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Background: Stress induces secretion of cathecolamines and glucocorticoids, which may produce liver injury. Followed by the production of inflammatory mediators, it causes apoptosis. Centella asiatica (CeA) has anti-inflammatory and hepatoprotective effects. The present study aims to determine the role of CeA in the attenuation of liver pro-inflammatory mediator expression in rats with electrical foot shock stress model. Materials and Methods: Twenty-four Sprague-Dawley rats were randomized into four groups consisted of six rats each: (1) Control group, (2) CeA-treated group, (3) Stress group, and (4) CeA + stress group. Reverse transcriptase PCR of inflammatory and apoptosis markers as well as Real-Time PCR of β2-adrenergic receptor were performed from liver tissues. Results: Electrical foot shock stress induced up-regulation of NFκB and TNF-α mRNA expressions as pro-inflammatory mediators, compared to control group. This alteration was followed by up-regulation of BAX and β2-adrenergic receptor, as well as the down-regulation of BCl2 compared to control. CeA treatment prevented enhancement of NFκB, TNF-α, TLR-4 and β-adrenergic receptor mRNA expressions, which was followed by down-regulation of BAX and up-regulation of BCl-2, compared to stress group. Conclusion: CeA prevents secretion of pro-inflammatory chemokines and cytokines as well as apoptotic markers in liver cells through the activation of β2-adrenergic receptor.

Mediation is one of the alternative dispute resolution methods. In recent years, mediation as an institute has developed very rapidly. Resolving disputes through alternative methods can be much faster, more efficient and the end result is satisfactory to both parties. Disputes as such have existed since the beginning of humanity. Therefore, in today's world, this type of alternative dispute resolution needs to be developed in order to deal more successfully and effectively with the relations of modern society. Nowadays, there is an increasing development of society and technology, as a result of which mediation as a legal institution will develop more and more rapidly. In Latvia, mediation is regulated by the Mediation Law. The regulation of Latvian legislation must be developed so that mediation as an institute can also develop.

Mediation is a structured process of voluntary cooperation in which the parties seek a mutually acceptable solution to a dispute through a mediator. Mediation is an alternative dispute resolution in civil law with the help of a neutral third party (mediator). It promotes and supports the harmonization of relations, social cooperation and mutual ethics in legal relations. Mediation is a relatively new legal institution with a number of issues.

This paper contributes to the public transport literature by ascertaining the role of involvement upon the service quality-satisfaction-behavioral intentions paradigm from the point of view of private vehicle users. This is the first study that provides a comprehensive understanding of this framework based on the private vehicle users’ perspective. The added value of this research is that, by using a structural equation modeling approach, it provides a comparison of alternative models and uses data from different samples collected in five large metropolitan areas (Berlin, Lisbon, London, Madrid and Rome) for modeling validation. In addition, a SEM-MIMIC approach was applied for controlling the heterogeneity of data due to specific characteristics of the interviewee (territorial setting, place of residence, demographic and socio-economic characteristics and travel related variables). The findings show that involvement is a full mediator between satisfaction and behavioral intentions, and that satisfaction is a full mediator between service quality and involvement. Furthermore, the SEM-MIMIC results revealed that the four latent factors investigated (service quality, satisfaction, involvement and behavioral intentions) dealt with highly heterogenous data. However, the most important finding is that private vehicle users’ involvement is the factor that contributes most to their behavioral intentions towards public transport. Hence, public transport managers might benefit from these outcomes when establishing detailed policies and specific guidelines for public transport systems to engage private vehicle users in a higher degree of usage of public transport services., Spanish Government TRA2015-66235-R

Inter-organizational citizenship collaborative behavior (OCCB) is critical for project team members to share information and integrate resources. However, prior studies found that high OCCBs are absent in project teams. This study aims to explore social exchange approaches to promote project team members’ OCCBs in the construction project team from the social exchange perspective. A questionnaire survey was undertaken online. A two-stage SEM was conducted to verify the measurement and structural models. Confirmatory factor analysis was conducted to verify the measurement model’s reliability and validity, the structural model was assessed by examining the model’s fitness, and path coefficients were used to test the hypotheses. The findings showed that relational social exchange is more effective than contractual social exchange for OCCBs. Meanwhile, contractual control and benevolence trust are verified as mediators between competence trust and OCCB. Three pathways are explored to enhance project team members’ OCCBs: relational social exchange dominated strategy (i.e., dominant competence trust strategy and competence trust-benevolence trust strategy) and relational-contractual hybrid strategy (i.e., competence trust-contractual control strategy). This study expands the social exchange theory in the inter-organizational citizenship collaborative behavior in construction project teams and supports project management by verifying the enabling mechanisms.

Due to demand for high performance inside and outside of the classroom, student-athletes are a unique subsection of college students. Researchers have focused on investigating protective factors, which may enhance student-athlete well-being and academic success in higher education and reduce athlete burnout. The current study examined grit as a mediator between parenting behaviors and academic success, mental health outcomes, and burnout in higher education among National Collegiate Athletic Association Division I and Division II student-athletes (N =202). Overparenting behaviors were negatively associated with psychological autonomy granting, mental health outcomes, and athlete burnout. Psychological autonomy granting behaviors were positively associated with grit and negatively associated with mental health outcomes and athlete burnout. Student-athlete grit mediated the relationship between overparenting behaviors and mental health outcomes. Clinical implications include improving student-athlete parent onboarding protocol; student-athlete psychoeducation; and preventative outreach and health promotion among athletes, athletic staff, and university practitioners. In summary, these findings suggest that parenting behaviors and grit are factors that require more attention in fostering student-athlete success.

In most eukaryotes, the largest subunit of RNAPII, Rpb1, contains a conserved carboxyterminal domain (CTD) containing a canonical structure of heptapeptide repeats. Two protein complexes of interest, Mediator and Integrator, are known to interact with this CTD in all eukaryotic models they have been described in to date. Recently, orthologs of Mediator and Integrator subunits have been identified within the ciliated protozoan Tetrahymena thermophila; one of the few eukaryotic lineages to lack a canonically organized CTD. To begin to characterize putative Mediator and Integrator complexes within T. thermophila, I engineered appropriate macronuclear tagging and knockout cassettes. Although the Tetrahymena MED31 ortholog was unable to rescue the slow growth phenotype of a yeast MED31 knockout, or co-purify with yeast Med8-TAP, I identified subunit Med3 as a member of the Med31 interactome in T. thermophila through tandem affinity purification coupled with mass spectrometry. I also targeted the Tetrahymena INTS6 locus for knockout as determined by colony PCR. If Mediator and Integrator exist in Tetrahymena despite its divergent CTD of Rpb1, perhaps these complexes have CTD-independent functions beyond what can be effectively studied using conventional model systems.

Phosphate is an essential macronutrient for fungal proliferation as well as a key mediator of antagonistic, beneficial, and pathogenic interactions between fungi and other organisms. In this review, we summarize recent insights into the integration of phosphate metabolism with mechanisms of fungal adaptation that support growth and survival. In particular, we highlight aspects of phosphate sensing important for responses to stress and regulation of cell-surface changes with an impact on fungal pathogenesis, host immune responses, and disease outcomes. Additionally, new studies provide insights into the influence of phosphate availability on cooperative or antagonistic interactions between fungi and other microbes, the associations of mycorrhizal and endophytic fungi with plants, and connections with plant immunity. Overall, phosphate homeostasis is emerging as an integral part of fungal metabolism and communication to support diverse lifestyles.

Background: Chronic disease is associated with increased risk of postpartum mental illness, but the mechanisms underlying this association are unclear. Our aim was to explore the mediating role of ...

Aims: Nonsteroidal anti-inflammatory drugs, including ketoprofen, induce adverse effects within the gastrointestinal (GI)-tract. Hydrogen sulfide (H2S) is an antioxidative gaseous mediator contribu...

Valuing diversity and intergroup contact predict less prejudice and discrimination, yet theirrelationship deservescloserattention. There is some evidence that valuing diversity and intergroup contact are associated, butit has not been tested whether the established effects of contact come about through changes in valuing diversity. We address thisin two studies(total N= 2,835)that consider valuing diversity as a mediator of intergroup contact. They show that valuingdiversity mediates the relationships of intergroup contact withprejudice, bystander intervention intentions,policy supportand approach intentions.Our results increase the understanding of pathwaysfrom intergroup contact to intergroup relations and offer a lever that contact interventions can target.

Introduction: A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb® interval and its intensity on the outcome. Methods: The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA. Results: Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59–76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS. Conclusions: In this group of septic shock patients, the earlier initiation of Cytosorb®, its longer duration and the higher volume of blood processed were associated with a better survival.

Spinal cord is the major communicating system between the brain and the body, injury to the spinal cord will completely cut or damage the information and signal exchanges between brain and different parts of the body. Spinal cord injury (SCI) regulates the physical, cellular, and molecular function of the body. SCI could cause impairment in blood flow, breathing, temperature, body pressure and sensory appendages. Thus, serious steps must be taken to prevent and heal SCI in human body by severe damages and shocks. Nanoparticles are emerging in the field of biomedicine and gained attention as drug carriers, imaging, mediator for supportive chemical and accelerating the immunes cells. In recent time, nanoparticles are gaining interest towards improving or modifying the immune system for the treatment of SCI. The drug delivery efficacy of nanoparticles makes them easy to incorporate and load with molecules used for the treatment of SCI, also it enhances the recovery time by targeting localization, altering the signalling pathways and cellular uptake. Researchers are using nanoparticles with different synthesis methods, morphology, incorporating materials, stability and site of target. But exploring the ability of nanoparticles towards improving the healing mechanism, regeneration of SCI and accelerating the treatment time is the major necessity. Thus considering the lesser exposure of nanoparticles in the area of spinal cord injury and regeneration of cells, the present review give a brief knowledge about the different types of nanoparticles and its role in SCI therapy.

The features of a holistic view in an organization create the data value of the Business Intelligence (BI) and Knowledge Management (KM) in viewing the big picture of organizational performance diagnostics framework. This research focuses on the specific features of railway supply chain performance in viewing the decision-making process and creating better knowledge formation. The intention of the study is to structure supplier performance using BI-KM framework development to determine holistic perspective factors. The outcomes indicate that BI and KM significantly increased the railway supply chain and significantly increased the information system. This BI-KM framework relates the current analytic characteristics in designing the railway supply chain towards information system in determining the strategic theme of the decision-making process of the decision support system together with system features, characteristics of data, the content of the themes, and the effect of the decision-making process and for executive strategic performance diagnostics tool that provides effective strategic decision making in supply chain performance. The quantitative research method uses SmartPLS software version 3.2.8 for empirical analysis through distributing survey questionnaires to 320 railway suppliers in Malaysia. Using a model-driven development framework, to measure the implementation success of the decision support system, the study is conducted in the railway supplier focusing on strategic management that helps to make the decision and facilitate the organizational success.

Management scholars view workplace spirituality as the main factor behind building trust among employees and playing a pivotal role in enhancing the organization's positive outcomes, i.e., knowledge sharing behavior & work engagement. Underpinning social exchange theory, we explored the linkage between workplace spirituality, knowledge sharing behavior, and work engagement. We further studied to look at the mediating effect of trust between workplace spirituality and positive outcomes. Data was collected from six private companies, the total number of respondents was (n=196). The study's analysis showed that workplace spirituality substantially positively impacts knowledge sharing behavior and work engagement. Furthermore, the link between workplace spirituality, knowledge sharing behavior, and work engagement is positively and statistically significantly mediated by trust. Thus, this work contributes significantly to the research paradigm by presenting workplace spirituality as a solution for high-rise trust among employees, fostering employee engagement in their work, and improving the capacity of knowledge-sharing behavior. Additionally, at the end of this study, theoretical and managerial suggestions, future avenues, and limitations are stated.

Background: Modified electrodes have advanced from the initial studies aimed at understanding electron transfer in films to applications in areas such as energy production and analytical chemistry. This review emphasizes the major classes of modified electrodes with mediators that are being explored for improving analytical methodology. Chemically modified electrodes (CMEs) have been widely used to counter the problems of poor sensitivity and selectivity faced in bare electrodes. We have briefly reviewed the organometallic and organic mediators that have been extensively employed to engineer adapted electrode surfaces for the detection of different compounds. Also, the characteristics of the materials that improve the electrocatalytic activity of the modified surfaces are discussed. Objective: Improvement and promotion of pragmatic CMEs have generated a diversity of novel and probable strong detection prospects for electroanalysis. While the capability of handling the chemical nature of the electrode/solution interface accurately and creatively increases , it is predictable that different mediators-based CMEs could be developed with electrocatalytic activity and completely new applications be advanced.

Diabetic nephropathy (DN) is the most common complication of diabetic patients, and has become a global healthcare problem. In this study, we used diabetic mice to evaluate the effect of Losartan on DN, in which the experimental animals were divided into three groups: non-diabetic mice (db/m group), untreated-diabetic mice (db/db group), and Losartan-treated diabetic mice (db/db-losartan). Next, immunohistochemistry and immunofluorescence were used to detect Wilms tumor protein 1 (WT-1) and synaptopodin expression, respectively. Protein levels of WT-1, synaptopodin, claudin1, and Pax-2 were assessed by Western blotting and real-time PCR. The miR-193a mRNA levels were quantitated by real-time PCR. The results showed that albuminuria was increased in diabetic mice compared with control animals and was significantly ameliorated by treatment with Losartan. In addition, Losartan significantly upregulated the immunopositive cell numbers of WT-1, the expression of WT-1 and synaptopodin in renal tissue. By contrast, expression of claudin1 and Pax-2 in renal tissue were decreased in db/db-losartan group. Besides, expression of miR-193a was decreased significantly in db/db-losartan group compared with the untreated diabetic group. Thus, Losartan has renoprotective effects on the control of tissue damage possibly by inhibiting the expression of miR-193a, thereby promoting the repair of podocyte injury in mice with DN.

Human specific endogenous retrovirus H (HERVH) is highly expressed in both naive and primed stem cells and is essential for pluripotency. Despite the proven relationship between HERVH expression and pluripotency, there is no single definitive model for the function of HERVH. Instead, several hypotheses of a regulatory function have been put forward including HERVH acting as enhancers, long noncoding RNAs (lncRNAs), and most recently as markers of topologically associating domain (TAD) boundaries. Recently several enhancer-associated lncRNAs have been characterized, which bind to Mediator and are necessary for promoter-enhancer folding interactions. We propose a synergistic model of HERVH function combining relevant findings and discuss the current limitations for its role in regulation, including the lack of evidence for a pluripotency-associated target gene.

Resolution of acute inflammation is an active process orchestrated by endogenous mediators and mechanisms pivotal in host defense and homeostasis. The macrophage mediator in resolving inflammation, maresin 1 (MaR1), is a potent immunoresolvent, stimulating resolution of acute inflammation and organ protection. Using an unbiased screening of greater than 200 GPCRs, we identified MaR1 as a stereoselective activator for human leucine-rich repeat containing G protein–coupled receptor 6 (LGR6), expressed in phagocytes. MaR1 specificity for recombinant human LGR6 activation was established using reporter cells expressing LGR6 and functional impedance sensing. MaR1-specific binding to LGR6 was confirmed using (3)H-labeled MaR1. With human and mouse phagocytes, MaR1 (0.01–10 nM) enhanced phagocytosis, efferocytosis, and phosphorylation of a panel of proteins including the ERK and cAMP response element-binding protein. These MaR1 actions were significantly amplified with LGR6 overexpression and diminished by gene silencing in phagocytes. Thus, we provide evidence for MaR1 as an endogenous activator of human LGR6 and a novel role of LGR6 in stimulating MaR1’s key proresolving functions of phagocytes.

BACKGROUND: Social capital is a significant predictor of suicidal behaviors among Chinese rural migrants. However, the mechanism, including the impact of employment and mental health, has not been fully understood. This study aims to exam the complex relationships linking social capital to suicidal behaviors. METHODS: Data were collected from a probability sample (n=1,245) of rural migrants in Wuhan, China. Social capital was used to predict suicidal behaviors with employment uncertainty as step 1 mediator and anxiety as step 2 mediator. Suicidal ideation and attempt were analyzed separately using a chained moderated mediation model. Years of migration was included as moderator in all models to control its confounding effect. RESULTS: Of the total sample, 50.9% were male with mean age of 32.0 (SD=7.8) years. The association between social capital and suicidal ideation was significantly mediated by employment uncertainty (indirect effect [95% CI] = −0.14 [−0.24, −0.04]), but not for suicidal attempt (−0.02 [−0.20, 0.15]). Anxiety significantly mediated the same association for both suicidal ideation (−0.19 [−0.37, −0.01]) and attempt (−0.20 [−0.40, −0.01]). The chained relationship from social capital to employment uncertainty, anxiety and suicidal behaviors was also significant with indirect effect of −0.05 [−0.09, −0.01] for both suicidal ideation and attempt. Similar results were observed for bonding and bridging capital. CONCLUSIONS: Social capital may exert effect on suicidal behaviors through employment and mental health among rural migrants in China. Social capital-based suicide prevention must consider both employment and mental health problem to obtain better effect.

The current study aims to explore personal nostalgia’s role in reducing suicidal ideation when mediated by the increase of meaning in life. All three variables will be measured using their respective questionnaires and a writing task recalling fond personal memories in the past will be given to induce nostalgia. Mediation analysis will be performed through Baron and Kenny's (1986) method of multiple regression.

The correlation of neuroinflammation with the development of cerebral vasospasm following subarachnoid hemorrhage has been well documented in the literature; both clinical and preclinical. The exact mechanisms by which this process occurs, however, are poorly elucidated. Recent evidence indicates that interleukin-6 is not only an important prognostic biomarker for subarachnoid hemorrhage and subsequent vasospasm development but also an integral component in the progression of injury following initial insult. In this review, we briefly highlight other pathways under investigation and focus heavily on what has been discovered regarding the role of interleukin 6 and cerebral vasospasm following subarachnoid hemorrhage. A proposed mechanistic pathway is highlighted in written and graphical format. A discussion regarding the human correlative findings and initial pre-clinical mechanistic studies is addressed. Finally, in the future investigation section, innovative developments and a clear description of areas warranting further scientific inquiry are emphasized. This review will catalyze continued discovery in this area of emerging significance and aid in the quest for effective vasospasm treatment where limited clinical therapeutics currently exist.

Celem niniejszego opracowania jest omówienie problematyki udziału osoby duchownej w postępowaniu mediacyjnym jako mediatora. Mediacja jest instytucją uregulowaną w prawie europejskim i polskim. Jest jednak znana od początków cywilizacji, co można dostrzec w relacjach między Bogiem a ludźmi i między człowiekiem a wspólnotą. W artykule przedstawiono najpierw wymiar religijny mediacji i przykłady pełnienia przez osoby duchowne na przestrzeni wieków funkcji mediatora. Następnie omówiono cele postępowania mediacyjnego na tle wybranych modeli mediacji. Stwierdzono, że w każdym modelu mediacji z jednej strony ważne są potrzeby i interesy stron, a także ich relacje oraz charakter sporu determinujący cele postępowania, z drugiej zaś, model mediacji nie stanowi uniwersalnej matrycy, którą można przełożyć na dany rodzaj sporu. W praktyce mediator w rozwiązywaniu jednego sporu stosuje kilka modeli postępowania mediacyjnego, dążąc do realizacji licznych celów stron sporu, co wymaga od niego posiadania wielorakich umiejętności. Zdaniem Autora, sprawowanie różnorakich funkcji religijnych powoduje, że duchowni posiadają liczne umiejętności przydatne do pełnienia funkcji mediatora. W ostatniej części opracowania dokonano analizy wymogów prawnych i specyficznych kompetencji duchownego – mediatora oraz sformułowano wnioski. This paper aims to discuss the issues connected with the participation of clergymen as mediators in mediation proceedings. Mediation is a legal institution regulated by European and Polish law. Yet it has been known since the beginnings of civilisation, which can be observed in relations between God and people and between man and community. First, the paper presents the religious dimension of mediation and provides some examples of participation of clergymen in mediations throughout the centuries. Next, the objectives of mediation proceedings are discussed against the background of selected mediation models. It is argued that, on the one hand, in each mediation model the needs and interests of the parties are important, but equally crucial is the relationship between the parties, as well as the nature of the dispute, which determine the goals of the proceedings. On the other hand, mediation models do not constitute a universal matrix that can be mapped onto every single type of dispute. In practice, mediators use several mediation models when resolving one dispute in order achieve various goals of the parties, which requires multiple skills from mediators. In the author’s opinion, the fact that clergymen fulfil a number of different religious functions makes them especially qualified to act as mediators. In the last part of the paper, the legal requirements and unique competencies of clergymen serving as mediators are analysed, and the relevant conclusions are drawn.

Healthcare systems encumbered by cardiovascular diseases demand adequate cardiovascular prevention. Indeed, even with the most novel therapies, the residual cardiovascular risk still fuels morbidity and mortality. Addressing inflammation as a putative mediator of this risk has brought along promising in vitro results, though large clinical trials have only in part confirmed them. To fully exploit the therapeutic potential between the inflammatory hypothesis, a change of viewpoint is required. Focus on microcirculation, whose dysfunction is the primary driver of cardiometabolic disease, is mandatory. Several factors play a pivotal role in the capacity of microvascular inflammation to promote a health-to-disease transition: the adipose tissue (in particular, perivascular and epicardial), the mitochondria function, the hyperglycemic damage and their epigenetic signature. Indeed, the low-grade inflammatory response, which is now an acknowledged hallmark of cardiometabolic disease, is promoted by these mediators and leaves a permanent epigenetic scar on the microvasculature. Even if a more profound knowledge about the mechanisms of metabolic memory has been brought to light by recent evidence, we still have to fully understand its mechanisms and clinical potential. Addressing the detrimental role of inflammation by targeting the microvascular phenotype and leveraging epigenetics is the road down which we must go to achieve satisfactory cardiovascular prevention, ultimately leading to disease-free ageing.

Background Previous research has identified a significant, positive relation between childhood maltreatment and depressive symptoms. However, the findings required replication at the within-person level. Moreover, the mediating mechanism of locus of control accounting for their relations has yet to be fully evaluated. Thus, this study examined the dynamic longitudinal relations between childhood maltreatment and depressive symptoms including whether locus of control functioned as a mediator between them after separating between-person effects from within-person effects. Methods A sample of 4110 Chinese children (50.60% boys; Mage = 9.89 at Wave 1) covering the transitional period from middle childhood to early adolescence completed a package of self-report measures on 5 occasions across 2.5 years, using 6-month intervals. Random Intercept Cross-Lagged Panel Models were applied to disaggregate between- and within-person effects. Also, alternative Cross-Lagged Panel Models were applied. Results Locus of control played a mediating role in the reciprocal relations between childhood maltreatment and depressive symptoms at the within-person level. Limitations Some limitations existed in the measures. Moreover, sexual abuse was not investigated in this study. Conclusions The findings highlighted the mediating role of locus of control in the reciprocal relations between childhood maltreatment and depressive symptoms at the within-person level, suggesting that interventions targeted at promoting internal locus of control may help prevent the developmental pathway from childhood maltreatment to depressive symptoms and vice versa from middle childhood to early adolescence.

Prematurity, observed in 15 million births worldwide each year, is a clinical condition that is a major cause of neonatal mortality and morbidity in the short and long term. Preterm infants are at high risk of developing respiratory problems, sepsis, and other morbidities leading to neurodevelopmental impairment and neurobehavioral disorders. Perinatal glucocorticosteroids have been widely used for the prevention and treatment of adverse outcomes linked to prematurity. However, despite their short-term benefits due to their maturational properties, some clinical trials have shown an association between steroids exposure and abnormal brain development in infants born preterm. Neuroinflammation has emerged as a preeminent factor for brain injury in preterm infants, and the major role of microglia, the brain resident immune cells, has been recently highlighted. Considering the role of microglia in the modulation of brain development, the aim of this review is to summarize the effects of endogenous and exogenous glucocorticosteroids on brain development and discuss the possible role of microglia as the mediator of these effects.

Understanding the mechanisms associated with engaging in physical activity (PA) is crucial for its promotion. The aim was to analyze the relationship between motor competence (MC) and PA and the role of physical fitness (PF). Participants were N = 1,064 children of both sexes (n =530 girls) and 7.87 +/- 1.17 years of age. MC was assessed with KorperkoordinationTest fur Kinder. PF was assessed with 50-yard dash, I-mile run/walk, and standing long jump. PA was assessed with a questionnaire. Mediation and moderation were determined according to Baron and Kenny using Sobel test for indirect effect and using PROCESS (version 3.4). Mediation results showed perfect mediation in girls but not in boys and not when all participants were included in the analysis. The linear moderation was significant for all participants and for boys and girls apart. However, the results of conditional effects of MC at the 16th, 50th, and 84th percentile of the PF, which became significant at the 50th percentile for all participants and for boys, were not significant in girls. In conclusion, perfect mediation seems to exist in girls but not in boys. In boys, the relationship between MC and PA seems conditioned by the PF levels. National Funding through the Portuguese Foundation for Science and Technology info:eu-repo/semantics/publishedVersion

The present work focused on assessing the functions and interrelationships of the mediator and the student in the context of pandemic involvement in the School of Agricultural and Veterinary Sciences of UNAN León, with the purpose of suggesting strategies and conceptual elements in the virtual learning environment (VLE), useful to the teacher and student. The meaningful learning methodology, the participatory action methodology approach, was used. The results show the importance of developing ICT skills in teachers and students and improving the administrative technical conditions of the virtual environment, as well as developing innovation in mediators to transmit quality knowledge in pedagogical processes. El presente trabajo se enfocó en valorar las funciones e interrelaciones del mediador y el estudiante en el contexto de la afectación pandémica en la Escuela de Ciencias Agrarias y Veterinarias de la UNAN León, con el propósito de sugerir estrategias y elementos conceptuales en el entorno virtual de aprendizaje (EVA), útiles al docente y estudiante. Se utilizó la metodología del aprendizaje significativo, el enfoque de la metodología acción participativa. Los resultados evidencian la importancia de desarrollar en los docentes y estudiantes habilidades en las TIC y mejorar las condiciones técnicas administrativas del entorno virtual, así como desarrollar la innovación en los mediadores para transmitir el conocimiento de calidad en los procesos pedagógicos.

The term ‘super enhancers’ (SE) has been widely used to describe stretches of closely localized enhancers that are occupied collectively by large numbers of transcription factors (TFs) and co-factors, and control the transcription of highly-expressed genes. Through integrated analysis of >600 DNase-seq, ChIP-seq, GRO-seq, STARR-seq, RNA-seq, Hi-C and ChIA-PET data in five human cancer cell lines, we identified a new class of autonomous SEs (aSEs) that are excluded from classic SE calls by the widely used Rank Ordering of Super-Enhancers (ROSE) method. TF footprint analysis revealed that compared to classic SEs and regular enhancers, aSEs are tightly bound by a dense array of master lineage TFs, which serve as anchors to recruit additional TFs and co-factors in trans. In addition, aSEs are preferentially enriched for Cohesins, which likely involve in stabilizing long-distance interactions between aSEs and their distal target genes. Finally, we showed that aSEs can be reliably predicted using a single DNase-seq data or combined with Mediator and/or P300 ChIP-seq. Overall, our study demonstrates that aSEs represent a unique class of functionally important enhancer elements that distally regulate the transcription of highly expressed genes.

The sponsorship of junior sport is a contentious issue with community concerns raised about the appropriateness of some marketing targetted at children. Parents and coaches are guardians of junior sports players and often faced with a moral dilemma. On the one hand they know sponsors, who are trying to generate goodwill through providing financial or in-kind support, are crucial to the affordability of junior sports when competition for securing sponsorships is intense. On the other hand, they hold concerns that some sponsors may exploit their access to these young, vulnerable players. Guardians are caught at a crossroads with equally undesirable alternatives—financially unviable junior sports without sponsors or junior sports with potentially exploitative sponsors. Our study fills a gap in the literature where the tensions of commercial sponsorship agendas and moral concerns in sponsorship has not been well explored with our study being the first to apply the construct of moral judgements in a sponsorship model. Mixed methodology is used to examine the role that moral judgements play in determining sponsor goodwill. A qualitative study ( n = 18) informed an online survey ( n = 306) of Australian junior sports guardians. Structural equation modelling revealed that guardians’ moral judgements mediated the relationships between sponsor fit, perceived sponsor altruism and the outcome variable, sponsorship goodwill. The findings of this study extend scholarly understanding of consumers’ appraisal of sponsorships and provide useful insights to guide practitioners in sponsorship decision making, particularly in contexts that stimulate community interest or concerns.

Objectives Determine which sociodemographic factors are most associated with increased maternal perceived stress during pregnancy. Evaluate the association between maternal stress and plasma immune-mediator concentrations (IMCs). Methods As part of a prospective, randomized clinical trial, 247 participants completed a Perceived Stress Scale survey (PSS-10) during each trimester of pregnancy. Blood samples were collected from participants and were analyzed for 25-hydroxyvitamin D (25(OH)D) concentration and for several IMCs: interferon-gamma, interleukins (IL-) IL-2, IL-4, IL-5, IL-10, vascular endothelial growth factor, c-reactive protein, and tumor necrosis factor alpha (TNF-α) (R&D Elisa). The potential associations between PSS-10 scores, sociodemographic factors, and IMCs were assessed. Results In bivariate analysis, participants who were not married and/or had high risk pregnancies were more likely to have increased PSS-10 scores (p Conclusions This study identifies specific sociodemographic factors that are associated with increased perceived stress during pregnancy. This study also provides evidence that increased perceived stress is associated with physiological changes as measured by changes in circulating IL-2, TNF-α, IL-10, and 25(OH)D concentrations.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by increased permeability of the alveolar-capillary barrier and impaired alveolar fluid clearance. Resolvin E1 (RvE1) is a specialized pro-resolving mediator derived endogenously from omega-3-polyunsaturated fatty acids. RvE1 (10 μg/kg i.v.) was injected to rats 6 h post-lipopolysaccharide (LPS) (14 mg/kg) induction. After another 3 h, alveolar fluid clearance was measured in live rats (n = 8-9). The primary Type II alveolar epithelial cell was isolated and treated by LPS (1 μg/mL) with or without RvE1 (250 nM). The expression of epithelial sodium channel (ENaC), Na+/K+-ATPase (NKA), AKT, serum- and glucocorticoid-induced kinase 1 (SGK1), and Nedd4-2 were detected. RvE1 improved survival rate (30% vs. 70%, P = 0.048), increased the clearance of alveolar fluid (13.34% vs. 18.73%, P 0.001), reduced lung wet-dry weight ratio (5.01 vs. 4.63, P 0.001), mitigated lung injury scores (13.38 vs. 7.0, P 0.05) and inflammation in LPS-induced ARDS in rats. RvE1 upregulated alveolar ENaC and NKA expression in vivo and in vitro. In addition, RvE1 significantly increased the expression of phosphorylated AKT, SGK1, and phosphorylated Nedd4-2 in LPS-stimulated primary alveolar type II cells. The effects of RvE1 were abrogated by blocking phosphatidylinositide3'-kinase (PI3K) and SGK1 with LY294002 and GSK650394, respectively. In summary, RvE1 upregulated ENaC and NKA expression by activating PI3K/AKT/SGK1 pathway to promote alveolar fluid clearance, suggesting that RvE1 may be a potentially effective drug for ARDS treatment.

Academic outcomes have long been one of the important issues of childhood research, which has a strong influence on the overall development of children. The present study aimed to explore the relationship between parental burnout and academic outcomes and the mediating role of parental behavioral control, and mindful parenting. The participants included 786 Vietnamese primary school students ( Mage = 9,980, SD = 0.889) and their parents. Parents completed questionnaires about demographic information, parental burnout, behavioral control, and mindful parenting. The student's academic grades are reported by the school office where the student is enrolled. The results support three main findings: (a) parental burnout has a direct influence on student's academic outcomes, (b) the mediating role of parental behavioral control was significant, and (c) the mediating role of mindful parenting was also significant. Practical implications of these findings highlight how parent's mental health status and parenting practices influence academic outcomes.

Assisted reproductive technologies (ART) induce premature vascular aging in human offspring. The related alterations are well-established risk factors for stroke and predictors of adverse stroke outcome. However, given the young age of the human ART population there is no information on the incidence and outcome of cerebrovascular complications in humans. In mice, ART alters the cardiovascular phenotype similarly to humans, thereby offering the possibility to study this problem.We investigated the morphological and clinical outcome after ischemia/reperfusion brain injury induced by transient (45 min) middle cerebral artery occlusion in ART and control mice.We found that stroke volumes were almost 3-fold larger in ART than in control mice (P 0.001). In line with these morphological differences, neurological performance assessed by the Bederson and RotaRod tests 24 and 48 h after artery occlusion was significantly worse in ART compared with control mice. Plasma levels of TNF-alpha, were also significantly increased in ART vs. control mice after stroke (P 0.05). As potential underlying mechanisms, we identified increased blood-brain barrier permeability evidenced by increased IgG extravasation associated with decreased tight junctional protein claudin-5 and occludin expression, increased oxidative stress and decreased NO-bioactivity in ART compared with control mice.In wildtype mice, ART predisposes to significantly worse morphological and functional stroke outcomes, related at least in part to altered blood-brain barrier permeability. These findings demonstrate that ART, by inducing premature vascular aging, not only is a likely risk factor for stroke-occurrence, but also a mediator of adverse stroke-outcome.This study highlights that ART not only is a likely risk factor for stroke-occurrence, but also a mediator of adverse stroke-outcome. The findings should raise awareness in the ever-growing human ART population in whom these techniques cause similar alterations of the cardiovascular phenotype and encourage early preventive and diagnostic efforts.

Ozone (O3) is a prevalent air pollutant causing lung inflammation. Previous studies demonstrate that O3 oxidizes lipids, such as cholesterol, in the airway to produce oxysterols, such as secosterol...

BACKGROUND Because of their cancer and treatment adverse effects, most pediatric oncology patients will experience 1 or more symptoms at one time that can seriously affect their quality of life. Because these children are attached to parents, their symptom burden directly influences the parental stress level and parental interpretations of their children's quality of life. OBJECTIVE The aim of this study was to examine the association between child-reported symptom burden and the pediatric quality of life reported by children with cancer and their parents, and whether parental perceived stress mediates these relationships. METHODS In a cross-sectional design, convenience sampling was used to recruit 80 parent-child dyads. Advanced statistical methods were adopted to analyze the mediating effects of parental stress between children's symptom burden and their quality of life. RESULTS The results revealed that parental stress was the mediator in the relationship between child-reported symptom burden and children's quality of life reported by parents. The results also showed that parental stress was not a mediator in the relationship between child-reported symptom burden and their quality of life. This underscored the differences in interpretations of quality of life reported by children and their parents. CONCLUSION Children's symptom burden is an important factor in predicting parental stress level and the quality of life reported by the children. Children's voice should be incorporated whenever possible. IMPLICATIONS FOR PRACTICE The knowledge gained from this study will facilitate intervention development to enhance parents' abilities in stress management and symptom management for their children with the support of the nursing profession.

Over the last few years, the Transforming growth factor- β (TGF-β) has been significantly considered as an effective and ubiquitous mediator of cell growth. The cytokine, TGF-β is being increasingly recognized as the most potent inducer of cancer cell initiation, differentiation, migration as well as progression through both the SMAD-dependent and independent pathways. There is growing evidence that supports the role of secretory cytokine TGF-β as a crucial mediator of tumor-stroma crosstalk. Contextually, the CAFs are the prominent component of tumor stroma that helps in tumor progression and onset of chemoresistance. The interplay between the CAFs and the tumor cells through the paracrine signals is facilitated by cytokine TGF-β to induce the malignant progression. Here in this review, we have dissected the most recent advancements in understanding the mechanisms of TGF-β induced CAF activation, their multiple origins, and most importantly their role in conferring chemoresistance. Considering the pivotal role of TGF-β in tumor perogression and associated stemness, it is one the proven clinical targets We have also included the clinical trials going on, targeting the TGF-β and CAFs crosstalk with the tumor cells. Ultimately, we have underscored some of the outstanding issues that must be deciphered with utmost importance to unravel the successful strategies of anti-cancer therapies.

PurposeThe study aims to investigate employees' overall justice perception and job stress as multiple mediators in the relationship between perceived talent management (TM) practices and turnover intention.Design/methodology/approachCovering various industries in Bangkok, Thailand, the sample of the study consists of 552 employees, including both talented employees and normal employees as defined by their organization. Online questionnaires were distributed internally by selected organizations, and structural equations modeling was used to analyze the data.FindingsThe results indicate that both overall justice perception and job stress mediate the relationship between perceived TM practices and turnover intention.Originality/valueThe study contributes to the lack of empirical evidence in TM literature and aids in the design of better TM strategies to deliver effective organizational investments in its people.

Mediation analysis has been a popular framework for elucidating the mediating mechanism of the exposure effect on the outcome in many disciplines including genetic studies. Previous literature in causal mediation primarily focused on the classical settings with univariate exposure and univariate mediator, with recent growing interests in high-dimensional mediator. In this paper, we study the mediation model with high-dimensional exposure, high-dimensional continuous mediator, and a continuous outcome. We introduce two procedures for mediator selection, MedFix and MedMix, and develop the corresponding causal effect tests. Our study is motivated by the causal gene identification problem in biomedical studies, where causal genes are defined as the genes that mediate the genetic effect. For this problem, the genetic variants are the high-dimensional exposure, the gene expressions the high-dimensional mediator, and the phenotype of interest the outcome. We evaluate the proposed methods using a mouse f2 dataset for diabetes study, and extensive real data-driven simulations. We show that the mixed model-based approach (MedMix) leads to higher accuracy in mediator selection with reasonable reproducibility across independent measurements of the response and is more robust against model misspecification. The R code and additional materials are available on Github ( https://github.com/QiZhangStat/highMed ).

The integrity of blood-brain-barrier (BBB) is essential for normal brain functions, synaptic remodeling, and angiogenesis. BBB disruption is a common pathology during Parkinson's disease (PD), and has been hypothesized to contribute to the progression of PD. However, the molecular mechanism of BBB disruption in PD needs further investigation. Here, A53T PD mouse and a 3-cell type in vitro BBB model were used to study the roles of α-synuclein (α-syn) in BBB disruption with the key results confirmed in the brains of PD patients obtained at autopsy. The A53T PD mouse studies showed that the expression of tight junction-related proteins decreased, along with increased vascular permeability and accumulation of oligomeric α-syn in activated astrocytes in the brain. The in vitro BBB model studies demonstrated that treatment with oligomeric α-syn, but not monomeric or fibrillar α-syn, resulted in significant disruption of BBB integrity. This process involved the expression and release of vascular endothelial growth factor A (VEGFA) and nitric oxide (NO) from oligomeric α-syn treated astrocytes. Increased levels of VEGFA and iNOS were also observed in the brain of PD patients. Blocking the VEGFA signaling pathway in the in vitro BBB model effectively protected the barrier against the harmful effects of oligomeric α-syn. Finally, the protective effects on BBB integrity associated with inhibition of VEGFA signaling pathway was also confirmed in PD mice. Taken together, our study concluded that oligomeric α-syn is critically involved in PD-associated BBB disruption, in a process that is mediated by astrocyte-derived VEGFA.

This study investigated the mediator effect of satisfaction with family life in the relationship between social ignore and social media addiction among adolescents. The research was conducted on 456 high school students studying in the 2019 academic year. Ages of the students vary between 14 and 16 years old. Social Media Addiction Scale, Social Ostracism Scale, and Satisfaction with Family Life Scale were used to collect data. SPSS 25 software package and PROCESS software package developed by Hayes as an add-on to SPSS were used in the data analysis. It was found that social ignore predicted social media addiction positive significantly and satisfaction with family life negatively. It was observed that satisfaction with family life predicted social media addiction negative significantly. It was also found that satisfaction with family life mediated the relationship between social ignore and social media addiction.

What is the central question of this study? What is the role of circulating exosomal miR-687 in remote hepatic injury following renal ischaemia-reperfusion injury (IRI) and does thymoquinone have a modulatory impact? What is the main finding and its importance? Exosomal miR-687 was expressed in renal IRI, entered the circulation and was deposited in the liver. Liver exosomal miR-687 was correlated with liver inflammation and apoptosis. Thymoquinone aborted the renal production of exosomal miR-687 and its further circulation to the liver.The pathophysiology of remote hepatic injury following acute renal ischaemia-reperfusion injury (IRI) is of particular clinical interest. Secreted small non-coding microRNA (miRs) are thought to exist in exosome-encapsulated form. Thymoquinone (TQ) is the main bioactive ingredient of Nigella sativa and has several renoprotective actions. We expected exosomal miR-687 to be relevant as it could act as a humoral mediator, with possible modulation by TQ. Thirty adult male Wister albino rats were assigned to three groups (n = 10); (1) sham-operated, (2) renal ischaemia-reperfusion injury (IRI), and (3) renal IRI pre-treated with TQ 10 mg/kg/day i.v. (TQ-IRI) for 10 days in addition to a dose administered at reperfusion onset. Following 24 h of reperfusion, the IRI group showed renal tissue hypoxia-inducible factor upregulation (P 0.001). Electron microscopy images of exosomes and analysis of miR-687 revealed elevated levels, which appeared in the circulation. Large amounts of exosomal miR-687 were transmitted to the liver tissue. In the IRI group, liver transaminases (alanine aminotransferase, aspartate aminotransferase) were markedly (P 0.001) elevated. The hepatic tissue inflammatory markers (vascular cell adhesion molecule-1, myeloperoxidase, monocyte chemotactic protein-1 and nuclear factor-κB) were upregulated (P 0.001) accompanied with elevated caspase-3. TQ suppressed (P 0.001) the renal expression and release of exosomal miR-687 into the circulation and its further deposition in the liver tissue; consequently, TQ diminished (P 0.001) liver tissue inflammation and cellular apoptosis. The results were confirmed by histological tissue assessment. In conclusion, exosomal miR-687 liberated from injured renal tissues into the circulation may be an important factor in inducing remote hepatic injury. Exosomal miR-687 inhibition by TQ protected both renal and hepatic tissues from injury.

[Image: see text] CDK8 and its paralog CDK19 are cyclin-dependent kinases that are core components of the so-called Mediator complex that has essential roles as a positive and negative regulator of gene expression. Several efforts to develop inhibitors have yielded natural and synthetic ATP-competitive compounds including cortistatin A, Sel120, BCD-115, CCT251921 (1), and MSC2530818 (2). Here, we used a hybridization approach starting from CCT251921 and MSC2530818 to derive new inhibitors with the aim of developing highly potent and selective inhibitors of CDK8/19. Initial compounds suffered from rapid aldehyde oxidase-mediated metabolism. This liability was overcome by utilizing a pyrazolopyridine hinge binder with a chlorine at the C-3 position. These efforts resulted in JH-XVI-178 (compound 15), a highly potent and selective inhibitor of CDK8/19 that displays low clearance and moderate oral pharmacokinetic properties.