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Parkinson's disease is a progressive neurodegenerative movement disorder. We aimed to investigate the effects of regular swimming exercise and melatonin applied in the 6-Hydroxydopamine-induced Parkinson's disease rats by analysing dendritic spine of striatal neurons. Twenty-four male Wistar albino rats were used. 6-Hydroxydopamine unilaterally injected four (control, exercise, melatonin and exercise + melatonin) groups were included in the study. Tyrosine hydroxylase expression was detected by immunohistochemistry. Neurons and structures were identified from three-dimensional images by Neurolucida software. There was not any apparent difference for tyrosine hydroxylase positive neurons in the substantia nigra pars compacta and fibres in the striatum between the lesion sides of hemiparkinsonian groups. The treatment groups blocked the apomorphine-induced increase in rotations compared to the control group. In stepping test, the treatment groups prevented the loss of stepping in the contralateral side of hemiparkinsonian groups. The melatonin mostly had a positive effect on motor activity tests. In morphological analyses, the 6-Hydroxydopamine-induced lesion led to the reduction of the total dendritic length and number of branches. In the treatment groups, the reduction of the dendritic parameters was not observed. 6-Hydroxydopamine lesion led to a decrease in the total spine density, spine densities of thin and mushroom types. The exercise and melatonin treatments prevented the loss of spine density. The exercise treatment prevented the loss of spine density of mushroom type spines. The melatonin treatment blocked the loss of spine density of stubby type. In conclusion, these results provide evidence for effective additional protective therapeutic strategies for Parkinson\"s disease. In conclusion, results from the current study provide evidence for swimming exercise and melatonin as a promising candidate for effective additional protective strategies for PD.

In this work, twenty hydrazide-hydrazone and 4-thiazolidinone derivatives were synthesized starting from m-cresol. Antimicrobial evaluation was carried out by microdilution method against Enterococcus faecalis and Staphylococcus aureus as Gram-positive bacteria and Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria, and three pathogenic fungi Candida albicans, Candida parapsilosis and Candida krusei. Some compounds possessed considerable antimicrobial properties against the tested microorganisms, particularly against E. coli. 4-Thiazolidinones containing 3-methoxyphenyl and 3,5-dichlorophenyl moieties (4h and 4i) were found to be the most active derivatives with MICs of 2 μg/mL against E. coli. N'-[(3,5-dichlorophenyl)methylidene]-2-(3-methylphenoxy)acetohydrazide (3i) also displayed antifungal activity against Candida krusei that was comparable to fluconazole. Calculated drug-likeness and ADMET parameters of the most active compounds confirmed their potential as antimicrobial drug candidates. Molecular docking investigations were carried out in the thiamine diphosphate-binding site of pyruvate dehydrogenase multienzyme complex E1 component (PDHc-E1) to clarify the potential antibacterial mechanism against E. coli. The results showed the potential and importance of developing new hydrazones and 4-thiazolidinones that would be effective against microbial strains. Communicated by Ramaswamy H. Sarma

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4\%), DCF (17.4\%) and ECF (8.1\%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2\%, R0 resection rate 86.4\%, and D2 dissection rate was 66.8\%. Rate of pCR and near-CR (24\%), and R0 resection (84\%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95\% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95\% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68\%). We still do not know which NACT regimen is the best choice for daily practice. Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Objective The aim of this study was to optimize the currently used direct spectrophotometric serum prolidase enzyme activity (SPEA) assay method and compare its diagnostic accuracy with current precipitation and direct spectrophotometric assay methods, AST-to-ALT ratio, age platelet index, AST-to-platelet ratio index, cirrhosis discriminate score, Doha score, FIB-4, FibroQ, fibrosis index, Goteborg University Cirrhosis Index , King’s score, and Pohl score for distinguishing Ishak F0 from F1–F3 in patients with chronic hepatitis B (CHB) infection. Methods Liver biopsy results from 112 patients were included in this study. Results The SPEA values were 529 (292–794) U/L, 671 (486–927) U/L, and 1077 (867–1399) U/L with the precipitation, current, and optimized direct spectrophotometric assay methods, respectively. According to multivariate logistic regression analysis optimized direct spectrophotometric SPEA was the only statistically significant parameter to predict the early stages of liver fibrosis. Conclusions Optimized direct spectrophotometric SPEA assay method could be used to distinguish early stages of liver fibrosis in patients with CHB infection instead of the currently used spectrophotometric SPEA assay methods and other evaluated liver fibrosis indexes.

Introduction: We aimed to study the characteristics of peritoneal dialysis (PD) patients with coronavirus disease-19 (COVID-19), determine the short-term mortality and other medical complications, and delineate the factors associated with COVID-19 outcome. Methods: In this multicenter national study, we included PD patients with confirmed COVID-19 from 27 centers. The baseline demographic, clinical, laboratory, and radiological data and outcomes at the end of the first month were recorded. Results: We enrolled 142 COVID-19 patients (median age: 52 years). 58.2% of patients had mild disease at diagnosis. Lung involvement was detected in 60.8% of patients. Eighty-three (58.4%) patients were hospitalized, 31 (21.8%) patients were admitted to intensive care unit and 24 needed mechanical ventilation. Fifteen (10.5%) patients were switched to hemodialysis and hemodiafiltration was performed for four (2.8%) patients. Persisting pulmonary symptoms (n = 27), lower respiratory system infection (n = 12), rehospitalization for any reason (n = 24), malnutrition (n = 6), hypervolemia (n = 13), peritonitis (n = 7), ultrafiltration failure (n = 7), and in PD modality change (n = 8) were reported in survivors. Twenty-six patients (18.31%) died in the first month of diagnosis. The non-survivor group was older, comorbidities were more prevalent. Fever, dyspnea, cough, serious-vital disease at presentation, bilateral pulmonary involvement, and pleural effusion were more frequent among non-survivors. Age (OR: 1.102; 95% CI: 1.032–1.117; p: 0.004), moderate-severe clinical disease at presentation (OR: 26.825; 95% CI: 4.578–157.172; p < 0.001), and baseline CRP (OR: 1.008; 95% CI; 1,000–1.016; p: 0.040) were associated with first-month mortality in multivariate analysis. Discussion/Conclusions: Early mortality rate and medical complications are quite high in PD patients with COVID-19. Age, clinical severity of COVID-19, and baseline CRP level are the independent parameters associated with mortality.

© 2022 Taylor & Francis Group, LLC.A simple, rapid, and precise high performance liquid chromatography (HPLC) method was developed to determine the flavonoid apigenin in cosmetic products containing chamomile extracts. A C18 column was used as stationary phase and 70:30 ethanol:water was used as mobile phase with a 1 mL/min flow rate and isocratic elution. The temperature was stabilized at 25 °C during the separation. The injection volume was 50 μL. The apigenin peak was eluted at 4.15 ± 0.4 min. The method was validated according to International Conference on Harmonisation (ICH) criteria in terms of linearity, limit of detection, limit of quantitation, selectivity, sensitivity, robustness, accuracy, and precision. The limits of detection and quantitation were 0.060 and 0.2 μg/mL respectively. The linear range was from 0.2 to 20 μg/mL. The relative standard deviation values for intraday and interday analyses were less than 1.64%. The developed procedure was applied to the analysis of various cosmetic products. It is expected that the method is suitable for routine analysis, quality control and standardization of cosmetic products for apigenin.

The apoptotic protease activating factor 1 (APAF1) gene encodes a cytoplasmic protein that initiates apoptosis and is a crucial factor in the mitochondria-dependent death pathway. APAF1 is implicated in many pathways such as apoptosis, neurodegenerative diseases, and cancer. The purpose of this study was to predict deleterious/damaging SNPs in the APAF1 gene via in silico analysis. To this end, APAF1 missense SNPs were obtained from the NCBI dbSNP database. In silico analysis of the missense SNPs was carried out by using publicly available online software tools. The stabilization and three-dimensional modeling of mutant proteins were also determined by using the I-Mutant 2.0 and Project HOPE webservers, respectively. In total, 772 missense SNPs were found in the APAF1 gene from the NCBI dbSNP database, 18 SNPs of which were demonstrated to be deleterious or damaging. Of those, 13 SNPs had a decreasing effect on protein stability, while the other 5 SNPs had an increasing effect. Based on the modeling results, some dissimilarities of mutant type amino acids from wild-type amino acids such as size, charge, and hydrophobicity were revealed. The SNPs predicted to be deleterious in this study might be used in the selection of target SNPs for genotyping in disease association studies. Therefore, we could suggest that the present study could pave the way for future experimental studies.