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Abstract Background Traditional pharmacy education often relies on fragmented, subject-centered curricula, which may inadequately prepare students for the complexities of advanced healthcare. This study evaluates the effectiveness of an integrated pharmacy education approach in enhancing foundational knowledge and practical skills. Methods An integrated course focused on respiratory diseases was developed and implemented for final-year pharmacy students at Tabriz University of Medical Sciences. The course utilized case-based learning and incorporated elements from various disciplines such as pharmacology, medicinal chemistry, and pharmaceutics. An educational controlled trial was conducted, comparing an intervention group (integrated course) with a control group (traditional course). Results Survey results revealed that over 60% of students reported substantial improvements in their ability to manage respiratory cases. The intervention group demonstrated significantly higher clinical decision-making skills, with an average test score of 31.4 compared to 15.75 in the control group (p

Abstract Central serous chorioretinopathy (CSCR) is a retinal disease characterised by the accumulation of subretinal fluid, which often resolves spontaneously in acute cases. However, approximately one-third of patients experience recurrences that may cause severe and irreversible vision. This study aimed to identify parameters derived from optical coherence tomography (OCT) that are associated with CSCR recurrence. Our dataset included 5211 OCT scans from 344 eyes of 255 patients diagnosed with CSCR. 178 eyes were identified as recurrent, 109 as non-recurrent, and 57 were excluded. We extracted parameters using artificial intelligence algorithms based on U-Nets, convolutional kernels, and morphological operators. We applied inferential statistics to evaluate differences between the recurrent and non-recurrent groups, and we used a logistic regression predictive model, reporting the coefficients as a measure of biomarker importance. We identified nine predictive biomarkers for CSCR recurrence: age, intraretinal fluid, subretinal fluid, pigment epithelial detachments, choroidal vascularity index, integrity of photoreceptors and retinal pigment epithelium layer, choriocapillaris and choroidal stroma thickness, and thinning of the outer nuclear layer, and of the inner nuclear layer combined with the outer plexiform layer. These results could enable future developments in the automatic detection of CSCR recurrence, paving the way for translational medical applications.

Background: In many diabetic patients, spermatogenesis complications are frequent causing infertility problems.This study aimed to demonstrate the effect of Forskolin on male reproductive dysfunction caused by type 2 diabetes.Materials and Methods: In this experimental study, type 2 diabetes was induced by a high-fat diet (HFD) for onemonth and then a low single dose injection (35 mg/kg) of streptozotocin (STZ) in Wistar rats. After 72 hours, rats withmore than 200 mg/dl of blood glucose were considered type 2 diabetic rats. Forty rats (200-250 g) were divided intofour groups (n=10) including group 1 (G1): rats with normal diet and buffer citrate (STZ solvent) injection, group 2(G2): control type 2 diabetic rats with HFD and STZ injection, group 3 (G3): type 2 diabetic rats received phosphatebuffer saline (PBS) as Forskolin solvent, and group 4 (G4): Forskolin treated diabetic rats (10 mg/kg) for 1 month.Results: In comparison to control group, in diabetic groups (G2 and G3) some parameters are increased significantly:The blood glucose (P=0.00078), testicular malondialdehyde (MDA) level and body weight (P=0.00009) and Baxgene expression (P=0.00007). Unlike, some parameters are decreased significantly: The serum level of testosterone(P=0.0009), testicular superoxide dismutase (SOD, P=0.00007) and glutathione peroxidase (GPX) levels (P=0.00008),sperm concentration (P=0.00008), motility (P=0.00009), normal morphological sperm (P=0.00008) and Bcl-2 geneexpression (P=0.00009). However, in Forskolin treated group (G4) the parameters stayed close to control values thatwas significantly (P=0.00007) higher than in G2 and G3 groups. Therefore, treatment with Forskolin significantlyimproved these abnormal changes in Forskolin-treated group.Conclusion: Our study demonstrates that Forskolin is an effective antidiabetic agent, which significantly improvessperm concentration, testosterone levels, and antioxidant activity in diabetic rats.

Abstract The influenza virus hemagglutinin is an important part of the virus attachment to the host cells. The hemagglutinin proteins are one of the genetic regions of the virus with a high potential for mutations. Due to the importance of predicting mutations in producing effective and low-cost vaccines, solutions that attempt to approach this problem have recently gained significant attention. A historical record of mutations has been used to train predictive models in such solutions. However, the imbalance between mutations and preserved proteins is a big challenge for the development of such models that need to be addressed. Here, we propose to tackle this challenge through anomaly detection (AD). AD is a well-established field in Machine Learning (ML) that tries to distinguish unseen anomalies from normal patterns using only normal training samples. By considering mutations as anomalous behavior, we could benefit existing rich solutions in this field that have emerged recently. Such methods also fit the problem setup of extreme imbalance between the number of unmutated vs. mutated training samples. Motivated by this formulation, our method tries to find a compact representation for unmutated samples while forcing anomalies to be separated from the normal ones. This helps the model to learn a shared unique representation between normal training samples as much as possible, which improves the discernibility and detectability of mutated samples from the unmutated ones at the test time. We conduct a large number of experiments on four publicly available datasets, consisting of three different hemagglutinin protein datasets, and one SARS-CoV-2 dataset, and show the effectiveness of our method through different standard criteria.

Introduction: Atherosclerosis is a complicated cascade of inflammatory processes, oxidative stress, and apoptosis, making it the most prevalent cardiovascular disease. The onset and progression of cardiovascular diseases are greatly influenced by oxidative stress. Targeting oxidative stress is an effective strategy for treating such diseases. Marrubiin is a bioactive furan labdane diterpenoid acts as a strong antioxidant to protect against oxidative damage. This study aimed to investigate the protective effects of marrubiin against oxidative stress and apoptosis in a cellular model of the vascular system. Methods: Human umbilical vein endothelial cells were treated with varying concentration of marrubiin and its IC50 value was determined. The antioxidant potential of marrubiin was assessed by measuring the intracellular level of glutathione (GSH) using a colorimetric technique. Since apoptosis plays a significant role in the plaque rupture, the study also evaluated the protective effects of marrubiin on the expression of key genes involved in apoptotic pathways. Results: Cells treated with marrubiin showed increased GSH levels compared to cell therapy control cells, indicating marrubiin’s ability to counteract the effects of TNF-α’s on GSH levels. Furthermore real-time PCR analysis demonstrated that marrubiin upregulated Bcl-xl while downregulating caspase3 and Nox4 in treated cells. These findings suggest that marrubiin protects against apoptosis and oxidative stress. Conclusion: Based on our findings, marrubiin is recommended as a preventive/therapeutic treatment for diseases caused by elevated intracellular reactive oxygen species levels in cardiovascular diseases.

Purpose: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)]. Conclusion: In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

Abstract Background The rhizomes of Cynodon dactylon are used for the treatment of heart failure in folk medicine. In the present study, we investigated the effects of hydroalcoholic extract of C. dactylon rhizomes on cardiac contractility in normal hearts and on cardiac functions in right-heart failure in rats. Methods Right-heart failure was induced by intraperitoneal injection of monocrotaline (50 mg/kg). Two weeks later, the animals were treated orally with different doses of the extract for fifteen days. At the end of the experiments cardiac functions and markers of myocardial hypertrophy were measured. Results The treated rats showed very less signs of fatigue, peripheral cyanosis and dyspnea. The survival rate was high in the extract treated groups (90%). Administration of C. dactylon in monocrotaline-injected rats led to profound improvement in cardiac functions as demonstrated by decreased right ventricular end diastolic pressure (RVEDP) and elevated mean arterial pressure. RVdP/dtmax, and RVdP/dt/P as indices of myocardial contractility were also markedly (p < 0.001; using one way ANOVA) increased by the extract. The extract reduced heart and lung congestion by decreasing tissue wet/dry and wet/body weight ratios (p < 0.01). In the isolated rat hearts, the extract produced a remarkable (P < 0.001) positive inotropic effect concomitant with a parallel decrease in LVEDP. Conclusion The results of this study indicated that C. dactylon exerted a strong protective effect on right heart failure, in part by positive inotropic action and improving cardiac functions.

Objective(s): 4-Phenyl butyric acid (4-PBA) is a chaperone-mediated autophagy (CMA) inducer, which eliminates unnecessary and damaged cellular components through lysosomal enzymes. It could reduce misfolded and unfolded proteins produced after myocardial infarction (MI) and can improve cardiac function. We aimed to investigate the effect of 4-PBA on isoproterenol-induced MI in rats. Materials and Methods: Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days simultaneous with an intraperitoneal (IP) injection of 4-PBA at 20, 40, or 80 mg/kg at 24-hr intervals for five days. On day 6, hemodynamic parameters, histopathological changes, peripheral neutrophil count, and total anti-oxidant capacity (TAC) were evaluated. The expression of autophagy proteins was measured by using western blotting. 4-PBA significantly improved post-MI changes in hemodynamic parameters.Results: Histological improvement was found in 4-PBA 40 mg/kg (P

Toll-like receptors (TLRs) are essential receptors of the innate immune system, playing a significant role in cardiovascular diseases. TLR4, with the highest expression among TLRs in the heart, has been investigated extensively for its critical role in different myocardial inflammatory conditions. Studies suggest that inhibition of TLR4 signaling pathways reduces inflammatory responses and even prevents additional injuries to the already damaged myocardium. Recent research results have led to a hypothesis that there may be a relation between TLR4 expression and 5' adenosine monophosphate-activated protein kinase (AMPK) signaling in various inflammatory conditions, including cardiovascular diseases. AMPK, as a cellular energy sensor, has been reported to show anti-inflammatory effects in various models of inflammatory diseases. AMPK, in addition to its physiological acts in the heart, plays an essential role in myocardial ischemia and hypoxia by activating various energy production pathways. Herein we will discuss the role of TLR4 and AMPK in cardiovascular diseases and a possible relation between TLRs and AMPK as a novel therapeutic target. In our opinion, AMPK-related TLR modulators will find application in treating different immune-mediated inflammatory disorders, especially inflammatory cardiac diseases, and present an option that will be widely used in clinical practice in the future.

Despite studies indicating that asthma patients do not exhibit a higher mortality rate or severity compared to the general population when infected with COVID-19, there have been few reports on predictive factors for mortality in this context. This study aimed to assess the predictive value of systemic inflammation indices including neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), systemic inflammation response index (SIR-I), and systemic inflammation index (SII) in determining mortality rate among patients with COVID-19 and asthma. In this prospective study, the laboratory parameters of 1792 COVID-19 patients were examined, with a subgroup consisting of 112 patients with asthma and 1680 patients without asthma. Receiver operating characteristic (ROC) analysis was employed to assess the potential of inflammatory indices in indicating COVID-19 severity, while Kaplan-Meier curves were utilized to analyze the survival probability with death as the outcome. In deceased non-asthma patients, the levels of leukocyte and differential cell counts, and the values of PLR, NLR, MLR, SII, and SIR-I were higher than in survivors. In contrast, all the above values except PLR and MLR were significant in the asthma groups. The Kaplan–Meier survival curves were consistent with the ROC analysis. However, a multivariate Cox regression analysis revealed that neutrophil counts in non-asthma subjects and leukocyte and neutrophil counts in asthma patients remained significant for survival. In conclusion, while numerous inflammatory indices were associated with mortality in COVID-19 patients without asthma, neutrophil counts could independently predict mortality risk in asthma COVID-19 patients.

Background: After recovery from acute phase of the COVID-19, some patients suffer from persistent/late-onset complications. The main objective of this study was to investigate the prevalence of such complications in a large scale of COVID-19 patients in Tehran, Iran. Methods: In this cross-sectional study, those patients who called Tehran emergency medical services center and were visited by the emergency medical technicians from 20 March 2020 until 21 September 2020 and diagnosed as a confirmed COVID-19 case were enrolled. The minimum required sample size was estimated 385 cases, and they were selected randomly. The patients were interviewed by phone at least 4 weeks since initiation of their symptoms. Using a pre-prepared checklist, made by an expert panel who were involved in management of COVID-19 patients, data were collected on the types and duration of the complications, clinical information, and factors which could interfere with developing the complications. All analyses were performed using STATA 16 software. The association of the prevalence of each complication with independent factor was assessed using Chi-square test (or Fisher’s exact test) for categorical variable, and the mean difference of numerical variables in the two groups (with and without complication) was assessed using independent t-test. Statistical significance was accepted at P value

Abstract Stroke is one of the most important health concerns worldwide. Calcium ions accumulation in the nerve cells and increase in the catecholamines level of the brain following cerebral ischemia/reperfusion (I/R) are accompanied by damaging effects. Therefore, the present study aimed to evaluate the effects of diltiazem, as a calcium channel blocker, and metoprolol, as a β-adrenoceptors antagonist, on I/R injury. In this study, 30 male Wistar rats were divided into control, I/R, metoprolol, diltiazem, and metoprolol plus diltiazem groups (n=6 in each). Metoprolol (1 mg/kg/day) and diltiazem (5 mg/kg/day) were injected intraperitoneally (i.p.) for 7 days before I/R induction. On day 8, the animals underwent ischemia by bilateral common carotid arteries occlusion for 20 min. Histopathological analysis showed a significant reduction in leukocyte infiltration in diltiazem, metoprolol, and diltiazem plus metoprolol treated rats compared with the I/R group (P

Background. Inflammation in the implant-abutment interface is one of the main factors that can reduce implant stability. Therefore, this study investigated the effect of chlorhexidine, tetracycline, saliva, and a dry environment on the interleukin IL-1β and interleukin IL-6 levels of the gingival groove fluid at the implant-abutment interface.Methods. Twenty-four (10 men and 14 women) patients referred to the Faculty of Dentistry for implant treatment, who met the inclusion criteria, were examined. Four different materials were used in each implant, including 2% chlorhexidine, 3% tetracycline, saliva, and a dry medium. Each test material was placed inside the implant screw during the anchorage session, and the healing screw was closed. Patients were then sampled in three implantation sessions and one month after prosthesis delivery. Interstitial fluid groove was used for sampling after cleaning the mouth (half an hour after three minutes of thorough brushing). The data were analyzed with SPSS 20 using ANOVA and relevant post hoc tests.Results. There was a significant difference in the mean IL-6 and IL-1β levels between the four materials (P

Background: Traditional pharmacy education often relies on fragmented, subject-centered curricula, which may inadequately prepare students for the complexities of advanced healthcare. This study evaluates the effectiveness of an integrated pharmacy education approach in enhancing foundational knowledge and practical skills. Methods: An integrated course focused on respiratory diseases was developed and implemented for final-year pharmacy students at Tabriz University of Medical Sciences. The course utilized case-based learning and incorporated elements from various disciplines such as pharmacology, medicinal chemistry, and pharmaceutics. An educational controlled trial was conducted, comparing an intervention group (integrated course) with a control group (traditional course). Results: Survey results revealed that over 60% of students reported substantial improvements in their ability to manage respiratory cases. The intervention group demonstrated significantly higher clinical decision-making skills, with an average test score of 31.4 compared to 15.75 in the control group (p < 0.05). Student feedback highlighted the value of integrated education, advocating for its broader inclusion in the curriculum and the addition of more diverse topics and case studies. Conclusions: Integrated pharmacy education, through a case-based approach, significantly enhances student competency and practical skills, better preparing them for real-world pharmacy practice. The study supports the implementation of integrated courses across pharmacy schools to develop curricula and improve educational outcomes. Future recommendations include continuous curriculum integration and expansion of topics to further enrich pharmacy education. [ABSTRACT FROM AUTHOR]

Central serous chorioretinopathy (CSCR) is a retinal disease characterised by the accumulation of subretinal fluid, which often resolves spontaneously in acute cases. However, approximately one-third of patients experience recurrences that may cause severe and irreversible vision. This study aimed to identify parameters derived from optical coherence tomography (OCT) that are associated with CSCR recurrence. Our dataset included 5211 OCT scans from 344 eyes of 255 patients diagnosed with CSCR. 178 eyes were identified as recurrent, 109 as non-recurrent, and 57 were excluded. We extracted parameters using artificial intelligence algorithms based on U-Nets, convolutional kernels, and morphological operators. We applied inferential statistics to evaluate differences between the recurrent and non-recurrent groups, and we used a logistic regression predictive model, reporting the coefficients as a measure of biomarker importance. We identified nine predictive biomarkers for CSCR recurrence: age, intraretinal fluid, subretinal fluid, pigment epithelial detachments, choroidal vascularity index, integrity of photoreceptors and retinal pigment epithelium layer, choriocapillaris and choroidal stroma thickness, and thinning of the outer nuclear layer, and of the inner nuclear layer combined with the outer plexiform layer. These results could enable future developments in the automatic detection of CSCR recurrence, paving the way for translational medical applications. [ABSTRACT FROM AUTHOR]

Abstract Objective Reperfusion of ischemic myocardium generates oxidative stress, which itself can mediate myocardial injury. So, in this study, we investigated the level of oxidative stress markers and its association with clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Results As indicated in the results, Post MI (Myocardial Infarction) heart failure was significantly higher in the group A (11% vs 4%, p = 0.047). Complete STR (ST-segment resolution) was observed to be significantly higher in the group B (36% vs 17%, p = 0.006). The SOD (Superoxide dismutase) and GPX (Glutathione peroxidase) levels were significantly higher in the group B compared to the other group (1547.51 ± 328.29 vs. 1449.97 ± 246.06, p = 0.019 and 60.62 ± 11.95 vs 57.41 ± 10.14, p = 0.042). The levels of GPX and SOD were shown to be directly related with complete STR and post PCI (Percutaneous coronary intervention)TIMI(Thrombolysis in Myocardial Infarction) flow 3 in the group A (p = 0.002 and p

Recently, an increasing number of studies have reported an association between the incidence of seizures and the use or abuse of tramadol. The aim of this study was to review articles involving patients with tramadol-induced seizures that reported their characteristics and the consumed tramadol dosage. The following databases were searched from their inception until October 30, 2018: PubMed, EMBASE, the Cochrane Library, Scopus, Ovid, Proquest and Science direct. All cross-sectional studies that reported the tramadol dosage and individual characteristics of patients with tramadol-induced seizure were included. The studies were assessed for any bias risk using the adapted Newcastle-Ottawa scale. The pooled estimates were reported using random-effects meta-analysis. Our search identified a total of 3,275 articles, and we finally extracted data from 11 studies involving 970 patients. The included studies were all conducted in developing countries. The pooled data resulted in an estimated mean (± standard deviation) of 1,454.5±333.6 mg for tramadol dosage that induces seizures in patients. The mean minimum tramadol dose causing seizure in the pooled data was 169.5±131.2 mg. The mean age of the patients was 25.85±0.86 years. In addition, 83.37±12.6% of the patients were male, and the manner of poisoning in 70.51±29.07% of the patients was suicide or abuse. Our findings demonstrated that the prevalence of seizures following the consumption of tramadol was higher among males. Therefore, the probability of seizure should be considered by physicians in prescribing tramadol, and the individuals receiving it, especially the ones at a higher risk of exposure, should be properly informed about its complications.

Background: Type 2 diabetes mellitus is a chronic metabolic disorder with prominent vascular injuries. In this condition, the levels of multiple pro- and anti-angiogenic factors have been shown to change. This study aimed to investigate the possible effect of metformin on pro-angiogenic factor, endocan levels, via the modulation of p-AMPK/AMPK axis in diabetic mice. Methods: Mice were randomly assigned to one of 4 groups (n=6): Control (normal saline) and the diabetic group was injected streptozotocin and two groups were given 50 and 100 mg/kg metformin orally, once daily for two weeks after diabetes induction. Endocan protein levels were detected in the liver and kidneys by ELISA and immunofluorescence analysis. Phosphorylation of AMPK was assessed using western blotting. Histological examination was performed to follow the metformin effect on Von Willebrand factor expression and diabetes-related pathologies. Results: ELISA assay showed an elevated levels of endocan in the renal and hepatic tissues of diabetic mice following treatment with metformin (p0.05). Conclusion: Metformin could change the endocan levels during diabetic condition possibly by the modulation of p-AMPK/AMPK axis.

Background: Astragaloside IV (AST) is a saponin from the roots of Astragalus plants which has been widely used in traditional medicine to treat cardiovascular diseases. However, the effect of AST on myocardial infarction remains unknown. Thus, we aimed to investigate the cardio protective effects of AST on isoproterenol-induced myocardial infarction in rats. Methods: AST was isolated from the roots of Astragalus caspicus. Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatment with 2.5, 5 and 10 mg/kg AST given orally immediately before MI induction. Subcutaneous injection of isoproterenol (100 mg/kg) for two consecutive days was used to induce myocardial infarction. AST was given orally once daily for 4 days. On the fifth day hemodynamic and electrocardiographic parameters were assessed, and serum and tissue samples were used to evaluate histological and biochemical changes. To more assessment of the effects of AST on myocardium, we also used three doses of 0.1, 1 and 2 µM of AST in isolated heart model. In statistical analysis with one-way-ANOVA test, any differences between groups were considered significant at p