Boundary exchange completes the marine Pb cycle jigsaw.

Material fluxes at the land-ocean interface impact seawater composition and global cycling of elements. However, most attention has been focused on the fluvial dissolved fluxes. For elements like lead (Pb), whose fluvial particulate flux into the ocean is two orders of magnitude higher than the dissolved counterpart, the role of particulates in elemental cycling is potentially important but currently less appreciated. Using both chemical analyses on samples collected from around equatorial Southeast Asia and model simulations, we show that particulate-dissolved exchange is an important mechanism controlling the concentration and isotopic composition of dissolved Pb in the ocean. Our model indicates that Pb contributed from particulate-dissolved exchange at ocean boundaries is larger than, or at least comparable to, other major Pb sources to the seawater before the Anthropocene, when the anthropogenic Pb was absent. Our work highlights the importance of boundary exchange in understanding marine element cycling and weathering-climate feedback.

Effects of climate change on forest plantation productivity in Chile.

Forest plantations in Chile occupy more than 2.2 million ha and are responsible for 2.1% of the GDP of the country's economy. The ability to accurately predictions of plantations productivity under current and future climate has an impact can enhance on forest management and industrial wood production. The use of process-based models to predict forest growth has been instrumental in improving the understanding and quantifying the effects of climate variability, climate change, and the impact of atmospheric CO2 concentration and management practices on forest growth. This study uses the 3-PG model to predict future forest productivity Eucalyptus globulus and Pinus radiata. The study integrates climate data from global circulation models used in CMIP5 for scenarios RCP26 and RCP85, digital soil maps for physical and chemical variables. Temporal and spatial tree growth inventories were used to compare with the 3-PG predictions. The results indicated that forest productivity is predicted to potentially increase stand volume (SV) over the next 50 years by 26% and 24% for the RCP26 scenario and between 73% and 62% for the RCP85 scenario for E. globulus and P. radiata, respectively. The predicted increases can be explained by a combination of higher level of atmospheric CO2 , air temperatures closer to optimum than current, and increases in tree water use efficiency. If the effect of CO2 is not considered, the predicted differences of SV for 2070 are 16% and 14% for the RCP26 scenario and 22% and 14% for RCP85 for the two species. While shifts in climate and increasing CO2 are likely to benefit promote higher productivity, other factors such as lack insufficient availability of soil nutrients, events such as increasing frequency and duration of droughts, longer periods of extreme temperatures, competing vegetation, and occurrence of new pests and diseases may compromise these potential gains.

Implementation of team-based learning (TBL) in a second year medical school course: does prior experience with TBL improve the impact of this pedagogy?

BACKGROUND: We have shown that use of Team-based learning (TBL) in a first-year Infectious Diseases (ID) course improved final examination and course performance. Therefore, we implemented TBL in the second-year Women's Health (WH) course to improve acquisition of course content. We hypothesized that prior experience with TBL in the first-year of medical school would lead to a strong correlation between TBL performance in the first and second years. METHODS: Our study is a retrospective review of student TBL and final examination performance in the ID and WH courses. The ID course has weekly TBL exercises that cover all course material, while the WH course has one TBL that covers a small portion of the course material. Final examination and TBL individual readiness assurance test (iRAT) scores in the ID and WH courses from three classes (n = 226) were obtained with institutional review board approval. Statistical analyses were performed including comparisons of means and correlation studies. RESULTS: Average WH iRAT scores were significantly higher than ID iRAT scores (9.19 vs. 7.40,p < 0.01), and iRAT scores in both courses were highly correlated (r = 0.35,p < 0.01). When stratifying students based on WH course performance, in struggling students, iRAT but not final examination scores were higher in the WH course than the ID course (8.73 vs. 7.00,p < 0.01 and 82.45 vs. 80.51,p > 0.05, respectively). CONCLUSIONS: Our results suggest that prior experience with TBL improves TBL iRAT scores, especially in struggling students. Prior TBL experience is also associated with consistent iRAT performance between first- and second-year courses in high performing students.

Weekly team-based learning scores and participation are better predictors of successful course performance than case-based learning performance: role of assessment incentive structure.

BACKGROUND: Incentives for preparation and participation in case-based (CBL) and team-based learning (TBL) differ by virtue of differences in assessment, allowing us to evaluate the role these incentives play in preparation and participation in these activities as well as overall course performance. METHODS: Weekly TBL and CBL participation and performance as well as performance on the course final examination were recorded. Student participation was quantified and correlated with: (1) CBL preparation, participation, teamwork and completion of learning objectives scores, and (2) TBL individual readiness assurance test (iRAT) scores. RESULTS: Student final examination scores (n = 95) were more strongly correlated with TBL than CBL performance. No significant correlation was found between iRAT and CBL scores. Student participation was measured in 3 CBL groups (8 students/group) and 4 TBL teams (6 students/team). TBL participation was more strongly correlated with final examination scores than CBL participation. TBL participation was also correlated with iRAT scores. CBL scores for preparation, participation, teamwork and completion of learning objectives did not significantly correlate with iRAT scores or TBL participation. CONCLUSION: These results suggest that the assessment incentives and methods used in TBL result in student performance that better predicts performance on summative examinations.

[Cognitive and legal aspects in older people]. / Aspectos cognitivos y legales en personas mayores: "Sano Juicio".

In Chile, 7.1% of people aged over 60 years have some type of cognitive disorder. The frequency of the latter increases to 13% in people between 75-79 years and 36.2% in people over 85 years. The concept of mild cognitive impairment (MCI) and dementia have evolved over time. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term minor and major neurocognitive disorder, replacing the DCL and dementia respectively. Major cognitive disorder impairs functional performance while minor disorders does not. There is an arbitrary discrimination against the elderly. A form of discrimination is the request made by some notaries of a medical certification of the cognitive function for older people willing to carry out a legal procedure. This request has the sole effect of pre-establishing evidence in favor of the notary and not protecting the testator or the vulnerable person. Assessing the ability of older people to care for themselves and their possessions has important implications for them and their families, since there is a serious risk of prejudice when someone is declared as disabled. Thus, considering the epidemiology of cognitive disorders in our country we propose a series of legal and medical discussion points aimed to protect autonomy and to protect individuals and their possessions when they have difficulties to control their decisions.

First year medical student performance on weekly team-based learning exercises in an infectious diseases course: insights from top performers and struggling students.

BACKGROUND: In Team-Based Learning (TBL) preparation of relevant coursework during self-directed learning time is evaluated by the individual readiness assurance test (iRAT). We recently reported that student performance on iRATs is strongly correlated with final examination scores in an infectious diseases (ID) course. We now investigated how student preparation for each individual iRAT exercise relates to course performance. METHODS: Two-hundred and sixty medical students were enrolled in this three-year study. Student TBL iRAT scores were collected and correlated with final examination scores using Kruskal-Wallis One-Way ANOVA and Newman-Keul's statistical methods. RESULTS: Students performing in the upper and middle 33rd percentile on the final examination showed highly significant (p < 0.01) weekly improvements in their iRAT scores. However, students performing in the lower 33rd percentile did not show improvement in their iRAT scores until the last week of the course. Although there was a highly significant correlation between final examination and iRAT scores amongst all students participating in the study, this correlation was stronger in students performing in the lower 33rd percentile. CONCLUSIONS: Our data suggest that students who do not consistently prepare for TBL, as evidenced by low iRAT scores, exhibit poorer performance on the final examination. This lack of preparation likely interferes with the efficacy of this learning method. iRAT scores can also be used for early identification of struggling students in need of additional supports. Additionally, changes in TBL incentive structure may provide more tangible rewards for pre-class preparation in particular for struggling students.

Evaluation of the role of incentive structure on student participation and performance in active learning strategies: A comparison of case-based and team-based learning.

BACKGROUND: Student participation is important for the success of active learning strategies, but participation is often linked to the level of preparation. At our institution, we use two types of active learning activities, a modified case-based learning exercise called active learning groups (ALG) and team-based learning (TBL). These strategies have different assessment and incentive structures for participation. Non-cognitive skills are assessed in ALG using a subjective five-point Likert scale. In TBL, assessment of individual student preparation is based on a multiple choice quiz conducted at the beginning of each session. METHODS: We studied first-year medical student participation and performance in ALG and TBL as well as performance on course final examinations. RESULTS: Student performance in TBL, but not in ALG, was strongly correlated with final examination scores. Additionally, in students who performed in the upper 33rd percentile on the final examination, there was a positive correlation between final examination performance and participation in TBL and ALG. This correlation was not seen in students who performed in the lower 33rd percentile on the final examinations. CONCLUSIONS: Our results suggest that assessments of medical knowledge during active learning exercises could supplement non-cognitive assessments and could be good predictors of performance on summative examinations.

Lead isotope exchange between dissolved and fluvial particulate matter: a laboratory study from the Johor River estuary.

Atmospheric aerosols are the dominant source of Pb to the modern marine environment, and as a result, in most regions of the ocean the Pb isotopic composition of dissolved Pb in the surface ocean (and in corals) matches that of the regional aerosols. In the Singapore Strait, however, there is a large offset between seawater dissolved and coral Pb isotopes and that of the regional aerosols. We propose that this difference results from isotope exchange between dissolved Pb supplied by anthropogenic aerosol deposition and adsorbed natural crustal Pb on weathered particles delivered to the ocean by coastal rivers. To investigate this issue, Pb isotope exchange was assessed through a closed-system exchange experiment using estuarine waters collected at the Johor River mouth (which discharges to the Singapore Strait). During the experiment, a known amount of dissolved Pb with the isotopic composition of NBS-981 (206Pb/207Pb = 1.093) was spiked into the unfiltered Johor water (dissolved and particulate 206Pb/207Pb = 1.199) and the changing isotopic composition of the dissolved Pb was monitored. The mixing ratio of the estuarine and spike Pb should have produced a dissolved 206Pb/207Pb isotopic composition of 1.161, but within a week, the 206Pb/207Pb in the water increased to 1.190 and continued to increase to 1.197 during the next two months without significant changes of the dissolved Pb concentration. The kinetics of isotope exchange was assessed using a simple Kd model, which assumes multiple sub-reservoirs within the particulate matter with different exchange rate constants. The Kd model reproduced 56% of the observed Pb isotope variance. Both the closed-system experiment and field measurements imply that isotope exchange can be an important mechanism for controlling Pb and Pb isotopes in coastal waters. A similar process may occur for other trace elements.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

G-protein receptor kinase 5 regulates the cannabinoid receptor 2-induced up-regulation of serotonin 2A receptors.

We have recently reported that cannabinoid agonists can up-regulate and enhance the activity of serotonin 2A (5-HT2A) receptors in the prefrontal cortex (PFCx). Increased expression and activity of cortical 5-HT2A receptors has been associated with neuropsychiatric disorders, such as anxiety and schizophrenia. Here we report that repeated CP55940 exposure selectively up-regulates GRK5 proteins in rat PFCx and in a neuronal cell culture model. We sought to examine the mechanism underlying the regulation of GRK5 and to identify the role of GRK5 in the cannabinoid agonist-induced up-regulation and enhanced activity of 5-HT2A receptors. Interestingly, we found that cannabinoid agonist-induced up-regulation of GRK5 involves CB2 receptors, ß-arrestin 2, and ERK1/2 signaling because treatment with CB2 shRNA lentiviral particles, ß-arrestin 2 shRNA lentiviral particles, or ERK1/2 inhibitor prevented the cannabinoid agonist-induced up-regulation of GRK5. Most importantly, we found that GRK5 shRNA lentiviral particle treatment prevented the cannabinoid agonist-induced up-regulation and enhanced 5-HT2A receptor-mediated calcium release. Repeated cannabinoid exposure was also associated with enhanced phosphorylation of CB2 receptors and increased interaction between ß-arrestin 2 and ERK1/2. These latter phenomena were also significantly inhibited by GRK5 shRNA lentiviral treatment. Our results suggest that sustained activation of CB2 receptors, which up-regulates 5-HT2A receptor signaling, enhances GRK5 expression; the phosphorylation of CB2 receptors; and the ß-arrestin 2/ERK interactions. These data could provide a rationale for some of the adverse effects associated with repeated cannabinoid agonist exposure.

Telangiectatic hyperplastic nodule associated with vascular malformation in a patient with chronic hepatitis B: radiologic and pathologic features.

Recognizing hepatocellular nodules that cannot be classified as typical for hepatocellular carcinoma, hepatocellular adenoma, or focal nodular hyperplasia is important, especially in a patient with high risk for hepatocellular carcinoma. The authors report a case of a 53-year-old man with chronic hepatitis B, who was referred to the hospital with a liver mass found on routine imaging follow-up. Abdominal ultrasound revealed a 2.4-cm hypoechoic lesion. Contrast computed tomography showed homogeneous arterial enhancement and mild hyperdensity on portal venous phase images. Due to the high risk for hepatocellular carcinoma, the patient underwent laparoscopic left lateral segmentectomy that revealed a 2.2-cm poorly defined red-brown lesion. The nodule was diagnosed as a hypervascular/telangiectatic hyperplastic hepatocellular nodule based on histopathologic findings and immunostaining profile with negative glutamine synthetase, diffuse positive CD34 highlighting hyperplastic endothelial cells along the telangiectatic sinusoids and dilated vascular channels, and CK7 and CK19 reactive normal bile ducts within the lesion.

Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5-HT(2A)) receptor activity via ERK1/2 signaling.

Recent behavioral studies suggest that nonselective agonists of cannabinoid receptors may regulate serotonin 2A (5-HT(2A)) receptor neurotransmission. Two cannabinoids receptors are found in brain, CB1 and CB2 receptors, but the molecular mechanism by which cannabinoid receptors would regulate 5-HT(2A) receptor neurotransmission remains unknown. Interestingly, we have recently found that certain cannabinoid receptor agonists can specifically upregulate 5-HT(2A) receptors. Here, we present experimental evidence that rats treated with a nonselective cannabinoid receptor agonist (CP 55,940, 50 µg/kg, 7 days) showed increases in 5-HT(2A) receptor protein levels, 5-HT(2A) receptor mRNA levels, and 5-HT(2A) receptor-mediated phospholipase C beta (PLCß) activity in prefrontal cortex (PFCx). Similar effects were found in neuronal cultured cells treated with CP 55,940 but these effects were prevented by selective CB2, but not selective CB1, receptor antagonists. CB2 receptors couple to the extracellular kinase (ERK) signaling pathway by Gα(i/o) class of G-proteins. Noteworthy, GP 1a (selective CB2 receptor agonist) produced a strong upregulation of 5-HT(2A) receptor mRNA and protein, an effect that was prevented by selective CB2 receptor antagonists and by an ERK1/2 inhibitor, PD 198306. In summary, our results identified a strong cannabinoid-induced upregulation of 5-HT(2A) receptor signaling in rat PFCx. Our cultured cell studies suggest that selective CB2 receptor agonists upregulate 5-HT(2A) receptor signaling by activation of the ERK1/2 signaling pathway. Activity of cortical 5-HT(2A) receptors has been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety and depression, and schizophrenia. Therefore, these results may provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to the pathophysiology of some cognitive and mood disorders in humans.

Cannabinoid agonists increase the interaction between ß-Arrestin 2 and ERK1/2 and upregulate ß-Arrestin 2 and 5-HT(2A) receptors.

We have recently reported that selective cannabinoid 2 (CB(2)) receptor agonists upregulate 5-HT(2A) receptors by enhancing ERK1/2 signaling in prefrontal cortex (PFCx). Increased activity of cortical 5-HT(2A) receptors has been associated with several neuropsychiatric disorders such as anxiety and schizophrenia. Here we examine the mechanisms involved in this enhanced ERK1/2 activation in rat PFCx and in a neuronal cell model. Sprague-Dawley rats treated with a non-selective cannabinoid agonist (CP55940, 50µg/kg, 7 days, i.p.) showed enhanced co-immunoprecipitation of ß-Arrestin 2 and ERK1/2, enhanced pERK protein levels, and enhanced expression of ß-Arrestin 2 mRNA and protein levels in PFCx. In a neuronal cell line, we found that selective CB(2) receptor agonists upregulate ß-Arrestin 2, an effect that was prevented by selective CB(2) receptor antagonist JTE-907 and CB(2) shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis, ERK1/2, and the AP-1 transcription factor also prevented the cannabinoid receptor-induced upregulation of ß-Arrestin 2. Our results suggest that sustained activation of CB(2) receptors would enhance ß-Arrestin 2 expression possibly contributing to its increased interaction with ERK1/2, thereby driving the upregulation of 5-HT(2A) receptors. The CB(2) receptor-mediated upregulation of ß-Arrestin 2 would be mediated, at least in part, by an ERK1/2-dependent activation of AP-1. These data could provide the rationale for some of the adverse effects associated with repeated cannabinoid exposure and shed light on some CB(2) receptor agonists that could represent an alternative therapeutic because of their minimal effect on serotonergic neurotransmission.

Effects of bile acid sequestration on hepatic steatosis in obese mice.

BACKGROUND. Bile acid sequestration (BAS) with resins has shown antidiabetic effects in both humans and animals. Since hepatic steatosis is commonly associated with type 2 diabetes mellitus and the effects of BAS on steatosis have not been explored in detail, we evaluated the effects of cholestyramine (CTM) administration on fatty liver development in the leptin-deficient obese mice. AIM. To study the effects of BAS on fatty liver development in obese (ob/ob) mice. MATERIAL AND METHODS. 4 week-old ob/ob mice (B6.V-Lepob/J, n = 4-6 per group) were fed with or without CTM (control group) during 8 weeks. Serum and biliary parameters, glucose tolerance test (GTT), hepatic triglyceride content, liver histology and hepatic gene expression of relevant genes related to bile secretion, lipid and glucose metabolism were assessed. RESULTS. Control 12-week-old mice exhibited marked obesity and hepatic steatosis. CTM administration expectedly determined a marked de-repression of 7-α-hydroxylase and decreased biliary bile acid secretion as well as improved GTT. CTM feeding showed no effects on hepatic triglyceride content or in the degree of steatosis on liver histology. CTM was associated with increased levels of serum alanine-aminotransferase. CONCLUSION. Although CTM administration positively affects glucose tolerance it does not prevent hepatic steatosis development in obese mice. Moreover, CTM feeding was associated to liver enzyme elevation in this model of NAFLD. Thus, the effects BAS on NAFLD need to be specifically addressed since this therapy might not be beneficial for this condition.

Overexpression of 11ß-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease.

BACKGROUND: The enzyme 11ß-hydroxysteroid-dehydrogenase type 1 (11ß-HSD1) catalyses the reactivation of intracellular cortisol. We explored the potential role of 11ß-HSD1 overexpression in visceral adipose tissue (VAT) in non-alcoholic fatty liver disease (NAFLD) assessing sequential changes of enzyme expression, in hepatic and adipose tissue, and the occurrence of portal hypercortisolism in obese mice. 11ß-HSD1 expression was also assessed in tissues from obese patients undergoing bariatric surgery. METHODS: Peripheral and portal corticosterone levels and liver histology were assessed in ob/ob mice at two time points (8-12 weeks of age). 11ß-HSD1 tissue expression was assessed in by RT-pcr in ob/ob mice and in 49 morbidly obese patients. RESULTS: Portal corticosterone serum levels were higher in obese mice with a 26% decrease between 8 and 12 weeks of age (controls: 78.3 ± 19.7 ng/ml, 8-week-old ob/ob: 167.5 ± 14.5 ng/ml and 12-week-old ob/ob: 124.3 ± 28 ng/ml, P < 0.05). No significant differences were found in peripheral corticosterone serum levels. Expression of 11ß-HSD1 was lower in the liver [-45% at 8 weeks and -35% at 12-weeks (P = 0.0001)] and highly overexpressed in VAT in obese mice, compared to controls (128-fold higher in 8-week-old ob/ob and 41-fold higher in 12-week-old ob/ob, P < 0.01). No significant differences were seen in the expression of 11ß-HSD1 in subcutaneous adipose tissue. In multivariate analysis, human 11ß-HSD1 expression in VAT (OR: 1.385 ± 1.010-1.910) was associated with NAFLD. CONCLUSION: Murine NAFLD is associated with portal hypercortisolism and11ß-HSD1 overexpression in VAT. In humans, 11ß-HSD1 VAT expression was associated with the presence of NAFLD. Thus, local corticosteroid production in VAT may contribute to NAFLD pathogenesis.

Monsoonal variations of lead (Pb) in coastal waters around Singapore.

Anthropogenic lead (Pb) has been the overwhelming Pb source to the global ocean, primarily contributed from Pb gasoline and industrial emissions. However, since Pb gasoline has been phased out globally, questions about whether there was a decrease in seawater Pb concentration, or if there are other sources taking over remains unclear in Southeast Asia. Here, combining Pb concentrations in seawater from Singapore Strait in 2010-2017; trap sediment in 2018-2019; and the previously published coral reconstruction covering 1975-2010; we found that the seawater Pb concentration in Singapore Strait over past decades followed the regional gasoline emissions, and no additional major source had contributed the Pb in the seawater since ~2010. The present-day Pb in Singapore Straits' water mainly follows the monsoonal current reversals, with variable degrees of scavenging that peak in inter-monsoon season. Minor Pb sources still contribute to some local-scale variabilities, despite a decadal-scale decreasing trend of Pb in seawater.

Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease.

BACKGROUND: The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis. AIM: To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients. MATERIAL AND METHODS: Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism. RESULTS: BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 ± 4.82) compared to controls (14.26 ± 11.4; p < 0.05). No differences were observed in the PAI-1 4G/5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 ± 4.35) compared to patients without liver fibrosis (10.61 ± 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6). CONCLUSIONS: Morbidly obese patients had significantly lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fibrosis in obese patients.

Helicobacter pylori-induced loss of the inhibitor-of-apoptosis protein survivin is linked to gastritis and death of human gastric cells.

Helicobacter pylori infects the human stomach and modifies signaling pathways that affect gastric epithelial cell proliferation and viability. Chronic exposure to this pathogen contributes to the onset of gastric atrophy, an early event in the genesis of gastric cancer associated with H. pylori infection. Susceptibility to H. pylori-induced cell death ultimately depends on the presence of protective host cell factors. Although expression of the inhibitor-of-apoptosis protein survivin in adults is frequently linked to the development of cancer, evidence indicating that the protein is present in normal gastric mucosa is also available. Thus, we investigated in human gastric tissue samples and cell lines whether H. pylori infection is linked to loss of survivin and increased cell death. Our results show that infection with H. pylori decreased survivin protein levels in the mucosa of patients with gastritis. Furthermore, survivin down-regulation correlated with apoptosis and loss of cell viability in gastrointestinal cells cocultured with different H. pylori strains. Finally, overexpression of survivin in human gastric cells was sufficient to reduce cell death after infection. Taken together, these findings implicate survivin as an important survival factor in the gastric mucosa of humans.

Cannabinoid 2 receptors regulate dopamine 2 receptor expression by a beta-arrestin 2 and GRK5-dependent mechanism in neuronal cells.

We have previously reported that the repeated exposure to cannabinoids upregulates and enhances the activity of serotonin 2A (5-HT2A) and dopamine 2 (D2) receptors and facilitates the formation of D2-5-HT2A receptor heterodimers in the rat prefrontal cortex and two neuronal cell lines. Because the repeated exposure to cannabinoids has been associated with adverse neuropsychiatric disorders, this study investigated the mechanisms that underly the cannabinoid-mediated regulation of D2 receptor expression in a neuronal cell model, CLU213 cells. We initially tested the effects of repeated exposure (72 h) to a non-selective cannabinoid agonist (1 nM CP55940), a selective CB1 receptor agonist (15 nM ACEA), or a selective CB2 receptor drug (1 nM GP1a) on the expression of postsynaptic D2 (D2L) receptors in CLU213 cells. Repeated CP55940, GP1a, or ACEA treatments significantly increased D2L receptor protein levels (99 % ± 7%, 30 % ± 7%, and 39 % ± 5% increases compared with control levels, respectively). Repeated exposure to both GP1a and ACEA increased D2L receptor protein levels by 73 % ± 8%. Interestingly, CP55940 and GP1a, but not ACEA, upregulated D2 mRNA. Using cells that were stably transfected with short-hairpin RNA (shRNA) lentiviral particles targeting CB2 receptors, G protein-coupled receptor kinase 5 (GRK5), and ß-arrestin 2, we found that CB2 receptors regulated D2 expression through a mechanism that is dependent on GRK5, ß-arrestin 2, and extracellular signal-related kinase (ERK)1/2. We also found that repeated exposure to either ACEA or GP1a selectively stimulated the protein and mRNA expression of GRK proteins. ACEA significantly upregulated GRK2 proteins, whereas GP1a upregulated GRK5 protein expression. Our results identified mechanisms associated with the upregulation of D2 receptors in neuronal cells after the repeated exposure to cannabinoids. These data can shed light on the mechanisms that can be targeted to prevent potential adverse effects, while simultaneously determining the therapeutic benefits of cannabinoids.

Effectiveness of a Team-Based Learning exercise in the learning outcomes of a medical pharmacology course: insight from struggling students.

We have previously reported that multiple Team-Based Learning (TBL™) exercises in a 4-week pre-clinical medical school course improved final exam performance and significantly reduced the number of course failures. Here, we conducted a long-term study, with eight cohorts of first-year medical students, to determine whether the implementation of a single TBL individual readiness assessment test (iRAT) exercise in a 4-week medical school pharmacology course produces similar effects in overall course performance. We implemented a single TBL iRAT exercise that covered the subjects addressed during one week of the medical pharmacology course, with the four most recent cohorts of students matriculating at Cooper Medical School of Rowan University (n = 403). The first four cohorts matriculating at CMSRU did not participate in the TBL exercises (n = 266). Correlation of individual student TBL iRAT and final examination scores in the medical pharmacology course was compared to a second, unrelated first-year course (physiology) to control for variation in student performance between cohorts. We found that there was a significant moderate correlation between final examination and TBL iRAT scores (r = 0.49, p < 0.01, n = 403). Interestingly this moderate correlation was seen in students performing in the lower 25th percentile on the course final examination (r = 0.41, p < 0.01, n = 101) and negligible in students performing in the upper 25th percentile (r = 0.11, n = 101, p > 0.05). Implementation of the single TBL exercise also significantly reduced variance or range of student final examination performance compared to the group of the first four cohorts. These results suggest that implementation of a single TBL exercise, which covers only one week of content delivered in a 1-month medical pharmacology course, benefits first-year medical students by reducing the disparity in knowledge acquisition among them and providing a means to identify students who may struggle with course content.

Assessment of Pathology Learning Modules With Virtual Microscopy in a Preclinical Medical School Curriculum.

OBJECTIVES: To evaluate the ability of pathology modules to promote learning of pathology-related course content in a preclinical medical education curriculum. METHODS: Pathology modules were created for the "Hematology/Oncology" and "Women's Health" (WH) courses. Students were recruited over 2 consecutive academic years; cohorts 1 and 2 refer to 2 separate groups of students in years 1 and 2, respectively, of the study. Course performance data were collected. RESULTS: Use of pathology modules resulted in a statistically significant higher correlation between performance on the final examination and pathology-related questions in the Hematology/Oncology course and written examination and pathology-related questions in cohort 1 in the WH course. There was statistically significant improvement (P = .026) on pathology-related laboratory practical examination questions in the WH course for cohort 1, and no other statistically significant improvement for the other cohorts and examinations. The percentage of students completing all or part of the modules was highest in the WH course for cohort 1 (60%) compared with WH course cohort 2 (33%) and Hematology/Oncology cohort 1 (30%) and cohort 2 (39%). CONCLUSIONS: Pathology modules may improve acquisition and retention of pathology-related course content when used appropriately.