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As the global population ages, nurses with a positive attitude toward caring for older adults is crucial. However, studies indicate that nursing students often exhibit negative attitudes toward older adults. This study aimed to determine if a three-phased educational intervention significantly improved nursing students’ attitudes toward older adults. A pre/post-test study design was used to measure the change in nursing students’ attitudes toward older adults, as measured by the UCLA Geriatrics Attitudes Survey, after participating in an Artificial Intelligence in Education learning event (n = 151). Results indicate that post-intervention scores (M = 35.07, SD = 5.34) increased from pre-intervention scores (M = 34.50, SD = 4.86). This difference was statistically significant at the 0.10 significance level (t = 1.88, p = 0.06). Incorporating artificial intelligence technology in a learning event is an effective educational strategy due to its convenience, repetition, and measurable learning outcomes. Improved attitudes toward older adults are foundational for delivering competent care to a rapidly growing aging population. This study was prospectively registered with the university’s Institutional Review Board (IRB) on 30 July 2021 with the registration number IRB-FY22-3.

Photobiomodulation therapy, also termed as low-level laser therapy, is commonly used as an adjunctive therapy for various medical conditions in veterinary practice. The ACTIVet PRO low-level laser has been used for treatment of various nondomestic species, yet the effects of dermal attributes such as pigment, feathers, or scales have not been evaluated. The effects of low-level laser therapy with the ACTIVet PRO have been investigated in laboratory animals, including a study in rats that evaluated the passage of laser light through the skin in postmortem samples. The objective of this study was to measure the power of a low-level laser (ACTIVet PRO) after penetration through dermal tissue (∼1 mm thickness) in a variety of postmortem animal tissue. This study sought to determine the impact of fur, feathers, scales, and different pigments on the ability of the laser to penetrate. Frozen and thawed skin tissue samples from various species were placed inside a light restricted laser box and exposed to a preprogrammed laser level from a Multi Radiance ACTIVet PRO photobiomodulation (PBM) device, with a power meter to measure the light penetration through the tissue samples. Light penetration measurements via power output measurements (mW) were recorded at 7 time points (range, 1–150 sec). A Friedman test was performed to evaluate the difference of the mean tissue penetration by each species at each time point. Lighter colored specimens had higher power readings than darker colored or pigmented samples, and feathers appeared to inhibit the laser, showing minimal to no power readings on bird skin covered in covert and down feathers. There was statistically significant mean tissue penetration for all time points between the rabbit and green sea turtle (p=0.0046), the red-tailed hawk and green iguana (p=0.0046), and the red-tailed hawk and green sea turtle (p=0.000034). Overall findings found that certain skin coverings, such as feathers, appear to inhibit passage of laser light through tissue to the photo meter. Darker pigmented areas of tissue appeared to absorb the laser light, which also did not allow light passage through the tissue to the photo meter. All of this illustrates that there are differences in tissue penetration between different animal species, at least in postmortem tissues. This could necessitate adjustment of machine settings for therapeutic effect in different species, though further studies would be warranted to determine the extent to which this would be necessary. Additional studies evaluating biologically active tissues would be needed as a next step, as photobiomodulation has an effect at the cellular level and the exact amount of medical benefit is not measurable in skin samples that are separate from a living organism.

Here, we report the first adult case of pancreatic yolk sac tumor with ectopic adrenocorticotropic hormone (ACTH) syndrome. The patient was a 27-year-old woman presenting with abdominal distension, Cushingoid features, and hyperpigmentation. Endogenous Cushing’s syndrome was biochemically confirmed. The ACTH level was in the normal range, which raised the suspicion of ACTH precursor-dependent disease. Elevated ACTH precursors were detected, supporting the diagnosis of ectopic ACTH syndrome. Functional imaging followed by tissue sampling revealed a pancreatic yolk sac tumor. The final diagnosis was Cushing’s syndrome due to a yolk sac tumor. The patient received a steroidogenesis inhibitor and subsequent bilateral adrenalectomy for control of hypercortisolism. Her yolk sac tumor was treated with chemotherapy and targeted therapy. Cushing’s syndrome secondary to a yolk sac tumor is extremely rare. This case illustrated the utility of ACTH precursor measurement in confirming an ACTH-related pathology and distinguishing an ectopic from a pituitary source for Cushing’s syndrome.

Qualitative migration researchers today often use one or more of three concepts – mobility, transnationalism and integration – to make sense of the complexities of contemporary migrants’ lives. Collectively, researchers identify these as the three fundamental characteristics of migranthood. Being a migrant is about, for example, planning return visits, maintaining (or not maintaining) relations with people in the sending country or being preoccupied with learning to speak the receiving-society majority language. Qualitative interviewing suggests that each migrant is uniquely situated along various mobility, transnational and integration continuums. Migrants have many social identities as well as migranthood and the existence of these other, intersecting, social identities (such as social class, lifestage and gender) helps to determine their location on the continuums: for example, how often they are mobile and how much they can be mobile. The article draws on interviews in Poland with Ukrainians and Polish return migrants to show how (former) migrants conceptualise shared Ukrainian-Polish migranthood along these three continuums.

Objective: The hypothalamus regulates feeding and glucose homeostasis through the balanced action of different neuropeptides, which are cleaved and activated by the proprotein convertases PC1/3 and PC2. However, the recent association of polymorphisms in the proprotein convertase FURIN with type 2 diabetes, metabolic syndrome, and obesity, prompted us to investigate the role of FURIN in hypothalamic neurons controlling glucose and feeding. Methods: POMC-Cre+/− mice were bred with Furinfl/fl mice to generate conditional knockout mice with Furin-deletion in neurons expressing proopiomelanocortin (POMCFurKO), and Furinfl/fl mice were used as controls. POMCFurKO and controls were periodically monitored on both normal chow diet and high fat diet (HFD) for body weight and glucose tolerance by established in-vivo procedures. Food intake was measured in HFD-fed FurKO and controls. Hypothalamic Pomc mRNA was measured by RT-qPCR. ELISAs quantified POMC protein and resulting peptides in the hypothalamic extracts of POMCFurKO mice and controls. The in-vitro processing of POMC was studied by biochemical techniques in HEK293T and CHO cell lines lacking FURIN. Results: In control mice, Furin mRNA levels were significantly upregulated on HFD feeding, suggesting an increased demand for FURIN activity in obesogenic conditions. Under these conditions, the POMCFurKO mice were hyperphagic and had increased body weight compared to Furinfl/fl mice. Moreover, protein levels of POMC were elevated and ACTH concentrations markedly reduced. Also, the ratio of α-MSH/POMC was decreased in POMCFurKO mice compared to controls. This indicates that POMC processing was significantly reduced in the hypothalami of POMCFurKO mice, highlighting for the first time the involvement of FURIN in the cleavage of POMC. Importantly, we found that in vitro, the first stage in processing where POMC is cleaved into proACTH was achieved by FURIN but not by PC1/3 or the other proprotein convertases in cell lines lacking a regulated secretory pathway. Conclusions: These results suggest that FURIN processes POMC into proACTH before sorting into the regulated secretory pathway, challenging the dogma that PC1/3 and PC2 are the only convertases responsible for POMC cleavage. Furthermore, its deletion affects feeding behaviors under obesogenic conditions.

Abstract Glucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modify peripheral metabolism. Therefore, the aim of this study was to examine the metabolic effects of chronic treatment with the GC corticosterone (Cort, 75 μg/ml in drinking water) in mice lacking the glucocorticoid receptor (GR) on AgRP neurons. Female AgRP-GR KO mice had delayed onset of Cort-induced hyperphagia. However, AgRP-GR KO had little impact on the increased body weight or adiposity seen with 3 weeks Cort treatment. Cort caused hepatic steatosis in control mice, but in Cort treated female AgRP-GR KO mice there was a 25% reduction in liver lipid content and lower plasma triglycerides. Additionally, Cort treatment led to hyperinsulinaemia, but compared to controls, Cort-treated AgRP-GR KO mice had both lower fasting insulin levels and lower insulin levels during a glucose tolerance test. In conclusion, these data indicate that GCs do act through AgRP neurons to contribute, at least in part, to the adverse metabolic consequences of chronic GC treatment.

Objective: Glucocorticoids (GCs) are widely prescribed medications that are well recognized to cause adverse metabolic effects including hyperphagia, obesity, and hyperglycemia. These effects have been recapitulated in a murine model of GC excess, and we hypothesize that they are mediated, in part, through central mechanisms. This study aimed to identify genes in the hypothalamic arcuate nucleus (ARC) that are altered with GC treatment and evaluate their contribution to GC-induced metabolic abnormalities. Methods: Corticosterone (Cort; 75 μg/ml) was administered in the drinking water to male C57Bl/6J mice for 2 days or 4 weeks. Phenotypic analysis of each group was undertaken and central and peripheral tissues were collected for biochemical and mRNA analyses. Arcuate nuclei were isolated by laser capture microdissection and tissue analyzed by RNA-seq. Results: RNA-seq analysis of ARC tissue from 4 week Cort treated mice revealed 21 upregulated and 22 downregulated genes at a time when mice had increased food intake, expansion of adipose tissue mass, and insulin resistance. In comparison, after 2 days Cort treatment, when the main phenotypic change was increased food intake, RNA-seq identified 30 upregulated and 16 downregulated genes. Within the genes altered at 2 days were a range of novel genes but also those known to be regulated by GCs, including Fkbp5, Mt2, Fam107a, as well as some involved in the control of energy balance, such as Agrp, Sepp1, Dio2, and Nmb. Of the candidate genes identified by RNA-seq, type-II iodothyronine deiodinase (Dio2) was chosen for further investigation as it was increased (2-fold) with Cort, and has been implicated in the control of energy balance via the modulation of hypothalamic thyroid hormone availability. Targeted knockdown of Dio2 in the MBH using AAV-mediated CRISPR-Cas9 produced a mild attenuation in GC-induced brown adipose tissue weight gain, as well as a 56% reduction in the GC-induced increase in Agrp. However, this conferred no protection from GC-induced hyperphagia, obesity, or hyperglycemia. Conclusions: This study identified a comprehensive set of genes altered by GCs in the ARC and enabled the selection of key candidate genes. Targeted knockdown of hypothalamic Dio2 revealed that it did not mediate the chronic GC effects on hyperphagia and hyperglycemia. Keywords: Glucocorticoid, Arcuate nucleus, RNA-Seq, Dio2, CRISPR-Cas9

Our article considers social remittances and social change in Central and Eastern Europe. We show how migration scholarship can be embedded into the wider study of social processes and relations. ‘Social remitting’ sometimes seems to be little more than a slippery catchphrase; however, this article defends the concept. If it is defined carefully and used cautiously, it should help the researcher to think about what, in addition to money, is sent from one society to another and exactly how, thus shedding light on important and insufficiently studied aspects of migration. A close-up view of the processes by which ideas, practices, norms, values and, according to some definitions, social capital and social skills are transferred by migrants across international borders helps researchers to understand more precisely how migration contributes to social change or, in some cases, prevents it from occurring. Our article reviews some of the most interesting arguments and findings presented recently by other scholars and discusses aspects of social remitting which particularly interested us in our own research. The context of our research is social change in Poland: we attempt to understand how migration has contributed to wider patterns of social change since 1989 and exactly how it intertwines with other social trends and globalisation influences. This entails a careful focus on both structural conditions and agency and therefore on social remittances.

Sixty undergraduate students made category membership decisions for each of 132 candidate exemplar-category name pairs (e.g., chess – Sports) in each of two separate sessions. They were frequently inconsistent from one session to the next, both for nominal categories such as Sports and Fish, and ad hoc categories such as Things You Rescue from a Burning House. A mixture model analysis revealed that several of these inconsistencies could be attributed to criterial vagueness: participants adopting different criteria for membership in the two sessions. This finding indicates that categorization is a probabilistic process, whereby the conditions for applying a category label are not invariant. Individuals have various functional meanings of nominal categories at their disposal and entertain competing goals for ad hoc categories.

Objective: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated. Methods: We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from human pluripotent stem cells (hPSCs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the sequence and quantify the production of hypothalamic neuropeptides, including those derived from POMC. Results: In both in vitro and in vivo hypothalamic cells, LC-MS/MS revealed the sequence of hundreds of neuropeptides as a resource for the field. Although the existence of β-melanocyte stimulating hormone (MSH) is controversial, we found that both this peptide and desacetyl α-MSH (d-α-MSH) were produced in considerable excess of acetylated α-MSH. In hPSC-derived hypothalamic neurons, these POMC derivatives were appropriately trafficked, secreted, and their production was significantly (P

Dishonesty is an intriguing phenomenon, studied extensively across various disciplines due to its impact on people’s lives as well as society in general. To examine dishonesty in a controlled setting, researchers have developed a number of experimental paradigms. One of the most popular approaches in this regard, is the matrix task, in which participants receive matrices wherein they have to find two numbers that sum to 10 (e.g., 4.81 and 5.19), under time pressure. In a next phase, participants need to report how many matrices they had solved correctly, allowing them the opportunity to cheat by exaggerating their performance in order to get a larger reward. Here, we argue, both on theoretical and empirical grounds, that the matrix task is ill-suited to study dishonest behavior, primarily because it conflates cheating with honest mistakes. We therefore recommend researchers to use different paradigms to examine dishonesty, and treat (previous) findings based on the matrix task with due caution.

The scattering of lower hybrid (LH) waves due to scrape-off layer filaments is investigated. It is revealed that scattering can account for the LH spectral gap without any ad hoc modification to the wave-spectrum. This is shown using a multiscale simulation approach which allows, for the first time, the inclusion of full-wave scattering physics in ray-tracing/Fokker–Planck calculations. In this approach, full-wave scattering probabilities are calculated for a wave interacting with a statistical ensemble of filaments. These probabilities are coupled to ray-tracing equations using radiative transfer theory. This allows the modeling of scattering along the entire ray-trajectory, which can be important in the multi-pass regime. Simulations are conducted for LH current drive (LHCD) in Alcator C-Mod, resulting in excellent agreement with experimental current and hard x-ray profiles. A region in filament parameter space is identified in which the impact of scattering on LHCD is saturated. Such a state coincides with experimental LHCD measurements, suggesting saturation indeed occurs in C-Mod, and therefore the exact statistical properties of the filaments are not important.

The COVID-19 lockdown in the UK during the spring of 2020 led to the closure of schools and school premises to most students, including complementary school pupils; yet while the lockdown in autumn 2020 allowed state schools to remain open, Polish complementary schools found themselves in an ambiguous position. This paper explores the experiences of eight Polish complementary school heads, focusing on their response to lockdown and the measures they took to provide online learning through the year. The paper also examines how changing lockdown policies impacted the running of their schools. Key findings suggest a creative approach was taken to learning, and that students were eager to respond. Meanwhile, there was increasing cooperation between different schools and support from external organisations. However, the challenges of online learning were also highlighted. Additionally, heads expressed concern about student retention and recruitment, and the potential long-term effects on their school. There was also discussion about the position of complementary schools within the broader education system. The paper argues that these findings highlight questions of inequality between the complementary and mainstream sectors, which has been exacerbated by the pandemic.

BACKGROUND:Small cell lung cancer (SCLC) is an extremely aggressive disease, commonly displaying therapy-resistant relapse. We have previously identified neuroendocrine and epithelial phenotypes in SCLC tumours and the neuroendocrine marker, pro-opiomelanocortin (POMC), correlated with worse overall survival in patients. However, the effect of treatment on these phenotypes is not understood. The current study aimed to determine the effect of repeated irradiation treatment on SCLC cell phenotype, focussing on the neuroendocrine marker, POMC. RESULTS:Human SCLC cells (DMS 79) were established as subcutaneous xenograft tumours in CBA nude mice and then exposed to repeated 2Gy irradiation. In untreated animals, POMC in the blood closely mirrored tumour growth; an ideal characteristic for a circulating biomarker. Following repeated localised irradiation in vivo, circulating POMC decreased (p< 0.01), in parallel with a decrease in tumour size, but remained low even when the tumours re-established. The excised tumours displayed reduced and distinctly heterogeneous expression of POMC compared to untreated tumours. There was no difference in the epithelial marker, cytokeratin. However, there were significantly more N-cadherin positive cells in the irradiated tumours. To investigate the tumour response to irradiation, DMS79 cells were repeatedly irradiated in vitro and the surviving cells selected. POMC expression was reduced, while mesenchymal markers N-cadherin, β1-integrin, fibroblast-specific protein 1, β-catenin and Zeb1 expression were amplified in the more irradiation-primed cells. There were no consistent changes in epithelial marker expression. Cell morphology changed dramatically with repeatedly irradiated cells displaying a more elongated shape, suggesting a switch to a more mesenchymal phenotype. CONCLUSIONS:In summary, POMC biomarker expression and secretion were reduced in SCLC tumours which regrew after irradiation and in repeatedly irradiation (irradiation-primed) cells. Therefore, POMC was no longer predictive of tumour burden. This highlights the importance of fully evaluating biomarkers during and after therapy to assess clinical utility. Furthermore, the gain in mesenchymal characteristics in irradiated cells could be indicative of a more invasive phenotype.

Human small cell lung cancer (SCLC) is highly aggressive, and quickly develops resistance to therapy. SCLC cells are typically insensitive to glucocorticoids due to impaired glucocorticoid receptor (GR) expression. This is important as we have previously shown that expression of a GR transgene induces cell death in-vitro, and inhibits tumor growth in-vivo. However, the underlying mechanism for loss of GR expression is unknown. The SCLC cell line, DMS79, has low GR expression, compared to non-SCLC cell lines and normal bronchial epithelial cells. Retroviral GR expression in DMS79 cells caused activation of the apoptotic pathway as evidenced by marked induction of caspase-3 activity. Methylation analysis of the GR promoter revealed some methylation in the 1D, and 1E promoters of the GR gene, however the ubiquitous constitutively active 1C promoter was heavily methylated. In the 1C promoter there was a highly significant increase in DNA methylation in a panel of 14 human SCLC cell lines compared to a mixed panel of GR expressing, and non-expressing cell lines, and to peripheral blood mononuclear cells. Furthermore, within the panel of SCLC cell lines there was a significant negative correlation seen between methylation of the 1C promoter, and GR protein expression. Reversal of GR gene methylation with DNA methyltransferase inhibition caused increased GR mRNA and protein expression in SCLC but not non-SCLC cells. This resulted in increased Gc sensitivity, decreased Bcl-2 expression and increased caspase-3 activity in SCLC cells. These data suggest that DNA methylation decreases GR gene expression in human SCLC cells, in a similar manner to that for conventional tumor suppressor genes.

Abstract Introduction ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial’s innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. Aim To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. Methods PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. Results PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise ‘initial information leaflet’ was developed to be sent with the initial invitations, with the ‘full’ information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. Conclusions PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial.