Clinical Significance and Patterns of Potential Drug-Drug Interactions in Cardiovascular Patients: Focus on Low-Dose Aspirin and Angiotensin-Converting Enzyme Inhibitors.

Objective: This study assessed the patterns and clinical significance of potential drug-drug interactions (pDDIs) in patients with diseases of the cardiovascular system. Methods: Electronic health records (EHRs), established in 2018-2023, were selected using the probability serial nested sampling method (n = 1030). Patients were aged 27 to 95 years (65.0% men). Primary diagnosis of COVID-19 was present in 17 EHRs (1.7%). Medscape Drug Interaction Checker was used to characterize pDDIs. The Mann-Whitney U test and chi-square test were used for statistical analysis. Results: Drug numbers per record ranged from 1 to 23 in T-List and from 1 to 20 in P-List. In T-List, 567 drug combinations resulted in 3781 pDDIs. In P-List, 584 drug combinations resulted in 5185 pDDIs. Polypharmacy was detected in 39.0% of records in T-List versus 65.9% in P-List (p-value < 0.05). The rates of serious and monitor-closely pDDIs due to 'aspirin + captopril' combinations were significantly higher in P-List than in T-List (p-value < 0.05). The rates of serious pDDIs due to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations were significantly lower in P-List compared with the corresponding rates in T-List (p-value < 0.05). Serious pDDIs due to administration of aspirin with fosinopril, perindopril, and ramipril were detected less frequently in T-List (p-value < 0.05). Conclusions: Obtained data may suggest better patient adherence to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations, which are potentially superior to the combinations of aspirin with fosinopril, perindopril, and ramipril. An abundance of high-order pDDIs in real-world clinical practice warrants the development of a decision support system aimed at reducing pharmacotherapy-associated risks while integrating patient pharmacokinetic, pharmacodynamic, and pharmacogenetic information.

scRNA sequencing technology for PitNET studies.

Pituitary neuroendocrine tumors (PitNETs) are common, most likely benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNET types are classified according to their expression of specific transcriptional factors (TFs) and hormone secretion levels. Some types show aggressive, invasive, and reoccurrence behavior. Current research is being conducted to understand the molecular mechanisms regulating these high-heterogeneous neoplasms originating from adenohypophysis, and single-cell RNA sequencing (scRNA-seq) technology is now playing an essential role in these studies due to its remarkable resolution at the single-cell level. This review describes recent studies on human PitNETs performed with scRNA-seq technology, highlighting the potential of this approach in revealing these tumor pathologies, behavior, and regulatory mechanisms.

Swelling, Protein Adsorption, and Biocompatibility of Pectin-Chitosan Hydrogels.

The study aims to determine how chitosan impacts pectin hydrogel's ability to attach peritoneal leukocytes, activate complement, induce hemolysis, and adsorb blood proteins. The hydrogels PEC-Chi0, PEC-Chi25, PEC-Chi50, and PEC-Chi75 were prepared by placing a mixture solution of 4% pectin and 4% chitosan in a ratio of 4:0, 3:1, 2:2, and 1:3 in a solution of 1.0 M CaCl2. Chitosan was found to modify the mechanical properties of pectin-calcium hydrogels, such as hardness and cohesiveness-to-adhesiveness ratio. Chitosan in the pectin-calcium hydrogel caused pH-sensitive swelling in Hanks' solution. The PEC-Chi75 hydrogel was shown to adsorb serum proteins at pH 7.4 to a greater extent than other hydrogels. PEC-Chi75's strong adsorption capacity was related to lower peritoneal leukocyte adherence to its surface when compared to other hydrogels, showing improved biocompatibility. Using the optical tweezers approach, it was shown that the force of interaction between pectin-chitosan hydrogels and plasma proteins increased from 10 to 24 pN with increasing chitosan content from 0 to 75%. Thus, the properties of pectin-calcium hydrogel, which determine interactions with body tissues after implantation, are improved by the addition of chitosan, making pectin-chitosan hydrogel a promising candidate for smart biomaterial development.

Photobiomodulation under Electroencephalographic Controls of Sleep for Stimulation of Lymphatic Removal of Toxins from Mouse Brain.

The meningeal lymphatic vessels (MLVs) play an important role in the removal of toxins from the brain. The development of innovative technologies for the stimulation of MLV functions is a promising direction in the progress of the treatment of various brain diseases associated with MLV abnormalities, including Alzheimer's and Parkinson's diseases, brain tumors, traumatic brain injuries, and intracranial hemorrhages. Sleep is a natural state when the brain's drainage processes are most active. Therefore, stimulation of the brain's drainage and MLVs during sleep may have the most pronounced therapeutic effects. However, such commercial technologies do not currently exist. This study presents a new portable technology of transcranial photobiomodulation (tPBM) under electroencephalographic (EEG) control of sleep designed to photo-stimulate removal of toxins (e.g., soluble amyloid beta (Aß)) from the brain of aged BALB/c mice with the ability to compare the therapeutic effectiveness of different optical resources. The technology can be used in the natural condition of a home cage without anesthesia, maintaining the motor activity of mice. These data open up new prospects for developing non-invasive and clinically promising photo-technologies for the correction of age-related changes in the MLV functions and brain's drainage processes and for effectively cleansing brain tissues from metabolites and toxins. This technology is intended both for preclinical studies of the functions of the sleeping brain and for developing clinically relevant treatments for sleep-related brain diseases.

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

A predictive model of super response to cardiac resynchronization therapy in short-term period.

BACKGROUND: The left bundle branch block, nonischemic heart failure (HF) and female gender are the most powerful predictors of a super response to cardiac resynchronization therapy (CRT). It is important to identify super responders who can derive most benefits from CRT. We aimed to establish a predicting model that could be used for prognosis of a super response to CRT in short-term period. METHODS: Patients with QRS ≥ 130 ms, New York Heart Association (NYHA) II-III class of HF, left ventricle ejection fraction (LVEF) ≤ 35% and indications for CRT were included in the study. Before and 6 month after CRT the electrocardiography, echocardiography and cardiac scintigraphy were performed. The study's primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6 month CRT. Based on collected data, we developed a predictive model regarding a super response to CRT. RESULTS: Of 49 (100.0%) patients, 32 (65.3%) had a super response to CRT. Patients with a super response were likelier to have a lower cardiac index (p = 0.007), higher rates of interventricular delay (IVD) (p = 0.003), phase standard deviation of left ventricle anterior wall (PSD LVAW) (p = 0.009) and ∆QRS (p = 0.02). Only IVD and PSD LVAW were independently associated with a super response to CRT in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.812 (sensitivity 90.62%; specificity 70.59%). CONCLUSION: Our predictive model is able to distinguish patients with a super response to CRT.

Effect of Cold Adaptation on the State of Cardiovascular System and Cardiac Tolerance to Ischemia/Reperfusion Injury.

Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary to develop novel drugs with mechanism of action different from those currently used in clinical practices. Studying the molecular mechanisms involved in the cardioprotective effect of adapting to cold could contribute to the development of drugs that increase cardiac tolerance to the impact of ischemia/reperfusion. An analysis of the published data shows that the long-term human stay in the Far North contributes to the occurrence of cardiovascular diseases. At the same time, chronic and continuous exposure to cold increases tolerance of the rat heart to ischemia/ reperfusion. It has been demonstrated that the cardioprotective effect of cold adaptation depends on the activation of ROS production, stimulation of the ß2-adrenergic receptor and protein kinase C, MPT pore closing, and KATP channel.

Effect of Callus Cell Immobilization on the Textural and Rheological Properties, Loading, and Releasing of Grape Seed Extract from Pectin Hydrogels.

The purpose of the present study was to prepare pectin hydrogels with immobilized Lemna minor callus cells and to identify the effect of cell immobilization on the textural, rheological, and swelling properties; loading; and releasing of grape seed extract (GSE) from the hydrogels. Hardness, adhesiveness, elasticity, the strength of linkage, and complex viscosity decreased with increasing cell content in the hydrogels based on pectin with a degree of methyl esterification (DM) of 5.7% (TVC) and during incubation in gastrointestinal fluids. An increase in the rheological properties and fragility of pectin/callus hydrogels based on pectin with a DM of 33.0% (CP) was observed at a cell content of 0.4 g/mL. TVC-based pectin/callus beads increased their swelling in gastrointestinal fluids as cell content increased. TVC-based beads released GSE very slowly into simulated gastric and intestinal fluids, indicating controlled release. The GSE release rate in colonic fluid decreased with increasing cell content, which was associated with the accumulation of GSE in cells. CP-based beads released GSE completely in the intestinal fluid due to weak textural characteristics and rapid degradation within 10 min. Pectin/callus hydrogels have the ability to preserve GSE for a long time and may have great potential for the development of proanthocyanidin delivery systems due to their novel beneficial physicochemical and textural properties.

The Positive Association between Melatonin-Containing Food Consumption and Older Adult Life Satisfaction, Psychoemotional State, and Cognitive Function.

The purpose of this study was to test the hypothesis that melatonin-containing food (FMT) consumption is associated with a better sleep schedule and cognitive and psychoemotional state in older adults. A cross-sectional study of 557 (79% females) older adults living in the community with a mean age of 68.9 ± 7.7, ranging from 50 to 90 years, was conducted. The study, conducted in May and September 2023 using a face-to-face interview, collected personal data and assessed FMT intake during the day (FMTday) and for dinner (FMTdinner), life satisfaction, positive and negative affect, depression severity, cognitive functions, and sleep characteristics. Multiple regression and logistic regression analysis, adjusted for co-factors, were used to assess the association between the studied indicators. Multiple regression analysis showed that older adults with higher FMT consumption are more satisfied with life (FMTdinner: ß = 0.107; ∆R2 = 0.011; p = 0.020), have a lower level of depression (FMTday: ß = -0.124; ∆R2 = 0.015; p = 0.003), and higher scores in positive affect (FMTday: ß = 0.169; ∆R2 = 0.016; p = 0.007; FMTdinner: ß = 0.136; ∆R2 = 0.019; p = 0.003). Logistic regression analysis showed that older adults with higher FMT consumption are less likely to have depression (FMTday: OR, 0.614; 95% CI, 0.436-0.864; p = 0.005; FMTdinner: OR, 0.671; 95% CI, 0.476-0.945; p = 0.023), and they perform better on logical thinking tests (FMTday: OR, 2.066; 95% CI, 1.131-2.204; p = 0.013; FMTdinner: OR, 1.887; 95% CI, 1.183-2.138; p = 0.033). A greater life satisfaction as well as a decrease in the cognitive impairment and psychoemotional state of older adults is associated with a higher consumption of melatonin-containing foods.

Angiotensin 1-7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart-The signaling mechanism.

BACKGROUND: The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue of modern cardiology. Over the past 10 years, there has been no significant reduction in mortality among patients with AMI. It is quite obvious that there is an urgent need to develop fundamentally new drugs for the treatment of AMI. Angiotensin 1-7 has some promise in this regard. OBJECTIVE: The objective of this article is analysis of published data on the cardioprotective properties of angiotensin 1-7. METHODS: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. RESULTS: Angiotensin 1-7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart. Angiotensin 1-7 can prevent not only ischemic but also reperfusion cardiac injury. The activation of the Mas receptor plays a key role in these effects of angiotensin 1-7. Angiotensin 1-7 alleviates Ca2+ overload of cardiomyocytes and reactive oxygen species production in ischemia/reperfusion (I/R) of the myocardium. It is possible that both effects are involved in angiotensin 1-7-triggered cardiac tolerance to I/R. Furthermore, angiotensin 1-7 inhibits apoptosis of cardiomyocytes and stimulates autophagy of cells. There is also indirect evidence suggesting that angiotensin 1-7 inhibits ferroptosis in cardiomyocytes. Moreover, angiotensin 1-7 possesses anti-inflammatory properties, possibly achieved through NF-kB activity inhibition. Phosphoinositide 3-kinase, Akt, and NO synthase are involved in the infarct-reducing effect of angiotensin 1-7. However, the specific end-effector of the cardioprotective impact of angiotensin 1-7 remains unknown. CONCLUSION: The molecular nature of the end-effector of the infarct-limiting effect of angiotensin 1-7 has not been elucidated. Perhaps, this end-effector is the sarcolemmal KATP channel or the mitochondrial KATP channel.

Y-Box-Binding Proteins Have a Dual Impact on Cellular Translation.

Y-box-binding proteins (YB proteins) are multifunctional DNA- and RNA-binding proteins that play an important role in the regulation of gene expression. The high homology of their cold shock domains and the similarity between their long, unstructured C-terminal domains suggest that Y-box-binding proteins may have similar functions in a cell. Here, we consider the functional interchangeability of the somatic YB proteins YB-1 and YB-3. RNA-seq and Ribo-seq are used to track changes in the mRNA abundance or mRNA translation in HEK293T cells solely expressing YB-1, YB-3, or neither of them. We show that YB proteins have a dual effect on translation. Although the expression of YB proteins stimulates global translation, YB-1 and YB-3 inhibit the translation of their direct CLIP-identified mRNA targets. The impact of YB-1 and YB-3 on the translation of their mRNA targets is similar, which suggests that they can substitute each other in inhibiting the translation of their mRNA targets in HEK293T cells.

Laparoscopic intracorporeal ileal ureter replacement: multi-institutional data from 102 patients.

OBJECTIVE: To present long-term results of our laparoscopic intracorporeal ileal ureter replacement (LIUR) cohort, including more complex cases of laparoscopic ileocalycostomy. MATERIAL AND METHODS: We collected records of patients undergoing LIUR. Follow-up included a chemical profile and urine cultures. Imaging consisted of renal ultrasonography, excretory urography, cystography, and computer tomographic or magnetic resonance urography. RESULTS: One hundred and two patients were included. Stricture location was left (46.1%), right (39.2%), or bilateral (14.7%). No open conversion was performed. Seventy-four patients (72.5%) underwent a total ureteral unit removal. The mean operative time was 289.4 (120 - 680) minutes. The estimated blood loss was 185.2 (10-400) mL. Three patients had intraoperative complications, and fifteen had early postoperative complications. The mean postoperative hospital stay was 12.2 (7-35) days. The mean follow-up duration period was 37.7 (12-162) months. Most patients' follow-up was uneventful (88%), and seven patients presented with Grade 2 late complications. CONCLUSIONS: Intracorporeal laparoscopic ileal ureteral replacement in cases of extensive ureteral lesions offers optimal long-term outcomes and a low complication rate. Ileocalycostomy constitutes a viable option in the small group of patients with long proximal ureteral strictures and intrarenal pelvis.

Effect of Homogenized Callus Tissue on the Rheological and Mechanical Properties of 3D-Printed Food.

The aim of the study was to develop ink enriched with a high content of lupine callus tissue (CT) suitable for 3D printing. Printable ink obtained using mashed potatoes (20 g/100 mL) and a 3% agar solution was used as the parent CT-free ink (CT0). Viscosity increased from 9.6 to 75.4 kPa·s during the cooling of the CT0 ink from 50 to 20 °C, while the viscosity of the ink with 80 g/100 mL of CT (CT80) increased from 0.9 to 5.6 kPa·s under the same conditions. The inclusion of CT was shown to decrease the hardness of 3D-printed food gel from 0.32 ± 0.03 to 0.21 ± 0.03 N. The storage modulus G' value was 7.9 times lower in CT80 samples than in CT0 samples. The values of fracture stress for CT80 and CT0 inks were 1621 ± 711 and 13,241 ± 2329 Pa, respectively. The loss tangent and the limiting strain did not differ in CT0 and CT80, although the value of the fracture strain was 1.6 times higher in the latter. Thus, the present study demonstrates that CT may be added to printing ink in order to enhance food with plant cell material and enable the 3D printing of specially shaped foods.

The intensity of free radical processes and chaperone activity in the saliva of patients with type 2 diabetes.

Introduction: Saliva is a clinically informative biological fluid that contains many biomarkers, allowing multiple analyses to be performed. Aim: The objectives of this study were the assessment of the serum and saliva levels of biochemical parameters and intensity of free radical processes in T2DM patients and the identification of the correlation between certain criteria. Methods: This case-control study included 40 T2DM patients, which were compared with 40 healthy individuals. The levels of glucose, cholesterol triglycerides, total protein, diene conjugates, and chaperone activity were measured using the spectrophotometric method. The concentration of 8-oxo-2'-deoxyguanosine was assessed by competitive enzyme-linked immunosorbent assay. Results: It was established that the progression of diabetes led to an increase in glucose in saliva. The content of 8-oxo-2'-deoxyguanosine and conjugated dienes increased in serum and this increase was associated with the level of glucose and glycated hemoglobin. The level of protein and chaperone activity increased in the saliva of patients with T2DM compared with the control. The correlation analysis revealed a relationship between total protein concentration and conjugated dienes and between chaperone activity and conjugated dienes in saliva. Conclusions: According to the results of the analysis, the pathological changes in DM affected the salivary glands and their secretions. The obtained results allowed us to recommend using saliva as an alternative to blood for the diagnosis and monitoring of T2DM treatments since it is readily available and quickly responds to changes in metabolism in the body.

Association of Chrononutrition Indices with Anthropometric Parameters, Academic Performance, and Psychoemotional State of Adolescents: A Cross-Sectional Study.

Adolescents are an at-risk group for circadian misalignment. The contribution of sleep-wake rhythm instability to the psychoemotional, cognitive, and weight disorders of adolescents has been studied in sufficient detail. At the same time, there is insufficient information about the association between chrononutrition indices and the well-being of adolescents. The aim of this study is to investigate the relationship between chrononutrition indices and academic achievement, psychoemotional state, and anthropometric indicators in adolescents. The study involved 12,759 students in grades 6-11 of secondary schools, aged 14.2 ± 1.7 years old; 57.2% of whom were girls. Participants provided personal data, frequency and time of meals during the day and at night, on weekdays and weekends, and completed the Zung Self-Rating Depression Scale and the Yale Food Addiction Scale. There is a U-shaped association between eating mid-phase (EPFc), eating jetlag (EJL), and eating window (EW) with GPA, ZSDSI, and FA. At the same time, the frequency of night eating (NE) is linearly associated with the studied parameters. NE is the strongest predictor of ZSDSI (ß = 0.24), FA (ß = 0.04), and GPA (ß = -0.22). EPFc, EJL, and EW practically do not differ in the strength of their association with the studied indicators. ZSDSI is most closely associated with the chrononutrition indices. There is a weak negative association between BMI and EW (ß = -0.03) and NE (ß = -0.04). Thus, circadian eating disorders are more often observed in adolescents with poor academic performance, high levels of depression, and food addiction.

Clinical Case Report of Non-Diabetic Hypoglycemia Due to a Combination of Germline Mutations in the MEN1 and ABCC8 Genes.

INTRODUCTION: Non-diabetic hypoglycemia (NDH) is a collective term including the multiple causes of hypoglycemic syndrome not due to diabetes mellitus. NDH may result from insulinoma, IGF-2-omas, hypocorticism, Hirata's disease, genital disorders of glucose metabolism, etc. One of the most common causes of NDH faced by an endocrinologist is insulinoma, which in turn can be part of the hereditary syndrome of multiple endocrine neoplasia type 1 (MEN1). Congenital disorders of glucose metabolism in adult patients, on the contrary, are diagnosed extremely rarely, since they usually manifest in childhood. This article presents a unique clinical case of a patient with NDH and genetically verified MEN1 in combination with congenital hyperinsulinism due to an ABCC8 gene mutation. CASE REPORT: A 43-year-old patient with hypoglycemic symptoms from childhood is presented, in whom multiple pancreatic tumors and fluctuations in glycemia from 38.7 mg/dL to 329.7 mg/dL (2.15 to 18.3 mmol/L) were detected in adulthood, but a mild course of hypoglycemic syndrome was noted. Numerous examinations that were performed to establish an accurate diagnosis are described, signs that served as a reason for expanding the complex of studies are indicated, possible pathogenetic mechanisms of the mild course of hypoglycemic syndrome and hyperglycemic conditions are discussed. CONCLUSION: This case report is original and highlights that we must always remain intolerant of the inexplicable. Conducting an extended gene study can help perform a correct diagnosis in complex cases.

Pharmacological EZH2 inhibition combined with retinoic acid treatment promotes differentiation and apoptosis in rhabdomyosarcoma cells.

BACKGROUND: Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (< 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign. The histone methyltransferase, Enhancer of Zeste Homolog 2 (EZH2) suppresses normal skeletal muscle differentiation and is highly expressed in RMS tumours. RESULTS: We demonstrate combining inhibition of the epigenetic modulator EZH2 with the differentiating agent retinoic acid (RA) is more effective at reducing cell proliferation in RMS cell lines than single agents alone. In PAX3-FOXO1 positive RMS cells this is due to an RA-driven induction of the interferon pathway resulting in apoptosis. In fusion negative RMS, combination therapy led to an EZH2i-driven upregulation of myogenic signalling resulting in differentiation. In both subtypes, EZH2 is significantly associated with enrichment of trimethylated lysine 27 on histone 3 (H3K27me3) in genes that are downregulated in untreated RMS cells and upregulated with EZH2 inhibitor treatment. These results provide insight into the mechanism that drives the anti-cancer effect of the EZH2/RA single agent and combination treatment and indicate that the reduction of EZH2 activity combined with the induction of RA signalling represents a potential novel therapeutic strategy to treat both subtypes of RMS. CONCLUSIONS: The results of this study demonstrate the potential utility of combining EZH2 inhibitors with differentiation agents for the treatment of paediatric rhabdomyosarcomas. As EZH2 inhibitors are currently undergoing clinical trials for adult and paediatric solid tumours and retinoic acid differentiation agents are already in clinical use this presents a readily translatable potential therapeutic strategy. Moreover, as inhibition of EZH2 in the poor prognosis FPRMS subtype results in an inflammatory response, it is conceivable that this strategy may also synergise with immunotherapies for a more effective treatment in these patients.

Prescribed Versus Taken Polypharmacy and Drug-Drug Interactions in Older Cardiovascular Patients during the COVID-19 Pandemic: Observational Cross-Sectional Analytical Study.

The study aimed to assess clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019-2022). Medscape Drug Interaction Checker was used to identify pairwise drug-drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, the total number of DDIs was significantly higher among the prescribed medications (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among the prescribed and taken medications, respectively (p < 0.05). Median numbers of DDIs between the prescribed vs. taken medications were Me = 2, IQR 0-7 vs. Me = 3, IQR 0-7 per record, respectively. Prevalence of polypharmacy was significantly higher among the prescribed medications compared with that among the taken drugs (p < 0.05). Women were taking significantly more drugs and had higher prevalence of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, implement patient engagement in reporting adverse drug reactions, and provide genetic profiling of patients to avoid potentially serious DDIs.

The Association between Melatonin-Containing Foods Consumption and Students' Sleep-Wake Rhythm, Psychoemotional, and Anthropometric Characteristics: A Semi-Quantitative Analysis and Hypothetical Application.

Food is an important source of melatonin (MT), which belongs to a group known as chronobiotics, a class of substances that affect the circadian system. Currently, no studies have been conducted on how the consumption of foods containing MT (FMT) is associated with indicators characterizing the human circadian system. In this study, we tested the hypothesis that FMT consumption is associated with chronotype and social jetlag. A total of 1277 schoolchildren and university students aged M (SD) 19.9 (4.1) years (range: 16-25 years; girls: 72.8%) participated in a cross-sectional study. Each participant completed an online questionnaire with their personal data (sex, age, height, weight, waist circumference, and academic performance) and a sequence of tests to assess their sleep-wake rhythm (the Munich Chronotype Questionnaire), sleep quality (the Pittsburgh Sleep Quality Index), and depression level (the Zung Self-Rating Depression Scale). Study participants also completed a modified food frequency questionnaire that only included foods containing MT (FMT). They were asked how many foods containing MT (FMT) they had eaten for dinner, constituting their daily serving, in the past month. The consumption of foods containing MT (FMT) during the day (FMTday) and at dinner (FMTdinner) was assessed using this test. Multiple regression analyses were performed to assess the association between the studied indicators. We found that higher FMTday values were associated with early chronotype (ß = -0.09) and less social jetlag (ß = -0.07), better sleep quality (ß = -0.06) and lower levels of depression (ß = -0.11), as well as central adiposity (ß = -0.08). Higher FMTdinner values were associated with a lower risk of central adiposity (ß = -0.08). In conclusion, the data obtained confirm the hypothesis that the consumption of foods containing MT (FMT) is associated with chronotype and social jetlag in adolescents and young adults.

A historical literature review of coronary microvascular obstruction and intra-myocardial hemorrhage as functional/structural phenomena.

The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon, also known as microvascular obstruction (MVO). However, studies performed in the isolated perfused hearts subjected to ischemia/reperfusion (I/R) do not suggest the involvement of microembolization and microthrombi in this phenomenon. The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction. Consequently, the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi, platelets, and neutrophils. Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries. However, reperfusion triggers more pronounced damage, possibly mediated by pyroptosis. MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling. Therefore, pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles. Ischemic conditioning protocols have been shown to prevent MVO, with L-type Ca 2+ channel blockers appearing the most effective in treating MVO.