Unraveling the protective effects of curcumin against drugs of abuse.

Curcumin, a natural compound derived from the turmeric plant (Curcuma longa), has garnered significant attention for its diverse neuroprotective properties. Curcumin has been widely recognized for its remarkable anti-inflammatory, antioxidant, and anti-apoptotic effects, which have shown great potential in the treatment of various disorders, encompassing psychiatric and neurodegenerative diseases. In this review, we delve into the protective effects of curcumin against drugs of abuse, including morphine, methamphetamine, cocaine, nicotine, and alcohol, with a particular focus on the underlying mechanisms from a neuroscience perspective. Overall, curcumin demonstrates promising effects against the neurotoxicity induced by abused drugs through a wide range of mechanisms. These include the modulation of inflammatory cytokines, maintenance of ion homeostasis, epigenetic regulation, enhancement of antioxidant capacity, as well as the activation of the cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) signaling pathways. These findings suggest that curcumin emerges as a promising therapeutic agent in combatting the detrimental effects induced by drugs of abuse, and further research is warranted to fully comprehend the molecular pathways and optimize its utilization for the prevention and treatment of substance abuse-related neurotoxicity.

Regulation of mitochondrial dysfunction by estrogens and estrogen receptors in Alzheimer's disease: A focused review.

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid-ß hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology. Fluctuation of the levels of ovarian sex hormones during perimenopause is associated with changes in glucose metabolism, as a possible window of opportunity to further understand the roles of sex steroid hormones and their associated receptors in the pathophysiology of AD. We review these dimensions, emphasizing the potential of estrogen receptors (ERs) to reveal mitochondrial functions in the search for further research and therapeutic strategies for AD pharmacotherapy. Understanding and addressing the intricate interactions of mitochondrial dysfunction and ERs potentially pave the way for more effective approaches to AD therapy.

The feedback dilemma in medical education: insights from medical residents' perspectives.

BACKGROUND: Feedback is a critical component of the learning process in a clinical setting. This study aims to explore medical residents' perspectives on feedback delivery and identify potential barriers to feedback-seeking in clinical training. METHODS: This cross-sectional study involved 180 medical residents across seventeen specialties. We employed the validated Residency Education Feedback Level Evaluation in Clinical Training (REFLECT) tool to assess residents' perspectives on their attitude toward feedback, quality of feedback, perceived importance, and reaction to feedback. Additionally, we explored barriers to feedback-seeking behavior among medical residents. RESULTS: The majority of medical residents held positive attitudes toward feedback. They agreed that feedback improves their clinical performance (77.7%), professional behavior (67.2%), and academic motivation (56.7%), while also influencing them to become a better specialist in their future career (72.8%). However, the study revealed critical deficiencies in the feedback process. Only 25.6% of residents reported receiving regular feedback and less than half reported that feedback was consistently delivered at suitable times and locations, was sufficiently clear or included actionable plans for improvement. A minority (32.2%) agreed that faculty had sufficient skills to deliver feedback effectively. Moreover, peer-to-peer feedback appeared to be a primary source of feedback among residents. Negative feedback, though necessary, often triggered feelings of stress, embarrassment, or humiliation. Notably, there were no significant differences in feedback perceptions among different specialties. The absence of a feedback-seeking culture emerged as a central barrier to feedback-seeking behavior in the clinical setting. CONCLUSIONS: Establishing shared expectations and promoting a culture of feedback-seeking could bridge the gap between residents' perceptions and faculty feedback delivery. Furthermore, recognizing the role of senior and peer residents as valuable feedback sources can contribute to more effective feedback processes in clinical training, ultimately benefiting resident development and patient care.

Ultrasound-guided femoral nerve block versus fascia iliaca compartment block for femoral fractures in emergency department: A randomized controlled trial.

Aim: Femoral fractures are one of the most debilitating injuries presenting to the emergency departments (EDs). The pain caused by these fractures is typically managed with opioids and adjunctive regional analgesia. These approaches are often associated with adverse side effects. Thus, appropriate alternative methods should be thoroughly investigated. To evaluate ultrasound-guided femoral nerve block (FNB) with ultrasound-guided fascia iliaca compartment block (FICB) in femoral fractures, to determine which provides better analgesia and less opioid requirement. Methods: This study was a randomized clinical trial performed on adult patients presenting to the ED within 3 h of isolated femoral fracture with initial numerical pain rating scale (NRS-0) score of more than 5. The patients were randomized to receive FNB or FICB. The outcomes were block success rates, pain at 20 (NRS-20) and 60 (NRS-60) min after the end of the procedures, as well as the number and total dose of fentanyl administration during ED stay. Results: Eighty-seven patients were recruited (40 FNB and 47 FICB). Success rates were 82.5% in FNB and 83.0% in FICB group, with no significant difference between the groups. NRS-20, NRS-60, the number of patients who received supplemental fentanyl, and the total dose of administered fentanyl were significantly lower following FNB. However, the length of the procedure was significantly lower in the FICB group. Conclusion: Both FNB and FICB are effective in pain reduction for fractures of femur, but FNB provides more pain relief and less need for supplemental fentanyl.

The burden of traumatic brain injury on caregivers: exploring the predictive factors in a multi-centric study.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide. With survivors often exhibiting degrees of function loss, a significant burden is exerted on their caregivers. The purpose of this study was to explore the predictive factors of caregiver burden among caregivers of patients with TBI. METHODS: Sixty-eight family members of individuals with a TBI who had been admitted to three hospitals were assessed in terms of caregiver burden using the Zarit Burden Interview. The association of caregiver burden with patients' baseline cognitive function according to the Montreal Cognitive Assessment (MoCA) test, as well as caregivers' sociodemographic characteristics, were evaluated using multiple regression analysis. RESULTS: Based on the multiple regression model, the MoCA score of the patients (std ß=-0.442, p < 0.001), duration of caregiving (std ß = 0.228, p = 0.044), and higher education of the caregivers (std ß = 0.229, p = 0.038) were significant predictors of caregiver burden. CONCLUSION: Overall, our findings highlight the importance of taking caregivers' psychosocial needs into account. Long-term caregivers of TBI patients with cognitive impairment should be viewed as vulnerable individuals who could benefit from psychosocial intervention programs, to improve their well-being and enabling them to enrich their care of the TBI patient.

COVID-19 vaccines breakthrough infection and adverse reactions in medical students: a nationwide survey in Iran.

Introduction: There are different types of COVID-19 vaccines approved worldwide. Since no national studies focus on vaccine-related adverse reactions and breakthrough cases, this study aimed to investigate the rate of adverse events and COVID-19 infection in medical students in Iran. Methods: This retrospective cohort study included Iranian medical students who received two doses of COVID-19 vaccines. The medical team gathered the demographic characteristics, comorbidities, type of vaccine, adverse events following vaccination, and history of COVID-19 infection data through a phone interview. The frequency of adverse events and breakthrough infection was stratified by vaccine type (ChAdOx1-S, Gam-COVID-Vac, and BIBP-CorV). Results: A total of 3,591 medical students enrolled in this study, of which 57.02% were females, with a mean age of 23.31 + 4.87. A PCR-confirmed and suspicious-for-COVID-19 breakthrough infection rate of 4.51 and 7.02% was detected, respectively. There was no significant relation between breakthrough infection and gender, BMI, blood groups, and comorbidities. However, there was a significant difference in breakthrough infection rate among different types of vaccines (p = 0.001) and history of COVID-19 infection (p = 0.001). A total of 16 participants were hospitalized due to COVID-19 infection after vaccination for reasons such as dyspnea, abnormal imaging, or decreased oxygen saturation. No severe infection or death was observed in the studied population. Conclusion: Vaccination prevented severe COVID-19 infection, although a high breakthrough infection rate was evident among Iranian medical students during the Delta variant's peak. Vaccine effectiveness may be fragile during emerging new variants and in high-exposure settings. Moreover, adverse events are rare, and the benefits of vaccination outweigh the side effects. However, many limitations challenged this study, and the results should be cautious.

The triangle of anxiety, perfectionism, and academic procrastination: exploring the correlates in medical and dental students.

INTRODUCTION: Academic procrastination is a common phenomenon among medical science students. This issue can negatively affect the students' academic performance. The aim of this study was to investigate perfectionism and anxiety as potential predictors of academic procrastination in medical and dental students. METHODS: This cross-sectional study was conducted among medical and dental students of a public medical sciences university in the south of Iran. Students were assessed using the procrastination assessment scale for students (PASS), Tehran multidimensional perfectionism scale (TMPS), and anxiety subscale of the general health questionnaire (GHQ). Predictors of academic procrastination were evaluated using multiple regression analysis with adjustments made for gender and academic semester. RESULTS: A total of 176 medical and 79 dental students participated in the study. None of the perfectionism components were predictors of academic procrastination. However, anxiety was a significant predictor of academic procrastination in the total sample of students (standardized ß = 0.404, p < 0.001), as well as dental (standardized ß = 0.356, p < 0.001) and medical (standardized ß = 0.478, p < 0.001) students. Anxiety and academic procrastination were both negatively correlated with students' grade point averages. CONCLUSIONS: The findings of this study suggest that anxiety, as opposed to perfectionism, has a more significant influence on academic procrastination among medical and dental students. Interventions aimed at lowering anxiety may be beneficial for reducing academic procrastination, thereby enhancing the academic performance of the students.

A population-based study on incidence trends of myeloma in the United States over 2000-2020.

Myeloma is one of the most common types of haematological malignancies. We aimed to investigate the incidence rates of myeloma by sex, race, age, and histological subgroups in the United States (US) over 2000-2020. Data were retrieved from the the Surveillance, Epidemiology, and End Results (SEER) 22 database. The International Classification of Diseases for Oncology version 3 morphological codes 9731, 9732, and 9734 were assigned for solitary plasmacytoma of bone, plasma cell myeloma, and extraosseous plasmacytoma, respectively. Average annual percent change (AAPC) and the pairwise comparison with the parallelism and coincidence were reported. All estimates were reported as counts and age-adjusted incidence rates per 100,000 individuals. Over 2000-2019, most of myeloma cases were among those aged at least 55 years (85.51%), men (54.82%), and non-Hispanic Whites (66.67%). Among different subtypes, plasma cell myeloma with 193,530 cases had the highest frequency over the same period. Also, there was a significant decrease in the age-standardized incidence rate of myeloma across all races/ethnicities in both sexes within all age groups (AAPC: - 8.02; 95% confidence interval (CI): - 10.43 to - 5.61) and those aged < 55 (AAPC: - 8.64; 95% CI - 11.02 to - 6.25) from 2019 to November 2020. The overall trends of myeloma incidence rates were not parallel, nor identical. There was an increase in myeloma incidence in both sexes, with a highly increasing rate, particularly among younger Hispanic and non-Hispanic Black women over 2000-2019. However, a remarkable decline was observed in the incidence rates following the COVID-19 pandemic in 2020.

Mature teratoma of conus medullaris: A case report and review of literature.

In conus medullaris, mature teratomas are rare. We report a case of a 40-year-old man who presented with urinary incontinence, low back pain, and muscle weakness. Magnetic resonance imaging revealed a mass in conus medullaris (T11-L1), further confirmed as a mature teratoma by pathological examination. We identified 63 cases of conus medullaris teratoma over the past two decades by systematically analyzing the case reports. Findings demonstrated that most cases were diagnosed in the fourth decade of life, with the majority of cases (57.6%) being male. Lower back pain, radiating pain in the extremities, hypoesthesia, and urinary dysfunction are the most common clinical presentations among patients with teratoma of conus medullaris. Mature teratoma is the dominant pathologic subtype of teratomas in this region, comprising more than 95% of cases. Our case highlights the importance of considering spinal teratoma as a differential diagnosis in patients presenting with urinary incontinence and lumbar pain.

Preventive putative effect of agmatine on cognitive and molecular outcomes in ventral tegmental area of male offspring following physical and psychological prenatal stress.

Prenatal stress (PS) results from a maternal experience of stressful events during pregnancy, which has been associated with an increased risk of behavioral disorders including substance abuse and anxiety in the offspring. PS is known to result in heightened dopamine release in the ventral tegmental area (VTA), in part through the effects of corticotropin-releasing hormone, which directly excites dopaminergic cells. It has recently been suggested that agmatine plays a role in modulating anxiety-like behaviors. In this study, we investigated whether agmatine could reduce negative cognitive outcomes in male mice prenatally exposed to psychological/physical stress, and whether this could be associated with molecular changes in VTA. Agmatine (37.5 mg/kg) was administrated 30 min prior to PS induction in pregnant Swiss mice. Male offspring were evaluated in a series of behavioral and molecular assays. Findings demonstrated that agmatine reduced the impairment in locomotor activity induced by both psychological and physical PS. Agmatine also decreased heightened conditioned place preference to morphine seen in PS offspring. Moreover, agmatine ameliorated the anxiety-like behavior and drug-seeking behavior induced by PS in the male offspring. Molecular effects were seen in VTA as the enhanced brain-derived neurotrophic factor (BDNF) induced by PS in the VTA was reduced by agmatine. Behavioral tests indicate that agmatine exerts a protective effect on PS-induced impairments in male offspring, which could be due in part to agmatine-associated molecular alterations in the VTA. Taken together, our data suggest that prenatal treatment with agmatine exerts protective effect against negative consequences of PS on the development of affective circuits in the offspring.

The relation between obesity and breast cancer risk in women by considering menstruation status and geographical variations: a systematic review and meta-analysis.

Given the increase in the incidence of breast cancer during the past decades, several studies have investigated the effects of variables on breast cancer, especially obesity. This systematic review and meta-analysis aims to evaluate any effects of obesity on breast cancer risk in women, before and after menopause, and in different continents.All forms of relevant literature examining any association between obesity and breast cancer, including cohort, case-control, and cross-sectional studies, were identified in the PubMed, Scopus, EMBASE, and Web of Science databases from January 1, 1990 until January 13, 2023. Body mass index (BMI) > 30 was used to indicate obesity. Every type of breast cancer was examined as outcome factors. The quality of the papers was evaluated using the Newcastle-Ottawa scale checklist. The Egger and Begg test was used to evaluate publication bias. To assess any extra impact of each research on the final measurement, a sensitivity analysis was carried out.One hundred and two studies were included in this meta-analysis. Respectively, 48 and 67 studies reported associations between obesity and breast cancer in pre and post menopausal women. Combining all studies, the pooled OR of the association between obesity and breast cancer in pre-menopausal women was OR = 0.93 CI: (0.85-1.1), (I2 = 65.4%), and for post-menopausal woman, OR = 1.26 CI: (1.19-1.34), (I2 = 90.5%).Obesity has a protective role in breast cancer among pre-menopausal women, but this relationship is statistically significant only in European women. The chance of developing breast cancer increases in post-menopausal women who are obese. This relationship is significant among Asian, North American, African and European women.

Administration of agmatine prior to physical or psychological stress in pregnant mice ameliorates behavioural and cognitive deficits in female offspring.

Physical or psychological stress experienced by a mother during gestation is often associated with serious behavioural and cognitive deficits in newborns. Investigations of protective agents, which could prevent the adverse outcomes of prenatal stress (PS), are warranted. Agmatine is a neurotransmitter putatively involved in the physiological response to stress, and exogenous administration of agmatine has been shown to produce a variety of neuroprotective effects. In this study, we aimed to assess whether prenatal agmatine exposure could ameliorate behavioural and cognitive deficits in female offspring born to prenatally stressed mice. Pregnant Swiss Webster (SW) mice were exposed to physical or psychological stress from the 11th to 17th days of gestation. Agmatine (37.5 mg/kg, i.p.) was administrated 30 min before the induction of stress for seven consecutive days. The pups were assessed using a variety of behavioural tests and molecular assays on postnatal days 40 to 47. Agmatine attenuated impairments in locomotor activity, anxiety-like behaviour, and drug-seeking behaviour associated with both physical and psychological PS. Furthermore, agmatine reduced PS-induced impairments in passive avoidance memory and learning. Neither PS nor agmatine treatment affected the mRNA expression level of hippocampal brain-derived neurotrophic factor (BDNF) or tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). Taken together, our findings highlight the protective effects of prenatally administered agmatine on PS-mediated behavioural and cognitive deficits of the offspring. Future studies are needed to elucidate the underlying mechanisms, which could allow for more targeted prenatal treatments.

Exploring the potential of a novel phenoxyethyl piperidine derivative with cholinesterase inhibitory properties as a treatment for dementia: Insights from STZ animal model of dementia.

Alzheimer's disease (AD) is a neurodegenerative disease, often characterized by progressive deficits in memory and cognitive functions. Cholinesterase inhibitors have been introduced as promising agents to enhance cognition and memory in both human patients and animal models of AD. In the current study, we assessed the effects of a synthetic phenoxyethyl piperidine derivative, compound 7c, as a novel dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), on learning and memory, as well as serum and hippocampal AChE levels in an animal model of AD. The model of dementia was induced by intracerebroventricular injection of streptozotocin (STZ, 2 mg/kg) to male Wistar rats. STZ-treated rats received compound 7c (3, 30, and 300 µg/kg) for five consecutive days. ​Passive avoidance (PA) learning and memory, as well as spatial learning and memory using Morris water maze, were evaluated. The level of AChE was measured in the serum and the left and right hippocampus. Findings demonstrated that compound 7c (300 µg/kg) was able to reverse STZ-induced impairments in PA memory, while also reduced the increased AChE level in the left hippocampus. Taken together, compound 7c appeared to act as a central AChE inhibitor, and its role in alleviating cognitive deficits in the AD animal model suggests that it may have therapeutic potential in AD dementia. Further research is required to assess the effectiveness of compound 7c in more reliable models of AD in light of these preliminary findings.

Reconstructing feedback in graduate medical education: development of the REFLECT scale to measure feedback delivery in medical residency training.

BACKGROUND: Feedback plays a pivotal role in graduate medical education, where medical residents are expected to acquire a wide range of practical and professional competencies. Assessing the feedback delivery status is a preliminary step for educators to enhance the quality of feedback provided. This study aims to develop an instrument to assess the various aspects of feedback delivery in medical residency training. METHODS: The fifteen-item REFLECT (Residency Education Feedback Level Evaluation in Clinical Training) questionnaire was developed. The content validity was evaluated according to a panel member consisting of fourteen clinical professors and medical education instructors. After evaluating the test-retest reliability, the questionnaire was distributed to a sample of 154 medical residents and was further assessed in terms of internal consistency and factor analysis. RESULTS: Content validity analysis resulted in an appropriate content validity ratio and content validity index for the final 15 items. The test-retest reliability resulted in an ICC of 0.949 (95% C.I. 0.870-0.980), indicating excellent reliability. The Cronbach's alpha for the 15-item questionnaire was α = 0.85, demonstrating good internal consistency. The factor analysis resulted in a four-factor structure: "attitude towards feedback", "quality of feedback", "perceived importance of feedback", and "reaction to feedback". CONCLUSIONS: REFLECT proved to a reliable tool that could be utilized as a quick assessment method of feedback delivery, making it a suitable aid for educational managers and faculties to design necessary interventions aiming to enhance the quantity and quality of feedback provided.

The hyperexcitability of laterodorsal tegmentum cholinergic neurons accompanies adverse behavioral and cognitive outcomes of prenatal stress.

Exposure to prenatal stress (PS) leads to the offspring's vulnerability towards the development of cognitive and behavioral disorders. Laterodorsal tegmentum (LDT) is a part of the brainstem cholinergic system that is believed to play a pivotal role in the stress-associated progression of anxiety, memory impairment, and addictive behaviors. In this study, we aimed to investigate the electrophysiological alterations of LDT cholinergic neurons and its accompanied behavioral and cognitive outcomes in the offspring of mice exposed to physical or psychological PS. Swiss Webster mice were exposed to physical or psychological stress on the tenth day of gestation. Ex vivo investigations in LDT brain slices of adolescent male offspring were performed to evaluate the effects of two stressor types on the activity of cholinergic neurons. Open field test, elevated plus maze, passive avoidance test, and conditioned place preference were conducted to assess behavioral and cognitive alterations in the offspring. The offspring of both physical and psychological PS-exposed mice exhibited increased locomotor activity, anxiety-like behavior, memory impairment, and preference to morphine. In both early- and late-firing cholinergic neurons of the LDT, stressed groups demonstrated higher firing frequency, lower adaptation ratio, decreased action potential threshold, and therefore increased excitability compared to the control group. The findings of the present study suggest that the hyperexcitability of the cholinergic neurons of LDT might be involved in the development of PS-associated anxiety-like behaviors, drug seeking, and memory impairment.

Antibiotics with Antiviral and Anti-Inflammatory Potential Against Covid-19: A Review.

In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection, as suggested by the evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting in co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of co-infection.

The apelin/APJ signaling system and cytoprotection: Role of its cross-talk with kappa opioid receptor.

Apelin, a regulatory peptide, is an endogenous ligand of the apelin receptor (APJ), which belongs to the G protein-coupled receptor family. The peptide and its receptor are distributed in animal and human tissues, including the cardiovascular and central nervous systems, and studies indicate that apelin signaling could play a role in cytoprotection of cells where it is found. Apelin activity may be modulated by interactions of the APJ receptor with other receptors that result in heteromerization. The interaction of the APJ with other receptor systems increases the signaling repertoire of apelin, thereby allowing it to exert a widened degree of control over cellular physiological functions. This article reviews studies which provide evidence for the physiological importance of APJ/Kappa opioid receptor (KOR) heterodimers in several critical cellular processes, including cell proliferation, and results are discussed that support a role of this peptide and the APJ receptor in functioning of the cardiovascular, gastrointestinal and central nervous systems under normal conditions and pathology, as well as novel signal transduction characteristics resulting following the interaction of APJ and KOR. A better understanding of the cellular protective actions of apelin, and the physiological outcomes from interaction of its receptor with other receptor types could lead to new pharmaceutical targets for various diseases affecting among other organs, the heart, the gastrointestinal system and the brain.

Looking into a Deluded Brain through a Neuroimaging Lens.

Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer's, and Parkinson's disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models. Advances in neuroimaging along with improved psychiatric and cognitive modeling offers us a new opportunity to look with more investigative power into the deluded brain. In this article, based on data obtained from neuroimaging studies, we have attempted to draw a picture of the neural networks involved when delusion is present and evaluate whether different manifestations of delusions engage different regions of the brain.