Nephrotoxicity is one of the main side effects caused by cisplatin (CP), a widely used antineoplastic agent. Here, we examined the effect of a novel water-soluble carbon monoxide-releasing molecule (CORM-3) on CP-mediated cytotoxicity in renal epithelial cells and explored the potential therapeutic benefits of carbon monoxide in CP-induced nephrotoxicity in vivo. Exposure of LLC-PK(1) cells to CP (50 microM) caused significant apoptosis as evidenced by caspase-3 activation and an increased number of floating cells. Treatment with CORM-3 (1-50 microM) resulted in a remarkable and concentration-dependent decrease in CP-induced caspase-3 activity and cell detachment. This effect involved activation of the cGMP pathway as 1H-oxadiazole [4, 3-a] quinoxaline-1-ore (ODQ), a guanylate cyclase inhibitor, completely abolished the protection elicited by CORM-3. Using a rat model of CP-induced renal failure, we found that treatment with CP (7.5 mg/kg) caused a significant elevation in plasma urea (6.6-fold) and creatinine (3.1-fold) levels, which was accompanied by severe morphological changes and marked apoptosis in tubules at the corticomedullary junction. A daily administration of CORM-3 (10 mg/kg ip), starting 1 day before CP treatment and continuing for 3 days thereafter, resulted in amelioration of renal function as shown by reduction of urea and creatinine levels to basal values, a decreased number of apoptotic tubular cells, and an improved histological profile. A negative control (iCORM-3) that is incapable of liberating CO failed to prevent renal dysfunction mediated by CP, indicating that CO is directly involved in renoprotection. Our data demonstrate that CORM-3 can be used as an effective therapeutic adjuvant in the treatment of CP-induced nephrotoxicity.

One barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs. learning from negative feedback (punishment). Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject’s relative sensitivity to positive vs. negative feedback showed that both the medicated MDD and HC groups conform to Kahneman and Tversky’s (1979) Prospect Theory, which expects losses (negative feedback) to loom psychologically slightly larger than gains (positive feedback). However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not “normal” when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the cognitive consequences of MDD from those of SSRI treatment, and from cognitive evaluation of MDD subjects in a medication-naïve state before the administration of antidepressants. Future research is needed to correlate the mood-elevating effects and the cognitive balance between reward- and punishment-based learning related to SSRIs.

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ObjectivesWe aimed to determine the prevalence and correlates of obesity and hypertension (HTN) among students at a central university in the West Bank.Materials and methodsThis cross-sectional study targeted a cohort of 553 students (59.5% males, 40.5% females) aged 17–26 years (median = 21) from Al-Quds University. Body mass index (BMI) and blood pressure (BP) were measured. Participants completed a questionnaire on physical activity, sedentary behavior, dietary factors, smoking and family history of obesity, HTN, and coronary artery disease. The magnitude of correlation was assessed by Spearman's rho (r s) and Chi-square tests.ResultsThe prevalence of overweight was 25% (31.1% males, 15.6% females) and obesity 7.2% (9.4% males, 4% females). Obesity and overweight were associated with family history of obesity in both genders (p<0.001) and physical activity in males (rs= − 0.162, p<0.005). No correlation was demonstrated between participants’ BMI and sedentary lifestyle or consumption of fast food. Pre-HTN was detected in 27.1% (38% males, 11.2% females) and HTN in 2.2% (3.3% males, 0.4% females). Pre-HTN and HTN were associated with obesity (rs=0.252, p<0.001) and smoking (p<0.05). No relationship was detected between students’ BP and sedentary behavior, family history of HTN/CAD, or consumption of fast food. The prevalence of increased BMI and BP among males was significantly higher than females (p<0.001).ConclusionsWe detected a high prevalence of elevated BP and excess weight gain among students at Al-Quds University. An interventional program is urgently needed to control these cardiovascular risk factors in this community.

To better understand how medication status and task demands affect cognition in Major Depressive Disorder (MDD), we evaluated medication-naïve patients with MDD, medicated patients with MDD receiving the Selective Serotonin Reuptake Inhibitors (SSRI) paroxetine, and healthy controls. All three groups were administered a computer-based cognitive task with two phases, an initial phase in which a sequence is learned through reward-based feedback (which our prior studies suggest is striatal-dependent), followed by a generalization phase that involves a change in the context where learned rules are to be applied (which our prior studies suggest is hippocampal-region dependent). Medication-naïve MDD patients were slow to learn the initial sequence but were normal on subsequent generalization of that learning. In contrast, medicated patients learned the initial sequence normally, but were impaired at the generalization phase. We argue that these data suggest (i) an MDD-related impairment in striatal-dependent sequence learning which can be remediated by SSRIs and (ii) an SSRI-induced impairment in hippocampal-dependent generalization of past learning to novel contexts, not otherwise seen in the medication-naïve MDD group. Thus, SSRIs might have a beneficial effect on striatal function required for sequence learning, but a detrimental effect on the hippocampus and other medial temporal lobe structures critical for generalization.

Purpose The COVID-19 pandemic resulted in a sudden shift from face-to-face to distance learning. We explored medical students’ views of online learning during this pandemic at the Arabian Gulf University in Bahrain. Methods This was a cross-sectional study of students in years two, three and four (n= 559) using an electronic questionnaire. Data were collected from April 10 to May 5, 2021. The survey included three domains: behavioral, affective, and cognitive. We also analyzed the association between students’ perceptions and certain demographic and institutional factors. Results The number of respondents was 311 (response rate: 55.6%; 27.7% males, 72.3% females). Participants were generally satisfied with distance learning (54.6%), although they had less motivation (46.3%) and required more effort (32.2%). Most students preferred distance learning for theoretical parts, and face-to-face approach for practical components (73.3%). Participants reported that distance learning, improved interaction with instructors and classmates (45.6% and 48.9%, respectively), small group learning (47.6%), independent learning (75.3%) and problem-solving skills (44.7%). The students were comfortable with online assessment (60.1%), and reported improved achievement in written (42.1%) and practical examinations (46%), but not in professional skills grades (21.6%). There was no association between students’ perceptions and gender (p= 0.079), year of study (p= 0.28) or attendance of live or recorded sessions (p= 0.904), but there was a positive association with the availability of WiFi (p< 0.01) and attendance of college-organized activities (p< 0.0001). Conclusion Distance learning was successfully implemented during the COVID-19 pandemic. Students were generally satisfied with distance learning and online assessment, but they had concerns about the clinical skills learning. After the pandemic is over, theoretical components of the curriculum can be delivered using distance learning, whereas hands on elements should be offered face-to-face. However, those curricular reforms will likely need investing in the information technology infrastructure.

Background The relationship between large-group classroom attendance by students and test achievement in problem-based learning (PBL) curricula is unclear. This study examined the correlation between attendance at resource sessions (hybrid lectures in the PBL curriculum) and test scores achieved in pharmacology and determined whether the score achieved was related to student gender. Methods A cross-sectional observational study over one academic year of 1404 pre-clerkship medical students was performed. Class attendance during pharmacology resource sessions and MCQ test scores achieved in pharmacology were analysed. Results The percentage of students’ attendance in resource sessions declined over three years of the programme, from 78.7 ± 27.5 in unit I to 22.1 ± 35.6 (mean ± SD) in unit IX. A significant but weakly positive correlation was evident between attendance and achievement in pharmacology ( r = 0.280; p < 0.0001). The mean score of the students who attended > 50% of the resource sessions was significantly higher ( p < 0.0001). Students who attended ≤50% were more likely to achieve lower tertile scores. The mean score achieved and the number of higher tertile scorers were higher among students who attended > 50% of the resource sessions. Although female students’ attendance was significantly higher, no significant gender-related differences in either mean scores or top grades achieved were found. Conclusions In a PBL curriculum, the classroom attendance of students in pharmacology declined during the pre-clerkship phase. A weak positive correlation was found between attendance and academic achievement, as measured by MCQ test scores. Factors other than motivation and attendance may confound gender-based academic performance and merit further research.

Currently, there are no reliably effective therapeutic options for metastatic pheochromocytoma (PCC) and paraganglioma. Moreover, there are no therapies that may prevent the onset or progression of tumors in patients with succinate dehydrogenase type B mutations, which are associated with very aggressive tumors. Therefore, we tested the approved and well-tolerated drugs lovastatin and 13-cis-retinoic acid (13cRA) in vitro in an aggressive PCC mouse cell line, mouse tumor tissue-derived (MTT) cells, and in vivo in a PCC allograft nude mouse model, in therapeutically relevant doses. Treatment was started 24 hours before sc tumor cell injection and continued for 30 more days. Tumor sizes were measured from outside by caliper and sizes of viable tumor mass by bioluminescence imaging. Lovastatin showed antiproliferative effects in vitro and led to significantly smaller tumor sizes in vivo compared with vehicle treatment. 13cRA promoted tumor cell growth in vitro and led to significantly larger viable tumor mass and significantly faster increase of viable tumor mass in vivo over time compared with vehicle, lovastatin, and combination treatment. However, when combined with lovastatin, 13cRA enhanced the antiproliferative effect of lovastatin in vivo. The combination-treated mice showed slowest tumor growth of all groups with significantly slower tumor growth compared with the vehicle-treated mice and significantly smaller tumor sizes. Moreover, the combination-treated group displayed the smallest size of viable tumor mass and the slowest increase in viable tumor mass over time of all groups, with a significant difference compared with the vehicle- and 13cRA-treated group. The combination-treated tumors showed highest extent of necrosis, lowest median microvessel density and highest expression of α-smooth muscle actin. The combination of high microvessel density and low α-smooth muscle actin is a predictor of poor prognosis in other tumor entities. Therefore, this drug combination may be a well-tolerated novel therapeutic or preventive option for malignant PCC.