. Nirhale, Pravin. Naphade, Sravya. Kotharu, Sahil. Gupta Neuromyelitis Optica (NMO) is a demyelinating disease predominantly involving optic nerves, spinal cord and peri-ventricular regions which [...]

Advertising was once touted as a 'big boys' marketing tool, but the advent of the Internet has led to the emergence of online advertising, which has benefitted marketing organizations of all sizes, especially small and medium enterprises (SMEs), for 20 years since the new millennium. However, the emergence and proliferation of digital natives as a new generation of consumers necessitate further research to ensure the continued attractiveness, effectiveness, and relevance of online advertising. Furthermore, there is a need to consolidate the multifaceted nature of technology and media in online advertising and the corresponding behavior enacted by consumers, particularly digital natives, today. In this regard, this paper endeavors to examine the perceptions and reactions of digital natives toward online advertising using the theory of planned behavior, technology acceptance model, and uses and gratifications theory as an integrated theoretical lens to guide this examination. Using covariance structural equation modeling on a sample of 380 digital natives, this paper finds that the ease of use, usefulness, entertainment gratification, credibility, design, and personalization of online advertisement positively influence the attitude of digital natives toward online advertisement. However, assurance from online advertisement did not produce any significant effect, a unique finding that exemplifies the confidence that digital natives exhibit in digital environments as a self-assured generation. Finally, this paper finds that the attitude and subjective norms among digital natives toward online advertisement and the security and responsiveness of the website of the online advertised product positively influence the intention of digital natives to purchase the online advertised product. The implications of these findings for theory and practice as well as its limitations and future research directions conclude the paper. [ABSTRACT FROM AUTHOR]

Macrophages in the tumor microenvironment respond to complex cytokine signals. How these responses shape the phenotype of tumor-associated macrophages (TAMs) is incompletely understood. Here we explored how cytokines of the tumor milieu, interleukin (IL)-6 and IL-4, interact to influence target gene expression in primary human monocyte-derived macrophages (hMDMs). We show that dual stimulation with IL-4 and IL-6 synergistically modified gene expression. Among the synergistically induced genes are several targets with known pro-tumorigenic properties, such as CC-chemokine ligand 18 (CCL18), transforming growth factor alpha (TGFA) or CD274 (programmed cell death 1 ligand 1 (PD-L1)). We found that transcription factors of the signal transducer and activator of transcription (STAT) family, STAT3 and STAT6 bind regulatory regions of synergistically induced genes in close vicinity. STAT3 and STAT6 co-binding further induces the basic leucine zipper ATF-like transcription factor (BATF), which participates in synergistic induction of target gene expression. Functional analyses revealed increased MCF-7 and MDA-MB 231 tumor cell motility in response to conditioned media from co-treated hMDMs compared to cells incubated with media from single cytokine-treated hMDMs. Flow cytometric analysis of T cell populations upon co-culture with hMDMs polarized by different cytokines indicated that dual stimulation promoted immunosuppressive properties of hMDMs in a PD-L1-dependent manner. Analysis of clinical data revealed increased expression of BATF together with TAM markers in tumor stroma of breast cancer patients as compared to normal breast tissue stroma. Collectively, our findings suggest that IL-4 and IL-6 cooperate to alter the human macrophage transcriptome, endowing hMDMs with pro-tumorigenic properties.

Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated in various macrophage functions including efferocytosis and ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and immune function in naïve and AAMs. Silencing or inhibiting the 15-LOX isoforms impaired sterol regulatory element binding protein (SREBP)-2 signaling by inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP-2 binding to sterol regulatory elements and subsequent target gene expression. Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX isoforms did not generally affect IL-4 gene expression but rather uniquely impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting in reduced T cell migration to macrophage conditioned media. In conclusion, we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages.

Persistent chest pain (PCP) following acute COVID‐19 infection is a commonly reported symptom with an unclear etiology, making its management challenging. This scoping review aims to address the knowledge gap surrounding the characteristics of PCP following COVID‐19, its causes, and potential treatments. This is a scoping review of 64 studies, including observational (prospective, retrospective, cross‐sectional, case series, and case–control) and one quasi‐experimental study, from databases including Embase, PubMed/MEDLINE, Cochrane CENTRAL, Google Scholar, Cochrane Database of Systematic Reviews, and Scopus. Studies on patients with PCP following mild, moderate, and severe COVID‐19 infection were included. Studies with patients of any age, with chest pain that persisted following acute COVID‐19 disease, irrespective of etiology or duration were included. A total of 35 studies reported PCP symptoms following COVID‐19 (0.24%–76.6%) at an average follow‐up of 3 months or longer, 12 studies at 1–3 months and 17 studies at less than 1‐month follow‐up or not specified. PCP was common following mild—severe COVID‐19 infection, and etiology was mostly not reported. Fourteen studies proposed potential etiologies including endothelial dysfunction, cardiac ischemia, vasospasm, myocarditis, cardiac arrhythmia, pneumonia, pulmonary embolism, postural tachycardia syndrome, or noted cardiac MRI (cMRI) changes. Evaluation methods included common cardiopulmonary tests, as well as less common tests such as flow‐mediated dilatation, cMRI, single‐photon emission computed tomography myocardial perfusion imaging, and cardiopulmonary exercise testing. Only one study reported a specific treatment (sulodexide). PCP is a prevalent symptom following COVID‐19 infection, with various proposed etiologies. Further research is needed to establish a better understanding of the causes and to develop targeted treatments for PCP following COVID‐19. [ABSTRACT FROM AUTHOR]

Drug use and road traffic injuries (RTIs) are significant public health concerns globally, with the majority of RTIs occurring in low- and middle-income countries. Driving under the influence of alcohol and drugs is a major factor in RTIs, as psychoactive drugs can impair mental functioning and vehicular control. While alcohol-related traffic deaths have declined, drug-impaired driving is increasing. In India, RTIs are on the rise, and there is a need for more research on drug use and driving under the influence. The lack of research evidence in India contributes to a lack of comprehensive laws and policies for prevention and treatment of drug-related RTIs. It is recommended that research focus on various aspects of drug-impaired driving, and trauma centers should be equipped with testing and treatment services. [Extracted from the article]