The influence of high-quality workplace relational systems and mindfulness on employee work engagement at the time of crises.

Workplace relational systems move the organizational processes therefore, the influence on employee work behavior is inevitable. Drawing on the relational systems and broaden & build theory, this study aimed to examine the impact of high-quality workplace relational systems and trait of mindfulness on employee work engagement. This study also posits that psychological capital mediates this relationship and negative affectivity plays a moderating role. Data was collected from 331 employees associated with the public and private sectors. PLS-SEM, Higher Component Modeling technique employed to analyze the data. Results showed a positive association between high-quality workplace relational systems and mindfulness with employee work engagement. Data also support the mediating role of psychological capital. This study contributes to understanding the internal mechanism of how workplace relational systems and mindfulness affect work engagement through mediating effect of psychological capital. The findings of this study showed that high-quality workplace relational systems and mindfulness are workplace factors that induce employees' work engagement. The present study advances the knowledge on the flourishment of the work environment. The findings of this study also contribute to further focusing research on the relational work environment in its response to employee behavioral dimension.

Soluble immune checkpoints are dysregulated in COVID-19 and heavy alcohol users with HIV infection

Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the worlds most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol abuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol abuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.

Consumer's Satisfaction with Community Pharmacies in Sindh, Pakistan.

OBJECTIVE: The present research is the first comprehensive cross-sectional study of consumer satisfaction with community pharmacies in Sindh, Pakistan. Moreover, the study has also designed a nonorder theoretical model for consumer satisfaction with community pharmacies. METHODS: This is a cross-sectional descriptive study from a general population of Sindh, Pakistan, with a total of four hundred and fifteen (n = 415) participants. A confirmatory factor analysis was used to verify the factor structure between Pharmaceutical services (PS), the Skill of Pharmacists, Non-pharmaceutical services (NPS), and pricing (P). Pearson correlation analysis, Kendall's tau correlation analysis, and Spearman's rho correlation analysis were used to identify the correlation between different factors, such as PS, SKP, NPS, and P. FINDINGS: The 23-item scale that consisted of four elements have shown an acceptable root mean squared error of approximation (0.076), Cronbach's alpha (0.787), and Chi-square value (3.381) (P < 0.001). Of the respondents, 56.4% rated their satisfaction on pharmacist attitude, whereas 67.2%, 41.4%, and 51.8% were satisfied with other services, such as receipt provided on medication they take, prescription drug service and availability of pharmacies on the weekend and public holidays, respectively. CONCLUSION: This cross-sectional study confirms that there are relationships among PS, SPK, NPS, and P. Moreover, there is a lack of facilities in community pharmacies in Sindh, such as the unavailability of a consultation room, immunization services, information on routine health matters, and medication record.

Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19

COVID-19 starts as a respiratory disease that can progress to pneumonia, severe acute respiratory syndrome (SARS), and multi-organ failure. Growing evidence suggests that COVID-19 is a systemic illness that primarily injures the vascular endothelium, yet the underlying mechanisms remain unknown. SARS-CoV-2 infection is believed to trigger a cytokine storm that plays a critical role in the pathogenesis of endothelialitis and vascular injury, eventually leading to respiratory and multi-organ failure in COVID-19 patients. We used a multiplex immunoassay to systematically profile and compare 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs). Patients with severe/critical and mild/moderate COVID-19 had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only one cytokine (MIF) was among these altered analytes, while the rest were chemokines and growth factors. In addition, only MMP-1 and VEGF-A were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. Given that excessive MMP-1 plays a central role in tissue destruction in a wide variety of vascular diseases and that elevated VEGF-A, an EC activation marker, increases vascular permeability, we further studied MMP-1 enzymatic activity and other EC activation markers such as soluble forms of CD146, ICAM-1, and VCAM-1. We found that plasma MMP-1 enzymatic activity and plasma levels of MMP-1 and EC activation markers were highly dysregulated in COVID-19 patients. Some dysregulations were associated with patients age or gender, but not with race. Our results demonstrate that COVID-19 patients have distinct inflammatory profiles that are distinguished from the cytokine storms in other human diseases. Excessive MMP-1 and hyperactivation of ECs occur in COVID-19 patients and are associated with the severity of COVID-19.

Aggregatibacter actinomycetemcomitans LtxA Hijacks Endocytic Trafficking Pathways in Human Lymphocytes.

Leukotoxin (LtxA), from oral pathogen Aggregatibacter actinomycetemcomitans, is a secreted membrane-damaging protein. LtxA is internalized by ß2 integrin LFA-1 (CD11a/CD18)-expressing leukocytes and ultimately causes cell death; however, toxin localization in the host cell is poorly understood and these studies fill this void. We investigated LtxA trafficking using multi-fluor confocal imaging, flow cytometry and Rab5a knockdown in human T lymphocyte Jurkat cells. Planar lipid bilayers were used to characterize LtxA pore-forming activity at different pHs. Our results demonstrate that the LtxA/LFA-1 complex gains access to the cytosol of Jurkat cells without evidence of plasma membrane damage, utilizing dynamin-dependent and presumably clathrin-independent mechanisms. Upon internalization, LtxA follows the LFA-1 endocytic trafficking pathways, as identified by co-localization experiments with endosomal and lysosomal markers (Rab5, Rab11A, Rab7, and Lamp1) and CD11a. Knockdown of Rab5a resulted in the loss of susceptibility of Jurkat cells to LtxA cytotoxicity, suggesting that late events of LtxA endocytic trafficking are required for toxicity. Toxin trafficking via the degradative endocytic pathway may culminate in the delivery of the protein to lysosomes or its accumulation in Rab11A-dependent recycling endosomes. The ability of LtxA to form pores at acidic pH may result in permeabilization of the endosomal and lysosomal membranes.