Teaching Them before We Teach:The Effectiveness of Conducting Classroom Experiments before Teaching the Underlying Theory

This study examines the effectiveness of classroom experiments conducted before the relevant theories were taught. The experiments were used to provide students with first-hand experience of decision-making under various rivalry settings and to demonstrate several key predictions of oligopoly models. Statistical methods were used to analyze the effectiveness of these experiments in helping students master the concepts covered by the experiments. In general, students had a positive experience in the process and they found the experiments useful in stimulating their interest and helping improve their understanding of the relevant theories. Statistically, students who took part in the experiments performed significantly better in an exam question on oligopoly markets

Electronic Solution for Low Census Requests

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Using Adherence-Contingent Rebates on Chronic Disease Treatment Costs to Promote Medication Adherence: Results from a Randomized Controlled Trial

Background: Poor adherence to medications is a global public health concern with substantial health and cost implications, especially for chronic conditions. In the USA, poor adherence is estimated to cause 125,000 deaths and cost $US100 Billion annually. The most successful adherence-promoting strategies that have been identified so far have moderate effect, are relatively costly, and raise availability, feasibility, and/or scalability issues. Objective: The main objective of SIGMA (Study on Incentives for Glaucoma Medication Adherence) was to measure the effectiveness on medication adherence of a novel incentive strategy based on behavioral economics that we refer to as adherence-contingent rebates. These rebates offered patients a near-term benefit while leveraging loss aversion and regret nd increasing the salience of adherence. Methods: IGMA is a 6-month randomized, controlled, open-label, single-center superiority trial with two parallel arms. total of 100 non-adherent glaucoma patients from the Singapore National Eye Centre were randomized into intervention (adherence-contingent rebates) and usual care (no rebates) arms in a 1:1 ratio. The primary outcome was the mean change from baseline in percentage of adherent days at Month 6. The trial registration number is NCT02271269 and a detailed study protocol has been published elsewhere. Findings: We found that participants who were offered adherence-contingent rebates were adherent to all their edications on 73.1$US5.94 as of 2 November 2017) per month during the intervention period. Conclusion: This study shows that simultaneously leveraging several insights from behavioral economics can significantly improve medication adherence rates. The relatively low cost of the rebates and significant health and cost implications of medication non-adherence suggest that this strategy has the potential to cost-effectively improve health outcomes for many conditions

ATP Hydrolysis Is Critically Required for Function of Caᵥ1.3 Channels in Cochlear Inner Hair Cells via Fueling Ca²⁺ Clearance

Sound encoding is mediated by Ca²⁺ influx-evoked release of glutamate at the ribbon synapse of inner hair cells. Here we studied the role of ATP in this process focusing on Ca²⁺ current through Caᵥ1.3 channels and Ca²⁺ homeostasis in mouse inner hair cells. Patch-clamp recordings and Ca²⁺ imaging demonstrate that hydrolyzable ATP is essential to maintain synaptic Ca²⁺ influx in inner hair cells via fueling Ca²⁺-ATPases to avoid an increase in cytosolic [Ca²⁺] and subsequent Ca²⁺/calmodulin-dependent inactivation of Caᵥ1.3 channels

Nanomedicine for glaucoma: liposomes provide sustained release of latanoprost in the eye

Purpose: To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye. Methods: We fabricated latanoprost-loaded egg-phosphatidylcholine (EggPC) liposomes using the film hydration technique. The delivery vehicles were nano-sized (Z avg = 109 ± 18 nm), had a narrow poly dispersity index (PDI = 0.19 ± 0.04), and a very high loading efficiency (94% ± 5%). Based on in vitro data, we evaluated this formulation for lowering intraocular pressure (IOP) in rabbit eyes. Following a single subconjunctival injection of the latanoprost loaded formulation, the eyes were clinically monitored and the IOP recorded. Results: Latanoprost-loaded EggPC liposomes demonstrated a high drug/lipid mole ratio of 0.181, remained stable for at least 6 months on storage (4°C), and at least 1 month at 25°C. A slow and sustained release of 60% of latanoprost was achieved by 14 days in the in vitro release study. The same formulation demonstrated a greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days (4.8 ± 1.5 vs 2.5 ± 0.9 mmHg; P < 0.001). No signs of inflammation were evident in the eyes from slit-lamp examination analysis. Conclusion: The loading required for a long-term sustained delivery of latanoprost for up to 90 days in the rabbit eyes was achieved with EggPC liposomes. A single injection of latanoprost-loaded EggPC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.Published versio

Puberty enables oestradiol‐induced progesterone synthesis in female mouse hypothalamic astrocytes

The development of oestrogen positive feedback is a hallmark of female puberty. Both oestrogen and progesterone signalling are required for the functioning of this neuroendocrine feedback loop but the physiological changes that underlie the emergence of positive feedback remain unknown. Only after puberty does oestradiol (E2) facilitate progesterone synthesis in the rat female hypothalamus (neuroP), an event critical for positive feedback and the LH surge. We hypothesize that prior to puberty, these astrocytes have low levels of membrane oestrogen receptor alpha (ERα), which is needed for facilitation of neuroP synthesis. Thus, we hypothesized that prepubertal astrocytes are unable to respond to E2 with increased neuroP synthesis due a lack of membrane ERα. To test this, hypothalamic tissues and enriched primary hypothalamic astrocyte cultures were acquired from prepubertal (postnatal week 3) and post-pubertal (week 8) female mice. E2-facilitated neuroP was measured in the hypothalamus pre- and post-puberty, and hypothalamic astrocyte responses were measured after treatment with E2. Prior to puberty, E2-facilitated neuroP synthesis did not occur in the hypothalamus, and mERα expression was low in hypothalamic astrocytes, but E2-facilitated neuroP synthesis in the rostral hypothalamus and mERα expression increased post-puberty. The increase in mERα expression in hypothalamic astrocytes corresponded with a post-pubertal increase in caveolin-1 protein, PKA phosphorylation, and a more rapid [Ca2+ ]i flux in response to E2. Together, results from the present study indicate that E2-facilitated neuroP synthesis occurs in the rostral hypothalamus, develops during puberty, and corresponds to a post-pubertal increase in mERα levels in hypothalamic astrocytes

Cytotoxic and Apoptotic Effects of Pinostilbene and Bortezomib Combination Treatment on Human Multiple Myeloma Cells.

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy. Resveratrol (RES), a phenolic compound found in grapes, has been shown to inhibit MM cell growth. We sought to identify a synergistic combination of BTZ with a RES derivative and analyze the effects on reducing viability and inducing apoptosis in human MM cells. BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3 in a dose-dependent manner. The combination of 5 nM BTZ and 5 μM PIN was identified to have synergistic cytotoxic effects in MM RPMI 8226 cells. MM RPMI 8226 cells treated with this combination for 24 h showed increased cleaved PARP1 and caspase-3 expression and higher percentages of apoptotic cells versus cells treated with the individual compounds alone. The treatment also showed increased apoptosis induction in MM RPMI 8226 cells co-cultured with human bone marrow stromal HS-5 cells in a Transwell model used to mimic the bone marrow microenvironment. Expression of oxidative stress defense proteins (catalase, thioredoxin, and superoxide dismutase) in RPMI 8226 cells were reduced after 24 h treatment, and cytotoxic effects of the treatment were ameliorated by antioxidant N-acetylcysteine (NAC), suggesting the treatment impacts antioxidant levels in RPMI 8226 cells. Our results suggest that this combination of BTZ and PIN decreases MM cell viability synergistically by inducing apoptosis and oxidative stress in MM cells