Advancing the study of life and death education: theoretical framework and research inquiries for further development.

Life and death education, also known as life education and death education, is an interesting subject that may coincide with the subject of lifespan development. In brief, from our theoretical perspective, which guides our teaching and curriculum development, life education considers personal understanding of life functioning on a daily basis, whereas death education explores matters that are related to death and dying. For example, how can a social worker utilize his life knowledge, or life wisdom, to assist a relative to understand the intricate nature of death? In a similar vein, how can a senior citizen use her personal experience of Buddhist meditation practice to overcome a minor Covid setback? Central to our teaching practice is the premise of 'active transformation' (i.e., transforming life knowledge into positive practice) and the premise of 'theoretical infusion' (e.g., the infusion of a distinctive epistemological belief in the teaching of life) that would, in turn, help to enhance and facilitate deep, meaningful understanding of life and death. The purpose of the present article is for us to discuss a proposition of a theoretical-conceptual model, which depicts the 'unification' or integration of three major viewpoints of life and death: the social viewpoint, the philosophical viewpoint, and the psychological viewpoint. We theorize that unification of the three theoretical viewpoints may help provide grounding for effective teaching and holistic understanding of the subject contents of life and death. Such discourse, importantly, may also assist to advance the scope and complexity of the lifespan development subject. Finally, in addition to our theoretical-conceptual model of life and death, we propose three major research inquiries for development: the meaning of situated mindset, the underlying nature of spiritual transcendence, and proposition of appropriate methodological accounts for usage. Overall, then, we purport that our conceptual analysis and discussion overview, based on philosophical reflection, may serve to stimulate interest, intellectual curiosity, scholarly dialog, etc.

Advancing the study of levels of best practice pre-service teacher education students from Spain: Associations with both positive and negative achievement-related experiences.

The study of optimal best practice, coinciding with a person's 'motivational mindset', is an interesting research inquiry for development. Optimal best practice, in brief, relates to the maximization of a person's state of functioning (e.g., cognitive functioning). Moreover, the nature of optimal best practice is positive and motivational, helping individuals to flourish in different courses of action (e.g., academic performance at school). Several research undertakings, non-experimental in design, have provided clear and consistent evidence to substantiate the existing viewpoints and perspectives of optimal best practice. Our proposed investigation, which involved physical education pre-service teacher students from Spain (N = 681), explored one notable focus of inquiry-namely, the formation of optimal best practice and its predictive and explanatory account on future adaptive outcomes. As such, using Likert-scale measures and path analysis techniques, we were able to identify two associative patterns: achievement of optimal best practice is positively accounted for by academic self-concept, optimism, and current best practice and, in contrast, negatively accounted for by pessimism; and that optimal best practice could act as a determinant of academic engagement for effective learning. Such associations are significant, providing relevant information for different teaching and research purposes.

A randomised preclinical trial of adrenaline use during cardiac arrest in mice.

Background: Adrenaline is routinely administered during cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study evaluates the effects of adrenaline use on survival and end-organ injury. Methods: A total of 58 mice, including cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (in CA only) for 4-minutes prior to intravenous adrenaline (+ADR;250 ul,32 ug/ml) or saline (-ADR;250 ul) and manual chest compressions (300 BPM) for 4-minutes. Mice with return of spontaneous circulation (ROSC) were assessed at 24- or 72-h timepoints. Results: Among animals that underwent CA, rates of ROSC (n = 21 (95 %) vs n = 14 (82 %), P = 0.18) and survival to the planned endpoint (n = 11 (50 %) vs n = 12 (71 %), P = 0.19) were similar when comparing those treated with (CA+ADR) and without (CA-ADR) adrenaline. However, in CA animals that initially achieved ROSC, subsequent mortality was approximately 3-fold greater with adrenaline treatment (48 % vs 14 %, P = 0.042). Among SHAM animals, adrenaline use had no impact on survival rates or other endpoints. Greater myocardial injury occurred in CA+ADR vs CA-ADR, with increased Hs-Troponin levels measured at 24- (26.0 ± 0.9 vs 9.4 ± 5.3 ng/mL, P = 0.015) and 72-h (20.9 ± 8.3 vs 5.0 ± 2.4 ng/mL, P = 0.012), associated with increased expression of pro-inflammatory and fibrotic genes within cardiac and renal tissue. Conclusion: Adrenaline did not improve ROSC or overall survival but following successful ROSC, its use resulted in 3-fold greater mortality rates. Adrenaline was also associated with increased myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further preclinical evaluation of alternate pharmacologic adjuncts for cardiopulmonary resuscitation that improve survival and limit end-organ injury.

Tenglong Buzhong granules inhibits the growth of SW620 human colon cancer.

OBJECTIVE: To observe the anticancer effects of the granular preparation of Tenglong Buzhong decoction (,TBD), i.e Tenglong Buzhong granules (, TBG), in human SW620 colon cancer. METHODS: BALB/c nude mice were subcutaneously transplanted with SW620 cells, and treated with TBG (2.56 g/kg, once per day) and/or 5-Fu (104 mg/kg, once per week) for 21 d. Apoptosis, Caspase activities and cellular senescence were measured by commercial kits. The protein expression and phosphorylation were detected by Western blot or immunohistochemistry. RESULTS: TBG and 5-Fu inhibited tumor growth. The tumor inhibition rate of the TBG, 5-Fu, and TBG+5-Fu groups was 42.25%, 51.58%, and 76.08%, respectively. Combination of TBG and 5-Fu showed synergetic anti-cancer effects. TBG and 5-Fu induced apoptosis, activated caspase-3, -8, and -9, increased SMAC expression, inhibited XIAP expression. TBG induced cellular senescence, upregulated cyclin-dependent kinase inhibitor 1a (CDKN1a) and cyclin-dependent kinase inhibitor 2a (CDKN2a) expression, and inhibited phosphorylation of retinoblastoma-associated protein (RB) and expression of cyclin E1 (CCNE1) and cyclin-dependent kinases (CDK) 2. TBG also inhibited angiogenesis accompanied by downregulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α). CONCLUSIONS: TBG inhibits SW620 colon cancer growth, induces apoptosis SMAC-XIAP-Caspases signaling, induces cellular senescence through CDKN1a/CDKN2a-RB-E2F signaling, inhibits angiogenesis by down-regulation of HIF-1α and VEGF, and enhances the effects of 5-Fu.

Applied educational practice and research development of 'goals of best practice' (GsBP): philosophical inquiries and conceptual analysis for consideration.

In educational settings, the notion of 'achieving optimal best' in a subject matter (e.g., an elementary school student's achievement in her Year 6 Science project) is relevant for educators to consider. Optimal best, or optimal functioning, reflects the proactivity, positivity, and motivation of a person. How does a student achieve optimal best in Calculus? Our extensive research of optimal best has recognized the potency of the process of human optimization, which may operate to explain a person's successful experience and achievement of optimal best. Recently, researchers have considered another theoretical concept, which is termed as 'goals of best practice' (i.e., abbreviated as 'GsBP'). Goals of best practice, in brief, are personal goals that a person may construct and set for a particular context. Specifically, however, a 'personal goal' may indicate and espouse a person's plan of intent to either remain on course without any desire or aspiration (i.e., 'goal of actual best', denoted as 'GAB') or, alternatively, to strive for maximization (i.e., 'goal of optimal best', denoted as 'GOB'). This article is theoretical and conceptual, reflecting the use of the paradigm of philosophical psychology to advance the study of the concept of GsBP. Specifically, we contend that our conceptual analysis of GsBP, entailing both GAB and GOB may provide a logical basis and rationale for the proposition of educational implications for consideration and inquiries for continuing research development.

Advancing the study of solving linear equations with negative pronumerals: A smarter way from a cognitive load perspective.

Central to cognitive load theory is the concept of element interactivity, which reflects the complexity of material. The complexity of linear equations depends on the number of operational and relational lines and the nature of the operation (balance versus inverse) in the solution procedure. A relational line refers to the quantitative relation whereby the right-hand side of the equation equals to its left-hand side. An operational line refers to the application of an operation and such a procedural step preserves the equality of the linear equation. The balance method and inverse method differ in the operational line (e.g., + 3 on both sides vs.- 3 becomes + 3) where the inverse operation imposes half the level of element interactivity as the balance method. Seventy-five students randomly assigned to either the balance group or inverse group to complete (i) one-step equations (Experiment 1), (ii) two-step equations (Experiment 2), and (iii) one-step and two-step equations with a focus on equations with negative pronumerals (Experiment 3). Performance favoured the inverse group when the gap between the low and high element interactivity equations was substantial enough. Both groups performed better and invested lower mental effort on the inverse operation than the balance operation.

Empirical validation of the psychological concept of a perceived feeling of 'energy': Advancement into the study of positive psychology.

The paradigm of positive psychology, significant in nature, helps to explain the proactivity and motivation of human agency, such as a secondary school student's state of autonomy, confidence, and personal resolve to strive for optimal learning and/or non-learning experiences. Our recent research development, in tandem with other scholars' inquiries, has focused on one aspect of positive psychology-namely, a person's achievement of 'optimal best', which reflects the maximization of his/her state of functioning (e.g., cognitive functioning). Capitalizing on our previous research, we develop a psychological concept that we term as a 'perceived feeling of energy'. A perceived feeling of energy (e.g., a perceived feeling of liveliness) is proposed to act as a 'motivational engine', or as a central driver, which then could predict and enhance a person's achievement of optimal best. Six hundred and twenty-seven university students (N = 438 women, 189 men) responded to a suite of self-report questionnaires. Structural equation modelling (SEM) techniques were used to test a conceptual model, where we focused on the antecedent (i.e., the direct impact of self-efficacy on a perceived feeling of energy) and consequence of a perceived feeling energy (i.e., the impact of a perceived feeling of energy on personal resolve, and the sustaining of optimal best). Analysis of results showed support for our original hypothesized model-for example: self-efficacy as an antecedent of energy and the central role of the energy as a predictor and potential mediator of future outcomes.

Interrelationships Between Psychosocial, Motivational, and Psychological Processes for Effective Learning: A Structural Equation Modeling Study.

We tested a theoretical-conceptual model that introduced our recently developed psychological concept, termed as psychological processes, which is defined as "a person's continuing frame of mind to focus on disposition toward strong resolute, structured thoughts and organization, and aspiration to strive for educational success." This proposition is innovative as it considers the notion that a person's mindset is malleable and, importantly, subjects to social experiences derived from a situated social context. Moreover, from our definition, we contend that psychological processes, as a distinct construct, is "latent," or underlying, with three comparable psychological attributes: personal resolve, effective functioning, and personal striving. Our conceptualization, acknowledging the importance of social contexts and individualized experience and personal belief, proposed that perceived social experiences (i.e., positive versus negative), as a source of information, would shape a student's psychological processes, his/her state of motivation, and engagement in different types of adaptive outcomes. Moreover, from our point of view, psychological processes would act as a predictor as well as a potential mediator of motivation and engagement in different types of adaptive outcomes. In a similar vein, from the positive effect of psychological processes, motivation could act as a predictor as well as a mediator of adaptive outcomes. Structural equation modeling, from Taiwanese university students' (N = 739) responses to various Likert-scale measures, showed support for our original a priori model - for example, the positive effects of perceived social experiences on psychological processes (ß = 0.81, p < 0.001) motivation (ß = 0.61, p < 0.001), and adaptive outcomes (ß = 0.36, p < 0.01), and the positive effect of psychological processes on motivation (ß = 0.31, p < 0.01). Interestingly, we also found some interesting findings with regard to the effects of measured indicators - for example, the positive effect of personal resolve, as a measured indicator, on adaptive outcomes (ß = 0.28, p < 0.001), and the effect of self-efficacy, as a measured indicator, on academic liking experience, also a measured indicator (ß = 0.12, p < 0.01). Overall, the results established have a wide range of implications for consideration - for example, the development of an educational program and/or instructional design that could promote and foster positive learning experiences.

The effect of dihydroceramide desaturase 1 inhibition on endothelial impairment induced by indoxyl sulfate.

Protein-bound uremic toxins (PBUTs) have adverse effects on vascular function, which is imperative in the progression of cardiovascular and renal diseases. The role of sphingolipids in PBUT-mediated vasculo-endothelial pathophysiology is unclear. This study assessed the therapeutic potential of dihydroceramide desaturase 1 (Des1) inhibition, the last enzyme involved in de novo ceramide synthesis, to mitigate the vascular effects of the PBUT indoxyl sulfate (IS). Rat aortic rings were isolated and vascular reactivity was assessed in organ bath experiments followed by immunohistochemical analyses. Furthermore, cultured human aortic endothelial cells were assessed for phenotypic and mechanistic changes. Inhibition of Des1 by a selective inhibitor CIN038 (0.1 to 0.3 µM) improved IS-induced impairment of vasorelaxation and modulated immunoreactivity of oxidative stress markers. Des1 inhibition also reversed IS-induced reduction in endothelial cell migration (1.0 µM) by promoting the expression of angiogenic cytokines and reducing inflammatory and oxidative stress markers. These effects were associated with a reduction of TIMP1 and the restoration of Akt phosphorylation. In conclusion, Des1 inhibition improved vascular relaxation and endothelial cell migration impaired by IS overload. Therefore, Des1 may be a suitable intracellular target to mitigate PBUT-induced adverse vascular effects.

A Perceived Zone of Certainty and Uncertainty: Propositions for Research Development.

Possessing expert schemas is a positive feat that may yield different types of adaptive outcomes (e.g., informing procedural understanding that may result in a student skipping a few of the solution steps involved). Limited schemas, in contrast, may deter progress of a novice learner, limiting his/her capability to flourish. Taken as a whole, it may be concluded that expert schemas are more advantageous than novice schemas, differentiating learners in terms of expert and novice. Having said this, however, more recently, researchers have argued that possessing expert schemas could serve as deterrence. Recently, researchers have acknowledged a theoretical concept known as cognitive entrenchment, which is defined as a high level of stability in domain schemas. This description interestingly suggests that "entrenchment" or "situated fixation" of a course of action (e.g., a subject matter) could hinder the progress and learning experience of a person, namely-his/her inability and/or unwillingness to adapt to a new context, and/or his/her inflexibility and insistence to stay on course without any intent to change. One example of cognitive entrenchment is observed in professional football, wherein it has been argued that some football coaches are cognitively entrenched within their expert schemas, resulting in their demised game plans and strategic acumen. We advance the study of cognitive entrenchment by proposing an alternative viewpoint, which we term as the "perceived zone of certainty and uncertainty." This proposition counters the perspective of cognitive entrenchment by arguing that it is cognitive appraisal, judgment, mental resolute, and determination of a person in cognitive certainty of his/her success or failure, or the cognitive uncertainty of success or failure, that would explain the notion of inflexibility and/or unwillingness to adapt, and/or insistence to stay on course without any attempt to deviate. Moreover, we rationalize that certainty of success or failure would closely associate with a feeling of comfort, whereas uncertainty would associate with his/her feeling discomfort. In this analysis, we strongly believe that willingness to change and adapt, reluctance and insistence to remain on course, and/or inclination to embrace flexibility may not necessarily relate to the concept of cognitive entrenchment; rather, inflexibility and/or reluctance to change for the purpose of adaptation has more to do with the desire of a person to seek a state of comfort. Finally, our conceptual analysis of cognitive entrenchment also considers an interesting theoretical concept, which we termed as "perceived optimal efficiency." Perceived optimal efficiency, similar to cognitive relevance theory, is concerned with the relationship between minimum investment of time, effort, cognitive resources, etc., and an optimal best outcome. The issue for discussion, from our point of view, is related to the extent to which the certainty of success or failure would associate with perceived optimal efficiency.

Cost-effectiveness of dapagliflozin in chronic heart failure: an analysis from the Australian healthcare perspective.

AIM: To assess the cost-effectiveness of dapagliflozin in addition to standard care versus standard care alone in patients with chronic heart failure and reduced ejection fraction. METHODS: A Markov model was constructed based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial to assess the clinical outcomes and costs of 1000 hypothetical subjects with established heart failure and reduced ejection fraction. The model consisted of three health states: 'alive and event-free', 'alive after non-fatal hospitalisation for heart failure' and 'dead'. Costs and utilities were estimated from published sources. The main outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. An Australian public healthcare perspective was employed. All outcomes and costs were discounted at a rate of 5% annually. RESULTS: Over a lifetime horizon, the addition of dapagliflozin to standard care in patients with heart failure and reduced ejection fraction prevented 88 acute heart failure hospitalisations (including readmissions) and yielded an additional 416 years of life and 288 quality-adjusted life-years (discounted) at an additional cost of A$3,692,440 (discounted). This equated to an incremental cost-effectiveness ratio of A$12,482 per quality-adjusted life-year gained, well below the Australian willingness-to-pay threshold of A$50,000 per quality-adjusted life-year gained. Subanalyses in subjects with and without diabetes resulted in similar incremental cost-effectiveness ratios of A$13,234 and A$12,386 per quality-adjusted life-year gained, respectively. CONCLUSION: Dapagliflozin is likely to be cost-effective when used as an adjunct therapy to standard care compared with standard care alone for the treatment of chronic heart failure and reduced ejection fraction.

Insulin-like growth factor-1 directly affects cardiac cellular remodelling via distinct pathways.

BACKGROUND: Studies of insulin-like growth factor 1 (IGF-1) as a novel therapy for the treatment of cardiovascular diseases have proven promising. However, elevated IGF-1 levels have also been associated with poor patient outcomes in heart failure with reduced ejection fraction. IGF-1 therapy has additionally been shown to not be beneficial in the percutaneous coronary intervention setting. Although IGF-1 activation of the PI3K/Akt and ERK1/2 pathways have been demonstrated as cardioprotective, other cellular mechanisms have not been fully investigated. METHODS: Neonatal rat cardiac myocytes (NCMs) and fibroblasts (NCFs) were isolated from 1 to 2-day old pups using enzymatic digestion. NCMs and NCFs were pre-treated with IGF binding protein 6, inhibitors for the PI3K/Akt Wortmannin, ERK1/2 U0126, Rho Associated Protein Kinase (ROCK) GSK576371, Apoptosis Signal-regulating Kinase-1 (ASK-1) G2261818A, and p38MAPK RWJ67657 pathways before stimulation with IGF-1 for 62 and 50 h, respectively. Cardiac myocyte hypertrophy and fibroblast collagen synthesis were determined by 3H-leucine and 3H-proline incorporation, respectively. RESULTS: IGF-1 dose-dependently stimulated NCM hypertrophy and NCF collagen synthesis.Treatment with IGFBP6 and the kinase inhibitors, Wortmannin, U0126, GSK576371, G2261818A and RWJ67657 significantly inhibited IGF-1 stimulated NCM hypertrophy and NCF collagen synthesis. CONCLUSION: This study is the first to demonstrate that IGF-1 treatment in NCMs and NCFs activates the ROCK, ASK-1 and p38MAPK pathways. Future research may be guided by consideration of the PI3K/Akt and ERK1/2 pathways potentially increasing collagen synthesis, and the utilisation of a biased agonist to reduce activation of the ROCK, ASK-1 and p38MAPK pathways to maximise cardioprotective benefit whilst mitigating risks.

Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFß induced collagen synthesis in cardiac fibroblasts.

The sphingolipid de novo synthesis pathway, encompassing the sphingolipids, the enzymes and the cell membrane receptors, are being investigated for their role in diseases and as potential therapeutic targets. The intermediate sphingolipids such as dihydrosphingosine (dhSph) and sphingosine (Sph) have not been investigated due to them being thought of as precursors to other more active lipids such as ceramide (Cer) and sphingosine 1 phosphate (S1P). Here we investigated their effects in terms of collagen synthesis in primary rat neonatal cardiac fibroblasts (NCFs). Our results in NCFs showed that both dhSph and Sph did not induce collagen synthesis, whilst dhSph reduced collagen synthesis induced by transforming growth factor ß (TGFß). The mechanisms of these inhibitory effects were associated with the increased activation of the de novo synthesis pathway that led to increased dihydrosphingosine 1 phosphate (dhS1P). Subsequently, through a negative feedback mechanism that may involve substrate-enzyme receptor interactions, S1P receptor 1 expression (S1PR1) was reduced.

Introducing the Concept of Consonance-Disconsonance of Best Practice: A Focus on the Development of 'Student Profiling'.

The present study, using a non-experimental approach, investigated a theoretical concept of best practice, which we recently introduced - namely: a 'state of consonance' and a 'state of disconsonance' of best practice. Consonance of best practice posits that different levels of best practice (e.g., low level of best practice versus optimal level of best practice), as well as other comparable psychological constructs (e.g., motivation towards learning) would cluster or 'group' together. Disconsonance of best practice, in contrast, would indicate non-overlapping of contrasting levels of best practice (i.e., low level of best practice versus optimal level of best practice). Taiwanese undergraduates (N = 831) from five private universities in Taipei City and New Taipei City, Taiwan took part in the study by responding to a suite of Likert-scale questionnaires (e.g., Best Practice Questionnaires, Motivation towards Learning Questionnaire), which took approximately 30-35 min to complete. Cluster analysis, commonly known as ClA, was used to analyze the data and seek theoretical understanding into the nature of the consonance of best practice. Results, overall, showed support for our proposition, resulting in four distinct profiles: 'a Balanced Profile,' 'an Intrinsic Motivation Profile,' 'a Current Best Practice + Interest Profile,' and 'a Current Best Practice + Motivation Profile.' This evidence, helping to advance further research development, has a number of practical implications for consideration. For example, how could we use the Balanced Profile to develop learning objectives and/or pedagogical practices that would encourage students to enjoy their learning experiences?

Life, death, and spirituality: A conceptual analysis for educational research development.

Life education, also known as life and death education, is an important subject in Taiwan. Life education is more than just the study of a person's development throughout the lifespan (e.g., cognitive development). Within the learning and sociocultural contexts of Taiwan, interestingly, the study of life and death education is concerned with the premise of the promotion and fulfillment of life qualities (e.g., a person's state of contentment), and the meaningful understanding of the nature of death. To facilitate appreciation and deep, meaningful understanding of the subject, and to emphasize its uniqueness, educators have included in their teaching the importance of Eastern-derived philosophical beliefs and religious faiths (e.g., Buddhism). For example, relatively significant in its emphasis, the teaching of this subject involves detailed examination of theoretical accounts of spiritual cultivation and its positive effect on a person's interpretation and enlightenment of life wisdom. The study of life education, or life and death education, we contend, is of significance as it provides life-related insights and theoretical understanding into the intricate nature of life and death. One notable aspect of the subject entails a person's acquired life wisdom, which in turn may shape his/her life practice on a daily basis (e.g., the proactive engagement in Buddhist meditation). Importantly, the study of life education may assist individuals with their coping of grief, and to approach death with a sense of peace, calmness, and dignity. In this analysis, coupled with Buddhist faith (or any other religious faith for that matter) and facilitated by spiritual cultivation (e.g., the belief in the notion of transcendence experience), a person may overcome grief by believing in the possibility that there is some form of post-death experience and the presence of a loved one's spiritual being. Given this emphasis, we consider an important focus for discussion in this article: to explore the significance of life and death education and to determine how its 'positive nature' could potentially yield two comparable implications for development: (i) to engage in appropriate pedagogical practices that would encourage and promote the study of life and death education, and (ii) to advance innovative research inquiries, theoretical, methodological, and/or empirical, which could highlight the significance of life education for life purposes (e.g., the significance of Chinese ideograms, such as ).

The Preventable Productivity Burden of Kidney Disease in Australia.

BACKGROUND: Kidney disease is associated with impaired work productivity. However, the collective effect of missed work days, reduced output at work, and early withdrawal from the workforce is rarely considered in health-economic evaluations. METHODS: To determine the effect on work productivity of preventing incident cases of kidney disease, using the novel measure "productivity-adjusted life year" (PALY), we constructed a dynamic life table model for the Australian working-age population (aged 15-69 years) over 10 years (2020-2029), stratified by kidney-disease status. Input data, including productivity estimates, were sourced from the literature. We ascribed a financial value to the PALY metric in terms of gross domestic product (GDP) per equivalent full-time worker and assessed the total number of years lived, total PALYs, and broader economic costs (GDP per PALY). We repeated the model simulation, assuming a reduced kidney-disease incidence; the differences reflected the effects of preventing new kidney-disease cases. Outcomes were discounted by 5% annually. RESULTS: Our projections indicate that, from 2020 to 2029, the estimated number of new kidney-disease cases will exceed 161,000. Preventing 10% of new cases of kidney disease during this period would result in >300 premature deaths averted and approximately 550 years of life and 7600 PALYs saved-equivalent to a savings of US$1.1 billion in GDP or US$67,000 per new case avoided. CONCLUSIONS: Pursuing a relatively modest target for preventing kidney disease in Australia may prolong years of life lived and increase productive life years, resulting in substantial economic benefit. Our findings highlight the need for investment in preventive measures to reduce future cases of kidney disease.

[Correlation between PNPLA3 rs738409 and TM6SF2 rs58542926 gene polymorphism and primary liver cancer in the Han Population of China's Northeast region].

Objective: To investigate the correlation between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 gene polymorphisms and the incidence of primary liver cancer in the Han population of China's Northeast region. Methods: A case-control study was used to enroll 521 patients with primary liver cancer as the case group and 164 healthy people as the control group. The case group was divided into groups with and without liver cirrhosis according to etiology. The polymerase chain reaction (PCR) method was used to detect the genetic polymorphisms of PNPLA3 rs738409 and TM6SF2 rs58542926, respectively. Results: Compared with the control group, the frequency distribution of PNPLA3 rs738409 G allele in the case group was significantly different (OR = 1.583, P = 0.001). Further grouping showed that there was no statistically significant difference between the control and hepatitis C-related liver cancer group (P = 0.161), but there were significant differences in other groups (P < 0.05). Compared with the control group, the frequency of TM6SF2 rs58542926 T allele in the case group was significantly higher than that in the control group (OR = 1.759, P = 0.048). After grouping, the frequency of CT/TT genotype in the liver cancer group combined with liver cirrhosis and the T allele frequency in the alcohol-related liver cancer group had statistically significant difference (P = 0.045 and 0.032, respectively) when compared with control group. The patients were divided into CG/GG group and CC group, and CT/TT group and CC group according to whether they carried PNPLA3 rs738409 G allele, and TM6SF2 rs58542926 T allele. Results showed that there were no statistically significant differences in liver enzyme indexes, albumin (ALB), total bilirubin (TBIL), alpha-fetoprotein (AFP) and fasting blood glucose between CG/GG group and CC group, and CT/TT group and CC group. The patients with liver cirrhosis in the case group were divided into≥7 groups and < 7 groups according to the Child-Pugh score. Results showed that there were no statistically significant difference in the Child-Pugh score between PNPLA3 rs738409 CG/GG group and CC group patients and TM6SF2 rs58542926 CT/TT group and CC group patients (P > 0.05). Conclusion: PNPLA3 rs738409 and TM6SF2 rs58542926 gene polymorphisms are correlated with the occurrence of primary liver cancer in the Han population of China's Northeast region. PNPLA3 rs738409 and TM6SF2 rs58542926 gene polymorphisms have no effect on indexes' such as liver enzymes, ALB, TBIL, AFP and FBS in primary liver cancer..

Perceived 'optimal efficiency': theorization and conceptualization for development and implementation.

We recently advanced the study of positive psychology by introducing the theory of optimization, which explains the underlying process of optimal best. Our continuing research interest has led us to a newly developed concept, termed as 'optimal efficiency'. Optimal efficiency, we contend, focuses on the utilization of resources as well as the amount of time and effort that a person would have to expend during the course of his/her learning. How much time and effort, for example, should a student expend before it is perceived as being 'inefficient'? Optimal efficiency, in this analysis, is concerned with an important relationship - namely: the minimization of expenditure of time, effort, resources, etc. versus the maximization in productivity. Perceived efficiency is related to the teaching and training of judgment, decision making, autonomy, and self-determination - for example, in terms of successful schooling, a student has to decide whether it is worthwhile to expend so much time and effort on a given task when he/she may not necessarily pass. In our conceptual analysis and proposition of optimal efficiency, we consider the impact of cognitive load theory, which places emphasis on calculated investment and subsequent use of cognitive resources to process information for the purpose of achieving effective learning in a subject matter. Using cognitive load theory as a basis, we attempt to validate the concept of optimal efficiency by taking into account three main types of cognitive load imposition: extraneous, intrinsic, and germane. For example, we consider the possibility that a reduction in extraneous cognitive load imposition could instill a perception of efficiency, resulting in a person's achievement of optimal best. Emphasis on encouragement of germane cognitive load, in contrast, could be perceived as being more efficient, likewise yielding exceptional outcomes in a subject matter.

Apoptosis signal-regulating kinase 1 inhibition reverses deleterious indoxyl sulfate-mediated endothelial effects.

AIMS: Indoxyl sulfate (IS), a protein-bound uremic toxin, is implicated in endothelial dysfunction, which contributes to adverse cardiovascular events in chronic kidney disease. Apoptosis signal regulating kinase 1 (ASK1) is a reactive oxygen species-driven kinase involved in IS-mediated adverse effects. This study assessed the therapeutic potential of ASK1 inhibition in alleviating endothelial effects induced by IS. MAIN METHODS: IS, in the presence and absence of a selective ASK1 inhibitor (GSK2261818A), was assessed for its effect on vascular reactivity in rat aortic rings, and cultured human aortic endothelial cells where we evaluated phenotypic and mechanistic changes. KEY FINDINGS: IS directly impairs endothelium-dependent vasorelaxation and endothelial cell migration. Mechanistic studies revealed increased production of reactive oxygen species-related markers, reduction of endothelial nitric oxide synthase and increased protein expression of tissue inhibitor of matrix metalloproteinase 1 (TIMP1). IS also increases angiopoietin-2 and tumour necrosis factor α gene expression and promotes transforming growth factor ß receptor abundance. Inhibition of ASK1 ameliorated the increase in oxidative stress markers, promoted autocrine interleukin 8 pro-angiogenic signalling and decreased anti-angiogenic responses at least in part via reducing TIMP1 protein expression. SIGNIFICANCE: ASK1 inhibition attenuated vasorelaxation and endothelial cell migration impaired by IS. Therefore, ASK1 is a viable intracellular target to alleviate uremic toxin-induced impairment in the vasculature.

The impact of coronary heart disease prevention on work productivity: a 10-year analysis.

AIMS: To determine the impact of preventing new (incident) cases of coronary heart disease (CHD) on years of life and productivity, using the novel measure 'productivity-adjusted life year' (PALY), over the next 10 years. METHODS AND RESULTS: A dynamic life table model was constructed for the total Australian working-age population (15-69 years) over 10 years (2020-2029), separated by CHD status. Productivity estimates were sourced from the literature. The PALY was ascribed a financial value in terms of gross domestic product (GDP) per equivalent full-time worker. The total number of years lived, PALYs, and economic burden (in terms of GDP per PALY) were estimated. The model simulation was repeated assuming incidence was reduced, and the differences represented the impact of CHD prevention. All outcomes were discounted by 5% per annum. Over 10 years, the total projected years lived and PALYs in the Australian working-age population (with and without CHD) were 133 million and 83 million, respectively, amounting to A$17.2 trillion in GDP. We predicted more than 290 000 new (incident) CHD cases over the next 10 years. If all new cases of CHD could be prevented during this period, a total of 4 000 deaths could be averted, resulting in more than 8 000 years of life saved and 104 000 PALYs gained, equivalent to a gain of nearly A$21.8 billion (US$14.8 billion) in GDP. CONCLUSION: Prevention of CHD will prolong years of life lived and productive life years, resulting in substantial economic benefit. Policy makers and employers are encouraged to engage in preventive measures addressing CHD.