Bayan Azizi

Metoprolol, a β1-selective blocker, is widely used for treating cardiovascular and non-cardiovascular conditions. Its pharmacokinetics (PK) and pharmacodynamics (PD) vary significantly between individuals, in part due to CYP2D6 genetic polymorphisms. Co-administration of CYP2D6 inhibitors can lead to phenotype-genotype discordance, known as phenoconversion, resulting in clinically significant changes in metoprolol exposure and response. This review examines studies of the combined impact of CYP2D6 genotype and inhibitor use on metoprolol PK and PD. A literature search of PubMed, Embase, and Scopus identified 17 relevant clinical studies. Strong inhibitors such as paroxetine and fluoxetine increased metoprolol exposure by up to 8-fold and induced phenoconversion in extensive metabolizers. Moderate inhibitors, including mirabegron and amiodarone, increased metoprolol exposure by 2- to 3-fold, particularly in those with high baseline CYP2D6 activity. These inhibitors also reduced heart rate and blood pressure, mimicking the response seen in poor metabolizers. Weak inhibitors caused minimal PK changes without notable PD effects. Severe adverse drug reactions, including bradycardia and hypotension, occurred with strong inhibitors, especially in patients with cardiovascular disease and reduced CYP2D6 function. CYP2D6 phenoconversion is a clinically important but often overlooked contributor to metoprolol response variability. Incorporating phenoconversion into clinical practice can lead to more effective pharmacotherapy with metoprolol.

Neurocognitive disorders are characterized by a decline in various components of cognitive function, resulting in a high rate of morbidity and mortality. Despite multiple efforts, there is still a lack of practical preventive and therapeutic approaches for these diseases, and current pharmaceuticals have failed to manage their progression. Consequently, this chapter aims to provide a concise overview of the existing preclinical and clinical evidence that explores the impact of plant-based therapies on the prevention and treatment of neurocognitive disorders. We thoroughly searched different web databases to identify preclinical and clinical studies that investigate the effect of plant-based medicines on cognitive function in animal models, as well as individuals who are healthy, those with mild cognitive decline, or those with Alzheimer’s disease. We included studies that examined plant extracts, multi-component herbal preparations, and phytochemicals such as Nigella sativa Linn., Rosmarinus officinalis L., Ginkgo biloba, and Melissa officinalis. The neuroprotective effects of these plants were associated with their anticholinesterase, anti-inflammatory, and antioxidative activities. None of the included studies reported severe adverse reactions. In conclusion, the results of the preclinical and clinical studies indicate the potential benefits of plant-based therapies on neurocognitive disorders. However, more extended and comprehensive clinical studies must confirm these findings thoroughly.

Purpose of Review Marital quality (MQ) is a psychosocial factor that has been neglected in cardiovascular prevention guidelines, although its association with cardiovascular diseases has been identified in several studies. Therefore, we aim to investigate how MQ either in positive or negative dimensions affect different cardiovascular risk factors and diseases. Recent Findings We systematically searched different databases in September 2023 for longitudinal studies conducted to assess the contribution of MQ to well-established cardiovascular risk factors and diseases. Two independent researchers screened studies and carried out data extraction and quality assessment of included ones. From 12,175 potential studies screened, 40 were included. The presence of significant heterogeneity in methodology, follow-up, and subsequent effect estimates made it unfeasible to do a meta-analysis. Despite the variation, most studies found a significant association of negative MQ measures with physical inactivity (2/2), high levels of smoking (4/5) and alcohol (3/3) use, increased metabolic syndrome risk (3/3), elevated type 2 diabetes mellitus (T2DM) risk and poor T2DM management (3/6), elevated cardiovascular disease risk and progression (9/11), increased body weight and obesity risk (2/3), elevated blood pressure and hypertension risk (7/8). Positive MQ measures were mainly associated with improvement in blood pressure control (2/2), reduced T2DM risk and its good management (1/1), reduced body weight and obesity risk (2/2), and increased survival in cardiovascular diseases (4/4). Summary Based on current evidence, MQ seems to play a crucial role in developing established cardiovascular risk factors and diseases and is worth considering in preventive strategies. Graphical Abstract

Background The pivotal role of oxidative stress and inflammation in the pathophysiology of type 2 diabetes mellitus (T2DM) has been firmly established. However, the evidence concerning hypoglycaemic medicinal plants' antioxidant and anti-inflammatory effects remains inconclusive due to inconsistencies in prior studies. To address this gap, our study aims to perform a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) to consolidate previous research findings in this field. Methods We conducted a comprehensive search in the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases to identify relevant English randomized controlled trials (RCTs). Our study adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. All eligible studies that evaluated concurrently the antioxidative and anti-inflammatory effects of hypoglycaemic plant-derived supplements on type 2 diabetes mellitus (T2DM) were included in the meta-analysis. The meta-analysis itself was carried out using both fixed and random effects models to synthesize the findings from the selected studies. Results Our study included 47 trials with a total of 2636 participants, both male and female, aged between 20 and 79 years, diagnosed with prediabetes, type 2 diabetes mellitus (T2DM), or metabolic syndrome. The meta-analysis revealed that plant-derived treatments, compared to placebos or other medicines, significantly improved oxidative stress (SMD = − 0.36, 95% CI − 0.64 to − 0.09), inflammation (SMD = − 0.47, 95% CI − 0.63 to − 0.31), total antioxidant capacity (SMD = 0.46, 95% CI 0.16–0.75), and antioxidant enzyme activity (SMD = 1.80, 95% CI 1.26–2.33). The meta-regression analysis showed that treatment duration exceeding 8 weeks significantly impacted the heterogeneity of the oxidative stress data. Conclusions Several hypoglycaemic plant-based treatments appear to positively affect T2DM patients by concurrently lowering oxidative stress and inflammatory indicators and boosting antioxidant enzyme activity. Clinical Trail Registry PROSPERO ID: CRD42021226147.

Hypertension (HTN) management continues to be a concern due to challenges with behavioral risk factors. Patient education to modify unhealthy behaviors appears to be effective in managing HTN. Therefore, this meta-analysis aimed to determine whether individualized face-to-face education and counseling have a beneficial effect on systolic and diastolic blood pressure (SBP and DBP) in hypertensive patients. Studies were extracted from PubMed, Scopus, Cochrane Library, and Web of Science databases. Nine studies, comprising 2627 participants, were included. Random effects models were used to pool estimates of mean differences (MDs) with 95% confidence intervals (CIs) in SBP and DBP between the intervention and usual care groups. SBP and DBP were significantly reduced at the 6-month (MD = −4.38 mmHg, 95% CI: −6.95 to −1.81; MD = −2.09 mmHg, 95% CI: −3.69 to −0.50, respectively) and 12-month time points (MD = −2.48 mmHg, 95% CI: −3.96 to −1.01; MD = −1.71 mmHg, 95% CI: −2.88 to −0.55, respectively) with intervention. At the 24-month time point, there was a significant change in SBP (MD = −2.13 mmHg, 95% CI: −3.94 to −0.32) with intervention compared with the usual care group. This study showed that individualized face-to-face education and counseling add significant benefits to usual care for lowering blood pressure in hypertensive patients. Graphical Abstract

Purpose This systematic review aimed to evaluate the effect of transcutaneous auricular vagus nerve stimulation on heart rate variability and baroreflex sensitivity in healthy populations. Method PubMed, Scopus, the Cochrane Library, Embase, and Web of Science were systematically searched for controlled trials that examined the effects of transcutaneous auricular vagus nerve stimulation on heart rate variability parameters and baroreflex sensitivity in apparently healthy individuals. Two independent researchers screened the search results, extracted the data, and evaluated the quality of the included studies. Results From 2458 screened studies, 21 were included. Compared with baseline measures or the comparison group, significant changes in the standard deviation of NN intervals, the root mean square of successive RR intervals, the proportion of consecutive RR intervals that differ by more than 50 ms, high-frequency power, low-frequency to high-frequency ratio, and low-frequency power were found in 86%, 75%, 69%, 47%, 36%, and 25% of the studies evaluating the effects of transcutaneous auricular vagus nerve stimulation on these indices, respectively. Baroreflex sensitivity was evaluated in six studies, of which a significant change was detected in only one. Some studies have shown that the worse the basic autonomic function, the better the response to transcutaneous auricular vagus nerve stimulation. Conclusion The results were mixed, which may be mainly attributable to the heterogeneity of the study designs and stimulation delivery dosages. Thus, future studies with comparable designs are required to determine the optimal stimulation parameters and clarify the significance of autonomic indices as a reliable marker of neuromodulation responsiveness. Graphical abstract

A fine speculation of enantioselectivity prior to the expensive experimental endeavors is truly one of the ultimate goals of the computational organic chemists. In this survey, we have predicted stereo specificity for hetero Diels–Alder (DA) cycloaddition of (E)‐3‐benzylidene‐indoline‐2‐thione (I) with C₂₀ to give (I_a) as drug delivery in the gas phase and in solution, at density functional theory (DFT)–self‐consistent reaction field (SCRF). The enthalpy difference between liquid (l) and gas (g) phases (∆H_l‐g), as well as activation energy (E_exo^≠, E_endo^≠) of I_a cycloadduct, appears proportional to the dielectric constant of solvent (ε). In contrast to the above trends, kinetic stability based on ∆E_L‐H of I_a, develops in opposite to that of ε. The more stability of I_a is attributed to its H―bonding, and dipole–dipole interaction in water. The energy barrier of exo transition states (TS) is low; hence, cycloaddition is recommended to be of synthetically interest for preparation of asymmetric nano compound. Moreover, the π‐π aromatic stacking among the substituted phenyl ring and C₂₀ (π_{substituted phenyl ring} ↔ π_C20) has significant effect on destabilization of endo TS. This DA reaction have polar nature according to one‐step mechanism, that comprises an initial hetero‐DA reaction yielding I_a, which experiences a subsequent [3,3] sigmatropic shift to yield the expected formal cycloadduct. This is a consequence of more polar nature of reaction, due to lower nucleophilicity (N), higher electrophilicity (ω), higher maximum electronic charge (ΔN_max), more polarity (μ), and more global electron density transfer (GEDT) of I_a in polar solvents (especially in water) in comparison to gas phase. This polar character is given by the electrophilic character of the C₂₀ dienophile (ω = 5.29 eV) and nucleophilic character of the 1,3‐diene molecule (I) (N = 3.70 eV). Additionally, molecular mechanism of the considered reaction is substantially different from the DA reactions between simple 1,3‐diene and dienophiles.

Background: Levofloxacin is prescribed widely as a first-line or alternative treatment option for different infectious diseases. The inappropriate use of this agent has increased the risk of antibiotic resistance, which has convinced researchers to address this issue by designing antibiotic prescription pattern studies. Aim: This study aimed to evaluate levofloxacin's prescription pattern and appropriateness in the outpatient setting in Iran. Methodology: This cross-sectional study included all admitted prescriptions containing levofloxacin from October 2018 to June 2019. Data regarding the demographics, clinical and laboratory presentations, preexisting comorbidities, dose and duration of levofloxacin, and the prescribers medical specialty were collected by reviewing the patient's prescriptions or history taking. The pattern and appropriateness of prescriptions were evaluated according to the assessment tool based on accepted international guidelines. Results: A total of 300 eligible patients (median age: 56.5 years; 56.7% male) were included in the study. Respiratory tract infections were the most common indication for levofloxacin prescription (55.6%); more than half of them were related to community-acquired pneumonia (29.6%). The inappropriateness rate for levofloxacin prescription was 55.3 %, of which 12.6% were related to community-acquired pneumonia, 9.6% skin infections, 8.4% rhinosinusitis, and 6.6% Urinary tract infection. Only 54 (18.0%) patients received levofloxacin with an appropriate indication, dose, and duration, indicating its rational use. Conclusion: This study found that more than half of all levofloxacin prescriptions in the outpatient setting are inappropriate, contributed mainly to respiratory tract diseases. Interventions that target these health care providers are essential to improve prescribing of this valuable antibiotic.