Exploring the Complex Dynamics: Examining the Influence of Deviant Personas in Online Gambling.

The widespread use of computers and the Internet has substantially changed the gaming environment during the past ten years. The gambling industry is no longer exclusive to land-based gaming establishments (such as casinos and racetracks). Today, a few keystrokes on a computer are all it takes to access gaming operations. Social media platforms like Facebook, Instagram, Snapchat and various other platforms constitute a particular form of access that has drawn more attention from academics in gambling studies. This increasing focus is partially attributable to the fact that social media sites have gained popularity as a means of accessing online gambling websites via hyperlinks hidden inside adverts. Users of social networking platforms can play free-to-play virtual gambling games using programmes. Virtual gaming platforms are the new name for these free-to-play simulation games of gambling. However, there is evidence to suggest that playing social casino games may serve as a "gateway" to real money gambling. The purpose of this study is to investigate the influence of deviant personas on online gambling behavior. By examining the relationship between deviant personas and online gambling, we seek to enhance our understanding of the factors that contribute to problematic gambling behaviors in virtual environments. Employing a robust methodological approach, this research amalgamates the analytical power of PLS-SEM (Partial Least Squares Structural Equation Modeling) to explore the factors influencing the intention to adopt online gambling services. The data for this study were obtained by administering an online survey questionnaire to a sample of 325 aware customers of online gambling. The study's discerning insights have notable implications for the academic community, brand strategists, online game designers, and online gambling platform providers, offering valuable guidance for decision-making and strategy formulation within the burgeoning online gambling industry.

Hyaluronate decorated polyethylene glycol linked poly(lactide-co-glycolide) nanoparticles encapsulating MUC-1 peptide augmented mucosal immune response in Balb/c mice through inhalation route.

BACKGROUND AND OBJECTIVES: NSCLC (Non-Small Cell Lung Cancer) clutches highest mortality rate in man and women globally. The present study was conducted to target MUC-1 peptide (M-1) into antigen presenting cells by cargo the peptide into hyaluronic acid decorated polyethylene glycol linked poly (D, l-lactide-co-glycolide) nanoparticles (M-1-PL-co-GA-PEG-sHA-NPs) for generating mucosal immunity through inhalation (i.h.) route. METHODOLOGY AND RESULTS: The mean particle size and surface charge of M-1-PL-co-GA-PEG-sHA-NPs was measured to be 136.2 ± 18.38-nm and - 28.34 ± 6.77-mV, respectively, prepared by non-aggregated emulsion-diffusion evaporation method. The 28.42% percentage release of M-1 peptide from M-1-PL-co-GA-PEG-NPs was observed to be at 2 h and 95.29% at 8 h while the percentage release of M-1 peptide from M-1-PL-co-GA-PEG-sHA-NPs was observed to be 26.02% at 4 h and 97.95% at 24 h that proved the prolonged release of antigen. M-1-PL-co-GA-PEG-sHA-NPs demonstrated higher (P < 0.05) cellular uptake of 86.2% in RAW 264.7 cells in comparison to 27.6% of M-1-PL-co-GA-PEG-NPs. In addition, M-1-PL-co-GA-PEG-sHA-NPs induced remarkably (P < 0.05) elevated release of 80.6-pg/ml of TNF-α in comparison to 5-pg/ml by culture medium and 57.9-pg/ml of TNF-α by M-1-PL-co-GA-PEG-NPs. Similarly, M-1-PL-co-GA-PEG-sHA-NPs persuade remarkably (P < 0.05) elevated release of 225-pg/ml of IL-1ß in comparison to 47-pg/ml by culture medium and 161.9-pg/ml of IL-1ß by M-1-PL-co-GA-PEG-NPs. M-1-PL-co-GA-PEG-sHA-NPs might have been endocytosed through receptor mediated pathway owing to presence of sHA. Mice immunized through i.h. route with M-1-PL-co-GA-PEG-sHA-NPs induced strong (P < 0.05) IgA antibody titre as compared to M-1-PL-co-GA-PEG-NPs and M-1 peptide in dose-dosage regimen. CONCLUSION: M-1-PL-co-GA-PEG-sHA-NPs nanovaccine warrants further analysis in xenograft model of NSCLC to showcase its antitumor capability.

Pretreament neutrophil-lymphocyte ratio (NLR): A felicitous prognostic marker in carcinoma lung.

BACKGROUND: Mechanics of inflammation and oncogenesis are intertwined with each other. Thus, the role of inflammatory markers like neutrophil-lymphocyte ratio (NLR) as a foreteller of lung carcinoma is retrospectively appraised in this study. MATERIAL AND METHODS: Retrospective assessment of hospital records of carcinoma lung patients was done between January 2018 and January 2020 and pretreatment NLR was calculated. Median NLR was taken as cut off and thereafter correlation was studied between pretreatment NLR and overall survival, using Kaplan-Meier survival analysis. Cox regression analysis was applied to identify factors affecting survival. RESULTS: Study population included 135 eligible patients with median age of 60 years and male to female ratio of 8.6:1. 47.41% patients were of stage III and 52.59% patients belonged to stage IV. The duration of follow-up ranged between 0.5 and 22 months. Median NLR was 3.1 (range, 0.90-11.25) and median overall survival in patients with NLR <3.1 and ≥3.1 was 6 months versus 3 months, respectively (P-value = 0.001). NLR value in nonsmall cell and small cell lung cancer was analyzed separately and showed significant variation in median survival in nonsmall cell lung cancer patients only (P-value = 0.001). CONCLUSIONS: Study results summarized that pretreatment NLR can be taken as a cheap and easily available predictor of prognosis in carcinoma lung cases and more so in nonsmall cell lung carcinoma cases. Large prospective trials are warranted to further potentiate this fact.

Differential miRNA Expression in Osteoporotic Elderly Patients with Hip Fractures Compared to Young Patients.

BACKGROUND: The expression pattern of micro-RNAs (miRNA) has been implicated in the pathomechanism of various bone disorders, and has a role in differentiation of osteoblasts and osteoclasts. The purpose of the study was to investigate the differential miRNA profiles of osteoporotic hip fractures compared to young patients with hip fractures. METHODS: Blood samples from ten osteoporosis patients and ten young, healthy patients, presenting with acute hip fractures were collected and subjected to an initial miRNA profiling to detect those miRNAs with significant variations between the two groups based on polymerase chain reactions performed in duplicate. A real-time quantitative polymerase chain reaction-based analysis was then performed for validation of specific miRNAs that were significantly different between the two groups. RESULTS: A total of 182 miRNAs were analyzed. Thirty-nine of them showed significant differences between the two groups in the initial miRNA profiling. The validation results suggested that five miRNAs related to bone metabolism had significantly different expression among the osteoporotic hip fracture group compared to the young, healthy group: miR-23b-3p and miR-140-3p were up-regulated; miR-21-5p, miR-122-5p and miR-125b-5p were down-regulated. CONCLUSIONS: Differential expression of selected miRNAs in patients with osteoporotic hip fracture suggests a possible role of miRNAs as potential biomarkers in prevention or timely prediction of osteoporotic fractures in the elderly. Further research is required to elucidate the mechanism of their involvement in osteoporosis. LEVEL OF EVIDENCE: Not applicable.

Epidemiological Insights from 1,652 Patients with Spinal Tuberculosis Managed at a Single Center: A Retrospective Review of 5-Year Data.

STUDY DESIGN: Retrospective cohort. PURPOSE: To report the demographic characteristics, clinico-radiological presentation, laboratory findings, and outcomes of "middlepath" treatment in patients with spinal tuberculosis from a single public healthcare facility in a developing country. OVERVIEW OF LITERATURE: Tuberculosis is a global health problem that is endemic in developing countries and undergoing resurgence in developed ones. Spinal tuberculosis can cause disabling back pain, progressive deformity, and neurological involvement. However, there is a lack of large-scale epidemiological studies quantifying the size and severity of the problem of spinal tuberculosis. METHODS: Hospital records of spinal tuberculosis patients treated at a single center over a period of 5 years were retrospectively reviewed. A diagnosis of spinal tuberculosis was based on standard clinical, radiological, microbiological, and histopathological evidence. Patients were treated in accordance with the "middle-path" regimen; surgery was reserved for selective indications. RESULTS: A total of 1,652 patients were included. Their median age was 32.4 years, with 53% being male. Axial pain (98%) was the most common presenting symptom; 19% of patients had neurological deficit. Lumbar spine (37%) was the most common site of involvement, with a paradiscal pattern (82%) of involvement predominating. Multi-level involvement was seen in 19% of patients; skip lesions were noted in 2.8%. Transpedicular biopsy was performed in 667 patients; at least one tissue test was diagnostic of tuberculosis in 65% of patients. Forty-four patients had drug resistance to rifampicin. Surgery was required in 10.5% of patients. The "middle-path" regimen was associated with high compliance and significant improvements in pain (Visual Analog Scale score) and function (36-Item Short Form Health Survey). CONCLUSIONS: Our findings confirm the widespread prevalence of spinal tuberculosis and describe various epidemiological characteristics of a large sample of spinal tuberculosis patients. Adoption of the "middle-path" regimen is associated with high compliance and favorable outcomes in spinal tuberculosis.

Implementation of Genetic Engineering and Novel Omics Approaches to Enhance Bioremediation: A Focused Review.

Bioremediation itself is considered to be a cost effective soil clean-up technique and preferred over invasive physical and chemical treatments. Besides increasing efficiency, application of genetic engineering has led to reduction in the time duration required to achieve remediation, overcoming the so called 'Achilles heel' of Bioremediation. Omics technologies, namely genomics, transcriptomics, proteomics, and metabolomics, are being employed extensively to gain insights at genetic level. A wise synchronised application of these approaches can help scrutinize complex metabolic pathways, and molecular changes in response to heavy metal stress, and also its fate i.e., uptake, transport, sequestration and detoxification. In the present review, an account of some latest achievements made in the field is presented.

Chitosan and phospholipid assisted topical fusidic acid drug delivery in burn wound: Strategies to conquer pharmaceutical and clinical challenges, opportunities and future panorama.

Burn is the immense public health issue globally. Low and middle income countries face extensive deaths owing to burn injuries. Availability of conventional therapies for burns has always been painful for patients as well as expensive for our health system. Pharmaceutical experts are still searching reliable, cheap, safe and effective treatment options for burn injuries. Fusidic acid is an antibiotic of choice for the management of burns. However, fusidic acid is encountering several pharmaceutical and clinical challenges like poor skin permeability and growing drug resistance against burn wound microbes like Methicillin resistant Staphylococcus aureus (MRSA). Therefore, an effort has been made to present a concise review about molecular pathway followed by fusidic acid in the treatment of burn wound infection in addition to associated pros and cons. Furthermore, we have also summarized chitosan and phospholipid based topical dermal delivery systems customized by our team for the delivery of fusidic acid in burn wound infections on case-to-case basis. However, every coin has two sides. We recommend the integration of in-silico docking techniques with natural biomacromolecules while designing stable, patient friendly and cost effective topical drug delivery systems of fusidic acid for the management of burn wound infection as future opportunities.

The DEAD-box RNA helicase eIF4A regulates plant development and interacts with the hnRNP LIF2L1 in Physcomitrella patens.

eIF4A is a RNA-stimulated ATPase and helicase. Besides its key role in regulating cap-dependent translation initiation in eukaryotes, it also performs specific functions in regulating cell cycle progression, plant growth and abiotic stress tolerance. Flowering plants encode three eIF4A paralogues, eIF4A1, eIF4A2 and eIF4A3 that share conserved sequence motifs but differ in functions. To date, however, no information is available on eIF4A in basal land plants. In this study we report that genome of the moss Physcomitrella patens encodes multiple eIF4A genes. The encoded proteins possess the highly conserved motifs characteristic of the DEAD box helicases. Spatial expression analysis shows these genes to be ubiquitously expressed in all tissue types with Pp3c6_1080V3.1 showing high expression in filamentous protonemata. Targeted deletion of conserved core motifs in Pp3c6_1080V3.1 slowed protonemata growth and resulted in dwarfing of leafy gametophores suggesting a role for Pp3c6_1080V3.1 in regulating cell division/elongation. Rapid and strong induction of Pp3c6_1080V3.1 under salt stress and slow recovery of knockout plants upon exposure to high salt further suggest Pp3c6_1080V3.1 to be involved in stress management in P. patens. Protein-protein interaction studies that show Pp3c6_1080V3.1 to interact with the Physcomitrella heterogenous ribonucleoprotein, LIF2L1, a transcriptional regulator of stress-responsive genes in Arabidopsis. The results presented in this study provide insight into evolutionary conserved functions of eIF4A and shed light on the novel link between eIF4A activities and stress mitigation pathways/RNA metabolic processes in P. patens.

Intersession Variations in Frequency Tuning of Ocular Vestibular Evoked Myogenic Potentials in Healthy Individuals.

Objective Frequency tuning of ocular vestibular evoked myogenic potential (oVEMP), which is the stimulus frequency corresponding to the largest oVEMP amplitude, has been used to diagnose cases with Ménière's disease and differentiate them from cases with benign paroxysmal positional vertigo with a high degree of sensitivity and specificity. However, this measure of oVEMP is carved out of the peak-to-peak amplitude of oVEMP, and studies on test-retest reliability of amplitude of oVEMP have shown moderate-to-excellent reliability of amplitude. This would theoretically render the frequency tuning of oVEMP susceptible to variations across multiple recordings. This being the case, erroneous conclusions regarding the presence of Ménière's disease could be made if the frequency tuning varies between recordings. However, there is no published report regarding the test-retest reliability of frequency tuning measure of oVEMP even in healthy individuals, to the best of our knowledge. Therefore, this study aimed to study the test-retest reliability of frequency tuning of oVEMP in healthy individuals. Method The study included 20 healthy adults in the age range of 18-25 years. All participants underwent oVEMP recording in 4 different sessions, with each session consisting of oVEMP recording for octave and midoctave tone-burst frequencies from 250 to 2000 Hz. Results The results revealed no significant difference in frequency tuning of oVEMP among the sessions (p > .05). The intraclass correlation coefficient for frequency tuning data was found to be .857. Conclusion The frequency tuning of oVEMP has excellent test-retest reliability and therefore lends itself to applications requiring multiple sessions of recording.

Myg1 exonuclease couples the nuclear and mitochondrial translational programs through RNA processing.

Semi-autonomous functioning of mitochondria in eukaryotic cell necessitates coordination with nucleus. Several RNA species fine-tune mitochondrial processes by synchronizing with the nuclear program, however the involved components remain enigmatic. In this study, we identify a widely conserved dually localized protein Myg1, and establish its role as a 3'-5' RNA exonuclease. We employ mouse melanoma cells, and knockout of the Myg1 ortholog in Saccharomyces cerevisiae with complementation using human Myg1 to decipher the conserved role of Myg1 in selective RNA processing. Localization of Myg1 to nucleolus and mitochondrial matrix was studied through imaging and confirmed by sub-cellular fractionation studies. We developed Silexoseqencing, a methodology to map the RNAse trail at single-nucleotide resolution, and identified in situ cleavage by Myg1 on specific transcripts in the two organelles. In nucleolus, Myg1 processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, Myg1 processes 3'-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins. We provide a molecular link to the possible involvement of Myg1 in chronic depigmenting disorder vitiligo. Our study identifies a key component involved in regulating spatially segregated organellar RNA processing and establishes the evolutionarily conserved ribonuclease as a coordinator of nucleo-mitochondrial crosstalk.

Mapping architectural and transcriptional alterations in non-lesional and lesional epidermis in vitiligo.

In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis presents a challenge for long-term tissue maintenance. The stable vitiligo patches are known to attain an irreversible depigmented state. However, the molecular and cellular processes resulting in this remodeled tissue homeostasis is unclear. To investigate the complex interplay of inductive signals and cell intrinsic factors that support the new acquired state, we compared the matched lesional and non-lesional epidermis obtained from stable non-segmental vitiligo subjects. Hierarchical clustering of genome-wide expression of transcripts surprisingly segregated lesional and non-lesional samples in two distinct clades, despite the apparent heterogeneity in the lesions of different vitiligo subjects. Pathway enrichment showed the expected downregulation of melanogenic pathway and a significant downregulation of cornification and keratinocyte differentiation processes. These perturbations could indeed be recapitulated in the lesional epidermal tissue, including blunting of rete-ridges, thickening of stratum corneum and increase in the size of corneocytes. In addition, we identify marked increase in the putrescine levels due to the elevated expression of spermine/spermidine acetyl transferase. Our study provides insights into the intrinsic self-renewing ability of damaged lesional tissue to restore epidermal functionality in vitiligo.

Water Buffalo (Bubalus bubalis) as a spontaneous animal model of Vitiligo.

Vitiligo is a multifactorial acquired depigmenting disorder. Recent insights into the molecular mechanisms driving the gradual destruction of melanocytes in vitiligo will likely lead to the discovery of novel therapies, which need to be evaluated in animal models that closely recapitulate the pathogenesis of human vitiligo. In humans, vitiligo is characterized by a spontaneous loss of functional melanocytes from the epidermis, but most animal models of vitiligo are either inducible or genetically programmed. Here, we report that acquired depigmentation in water buffalo recapitulates molecular, histological, immunohistochemical, and ultrastructural changes observed in human vitiligo and hence could be used as a model to study vitiligo pathogenesis and facilitate the discovery and evaluation of therapeutic interventions for vitiligo.

Transcriptome profiling unveils the role of cholesterol in IL-17A signaling in psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by altered proliferation and differentiation of keratinocytes as well as infiltration of immune cells. Increased expression of Th17 cells and cytokines secreted by them provides evidence for its central role in the pathogenesis of psoriasis. IL-17A, signature cytokine of Th17 cells was found to be highly differentially expressed in psoriatic lesional skin. However, cellular and molecular mechanism by which IL-17A exerts its function on keratinocyte is incompletely understood. To understand IL-17A mediated signal transduction pathways, gene expression profiling was done and differentially expressed genes were analysed by IPA software. Here, we demonstrate that during IL-17A signaling total cholesterol levels were elevated, which in turn resulted in the suppression of genes of cholesterol and fatty acid biosynthesis. We found that accumulation of cholesterol was essential for IL-17A signaling as reduced total cholesterol levels by methyl ß cyclodextrin (MBCD), significantly decreased IL-17A induced secretion of CCL20, IL-8 and S100A7 from the keratinocytes. To our knowledge this study for the first time unveils that high level of intracellular cholesterol plays a crucial role in IL-17A signaling in keratinocytes and may explain the strong association between psoriasis and dyslipidemia.

De novo methyltransferase, OsDRM2, interacts with the ATP-dependent RNA helicase, OseIF4A, in rice.

Domains rearranged methyltransferases (DRMs) are the de novo methyltransferases that regulate cytosine methylation in plants in a manner similar to the animal de novo methyltransferases, DNMT3a and DNMT3b. These enzymes catalyze the establishment of new methylation patterns and are guided to target sites by small RNAs through the process of RNA-directed DNA methylation (RdDM). In the current accepted view for RdDM, intricate interactions among transcription factors/chromatin modifying proteins and the large subunits of plant-specific polymerases, Pol IV and Pol V, regulate the 24-nt small interfering RNA guided de novo methylation of cytosines. The RNA-induced silencing complex assembled on Pol-V-transcribed non-coding RNA finally facilitates the recruitment of DRM2 by unknown mechanism/protein interactions to chromatin sites. In an attempt to determine the cellular proteins that specifically interact with DRM2, a yeast two-hybrid screen was performed using young rice panicles. We report that rice DRM2 interacts with the ATP-dependent RNA helicase, eIF4A. Direct interaction between the two proteins is demonstrated in vivo by bimolecular fluorescence complementation method and in vitro by histidine-pull-down assays. Deletion analysis reveals that interaction between OsDRM2 and OseIF4A is specifically mediated through ubiquitin-associated domain of OsDRM2 while, both domains 1 and 2 of OseIF4A are critical for mediating strong interaction with OsDRM2 in vivo. Interaction between Arabidopsis eIF4AI and eIF4AII with OsDRM2 and nuclear localization of these complexes suggests possible conservation of functional interaction between de novo methyltransferases and the translation initiation factor, eIF4A, in RdDM across plant species.

Role of DNA methylation in growth and differentiation in Physcomitrella patens and characterization of cytosine DNA methyltransferases.

Epigenetic mechanisms such as DNA methylation are known to regulate important developmental processes in higher eukaryotes. However, little is known about the necessity and role of this process in early land plants. Using the methyltransferase (MTase) inhibitor zebularine (1-(ß-d-ribofuranosyl)-1,2-dihydropyrimidine-2-one), the impact of loss of genome-wide methylation on the overall development in Physcomitrella patens was analyzed. It is observed that various aspects of growth and differentiation during gametophyte development become aberrant. A search for the core molecular components of methylation machinery, cytosine DNA MTases, revealed the presence of seven loci in the P. patens genome. Five of the loci code for MTases that are similar to corresponding proteins in higher plants, while two MTases appear specific to P. patens and are closely related to human DNMT3a and DNMT3b, respectively. These proteins possess all the conserved catalytic motifs characteristic of MTases and a domain of unknown function, DUF3444. Association of these highly conserved motifs with a DUF has not been reported in any of the MTases known so far. All the seven genes are differentially but ubiquitously expressed in gametophytes at low levels. Subcellular localization of GFP-fused proteins shows patterns of distribution that can be correlated with their putative cellular functions. This work bridges the knowledge of MTases in P. patens and makes this simple model plant accessible for studies on epigenetic aspects that remain intractable in higher plants.

Rice cytosine DNA methyltransferases - gene expression profiling during reproductive development and abiotic stress.

DNA methylation affects important developmental processes in both plants and animals. The process of methylation of cytosines at C-5 is catalysed by DNA methyltransferases (MTases), which are highly conserved, both structurally and functionally, in eukaryotes. In this study, we identified and characterized cytosine DNA MTase genes that are activated with the onset of reproductive development in rice. The rice genome (Oryza sativa L. subsp. japonica) encodes a total of 10 genes that contain the highly conserved MTase catalytic domain. These genes have been categorized into subfamilies on the basis of phylogenetic relationships. A microarray-based gene expression profile of all 10 MTases during 22 stages/tissues that included 14 stages of reproductive development and five vegetative tissues together with three stresses, cold, salt and dehydration stress, revealed specific windows of MTase activity during panicle and seed development. The expression of six methylases was specifically/preferentially upregulated with the initiation of floral organs. Significantly, one of the MTases was also activated in young seedlings in response to cold and salt stress. The molecular studies presented here suggest a greater role for these proteins and the epigenetic process in affecting genome activity during reproductive development and stress than was previously anticipated.