Crossing horizons: unraveling perspectives on enhancing medical students' success through at-risk factor exploration.

BACKGROUND: Medical universities often face the ongoing challenge of identifying and supporting at-risk students to enhance retention rates and academic success. This study explores a comprehensive analysis of perceived at-risk factors impeding academic and career aspirations and compares the perspectives of students and faculty in a medical school. METHODS: We focused on first and second-year medical (MBBS) students and teaching faculty in an international medical college offering a twinning program in India and Malaysia. Our investigation involved a comprehensive assessment of 25 at-risk factors through Likert-type questionnaires distributed to 250 MBBS students and 50 teaching faculty. RESULTS: Our findings revealed distinct disparities in perceptions between faculty and students regarding mean scores of classroom engagement (p = 0.017), procrastination (p = 0.001), unrealistic goals (p = 0.026), emotional/behavioral problems (p = 0.008), limited key social skills (p = 0.023), and a non-supportive home environment (p = 0.001). These differences underscore the need for increased communication and understanding between faculty and students to address these risk factors effectively. In contrast, no significant disparities were observed among faculty and students' perceptions concerning mean scores of various potential at-risk factors, including academic unpreparedness, cultural/language barriers, individual guidance/mentoring, limited communication skills, racism/sexism, self-confidence, self-respect, self-concept, motivation, underprepared for current academic challenges, self-discipline, negative social network, negative peer culture, transportation time, college financial cost, college evaluation culture bias, broken college relationships, teaching methodology, and learning disabilities. However, varying degrees of influence were perceived by faculty and students, suggesting the importance of individualized support. CONCLUSION: This study contributes to the academic community by shedding light on the multifaceted nature of at-risk factors influencing student success. It underscores the need for proactive measures and tailored interventions to enhance student retention in higher education and academic achievement, fostering a sustainable foundation for lifelong learning and growth.

Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats.

This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl4. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl4-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl4-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl4-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways.

Metformin and Dapagliflozin Attenuate Doxorubicin-Induced Acute Cardiotoxicity in Wistar Rats: An Electrocardiographic, Biochemical, and Histopathological Approach.

Doxorubicin is a widely used anticancer drug whose efficacy is limited due to its cardiotoxicity. There is no ideal cardioprotection available against doxorubicin-induced cardiotoxicity. This study aimed to investigate the anticipated cardioprotective potential of metformin and dapagliflozin against doxorubicin-induced acute cardiotoxicity in Wistar rats. At the beginning of the experiment, cardiac screening of experimental animals was done by recording an electrocardiogram (ECG) before allocating them into the groups. Thereafter, a total of thirty healthy adult Wistar rats (150-200 g) were randomly divided into five groups (n = 6) and treated for eight days as follows: group I (normal control), group II (doxorubicin control), group III (metformin 250 mg/kg/day), group IV (metformin 180 mg/kg/day), and group V (dapagliflozin 0.9 mg/kg/day). On the 7th day of the treatment phase, doxorubicin 20 mg/kg was administered intraperitoneal to groups II, III, IV, and V. On the 9th day (immediately after 48 h of doxorubicin administration), blood was collected from anesthetized animals for glucose, lipid profile, CK-MB & AST estimation, and ECG was recorded. Later, animals were sacrificed, and the heart was dissected for histopathological examination. We found that compared to normal control rats, CK-MB, AST, and glucose were significantly increased in doxorubicin control rats. There was a significant reversal of doxorubicin-induced hyperglycemia in the rats treated with metformin 250 mg/kg compared to doxorubicin control rats. Both metformin (180 mg/kg and 250 mg/kg) and dapagliflozin (0.9 mg/kg) significantly altered doxorubicin-induced ECG changes and reduced the levels of cardiac injury biomarkers CK-MB and AST compared to doxorubicin control rats. Metformin and dapagliflozin protected the cellular architecture of the myocardium from doxorubicin-induced myocardial injury. Current study revealed that both metformin and dapagliflozin at the FDA-recommended antidiabetic doses mitigated doxorubicin-induced acute cardiotoxicity in Wistar rats. The obtained data have opened the perspective to perform chronic studies and then to clinical studies to precisely consider metformin and dapagliflozin as potential chemoprotection in the combination of chemotherapy with doxorubicin to limit its cardiotoxicity, especially in patients with comorbid conditions like type II diabetes mellitus.

Endogenous Sex Hormones Modulate the Analgesic Effect of Tramadol in Lean and High-Fat Diet-Induced Obese Wistar Rats: A Preclinical Molecular Approach.

INTRODUCTION: Differences in pain thresholds may have implications in pain management, as they may account in part for the variability in analgesic requirements between individuals. We planned to investigate the influence of endogenous sex hormones on the analgesic modulation of tramadol in lean and high-fat diet-induced obese Wistar rats. METHODS: The whole study was carried out on 48 adult Wistar rats (24 male: 12 obese and 12 lean and 24 female: 12 obese and 12 lean). Each male and female rat group was further subdivided into two groups (n = 6/group) and treated with normal saline/tramadol for 5 days. On the fifth day, 15 min after tramadol/normal saline treatment, animals were tested for pain perception toward noxious stimuli. Later, endogenous 17 beta-estradiol and free testosterone levels in serum were estimated through ELISA methods. RESULTS: The present study revealed that female rats experienced more pain sensitivity to noxious stimuli compared to male rats. High-fat diet-induced obese rats experienced more pain sensations to noxious stimuli than lean rats. Obese male rats were found to have significantly low free testosterone and high 17 beta-estradiol levels compared to lean male rats. An increase in serum 17 beta-estradiol level led to increased pain sensation to noxious stimuli. While an increase in free testosterone level resulted in the lowering of pain sensation to noxious stimuli. CONCLUSION: The analgesic effect of tramadol was more pronounced in male rats compared to female rats. The analgesic effect of tramadol was more marked in lean rats compared to obese rats. Additional research to elucidate obesity-induced endocrine changes and the mechanisms driving sex hormones in pain perception is needed to foster future interventions to reduce disparities in pain.

Neuronutraceuticals Combating Neuroinflammaging: Molecular Insights and Translational Challenges-A Systematic Review.

Neuropathologies, such as neuroinflammaging, have arisen as a serious concern for preserving the quality of life due to the global increase in neurodegenerative illnesses. Nowadays, neuronutraceuticals have gained remarkable attention. It is necessary to investigate the bioavailability, off-target effects, and mechanism of action of neuronutraceuticals. To comprehend the comprehensive impact on brain health, well-designed randomized controlled trials testing combinations of neuronutraceuticals are also necessary. Although there is a translational gap between basic and clinical research, the present knowledge of the molecular perspectives of neuroinflammaging and neuronutraceuticals may be able to slow down brain aging and to enhance cognitive performance. The present review also highlights the key emergent issues, such as regulatory and scientific concerns of neuronutraceuticals, including bioavailability, formulation, blood-brain permeability, safety, and efficacy.

Protective effect of Mucuna pruriens against arsenic-induced liver and kidney dysfunction and neurobehavioral alterations in rats.

BACKGROUND AND AIM: Intoxication of arsenic in rats is known to result in neurological effects as well as liver and kidney dysfunction. Mucuna pruriens has been identified for its medicinal properties. The aim of the study was to investigate the protective effect of aqueous seed extract of M. pruriens on sodium arsenite-induced memory impairment, liver, and kidney functions in rats. MATERIALS AND METHODS: The experiment was divided into short-term treatment (45 days) and long-term treatment (90 days), with each group divided into nine sub-groups consisting of six animals each. Sub-groups 1 and 2 served as normal, and N-acetylcysteine (NAC) controls, respectively. Sub-groups 3-9 received sodium arsenite in drinking water (50 mg/L). In addition, sub-group 4 received NAC (210 mg/kg b.wt) orally once daily, sub-groups 5-7 received aqueous seed extract of M. pruriens (350 mg/kg b.wt, 530 mg/kg b.wt, and 700 mg/kg b.wt) orally once daily and sub-groups 8 and 9 received a combination of NAC and aqueous seed extract of M. pruriens (350 mg/kg b.wt and 530 mg/kg b.wt) orally once daily. Following the treatment, the blood was drawn retro-orbitally to assess the liver (serum alanine transaminase [ALT], serum aspartate transaminase, and serum alkaline phosphatase) and kidney (serum urea and serum creatinine) functions. Learning and memory were assessed by passive avoidance test. Animals were sacrificed by an overdose of ketamine, and their Nissl stained hippocampal sections were analyzed for alterations in neural cell numbers in CA1 and CA3 regions. RESULTS: In the short-term treatment, groups administered with M. pruriens 530 mg/kg b.wt alone and combination of NAC + M. pruriens 350 mg/kg b.wt exhibited a significant improvement in memory retention, less severe neurodegeneration, and decrease in serum ALT levels. In long-term treatment, groups administered with M. pruriens 700 mg/kg b.wt alone and combination of NAC+M. pruriens 350 mg/kg b.wt, respectively, showed better memory retention, decreased neural deficits, and reduced levels of kidney and liver enzymes. CONCLUSION: The seed extract of M. pruriens showed significant enhancement in memory and learning. The number of surviving neurons in the CA1 and CA3 regions also increased on treatment with M. pruriens. Serum ALT, serum urea, and serum creatinine levels showed significant improvement on long-term treatment with M. pruriens.

Determining factors for optimal neuronal and glial Golgi-Cox staining.

Golgi staining allows for the analysis of neuronal arborisations and connections and is considered a powerful tool in basic and clinical neuroscience. The fundamental rules for improving neuronal staining using the Golgi-Cox method are not fully understood; both intrinsic and extrinsic factors may control the staining process. Therefore, various conditions were tested to improve the Golgi-Cox protocol for vibratome-cut rat brain sections. Optimal staining of cortical neurons was achieved after 72 h of impregnation. Well-stained neurons in both cortical and subcortical structures were observed after 96 h of impregnation. The dendritic arborisation pattern of cortical neurons derived from the 72-h impregnation group was comparable to those of the 96 and 168-h impregnation groups. The entire brain was stained well when the pH of the Golgi-Cox solution was 6.5 and that of the sodium carbonate solution was 11.2. Lack of brain perfusion or perfusion with 0.9% NaCl did not influence optimal neuronal staining. Perfusion with 37% formaldehyde, followed by impregnation, only resulted in glial staining, but perfusion with 4% formaldehyde facilitated both glial and neuronal staining. Whole brains required longer impregnation times for better staining. Although every factor had a role in determining optimal neuronal staining, impregnation time and the pH of staining solutions were key factors among them. This modified Golgi-Cox protocol provides a simple and economical procedure to stain both neurons and glia separately.

Association between functional polymorphisms in serotonin transporter gene (SLC6A4) and escitalopram treatment response in depressive patients in a South Indian population.

PURPOSE: Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder. METHODS: A total of 148 depressive patients receiving escitalopram 10-20 mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student's t test or one-way ANOVA. RESULTS: Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value < 0.001) association between LL genotype, LALA haplotypes, and 2 LA functional group with better treatment response to escitalopram. The decline in HDRS17 and MADRS score from baseline was significantly higher (p value < 0.001) in LL genotypes and homozygous LA carriers compared with other groups. CONCLUSION: Results suggest that 5HTTLPR and rs-25531 polymorphisms can influence escitalopram treatment response in depressive patients in a South Indian population, LL genotypes and LALA haplotypes being the predictors of better treatment response.

Safety Assessment of Human Bone Marrow-derived Mesenchymal Stromal Cells Transplantation in Wistar Rats.

INTRODUCTION: Bone Marrow-derived Mesenchymal Stromal Cells (BM-MSCs) are multipotent stem cells isolated from adult human bone marrow. Properties of MSCs make them potentially ideal candidates for regenerative medicine. The preclinical data available in the literature regarding the safety assessment of MSCs at different dosage group is scanty. AIM: To evaluate the safety of BM-MSCs transplantation in Wistar rats. MATERIALS AND METHODS: Eighteen adult female Wistar rats were used in the study. They were randomly divided into normal control, low dose MSCs and high dose MSCs groups. Low dose group received 3.25 million BM-MSCs/kg body weight; high dose group received 9.75 million BM-MSCs/kg body weight intravenously. Body weight, food and water intake of each rat were measured statistically using SPSS version 16.0; animals were observed for changes in behaviour, general clinical signs, presence of any abnormal response, mortality for thirty days. RESULTS: Repeated measures ANOVA indicated a significant increase in body weight, food, and water intake of all animals at all weeks of the study period compared to week zero (p<0.05). Between the low dose and high dose MSCs group, increase in absolute body weight was seen at the end of the 30th day which was statistically significant (p=0.01). There was no significant difference in body weights, food and water intake in MSCs group when compared to normal control. All the animals survived for the entire duration of the study. Further, there was no change in the behaviour of the animals, no adverse clinical signs or complications following the MSCs treatment. CONCLUSION: Results indicate that administration of BM-MSCs is safe when given by a slow intravenous infusion as it did not alter the food and water intake behaviour of the animals and did not have any negative effect on its body weight.

Effect of Sodium Valproate and Docosahexaenoic Acid on Pain in Rats.

INTRODUCTION: Analgesics are commonly prescribed medications used to alleviate pain of various aetiologies without affecting the patient's consciousness. They interfere with the transmission of pain signals. A commonly used antiepileptic drug, sodium valproate has been used in various non-epileptic conditions like migraine prophylaxis and in the treatment of bipolar disorder because of the multiple mechanisms by which it acts. Docosahexanoic Acid (DHA), an omega 3 fatty acid, is known to possess analgesic activity. We planned a study to assess the effect of sodium valproate alone and in combination with DHA in rat models of pain. AIM: To evaluate the analgesic activity of sodium valproate and DHA supplementation using various experimental models in albino Wistar rats. MATERIALS AND METHODS: For analgesic activity, A total of 48 adult Wistar albino rats were divided into eight groups of six rats each. Group I was control (distil water 1 ml/kg), Group II received intraperitoneal injection of tramadol (10 mg/kg), Group III, IV, V were injected intraperitoneal sodium valproate 100, 200, 400 mg/kg with distil water respectively and Group VI, VII, VIII were given sodium valproate 100, 200, 400 mg/kg plus DHA 300 mg/kg (intraperitoneal) respectively. Analgesic activity was assessed using hot plate, tail flick and acetic acid writhing models. RESULTS: We found that sodium valproate at higher doses (400 mg/kg) used either alone along with DHA (300 mg/kg) showed statistically significant analgesic activity in comparison to control in various experimental models for assessing pain. CONCLUSION: Combination of sodium valproate along with DHA has shown promising analgesic activity.

A Study to Assess the Therapeutic Effect of Enalapril on Olanzapine Induced Metabolic Syndrome in Wistar Rats.

INTRODUCTION: Metabolic Syndrome (MS) is a complex of risk factors for the development of cardiovascular complications and Type 2 Diabetes Mellitus (DM). Pharmacological management of the condition is complex, as multiple drug groups have to be used, as the syndrome itself is multi faceted. Angiotensin Converting Enzyme Inhibitors (ACEIs) are chiefly used to manage the hypertensive component of the syndrome. However, recent studies have shown that these drugs may have a role in the non hypertensive aspects of the syndrome as well. AIM: To evaluate the therapeutic effect of enalapril on total body weight, random blood glucose and serum lipid profile in a rodent model of olanzapine induced MS. MATERIALS AND METHODS: Three different dosages (1 mg/kg/day, 10 mg/kg/day and 20 mg/kg/day) of oral enalapril were administered (for three weeks) in albino wistar rats, which received prior intra peritoneal olanzapine (for three weeks), and compared against control (normal saline) and standard (olanzapine only and enalapril only) groups. Parameters like total body weight, random blood glucose and serum lipid profile were measured at baseline, at three weeks and at six weeks. RESULTS: Enalapril at 20 mg/kg/day was found to be effective in reversing the weight gain, hyperglycaemia and hypercholesterolaemia, without any changes in triglycerides, High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). 10 mg/kg/day of enalapril prevented any further rise in body weight, blood glucose, total cholesterol and serum triglycerides, after olanzapine was stopped. 1 mg/kg/day of enalapril was ineffective. CONCLUSION: High dose of enalapril may be considered as a component of therapeutic regimens to combat weight gain, hyperglycaemia and dyslipidaemia seen in MS, in addition to its antihypertensive utility. Further rodent and clinical studies may be required to ascertain the same.

Advances in pharmacovigilance initiatives surrounding antimicrobial resistance-Indian perspective.

INTRODUCTION: In recent years the development of antimicrobial resistance has been accelerating, the discovery of new antimicrobial agents has slowed substantially in past decades. AREA COVERED: This review mainly focuses on the problem of antimicrobial resistance(AMR); the various contributor mechanisms, consequences and future of AMR. The review also highlights the irrational use of antimicrobials, improving their usage and problems associated with pharmacovigilance of antimicrobial resistance. EXPERT OPINION: Pharmacovigilance in the form of surveillance of antibiotic use is being done in 90% of the countries worldwide through the WHONET program developed by WHO. However, the data comes from a limited area of the globe. Data from every part of the world is required, so that there is geographical representation of every region. A major hurdle in quantifying the extent of antimicrobial resistance is the fact that there are several known microbes, that may turn out to be resistant to one or more of the several known antimicrobial agents. The global action plan initiated by WHO, if implemented successfully will definitely reduce AMR and will help in evaluating treatment interventions.

Effect of sorafenib on sperm count and sperm motility in male Swiss albino mice.

The issue of male germ line mutagenesis and the effects on developmental defects in the next generation has become increasingly high profile over recent years. Mutagenic substance affects germinal cells in the testis. Since the cells are undergoing different phases of cell division and maturation, it is an ideal system to study the effect of chemotherapeutic agents. There are lacunae in the literature on the effect of sorafenib on gonadal function. With background, a study was planned to evaluate the effects of sorafenib on sperm count and sperm motility in male Swiss albino mice. Male Swiss albino mice were used for the study. The animals were segregated into control, positive control (PC) and three treatment groups. PC received oral imatinib (100 mg/kg body weight) and treatment groups received 25, 50, and 100 mg/kg body weight of sorafenib orally for 7 consecutive days at intervals of 24 h between two administrations. The control group remained in the home cage for an equal duration of time to match their corresponding treatment groups. The animals were sacrificed at the end of 1(st), 2(nd), 4(th), 5(th), 7(th), and 10(th) weeks after the last exposure to drug, respectively. Sperm suspensions were prepared and introduced into a counting chamber. Total sperm count and motility were recorded. There was a significant decrease in sperm count and sperm motility by sorafenib which was comparable with the effect of PC imatinib. Sorafenib adversely affects sperm count and sperm motility which are reversible after discontinuation of treatment.

Assessment of oxidative stress in hippocampus, cerebellum and frontal cortex in rat pups exposed to lead (Pb) during specific periods of initial brain development.

Epidemiological studies in children have proved that lead (Pb) exposure causes deficits in neural and cognitive functions. The present study assessed the oxidative stress on postnatal day 30, in the hippocampus, cerebellum and frontal cortex of rat pups exposed to Pb during specific periods of early brain development. Five groups of rat pups were investigated, and 0.2% Pb acetate in drinking was the dosage used. (i) Gestation and lactation (GL) group (n = 9) of rat pups was exposed to Pb during gestation and lactation through their mother, (ii) gestation (G) group (n = 9) of rat pups was exposed to Pb during gestation only, (iii) lactation (L) group (n = 9) of rat pups was exposed to Pb during lactation only, (iv) pre-gestation (PG) group (n = 9) of rat pups was born to mothers who were exposed to Pb for 1 month before conception, and (v) normal control (NC) (n = 9) group of rats pups had no exposure to Pb during gestation and lactation period. From the present study, it is evident that Pb exposure during different periods of early brain development (GL, G, L and PG groups) causes oxidative stress and lactation period (postnatal period) of Pb exposure produces maximum oxidative stress.

Influence of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement on lipid profile in normal and diet-induced hypercholesterolemic rats.

BACKGROUND: Zincovit tablet is combination of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement. AIMS: To investigate the influence of single combined formulation of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement tablets (Zincovit) on lipid profile in normal and diet-induced hypercholesterolemic rats. MATERIALS AND METHODS: Anti-hyperlipidemic activity of combined formulation of grape seed extract and Zincovit tablets doses ranged from 40 to 160 mg/kg, p.o. was evaluated in normal and diet-induced hypercholesterolemic rats. RESULTS: Hypercholesterolemic animals treated with combined formulation of grape seed extract and Zincovit tablets (nutritional food supplement) at 40, 80 and 160 mg/kg exhibited drastic decrease in serum triglycerides, total cholesterol, LDL-C, VLDL-C and rise of HDL-C in comparison to hypercholesterolemic control group animals. The anti-hyperlipidemic effect of single combined formulation of grape seed extract and Zincovit tablet was comparable with the standard drug atorvastatin treated animals and the variations were statistically non-significant. There was no significant impact of combined formulation of grape seed extract and Zincovit tablets on lipid profile among normal animals in comparison with normal control group. CONCLUSION: The present study demonstrated that the single combined formulation of grape seed extract and Zincovit tablet is the potential functional nutritional food supplements that could offer a novel therapeutic opportunity against diet-induced hypercholesterolemia in Wistar rats.