Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding

The nuclear factor E2-related factor 2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid-binding protein 4, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by downregulation of insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome

What for the future, from learning the past? Exploring the implications of the compulsory Aotearoa New Zealand histories curriculum

(c) The Author/sImportant curriculum development work has progressed since the 2019 announcement that Aotearoa New Zealand histories would become compulsory learning across all schools. Much effort has gone into considering how learning ‘our’ histories can engage, inspire and empower children in schools through years 1 to 10, and recent writing has focused on how to address challenges in building knowledge and capability to meet those aims. However, what will be the effects beyond those years? Will students still be drawn to choose history in their senior school years, or will they be ‘over it’? In a quest to gauge the implications of the new curriculum, our research team surveyed secondary school history students on their motivations and areas of interest in learning history, and their views on Aotearoa New Zealand history becoming compulsory for Years 1-10. Findings from our research confirmed that students’ past engagement with history influenced their ongoing interest, motivation and understanding of the subject. However, the positive learning that had drawn them to history was often about everyone else’s history rather than their own. Students identified international histories – often involving war or conflict – as favourite topics. So, while most supported the implementation of the new curriculum, they equally expressed concern that the local focus should not be at the expense of wider perspectives. They felt history could become repetitive and boring; elements which could put students off engaging with history in future. We conclude by presenting important considerations for ensuring such negative impacts do not occur.fals

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

The Social and Cultural Context of Coping with Sickle Cell Disease: I. A Review of Biomedical and Psychosocial Issues

Sickle cell disease (SCD) is widely conceived in the United States as a group of blood disorders that principally affect African Americans. Although pain is its principal feature, strokes, lung problems, sepsis, anxiety, depression, impaired social functioning, and maladjustment at work are frequent concomitants. This article selectively reviews biomedical and psychosocial aspects of SCD related to pain assessment, medical treatment, genetic counseling, education, and employment. The strongest support exists for claims of social deficits among adolescents and depression and work-related problems among adults. The social context of SCD, including issues related to socioeconomic status (SES), urbanicity, ethnicity, cultural values, and racial stigmatization, are important to include in empirical assessments and theoretical analyses of the effects of SCD on children and their families. The adverse psychosocial functioning often described as an effect of SCD might indeed be a consequence of these factors acting alone or in concert with the strains of SCD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67048/2/10.1177_0095798499025003002.pd

“Cautiously Optimistic” Older Parent-Carers of Adults with Intellectual Disabilities response to the Care Act 2014

This paper discusses potential opportunities for best practice in the UK that may be brought about by the Care Act (2014). Carers in the UK were given new rights within this legislation with a focus on needs led assessment. The underpinning philosophy of the Care Act is to streamline previous legislation and offer a framework for carers and people in receipt of care, to enable a more personalised approach to care and support

Intergenerational Communication – an interdisciplinary mapping review of research between 1996 and 2017

Concerns have been raised regarding the limited opportunities for intergenerational communication both outside and within the family. This “mapping review” draws together empirical literature in the topic published since 1996. Three hundred and twenty-four published studies met inclusion criteria, based on abstract review. The contents of each study were subjected to thematic analysis and nine broad themes emerged. These were (1) Dynamics of relationships, (2) Health & Well-being, (3) Learning & Literacy, (4) Attitudes, (5) Culture, (6) Digital, (7) Space, (8) Professional Development, and (9) Gender & Sexual Orientation. Studies commonly intersected disciplinary research areas. There was a marked rise across three key academic journals since 2007. An emergent finding was that a third of the studies relate to programs addressing intergenerational interventions, but many of these were primarily descriptive and failed to specify a primary outcome. Review implications and future research directions are discussed

AI for social good: unlocking the opportunity for positive impact

Advances in machine learning (ML) and artificial intelligence (AI) present an opportunity to build better tools and solutions to help address some of the world’s most pressing challenges, and deliver positive social impact in accordance with the priorities outlined in the United Nations’ 17 Sustainable Development Goals (SDGs). The AI for Social Good (AI4SG) movement aims to establish interdisciplinary partnerships centred around AI applications towards SDGs. We provide a set of guidelines for establishing successful long-term collaborations between AI researchers and application-domain experts, relate them to existing AI4SG projects and identify key opportunities for future AI applications targeted towards social good

Risk aversion in a performativity culture – what can we learn from teachers’ curriculum decision making in history?

Using the notion of risk aversion, this study explores the decisions teachers make when constructing a curriculum. Adopting a qualitative, grounded approach, this study used semi-structured interviews with nine history teachers to examine the decisions they were making during a period of considerable curriculum change in England. Five key categories were identified, which were then defined as risk averse or high risk. The findings show that teachers largely adopt a low risk approach when constructing a curriculum. In particular choice of content, pedagogical and assessment approaches are affected. Also, changes to the curriculum in high stakes examination courses have a major distorting impact on the curriculum choices for the phase of schooling prior to the examination course. This study would suggest that teachers generally aim to maximise examination outcomes through adopting a low risk approach to curriculum change. However, according to the literature, these low risk approaches appear unlikely to improve examination outcomes, whilst at the same time narrowing students’ experience of the curriculum

Native American Children and Their Reports of Hope: Construct Validation of the Children's Hope Scale

Child reports of hope continue to be utilized as predictors of positive adjustment; however, the utilization of the hope construct has not been assessed within the culturally diverse Native American child group. The present study investigated the applicability of the Hope theory among 96 Native American children in the Midwest. Measures included the Children’s Hope Scale and a Hope Interview. Native American children in the current sample appear to conceptualize hope as a way to reach goals as did the children in the normative sample. Results from the factor analysis demonstrate that the factor structure found in the current study was similar to the factor structure found in the standardization sample. Because of the similar Hope theory conceptualization and factor structure, interventions focused on the positive psychology construct of hope may be applicable within a Native American child population

Depression and loneliness in Jamaicans with sickle cell disease

<p>Abstract</p> <p>Background</p> <p>Sickle cell disease (SCD) is the commonest genetic disorder in Jamaica, and has life-long implications for those afflicted with it. It is well known that depression and loneliness may exist in those with chronic diseases, but the coexistence of depression and loneliness in people with sickle cell disease is not clear. The aim of this study is to determine the prevalence of and factors associated with depression and loneliness in the Jamaica Sickle Cell Cohort Study and its age and sex matched controls.</p> <p>Methods</p> <p>277 patients with SCD and 65 controls were administered a questionnaire that studied demographics, disease severity, depression, and loneliness. Regression analyses were done to examine relationships between outcomes and associated variables.</p> <p>Results</p> <p>Depression was found in 21.6% of patients and 9.4% in controls. Loneliness scores were also significantly higher in patients (16.9 ± 5.1) than in controls (14.95 ± 4.69). Depression was significantly associated with unemployment [OR = 2.9, p-value: < 0.001], whereas unemployment (p-value: 0.002), and lower educational attainment were significantly associated with loneliness.</p> <p>In patients with SCD, depression was significantly associated with being unemployed (OR 2.4, 95% CI 1.2,4.6, p-value:0.01), presence of a leg ulcer (OR = 3.8, 95% CI: 1.7, 8.4, p-value: 0.001), frequent visits (OR = 3.3, 95% CI: 1.2, 8.9, p-value: 0.019), and frequent painful crises (OR = 2.5, 95% CI: 1.1, 5.8, p-value: 0.035). Not being employed (Coef.: 2.0; p-value: 0.004) and higher educational attainment (tertiary vs. primary education, Coef.: -5.5; p-value: < 0.001) were significant associations with loneliness after adjusting for genotype.</p> <p>Conclusions</p> <p>Health workers need to actively look for and manage these problems to optimize their patients' total biopsychosocial care.</p