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The aim of the current research was to provide recommendations to facilitate the development and use of anchoring vignettes (AVs) for cross-cultural comparisons in education. Study 1 identified six factors leading to order violations and ties in AV responses based on cognitive interviews with 15-year-old students. The factors were categorized into three domains: varying levels of AV format familiarity, differential interpretations of content, and individual differences in processing information. To inform the most appropriate approach to treat order violations and re-scaling method, Study 2 conducted Monte Carlo simulations with the manipulation of three factors and incorporation of five responses styles. Study 2 found that the AV approach improved accuracy in score estimation by successfully controlling for response styles. The results also revealed the reordering approach to treat order violations produced the most accurate estimation combined with the re-scaling method assigning the middle value among possible scores. Along with strategies to develop AVs, strengths and limitations of the implemented nonparametric AV approach were discussed in comparison to item response theory modeling for response styles.

Williams syndrome (WS) is a rare genetic disorder with multisystem involvement associated with hypercalcemia. The cause of this hypercalcemia is poorly understood and while primarily associated with WS children, it is also observed in adults. A 51-year-old woman with intellectual disability, renal insufficiency, recurrent pancreatitis, and intermittent hypercalcemia despite partial parathyroidectomy presented with hypercalcemia to 14 mg/dL (3.49 mmol/L; normal 8.6-10.5 mg/dL [2.12-2.62 mmol/L]) at routine follow-up. Laboratory testing was notable for acute-on-chronic renal failure with unremarkable vitamin D, urine calcium, and parathyroid hormone. She presented to the emergency department and was admitted. Treatment with bisphosphonates, calcitonin, and intravenous fluids decreased calcium to 9.4 mg/dL (2.35 mmol/L) and improved kidney function. She was discharged with recommendations for increased oral hydration, a low-calcium diet, and outpatient follow-up. Her phenotype was suspicious for WS, later confirmed with genetic testing. This case exemplifies both the increased risk of hypercalcemia in WS adults and the need to consider WS in hypercalcemic adults with intellectual disability. It also serves to illustrate the importance of recognizing WS features in potentially undiagnosed adults and reviews guidelines for hypercalcemia surveillance and management in WS adults. [ABSTRACT FROM AUTHOR]

Complications of diabetes affect tissues throughout the body, including the central nervous system. Epidemiological studies show that diabetic patients have an increased risk of depression, anxiety, age-related cognitive decline, and Alzheimer's disease. Mice lacking insulin receptor (IR) in the brain or on hypothalamic neurons display an array of metabolic abnormalities; however, the role of insulin action on astrocytes and neurobehaviors remains less well studied. Here, we demonstrate that astrocytes are a direct insulin target in the brain and that knockout of IR on astrocytes causes increased anxiety- and depressive-like behaviors in mice. This can be reproduced in part by deletion of IR on astrocytes in the nucleus accumbens. At a molecular level, loss of insulin signaling in astrocytes impaired tyrosine phosphorylation of Munc18c. This led to decreased exocytosis of ATP from astrocytes, resulting in decreased purinergic signaling on dopaminergic neurons. These reductions contributed to decreased dopamine release from brain slices. Central administration of ATP analogs could reverse depressive-like behaviors in mice with astrocyte IR knockout. Thus, astrocytic insulin signaling plays an important role in dopaminergic signaling, providing a potential mechanism by which astrocytic insulin action may contribute to increased rates of depression in people with diabetes, obesity, and other insulin-resistant states., Introduction Over the past decade it has become clear that the brain is an insulin-sensitive organ. Insulin receptors (IRs) are widely distributed in the brain (1). Intracerebroventricular insulin infusion reduces [...]

Glucocorticoids are a powerful tool used to treat a range of human illnesses, including autoimmune diseases and cancer, and to prevent rejection following organ transplantation. While lifesaving for many, they come with a steep price, often leading to obesity, insulin resistance, diabetes, and osteoporosis. In this issue of the JCI, Brennan-Speranza and colleagues provide evidence that the osteoblast-derived peptide osteocalcin is one of the drivers of the metabolic derangements associated with glucocorticoid therapy. This novel mechanism could open up new avenues for the treatment of these disorders., Glucocorticoids act by binding to the glucocorticoid receptor and promoting binding of the receptor to glucocorticoid response elements or association with other transcription factors, such as AP1, leading to either [...]

Alzheimer's disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, tau tangles, inflammation, and loss of cognitive function. Genetic variation in a cholesterol transport protein, apolipoprotein E (apoE), is the most common genetic risk factor for sporadic AD. In vitro evidence suggests that apoE links to Aβ production through nanoscale lipid compartments (lipid clusters), but its regulation in vivo is unclear. Here, we use superresolution imaging in the mouse brain to show that apoE utilizes astrocyte-derived cholesterol to specifically traffic neuronal amyloid precursor protein (APP) in and out of lipid clusters, where it interacts with β- and γ-secretases to generate Aβ-peptide. We find that the targeted deletion of astrocyte cholesterol synthesis robustly reduces amyloid and tau burden in a mouse model of AD. Treatment with cholesterol-free apoE or knockdown of cholesterol synthesis in astrocytes decreases cholesterol levels in cultured neurons and causes APP to traffic out of lipid clusters, where it interacts with α-secretase and gives rise to soluble APP-α (sAPP-α), a neuronal protective product of APP. Changes in cellular cholesterol have no effect on α-, β-, and γ-secretase trafficking, suggesting that the ratio of Aβ to sAPP-α is regulated by the trafficking of the substrate, not the enzymes. We conclude that cholesterol is kept low in neurons, which inhibits Aβ accumulation and enables the astrocyte regulation of Aβ accumulation by cholesterol signaling. [ABSTRACT FROM AUTHOR]