Search

Purpose: The purpose of this paper is to examine individuals' levels of work ethic amongst current and recent university attendees across three countries. This article presents the results of a survey of 537 respondents from the United States of America, Korea and China, thus extending the previous research into work ethic, often conducted from a Western perspective. The comparative study aims to enhance the understanding of cross-cultural and gender differences and similarities whilst probing for the levels of work ethic amongst the respondents. Design/methodology/approach: A comparative research method was adopted because the authors' aim was to probe similarities and differences across three societies. Multiple analysis of variance (ANOVA) and t-tests were utilised to explore gender and country-related differences. Cluster analysis was applied to probe for segments highly similar to each other in the levels of work ethic of the respondents. Findings: The results confirm the hypothesised differences between countries as well as across gender groups, with American females having the highest levels of work ethic, closely followed by Chinese males and females. Three distinct segments -- low, medium and high levels of work ethic -- were found in all three countries, indicating that there are individuals in each of the societies who could benefit from strategies for increasing the individuals' levels of work ethic. Originality/value: Novel gender comparisons of the three country groups revealed American females as having the highest levels of work ethic and Korean females the lowest, whilst the identification of clusters of low, medium and high levels of work ethic provides evidence of the need to increase levels of work ethic to enhance productivity, regardless of the country of origin.

Abstract Background Angiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN). Results Zofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect. Conclusions Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.

BackgroundMalignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern.MethodsHere, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas.ResultsEGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations.ConclusionsOur findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.

Abstract Gliomas are the most common central nervous tumors in children and adolescents. However, spinal cord low-grade gliomas (sLGGs) are rare, with scarce information on tumor genomics and epigenomics. To define the molecular landscape of sLGGs, we integrated clinical data, histology, and multi-level genetic and epigenetic analyses on a consecutive cohort of 26 pediatric patients. Driver molecular alteration was found in 92% of patients (24/26). A novel variant of KIAA1549:BRAF fusion (ex10:ex9) was identified using RNA-seq in four cases. Importantly, only one-third of oncogenic drivers could be revealed using standard diagnostic methods, and two-thirds of pediatric patients with sLGGs required extensive molecular examination. The majority (23/24) of detected alterations were potentially druggable targets. Four patients in our cohort received targeted therapy with MEK or NTRK inhibitors. Three of those exhibited clinical improvement (two with trametinib, one with larotrectinib), and two patients achieved partial response. Methylation profiling was implemented to further refine the diagnosis and revealed intertumoral heterogeneity in sLGGs. Although 55% of tumors clustered with pilocytic astrocytoma, other rare entities were identified in this patient population. In particular, diffuse leptomeningeal glioneuronal tumors (n = 3) and high-grade astrocytoma with piloid features (n = 1) and pleomorphic xanthoastrocytoma (n = 1) were present. A proportion of tumors (14%) had no match with the current version of the classifier. Complex molecular genetic sLGGs characterization was invaluable to refine diagnosis, which has proven to be essential in such a rare tumor entity. Moreover, identifying a high proportion of drugable targets in sLGGs opened an opportunity for new treatment modalities.

Infant gliomas behave differently to their childhood or adult counterparts. Here, the authors perform a large-scale genetic analysis of these tumours, revealing genetic alterations which may offer therapeutic opportunities.

The aim of our study was to determine the influence of inhibition of insulin-regulated aminopeptidase/oxytocinase (IRAP) on glucose tolerance and metabolism of skeletal muscle and visceral adipose tissue in obese Zucker rats. Obese Zucker rats administered with IRAP inhibitor–HFI-419 at a dose of 29 μg/100 g BW/day by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hour intraperitoneal glucose tolerance test (ipGTT) was performed in fasting rats. Plasma oxytocin levels were measured by enzyme immunoassay after plasma extraction. In the musculus quadriceps and epididymal adipose tissue, the expression of factors affecting tissue oxidative status and metabolism was determined by real-time qPCR and/or Western blot analysys. The plasma and tissue enzymatic activities were determined by colorimetric or fluorometric method. Circulated oxytocin levels in obese animals strongly tended to increase after HFI-419 administration. This was accompanied by significantly improved glucose utilization during ipGTT and decreased area under the curve (AUC) for glucose. In skeletal muscle IRAP inhibitor treatment up-regulated enzymes of antioxidant defense system – superoxide dismutase 1 and 2 and improved insulin signal transduction pathway. HFI-419 increased skeletal muscle aminopeptidase A expression and activity and normalized its plasma levels in obese animals. In epididymal adipose tissue, gene expression of markers of inflammation and adipocyte hypertrophy was down-regulated in obese rats after HFI-419 treatment. Our results demonstrate that IRAP inhibition improves whole-body glucose tolerance in insulin-resistant Zucker fatty rats and that this metabolic effect of HFI-419 involves ameliorated redox balance in skeletal muscle.

Purpose: The purpose of this paper is to combine seemingly unrelated factors to explain global competitiveness. The study argues that school discipline and education investment affect competitiveness with the association being mediated by educational performance. Crucially, diachronic effects of discipline on performance are tested to demonstrate effects over time. Design/Methodology/Approach: Partial least square (PLS) modelling is used to analyse the Organization for Economic Co-operation and Development's Programme for International Student Assessment (PISA) data. The study further draws from World Bank data on Government Expenditure and World Economic Forum data on competitiveness. Five PISA dimensions of school discipline (students listening well, noise levels, teacher waiting time, students working well, class start time) are hypothesised to affect academic performance in reading, math and science, and to ultimately impact competitiveness. Findings: Findings confirm the relative importance of school discipline (88 per cent) in comparison to education investment (12 per cent) on educational performance, with both variables also being found to be significantly associated with competitiveness directly. Originality/Value: This study demonstrates the time effects of discipline, more specifically that discipline dimensions (students listen well in 2003 and students work well in 2009) are associated with competitiveness in 2012. Implications for school policy and further research are discussed.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects host cells through angiotensin-converting enzyme 2 (ACE2). Concurrently, the product of ACE2 action, angiotensin 1–7 (Ang 1–7), binds to Mas receptors within the cardiovascular system and provides protective effects. Therefore, it is crucial to reveal the role of ACE2 inhibition, especially within pre-existing cardiovascular pathologies. In our study, we imitated the action of SARS-CoV-2 in organisms using the low dose of the ACE2 inhibitor MLN-4760 with the aim of investigating to what degree ACE2 inhibition is detrimental to the cardiovascular system of spontaneously hypertensive rats (SHRs), which represent a model of human essential hypertension. Our study revealed the complex action of MLN-4760 in SHRs. On the one hand, we found that MLN-4760 had (1) (pro)obesogenic effects that negatively correlated with alternative renin-angiotensin system activity and Ang 1–7 in plasma, (2) negative effects on ACE1 inhibitor (captopril) action, (3) detrimental effects on the small arteries function and (4) anti-angiogenic effect in the model of chick chorioallantoic membrane. On the other hand, MLN-4760 induced compensatory mechanisms involving strengthened Mas receptor-, nitric oxide- and hydrogen sulfide-mediated signal transduction in the aorta, which was associated with unchanged blood pressure, suggesting beneficial action of MLN-4760 when administered at a low dose.

The aim of this study was to improve insulin sensitivity in fructose-treated animals by ingestion of flavonoid quercetin. Several signs of insulin resistance have been developed in rats by drinking 10% fructose solution for 9 weeks. The effect of 6-week-gavage-administrated quercetin (20 mg/kg/day in 1% methyl cellulose solution) was monitored. Rats of the control groups received methyl cellulose vehicle as well. The most striking result of the quercetin treatment was the normalization of the fructose solution drinking to the level of drinking water intake. In addition, quercetin supplementation considerably decreased the plasma glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index in rats consuming fructose. Surprisingly, fructose ingestion did not elevate plasma uric acid, thiobarbituric acid reactive substances, nitrotyrosine, or advanced glycation end products fluorescence. Instead, a reduction of the above parameters was observed. In summary, these results indicate that quercetin supplementation reduces fructose drinking and decreases plasma glucose and the HOMA-IR index. Furthermore, methyl cellulose, in combination with fructose, causes uric acid - lowering, antioxidant and anti-glycation effects. Thus, methyl cellulose possibly shifts fructose metabolism in favor of the utilization of antioxidant features of fructose. Our results call for using methyl cellulose in sweetened beverages and other sweetened food. [ABSTRACT FROM AUTHOR]

Renin angiotensin aldosterone system (RAAS) plays an essential role in the homeostatic control of arterial blood pressure, perfusion of tissues, and control of extracellular fluid. Its components are highly expressed in the developing kidney, general vasculature, brain, and heart. A modified intrauterine environment alters mechanisms controlling blood pressure (BP) and can lead to hypertension in the adult offspring and developmentally programmed RAAS can be involved in this process. There are very little data about the effects of increased angiotensin II (Ang II) concentrations during pregnancy on in utero development of the fetus. In our study, we administered Ang II to pregnant female rats via osmotic mini-pumps and evaluated the postnatal development and BP control in the offspring. To estimate possible developmental changes in sensitivity to salt, we exposed the offspring to a diet with increased salt content and measured plasma aldosterone levels and plasma renin activity. Increased Ang II during pregnancy raised BP in the offspring; however, salt sensitivity was decreased in comparison to controls. Relative weight of the left ventricle was decreased in the offspring prenatally exposed to Ang II, while relative kidney weight was reduced only in female offspring. Prenatal treatment led to increased aldosterone levels and decreased plasma renin activity, suggesting a complex physiological response. Our results suggest that conditions leading to upregulation of RAAS during pregnancy can influence the cardiovascular system of the fetus and have a long-term impact on the offspring’s health.

Purpose: The purpose of this paper is to examine the role of school discipline in achieving academic performance. The study aims to clarify the role of permissive "vis-à-vis" authoritative teaching styles with an overarching hypothesis that better discipline leads to better academic performance. The authors also probe whether uniformed students have better discipline. Design/methodology/approach: The authors analyse Organisation for Economic Co-operation and Development's Programme for International Student Assessment data on school discipline dimensions: students listening well, noise levels, teacher waiting time, students working well, class start time. Analysis of variance (ANOVA) with "post hoc" analysis on five geographic groups established by Baumann and Winzar (2016) was applied to test for geographic differences (Europe, Americas, Far East Asia, Rest of Asia, Anglo-Saxon cluster) in school discipline. ANOVA was further used to test for school discipline and academic performance. Third, t-tests on five discipline dimensions were run to test for differences between students who wear uniforms and those who do not. Findings: The results demonstrate differences in school discipline across five geographic clusters, with East Asia leading the way. The authors demonstrate significant differences in discipline for low, medium and high performing students. Peak-performing students have the highest level of discipline. Students wearing a uniform listen better with lower teacher waiting times. Originality/value: Students peak perform when teachers create a disciplined atmosphere where students listen to teachers, where noise levels in the classroom are low and they do not have to wait to start class and teach. Good discipline allows students to work well and this ultimately leads to better academic performance. Uniforms contribute to better discipline in everyday school operations. The findings support that in general, implementing school uniforms at schools might enhance discipline and allow for better learning. The authors recommend keeping uniforms where they are already used and to consider introducing uniforms where they are not yet common.

Adipose tissue expresses all the renin-angiotensin system (RAS) components that play an important role in the adipogenesis, lipid and glucose metabolism regulation in an auto/paracrine manner. The classical RAS has been found to be over-activated during the adipose tissue enlargement, thus elevated generation of angiotensin II (Ang II) may contribute to the obesity pathogenesis. The contemporary view on the RAS has become more complex with the discovery of alternative pathways, including angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor, (pro)renin receptor, as well as angiotensin IV(Ang IV)/AT4 receptor. Ang-(1-7) via Mas receptor counteracts with most of the deleterious effects of the Ang II-mediated by AT1 receptor implying its beneficial role in the glucose and lipid metabolism, oxidative stress, inflammation, and insulin resistance. Pro(renin) receptor may play a role (at least partial) in the pathogenesis of the obesity by increasing the local production of Ang II in adipose tissue as well as triggering signal transduction independently of Ang II. In this review, modulation of alternative RAS pathways in adipose tissue during obesity is discussed and the involvement of Ang-(1-7), (pro)renin and AT4 receptors in the regulation of adipose tissue homeostasis and insulin resistance is summarized.