Effect of post-gastrulation exposure to acrylamide on chick embryonic development.

The critical developmental stages of the embryo are strongly influenced by the dietary composition of the mother. Acrylamide is a food contaminant that can form in carbohydrate-rich foods that are heat-treated. The aim of this study was to investigate the toxicity of a relatively low dose of acrylamide on the development of the neural tube in the early stage chick embryos. Specific pathogen-free fertilized eggs (n = 100) were treated with acrylamide (0.1, 0.5, 2.5, 12.5 mg/kg) between 28-30th hours of incubation and dissected at 48th hours. In addition to morphological and histopathological examinations, proliferating cell nuclear antigen (PCNA) and caspase 3 were analyzed immunohistochemically. The brain and reproductive expression gene (BRE) was analyzed by RT-PCR. Acrylamide exposure had a negative effect on neural tube status even at a very low dose (0.1 mg/kg) (p < 0.05). Doses of 0.5 mg/kg and above caused a delay in neural tube development (p < 0.05). Crown-rump length and somite count decreased dose-dependently, while this decrease was not significant in the very low dose group (p > 0.05), which was most pronounced at doses of 2.5 and 12.5 mg/kg (p < 0.001). Acrylamide exposure dose-dependently decreased PCNA and increased caspase 3, with this change being significant at doses of 0.5 mg/kg and above (p < 0.001). BRE was downregulated at all acrylamide exposures except in the very low dose group (0.1 mg/kg). In conclusion, we find that acrylamide exposure (at 0.5 mg/kg and above) in post-gastrulation delays neural tube closure in chicken embryos by suppressing proliferation and apoptosis induction and downregulating BRE gene expression.

Evaluation of anti-seizure medications and their serum concentration with regard to cardiovascular risk parameters: A cross-sectional study.

OBJECTIVE: Epilepsy is a chronic disease that requires long-term monitoring and treatment. It is suspected that there is a interaction between the use of anti-seizure medications and the risk of cardiovascular disease. The aim of the study is to investigate the association between the intake of phenobarbital, carbamazepine and valproic acid and their serum drug concentrations (SDC) with various cardiovascular risk parameters (homocysteine, folic acid, vitamin B12, total cholesterol (TC), triglycerides, high- and low-density lipoprotein (LDL)). METHODS: This is a cross-sectional study. Data (demographic characteristics and laboratory results) of patients treated for epilepsy in a tertiary care hospital between January 2020 and February 2022 were analyzed retrospectively (n = 2014). Kruskal Wallis, Mann-Whitney U, correlation analysis was used, p < 0.05 was considered statistically significant. RESULTS: The median age of patients was 15 years (IQR:8-31) and 48.3 % were women. The highest homocysteine level was found in patients receiving valproic acid, but it was not statistically significant. Patients receiving phenobarbital had the highest levels of folic acid and B12 and the lowest levels of total cholesterol and low-density lipoprotein cholesterol, which was statistically significant. In patients receiving carbamazepine, a moderately negative significant association was found between serum drug concentration and folic acid levels and a moderately positive significant association was found between TC and LDL levels. CONCLUSION: In our study, the majority of patients were children and adolescents. Regular monitoring of drug serum concentrations and metabolic parameters may be useful to select the safest drug in terms of cardiovascular disease risk. Randomized controlled trials on the long-term effects of anti-seizure treatment are needed.

Evaluation of the relationship of treatment and vaccination with prognosis in patients with a diagnosis of COVID-19.

PURPOSE: Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide and caused mortality. Many factors have been reported to affect the prognosis of COVID-19. In this study, we aimed to investigate the effects of drug therapy and vaccination on prognosis in patients hospitalized with a COVID-19 diagnosis. METHODS: In this single-center, cross-sectional study, data were retrospectively collected from patients receiving inpatient treatment at a university hospital with a diagnosis of COVID-19 between January 1, 2020, and April 30, 2022. The patients' demographic and clinical characteristics were recorded. The Chi-square, Cox and logistic regression was performed, P < 0.05 was considered statistically significant. RESULTS: Total 1723 patients (50.1% were men, mean age: 60.6 ± 16.90) who had not been vaccinated rate was 27.0% (> 3 doses: 45.7%). Mortality rate was 17.0%. Increasing age, male, a high Charlson Comorbidity Index (CCI), and no vaccination significantly increased mortality (P < 0.05). The mortality rate was significantly lower in the chloroquine treatment group than in the other treatment groups. Increasing age, male, and a high CCI were determined to be factors that significantly increased the length of hospital stay (LOHS). LOHS found to be significantly lower in the favipiravir or chloroquine groups compared to the remaining treatment groups (P < 0.001). Both mortality and the LOHS significantly differed according to AST, d-dimer, ferritin, and GFR. CONCLUSION: This study primarily investigated the effect of treatment and vaccination on the prognosis of COVID-19. This was determined to be prepared for another potential pandemic that may arise due to COVID-19.

Retrospective Evaluation of Survival and Prognostic Factors in Immune Thrombocytopenia: A Single-Center and Cross-Sectional Study.

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Mugla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015-2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids (p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase.

Knowledge, opinions and attitudes of primary care physicians about generic drugs: a cross-sectional study.

BACKGROUND: Generic drug (GD) use is affected by many factors, including physicians' approach. OBJECTIVE: This study aimed to investigate the knowledge, opinions and attitudes of primary care physicians (PCPs) about GDs and potentially associated factors. METHODS: An adequately representative sample (n = 354) of PCPs was determined via stratified and simple random sample selection method in this descriptive, cross-sectional study. The research data were collected through a face-to-face 40-item survey, where the knowledge, opinions and attitudes about GDs were questioned. The prescribing percentage of GDs overall was also examined. RESULTS: The survey was completed by 305 PCPs (mean age: 49.2 ± 7.9 years; 57.4% male). The rate of correct responses about GDs was 67.6% for basic knowledge and 46.6% for the development process. The percentages of PCPs who declared that GDs were 'less efficacious', 'of lower quality' and 'less safe' than original drugs were 65.2%, 53.4% and 35.4%, respectively. More than half (60.3%) of the PCPs declared not to pay attention to whether the drug is generic while prescribing. It was observed that, as the knowledge level of the physicians increased, negative opinions and prescribing attitudes regarding the effectiveness, quality and safety of the GDs decreased. The rate of GD prescribing (51.6%) in Izmir was lower than the rest of the country (54.6%; P < 0.001). CONCLUSION: This study shows that the knowledge of PCPs about GDs is generally inadequate, which reflects negatively on their opinions and attitudes regarding the use of GDs. Educational activities can help establish awareness that GDs can be used without doubt of their effectiveness, quality and safety.

Potentially inappropriate medication use in elderly patients treated in intensive care units: A cross-sectional study using 2019 Beers, STOPP/v2 Criteria and EU(7)-PIM List.

OBJECTIVE: To determine the prevalence of and the risk factors for Potentially Inappropriate Medication (PIM), the drug groups most commonly evaluated as PIMs in elderly patients in the ICUs by using 2019 Beers Criteria, STOPP version 2 (v2) Criteria and EU(7)-PIM List. The relation between mortality rate and length of ICU stay with PIMs was also examined. METHODS: This was a cross sectional study conducted on patients aged ≥65 years, treated in ICUs (n = 139) between June 8, 2020, and January 11, 2021. Patients' demographic characteristics, clinical data and laboratory findings about the drugs used were collected prospectively. PIMs were evaluated according to each of the criteria applied. Relationship of dependent and independent variables was evaluated using chi-square analysis, t-test and logistic regression analysis. P < .05 was considered statistically significant. RESULTS: The number of patients with at least 1 PIM according to three criteria was 118 (84.9%) (80.6%, 59.7%, 48.2%, Beers, STOPP/v2 and EU(7)-PIM List, respectively). In the univariate analysis, receiving renal replacement therapy and high number of drugs were the covariates that significantly affected the presence of PIM according to all three criteria (P < .05). Combined use of anxiolytics and opioids in Beers Criteria (58.3%), antipsychotics (26.6%) in STOPP/v2 Criteria, and antiarrhythmics (23.7%) in EU(7)-PIM List were the drugs that caused PIM at most. No relationship was found between the presence of PIM and mortality. The length of ICU stay was determined significantly longer in the presence of PIM according to Beers Criteria (P = .028). CONCLUSIONS: In this study, the prevalence of PIM was determined higher in elderly patients in ICU. Our results supported that 2019 Beers Criteria for ICU patients seems to be more directive in detecting PIMs and determining the prognosis. Reducing the number of drugs administered may be the first step to decrease PIMs in elderly patients in ICU and to maintain the treatment safely.

Daidzein nanosuspension in combination with cisplatin to enhance therapeutic efficacy against A549 non-small lung cancer cells: an in vitro evaluation.

Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-ß1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.

Anti-Cataract Effect of the Traditional Aqueous Extract of Yerba Mate (Ilex paraguariensis A. St.-Hil.): An In Ovo Perspective.

INTRODUCTION: The therapeutic effect of different doses of the traditional aqueous extract of dried leaves of yerba mate (Ilex paraguariensis A. St.-Hil.) was investigated in an experimental cataract model in chicken embryos. METHODS AND RESULTS: LC-MS/MS analysis allowed the identification and quantification of 53 metabolites. In the hydrocortisone-induced cataract model, lenses were examined morphologically after treatment and parameters related to oxidative stress (total antioxidant/oxidant status (TAS/TOS), glutathione (GSH), and malondialdehyde (MDA)) were evaluated. Antiproliferative cell nuclear antigen (PCNA) and caspase-3 H-scores were determined and crystallin alpha A (CRYAA) gene expression in the lenses was measured by RT-PCR. The degree of cataract decreased in all treatment groups. While there was no significant difference in TAS levels compared to the negative control, TOS, GSH, and MDA levels were dose-dependently regulated. Treatment groups other than the high-dose group regulated the decrease in PCNA and the increase in caspase-3. CRYAA gene expression increased significantly only at the lowest dose. CONCLUSION: YM, which is becoming increasingly popular as a traditional tea, showed a therapeutic effect on hydrocortisone-induced cataracts in chicken embryos at relatively low doses.

Educational intervention to improve appropriate digoxin therapeutic drug monitoring: a quasi-experimental study.

OBJECTIVES: Our previous retrospecive study evaluating the appropriateness of serum digoxin concentration (SDC) measurements revealed errors in the timing of blood specimen collection in 98% of the tests. The aim of this study is to evaluate the appropriateness of the SDC measurements and the factors involved in inappropriate test-ordering, after training health personnel in digoxin therapeutic drug monitoring. METHODS: This is a training-based quasi-experimental study. The residents and nurses of the Cardiology Clinic were trained first in December 2017, and refresher training courses were carried out every month throughout the study. The medical data of the inpatients receiving digoxin therapy were recorded prospectively, between January and December 2018. The appropriateness of the physicians' orders for SDC measurement was evaluated according to the criteria of the right indication and right timing of blood collection. The results are presented by descriptive statistics, Student's t-test and χ2 analysis. RESULTS: A total of 232 SDC tests were ordered for 121 patients (age: 71.0±12.6 years, 56.2% women). Of these orders,129 (55.6%) were considered appropriate: 205 (88.4%) for indication and 129 (62.9%) for blood collection timing. There was a significant correlation between inappropriate order for SDC test and the age of the patient, female gender, impairment of renal function tests, high levels of serum BNP and the number of medications used (P<0.005). CONCLUSIONS: Approximately a one-half decrease in inappropriate tests compared with our previous study results imply that education has a positive effect on physician behaviour. However, physicians' concerns due to increased risk factors for the patient still play a role in inappropriate test-ordering.

Appropriateness of digoxin measurement in hospitalized patients.

INTRODUCTION: Measurement of serum digoxin concentrations before steady-state is reached results in a falsely low concentration, and may affect treatment safety. We evaluated the proportion of serum digoxin measurements performed before steady-state is reached and the reasons for inappropriate sampling in hospitalized patients. MATERIALS AND METHODS: Electronic medical records of patients hospitalized between January 2011 and December 2015 treated with oral digoxin, that had more than one digoxin measurement were included. Serum digoxin measurements performed before achievement of pharmacological steady state were considered as inappropriate. The chi-square and chi-square for trend tests were used to analyse the relationship between inappropriate measurements and age, gender, diagnosis, inpatient service, serum digoxin, potassium and creatinine concentrations. RESULTS: We evaluated 2065 hospital admissions for 1621 patients and 11,407 digoxin measurements. The time between consecutive measurements was 1.9 ± 2.4 days and 97% of all measurements were classified as inappropriate. There was no releationship between patient age, gender, serum creatinine concentration and inappropriate measurement. As opposed to expected, inappropriate digoxin measurement was higher when potassium concentrations were within the normal range (P = 0.025). Share of inappropriate determinations of digoxin was higher when concentrations > 2.6 nmol/L were recorded (P < 0.05). These measurements were requested most often in coronary care unit and cardiology department. CONCLUSIONS: In our study, inappropriate serum digoxin measurement was found to be very high although only one of the appropriateness criteria was evaluated. The findings reveal the need for some strategies to prevent inappropriate measurements and reduce costs.