Group Of Drugs Research Articles

In Silico Screening of Sulfonamide Derivatives against Glycolytic Enzymes Reveals Mutation‐Independent Interactions of Sulfisoxazole and Sulfamethazine

AbstractGlycolysis is a highly conserved biochemical process that involves the sequential conversion of glucose to pyruvate and the generation of adenosine triphosphate (ATP), generating energy for cellular functions. This is carried out by several enzymes that play an important role in glucose metabolism. The sulfonamide group of drugs is commonly used as an antibiotic that inhibits the bacterial folic acid production pathway, although its effects on glycolytic enzymes are unclear. Since altered glycolytic enzyme expression is linked to a variety of metabolic disorders as well as cancer, the quest for new ligands against glycolytic enzymes is never over. We revealed that different sulfonamide derivatives interact with glycolytic enzymes with varying binding affinities. Among the selected sulfonamides, sulfisoxazole and sulfamethazine had greater binding scores to certain glycolytic enzymes than others. In silico point mutation analysis predicts that sulfisoxazole and sulfamethazine interact with certain glycolytic enzymes in a residue‐independent manner. This research generates a repository of the 2D interactions of sulfonamide derivatives with glycolytic enzymes, binding energies, impacts of induced point mutations on the local environment, and changes in protein structural flexibility. In the future, sulfisoxazole and sulfamethazine may be repurposed as specific glycolytic enzyme inhibitors to combat a variety of glycolysis‐related metabolic disorders.

P017 AFTER 14 YEARS OF WAR - HYPERTENSION IN SYRIA: BETWEEN CLINICAL PRACTICE AND AVAILABLE MEDICATIONS (ANALYTICAL STATISTICAL STUDY)

Background: Hypertension is one of the most common chronic diseases worldwide. It is also one of the most important risk factors related to public health that leads to multiple consequences. On the other hand, hypertension constitutes a heavy burden on health expenditures, especially in developing countries with limited income. Through this study, we aim to identify the reality of hypertension in Syria as a country that has been suffering from war for more than 14 years, through the distribution of doctors practicing and treating hypertension, the availability of various medications to treat it, and the extent to which international guidelines can be applied in clinical practice. Methods: Cardiologists and nephrologists were mainly counted and distributed in Syrian cities. Pharmaceutical companies and drug types produced by these companies were also counted, and drugs were distributed according to therapeutic drug groups. A questionnaire was conducted on the most important types of drugs used by doctors according to different indications. Results: We found that the largest number of cardiologists and nephrologists are located in the capital, Damascus, with a significant preponderance of cardiologists. We also found a significant shortage in the presence of specialists in the eastern governorates and a severe shortage in the number of kidney doctors in the central, northern and eastern governorates, with most of them being in the capital. There was diversity and distribution in most of the drug categories for treating high blood pressure in the first lines of treatment, noting the lack of sufficient intravenous categories. Conclusions: There is a clear shortage in cardiologists and nephrologists in most governorates, with an almost complete absence of intravenous hypertension medications.

Identification of risk factors for adverse drug events in a general hospital.

Adverse events (AEs), and particularly adverse drug events (ADEs), represent a health problem as they can cause permanent damage or death. Understanding the frequency, location, and causes of ADEs can prevent harm to patients. The Global Trigger Tool, produced by the Institute for Healthcare Improvement (GTT/IHI), is widely used to identify AEs. Recognizing the profile of patients who suffer ADEs can reveal clinical or individual characteristics that predispose to the occurrence of AEs. A cross-sectional study was carried out through a retrospective analysis of 120 medical charts of patients discharged from hospital between October 2020 and April 2021. Patients over 18 years old, with a length of stay of more than 24 h, were included. The list of triggers used was from the medication module of the GTT/IHI, which was adapted for use in the institution. Two primary reviewers and a medical reviewer applied this tool. The primary reviewers independently assessed the randomized charts. A meeting to achieve consensus among the reviewers was held every 2 weeks to validate the identified ADEs; classifications were based on harm severity. Multivariate logistic regression was utilized to assess the variables that predicted the occurrence of ADEs, using the backward stepwise method. A total of 43 ADEs were identified, with a frequency of 36 per 100 admissions (43/120). Of these, five ADEs (12%) were responsible for patients being admitted to hospital. In the case of in-hospital ADEs, there were 42.2 per 1000 patients/day. The clinical manifestation of altered kidney function (16%) and the anatomical drug group of the nervous system (33%) were the most frequent ADEs. The multivariate logistic regression model was significant (×2 = 44.960, P < .001), indicating that factors such as: known drug allergy [odds ratio 5.728; 95% confidence interval (CI): 1.249, 26.274, P = .025]; being clinically hospitalized (odds ratio 7.504; 95% CI: 1.654, 34.037; P = .009); number of medicines used (odds ratio 1.100; 95% CI: 1.054, 1.148; P < .001); and being under the care of internal medicine (odds ratio 3.633; 95% CI: 1.257, 10.511; P = .017) were predictor variables associated with the occurrence of ADEs. A significant percentage of hospitalized patients experienced at least one ADE, with rates surpassing those found in similar studies. The GTT/IHI effectively assessed medication-related harm, emphasizing the need for tailored triggers based on population characteristics. Predictor variables can inform preventive strategies. Overall, the tool facilitated a localized risk assessment of medication use.

A proteomics-based study of the mechanism of oxymatrine to ameliorate hepatic fibrosis in mice

ObjectiveThis study investigated the protective effect of oxymatrine (OMT) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice and explored its possible targets and signaling pathways. MethodsMale BALB/c mice were randomly divided into blank control, model, positive drug (silymarin), and OMT administration groups, respectively, with 10 mice in each group. Hepatic fibrosis was induced in mice using CCl4 and the corresponding drug intervention was given. After the final administration, ultrasonography tests, blood tests, and analysis of liver differential proteins using tandem mass tag labeling and liquid chromatography-mass spectrometry were performed. ResultsOMT intervention ameliorated CCl4-induced hepatic fibrosis in mice, significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, down-regulated the expression of fibrosis factors, such as type IV collagen IV, laminin, type III procollagen III, and alpha-smooth muscle actin, and improved liver function. The results of the proteomic analysis showed that the intervention of OMT significantly down-regulated 130 out of 440 up-regulated proteins and up-regulated 70 out of 294 down-regulated proteins, primarily involving the transient receptor potential (TRP) signaling pathway, the peroxisome proliferator-activated receptors (PPAR) signaling pathway, and the metabolic pathway of arachidonic acid. The main differential proteins involved were Cyp2c37, SCP-2, and Tbxas1. In addition, OMT intervention significantly reversed the expression of sterol carrier protein-2 (SCP2) and upregulated the expression of peroxisome proliferator-activated receptor gamma, Cyp2c37, and transient receptor potential cation channel subfamily V member 1 proteins. ConclusionOMT inhibited the proliferative capacity of hepatic stellate cells, induced apoptotic properties, and suppressed the development of fibrosis by elevating Cyp2c37/TRP signaling axis activity and upregulating PPAR pathway activity by inhibiting SCP2.

NSAIDs, analgesics, antiplatelet drugs, and decline in renal function: a retrospective case-control study with SIDIAP database

IntroductionWe aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR).MethodsWe performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m2 in the period 2010–2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88–0.97), SYSADOA (0.87;0.83–0.91) and acetaminophen (0.84;0.79–0.89), and an high risk for metamizole (1.07;1.03–1.12), and antiplatelet drugs (1.07;1.03–1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88–0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03–1.15) and Coxibs (1.19;1.08–1.30). Medium and high use of major opioids shows a high risk (1.15;1.03–1.29). Triflusal showed high risk at medium (1.23;1.02–1.48) and high use (1.68;1.40–2.01).ConclusionWe observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results.

Machine learning assessment of vildagliptin and linagliptin effectiveness in type 2 diabetes: Predictors of glycemic control.

Differential effects of linagliptin and vildagliptin may help us personalize treatment for Type 2 Diabetes Mellitus (T2DM). The current study compares the effect of these drugs on glycated hemoglobin (HbA1c) in an artificial neural network (ANN) model. Patients with T2DM who received either vildagliptin or linagliptin, with predefined exclusion criteria, qualified for the study. Two input variable datasets were constructed: with or without imputation for missing values. The primary outcome was HbA1c readings between 3 to 12 months or the reduction in HbA1c levels. The cohort comprised 191 individuals (92 vildagliptin and 99 linagliptin). Linagliptin group had significantly higher disease burden. For imputed dataset, HbA1c was lower with linagliptin at 3 to 12 months (7.442 ± 0.408 vs. 7.626 ± 0.408, P < 0.001). However, there was a small yet significant difference in HbA1c reduction favoring vildagliptin over linagliptin (-1.123 ± 0.033 vs. -1.111 ± 0.043, P < 0.001). LDL level, uric acid, and the drug group were identified as predictors for HbA1c levels. In the non-imputed dataset HbA1c at 3 to 12 months was lower with linagliptin (median ± IQR: 7.489 ± 0.467 vs. 7.634 ± 0.467, P-value < 0.001). However, both linagliptin and vildagliptin exhibited similar reductions in HbA1c levels (both median ± IQR of -1.07 ± 0.02). Predictors for HbA1c levels included eGFR level and the drug group. Linagliptin effectively lowers HbA1c levels more than vildagliptin including in patients with comorbidities. DPP4-I choice is a constant predictor of HbA1c in all models.

Hepatic focal nodular hyperplasia during follow-up of patients after cyclophosphamide- or oxaliplatin-based chemotherapy: differentiation from liver metastasis

ObjectivesNewly detected hepatic nodules during follow-up of cancer survivors receiving chemotherapy may pose a diagnostic dilemma. We investigated a series of hepatic focal nodular hyperplasia (FNH) diagnosed by either typical MRI features and follow-up or pathology in cancer survivors.MethodsThis retrospective study evaluated 38 patients with tumours who developed new hepatic FNH after cyclophosphamide-based (n = 19) and oxaliplatin-based (n = 19) chemotherapies. The main tumour types were breast cancer (n = 18) and colorectal cancer (n = 17). MRI findings, clinical features, and temporal evolution of all target hepatic lesions (n = 63) were reported. In addition, the two chemotherapy drug groups were compared.ResultsThe median interval between chemotherapy completion and FNH detection was 30.4 months (12.9, 49.4). Six patients underwent biopsy or surgery, while the remaining patients were diagnosed based on typical MRI features and long-term follow-up. Among the patients, 60.5% (23/38) presented with multiple nodules and 63 target lesions were detected. The median size of target lesions was 11.5 mm (8.4, 15.1). The median follow-up time was 32.5 months (21.2, 48.6), and 15 patients experienced changes in their lesions during the follow-up period (11 increased and 4 decreased). The cyclophosphamide-based treatment group had a younger population, a greater proportion of females, and a shorter time to discovery than the oxaliplatin-based chemotherapy group (all p ≤ 0.016).ConclusionsFNH may occur in cancer survivors after cyclophosphamide- or oxaliplatin-based chemotherapy. Considering a patient’s treatment history and typical MRI findings can help avoid misdiagnosis and unnecessary invasive treatment.Clinical relevance statementWhen cancer survivors develop new hepatic nodules during follow-up, clinicians should think of the possibility of focal nodular hyperplasia in addition to liver metastasis, especially if the cancer survivors were previously treated with cyclophosphamide or oxaliplatin.Key PointsCancer survivors, after chemotherapy, can develop hepatic focal nodular hyperplasia.Cyclophosphamide and oxaliplatin are two chemotherapeutic agents that predispose to focal nodular hyperplasia development.Focal nodular hyperplasia occurs at shorter intervals in patients treated with cyclophosphamide.Graphical

Evaluation of comparative efficacy of Mashadi oil (Tinospora cardifolia) and Erandadi oil Ricinus communis via nasal administration in the management of cervical spondylosis: a randomized controlled trial protocol

Background- Cervical spondylosis is a disease that is caused by the vitiation of only one bodily humor (dosha) (Vataja nanatmaja). The vata bodily humor (dosa) becomes vitiated and settles in the cervical (manya), creating neck pain and stiffness, which ultimately led to cervical spondylosis. Cervical spondylosis can be examined primarily under the generalization of cervical spondylosis because both conditions have many of the same symptoms. A disorder known as cervical spondylosis, which affects the cervical vertebra, is a degenerative condition of the cervical spine. In addition to having negative effects on a person's health, the disease also significantly lowers the quality of life and daily activities. Ayurveda suggested a treatment for cervical spondylosis to avoid and control the condition. There are numerous therapies in Ayurveda, and Oil administration through the nostrils has been given a significant role in upper clavicular disease (Uurdhvajatrugata roga). Oil administration through nostril therapy has been specifically recommended by Acharya Charka for the treatment of cervical spondylosis. The purpose of certain ayurvedic approaches in the management of cervical spondylosis. Methods: - 60 patients will be split into two groups for this investigation. A tinospora cardifolia and a group of drugs (Mashadi oil) will be given to the group through the nostrils for seven days at a dose of eight drops. The same will be used for the other 30 patients, i.e., group B with Ricinus Communis and a group of drugs (Erandadi oil) administered through the nostrils. Expected result: The result will be assessed on the baseline of objective parameters, and data will be compared after the treatment.

Lamotrigine: A Safe and Effective Mood Stabilizer for Bipolar Disorder in Reproductive-Age Adults.

Lamotrigine belongs to the group of antiepileptic drugs and mood stabilizers, and its action is based on the selective blocking of voltage-deficient sodium channels. The effect of this mechanism is the stabilization of the presynaptic part of the neuronal membrane and subsequent inhibition of the secretion of the neurotransmitters glutamate and aspartate into the postsynaptic part of the neuron. Lamotrigine has been approved by the Food and Drug Administration for the maintenance treatment of adults with bipolar disorder since 1994. In the field of psychiatry, this medicine is also used off-label in the treatment of acute bipolar depression. Studies show promising effects of the use of lamotrigine in bipolar disorder type II with rapid phase change. Bipolar disorder is a common psychiatric problem that most often affects young adults. Lamotrigine is most effective in bipolar disorder in preventing depressive episodes, which dominate the clinical picture of this disease. The latest research focuses on extending its action, to include manic episodes. Lamotrigine, through an unexplained mechanism, can affect the immune system, causing Stevens-Johnson syndrome, hemophagocytic lymphohistiocytosis, and drug reaction with eosinophilia and systemic symptoms syndrome. These are rare, life-threatening adverse effects that require urgent intervention in the form of drug discontinuation and immunosuppressive treatment. Strict contraindications to the use of lamotrigine include sensitivity reactions accompanied by systemic symptoms. Phenotype testing enables screening of patients predisposed to serious hypersensitivity reactions. The aim of the article is to review the indications, contraindications, and adverse effects of lamotrigine in the treatment of bipolar disorder and depression.

Assessment of nebivolol efficacy in experimental models of toxoplasmosis: insights into parasite burden reduction and neuronal protection.

This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2mg/kg/day and 4mg/kg/day for 8days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41days post-infection and were evaluated after 10days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV's potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV's mechanisms of action and its clinical application in managing toxoplasmosis.

A Retrospective Study (2019-2023) on the Prevalence and Antimicrobial Resistance of Isolates from Canine Clinical Samples Submitted to the University Veterinary Hospital in Stara Zagora, Bulgaria.

The identification of local susceptibility patterns is important for the elaboration of effective local antimicrobial use guidelines and improvement in treatment outcomes. This retrospective study investigated the prevalence of microbial pathogens in dogs over a five-year period (2019-2023) and their antimicrobial resistance patterns with an emphasis on multidrug-resistant strains on the basis of 896 swab samples submitted to the microbiological laboratory at the University Veterinary Hospital, Stara Zagora, Bulgaria. A total of 1247 strains-1046 bacteria and 201 yeasts-were isolated. An increased proportion of Staphylococcus spp. as an agent of infections in dogs along with significant decrease in the share of Streptococcus spp. (from 16.2% in 2019 to 7.7% in 2023) was found. The occurrence of Staphylococcus spp. in otitis externa increased from 53.4% in 2019 to 84.5% in 2023 (p < 0.0001). The resistance of Staphylococcus spp. isolates to amoxicillin/clavulanic acid and cephalexin increased significantly in 2023 vs. 2022. At the same time, increased susceptibility to amikacin was observed in 2023 vs. 2019. For Enterobacteriaceae, significantly decreased resistance against amikacin and marbofloxacin was demonstrated in 2023 compared to 2019. Multidrug resistance (MDR) was present in 405 of 1046 bacterial isolates (38.7%). More than 50% of streptococci and pseudomonads were MDR. Of the MDR staphylococci, 41.7% were isolated from skin lesions and 28.3% were isolated from otitis. More than half of the strains resistant to seven, eight and nine groups of antimicrobial drugs (AMDs) were from wounds/abscesses. The results highlighted the importance of regular local monitoring of the spread of bacterial strains in veterinary clinics and their susceptibility to AMDs with regard to successful therapy outcomes and control on MDR spread.

Pharmaceutical care in the screening process of phase I oncohaematological clinical trials

ObjectiveTo determine the pharmaceutical interventions in patients eligible for phase I cancer clinical trials, focusing specifically on exclusion criteria related to medication or relevant interactions.MethodDescriptive, observational study conducted at a...

Effects of isotretinoin on tooth movement, orthodontically induced and non-orthodontic root resorption: A micro-CT study.

This study aims to investigate whether cumulative dose-dependent isotretinoin (Roaccutane®) could affect orthodontic tooth movement (OTM) and root resorption. Ninety male Wistar Albino rats were divided into 4 groups. While, the control (SALINE), solvent (SOYBEAN) and orthodontic drug (ISOTM) groups underwent orthodontic force, the non-orthodontic drug group (ISO) did not. The rats were administrated saline, soybean oil (SBO) and isotretinoin diluted in SBO (ISOTM, ISO) for 30 days, respectively. Six rats were euthanized in each orthodontic group. Fifty grams of orthodontic force was applied to the remaining rats' first molars using the incisors as anchorage. Six more rats in each group were euthanized on the 7th, 14th and 21st days of the force application. In the ISO group, six rats were euthanized on the 37th, 44th and 51st days of administration. Six rats that were euthanized for ISOTM on the 30th day were also used for ISO to reduce the number of rats used. Micro-computed tomography (micro-CT) and histological analysis were performed. Independent of orthodontic force, isotretinoin caused root resorption in the apical region. However, there was no statistically significant influence of isotretinoin on OTM and orthodontically induced root resorption (OIRR). Despite the lack of strong evidence supporting the orthodontically induced resorptive effect of isotretinoin, this study provided findings regarding the resorptive effects of isotretinoin on non-orthodontic root resorption. Therefore, the present results underscore the importance of close monitoring during orthodontic treatment to mitigate potential root resorption in patients who use isotretinoin because of acne complaints.

Allergy in HIV-Infected patients (on the example of clinical observation)

The article is devoted to the study of the causes of the formation of allergic diseases in patients with HIV infection on the example of a clinical case. Patient C., 35 years old, was under medical supervision at the Victory Clinic from 2013 to 2015 with manifestations of skin allergies. Over the next four years, the patient received therapy for exacerbation of atopic dermatitis, followed a diet with the exception of dairy products and beef. The patient’s condition could be assessed as satisfactory; relapses of atopic dermatitis were noted 2 times after a violation of the diet. In 2017, after an unprotected contact, the patient noticed: weakness, weight loss, dry skin and enlarged peripheral lymph nodes. In June 2017, the patient turned to the district pediatrician, who prescribed a referral for a general blood and urine test, a blood test for AIDS and hepatitis. As a result of the examination, the patient was diagnosed with HIV infection. The patient was examined and treated at the Yakutsk AIDS center. Since August 2017, the patient has been worried about nasal congestion, sneezing, watery eyes, and headaches. In early September 2017, the patient turned to an allergist-immunologist. An examination was conducted: a blood test was taken for allergoscreen panel No. 1 and an immunogram, rhinocytogram. The following results were obtained: according to allergoscreen No. 1, allergy to birch 3.0, milk 3.2, wheat flour 2.8. Rhinocytogram data from 09/28/2017: neutrophils 67 per-field and eosinophils 10 per-field. People infected with the human immunodeficiency virus (HIV) have high levels of allergic conditions, including allergic rhinitis (hay fever), drug allergies and asthma. The HIV virus infects and destroys CD4+T cells, a type of white blood cell. This leads to a change in immune function, which contributes to the development of allergies, infections, cancer and other immune problems. In a patient with HIV infection, after the pathology is detected, the formation and transformation of allergic diseases is observed. The formation of allergopathology in HIV patients is associated with a reduced level of CD4+ cells, which is one of the factors contributing to the development of allergy transformation. The treatment of allergic diseases such as: bronchial asthma, atopic dermatitis, allergic rhinitis and allergic urticaria in patients with HIV is the same as in patients not infected with HIV. Oral administration of glucocorticosteroids should be avoided due to the immunosuppressive effects of this group of drugs.

State of the cardiovascular system in thyroid pathology

The review presents the data on cardiac damage in patients with thyroid dysfunction (hyper- and hypothyroidism). The features of cardiovascular pathology in patients with hyperthyroidism and the possibility of using certain groups of drugs (beta blockers, antiplatelet agents, anticoagulants) are described. The association of hypothyroidism (including subclinical) with atherosclerosis and diastolic arterial hypertension, an increased risk of developing ischemic heart disease and myocardial infarction, heart failure and cardiovascular mortality, regardless of gender, age and previous cardiovascular diseases, has been shown. Available facts indicate the need to determine thyroid hormones in patients with cardiovascular pathology and mandatory assessment of the state of the cardiovascular system in patients with thyroid pathology.

Influence of static cartoons combined with dynamic virtual environments on preoperative anxiety of preschool-aged children undergoing surgery.

Preschoolers become anxious when they are about to undergo anesthesia and surgery, warranting the development of more appropriate and effective interventions. To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery. One hundred and sixteen preschool-aged children were selected and assigned to the drug (n = 37), intervention (n = 40), and control (n = 39) groups. All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation. The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments. The control group received no intervention. The modified Yale Preoperative Anxiety Scale was used to evaluate the children's anxiety level on the day before surgery (T0), before leaving the preoperative preparation room (T1), when entering the operating room (T2), and at anesthesia induction (T3). Compliance during anesthesia induction (T3) was evaluated using the Induction Compliance Checklist (ICC). Changes in mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) were also recorded at each time point. The anxiety scores of the three groups increased variously at T1 and T2. At T3, both the drug and intervention groups had similar anxiety scores, both of which were lower than those in the control group. At T1 and T2, MAP, HR, and RR of the three groups increased. The drug and control groups had significantly higher MAP and RR than the intervention group at T2. At T3, the MAP, HR, and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group. Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction (T3), both of which were higher than those of the control group. Combining static cartoons with dynamic virtual environments as effective as medication, specifically midazolam, in reducing preoperative anxiety and fear in preschool-aged children. This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.

Porous egg microparticles for controllable drug delivery and oncotherapy

AbstractBaicalein (BAI) extracted from Chinese herb has been proved to increase the sensitivity of tumor cells to gemcitabine (GEM) and effectively solve the problem of drug resistance of tumor cells. Nevertheless, intravenous administration often leads to intolerance of patients and side effects. In this paper, we introduced egg‐based porous microparticles for controllable drug delivery and oncotherapy, which avoided frequent intravenous administration. The interconnected porous structure endowed the microparticles with the capacity of loading sufficient drugs and releasing in a controllable way by adjusting the concentration and proportion of egg white and yolk. We have demonstrated that the cell viability of drug delivery system group was less than 50%, while the single drug group was more than 70%, which indicated that the co‐delivery of GEM and BAI could significantly reduce the proliferation of cells. These features indicated that the egg porous microparticles are ideal for controllable drug delivery and oncotherapy.

Software-assisted automated detection and identification of "unknown" analogues of benzodiazepines in liquid chromatography mass spectrometry analysis.

Benzodiazepines (BZDs) construct a large group of psychoactive drugs acting as depressants of the central nervous system (CNS) and used in medicine as sedatives and anxiolytic and antiepileptic agents. The illicit use of these materials is a worldwide problem, and for many years, part of the benzodiazepines have been abused as rape drugs. For example, flunitrazepam (Rohypnol) is most commonly linked by media reports to drug-facilitated sexual assaults, more commonly referred to as "date rape." Furthermore, there are growing concerns for other misuses of these drugs. Over the last few years, there was an increase in the number, type, and availability of new psychoactive substances (NPS) belonging to the benzodiazepine group, challenging standard forensic labs to fully identify the chemical structure of new, unknown benzodiazepines. This work demonstrates a new application of the automated tool for the detection and identification of benzodiazepine analogues using high-resolution-accurate-mass LC-MS analysis, followed by "Compound Discoverer" (CD) software data processing, to automatically detect various benzodiazepine analogues by picking peaks and compare them to in silico calculated modifications made on a predefined basic backbone. Subsequently, a complete structural elucidation for the proposed molecular formula is obtained by MS/MS data analysis of the suspected component. This method was found to be useful for the automated detection and putative identification of a series of nine "unknown" benzodiazepine analogues, at concentrations in the low ng/mL range. We hereby present a general demonstration of this powerful tool for the forensic community in the detection and identification of hazardous unknown compounds.

Genome-wide association study of therapeutic response to statin drugs in cardiovascular disease

Cardiovascular disease (CVD) is one of the main causes of death in the world. The increased level of blood cholesterol is significantly correlated to CVD incidents. Statins are a group of drugs that decrease the synthesis of cholesterol in the liver by inhibiting the final enzyme of the pathway named HMG-CoA reductase. Several investigations showed that different patients give different responses to the administration of statin drugs according to their genetic background. In this research study, using Genome-Wide Association Studies (GWAS) data analysis methods, such as the SimpleM statistical approach and genomic connection matrix, we tried to discover the novel candidate SNPs that were involved in response to statin drugs. The investigation was carried out using 3,221 cardiovascular patients' data about genotypes and phenotypes of two important parameters including total cholesterol, and LDL level, in response to statin administration. Functional annotation of nearest genes to candidate SNPs was also carried out by using comprehensive databases and tools such as BioMart-Ensembl, UCSC, NCBI, and WebGestalt software. Our results represented eight novel SNPs (rs10820084, rs4803750, rs10989887, rs1966503, rs17502794, rs10785232, rs484071, rs4785621) significantly associated with statin response in different individual cardiovascular patients for the first time. In addition, the groups of genes that are close to the SNPs were also represented and evaluated in detail. Our results illustrated that some of the genes such as BAAT, BCL3, and CMTM6 have a direct functional impact on cholesterol level or LDL biosynthesis which confirmed the effects of neighbor SNPs on the response to statin drugs. Today, finding the loci, genes, and molecular mechanisms involved in the response to drugs is of great importance in pharmacogenomics and personalized medicine.

The relationship between clinical impairment and blood drug concentration: Comparison between the most prevalent traffic relevant drug groups

AimThe aim of the present study was to investigate the relationship between blood concentrations of four different drug classes; ethanol, benzodiazepines, amphetamines and tetrahydrocannabinol (THC) and driver impairment as assessed by a clinical test of impairment (CTI). MethodsData was retrieved from a national database on CTI assessments and accompanying blood drug concentrations from apprehended drivers. All drug concentrations in blood were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), and compared to the results of the CTI which were categorized as either “not impaired”, “mildly impaired”, “moderately impaired”, or “considerably impaired”. ResultsA total number of 15 514 individual mono drug-cases collected over 9 years was included. 89 % were men and the median age was 34 years. In addition, 3 684 individual cases with similar age and gender distribution where no drugs were detected, were included as a reference group. For ethanol and benzodiazepines the percentage of clinically impaired cases increased markedly from lower to higher concentration windows, from 60 % to 97 % for ethanol and from 38 % to 76 % for benzodiazepines. The corresponding increase for amphetamines and THC was modest, from 43 % to 58 % for amphetamines and from 41 % to 55 % for THC. The correlation between drug concentration and degree of impairment was high for ethanol (Spearman´s rho=0.548, p<0.001) and relatively high for benzodiazepines (Spearman´s rho=0.377, p<0.001), but low for amphetamines (Spearman´s rho=0.078, p<0.001) and THC (Spearman´s rho=0.100, p<0.001). ConclusionThe percentage of impaired drivers increased with increasing blood drug concentration for all four drug classes, most pronounced for ethanol and benzodiazepines and much less for amphetamines and THC. The median blood drug concentration increased with increasing magnitude of impairment for ethanol and benzodiazepines, while this was much less pronounced for amphetamines and THC. The ranges of drug concentrations, however, were wide for all four drug classes in all impairment categories as assessed by individual clinical examination.