Modeling of Effectiveness of N3-Substituted Amidrazone Derivatives as Potential Agents against Gram-Positive Bacteria.

Prediction of the antibacterial activity of new chemical compounds is an important task, due to the growing problem of bacterial drug resistance. Generalized linear models (GLMs) were created using 85 amidrazone derivatives based on the results of antimicrobial activity tests, determined as the minimum inhibitory concentration (MIC) against Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Nocardia corallina, and Mycobacterium smegmatis. For the analysis of compounds characterized by experimentally measured MIC values, we included physicochemical properties (e.g., molecular weight, number of hydrogen donors and acceptors, topological polar surface area, compound percentages of carbon, nitrogen, and oxygen, melting points, and lipophilicity) as potential predictors. The presence of R1 and R2 substituents, as well as interactions between melting temperature and R1 or R2 substituents, were also considered. The set of potential predictors also included possible biological effects (e.g., antibacterial, antituberculotic) of tested compounds calculated with the PASS (Prediction of Activity Spectra for Substances) program. Using GLMs with least absolute shrinkage and selection (LASSO), least-angle regression, and stepwise selection, statistically significant models with the optimal value of the adjusted determination coefficient and of seven fit criteria were chosen, e.g., Akaike's information criterion. The most often selected variables were as follows: molecular weight, PASS_antieczematic, PASS_anti-inflam, squared melting temperature, PASS_antitumor, and experimental lipophilicity. Additionally, relevant to the bacterial strain, the interactions between melting temperature and R1 or R2 substituents were selected, indicating that the relationship between MIC and melting temperature depends on the type of R1 or R2 substituent.

The Influence of Electroconvulsive Therapy (ECT) on Brain-Derived Neurotrophic Factor (BDNF) Plasma Level in Patients with Schizophrenia-A Systematic Review and Meta-Analysis.

The main aim of this systematic review and meta-analysis is to establish whether there is a correlation between the brain-derived neurotrophic factor (BDNF) level and electroconvulsive therapy (ECT) treatment and the reduction in psychotic symptoms in patients diagnosed with schizophrenia. A systematic search of PubMed/Medline, Cochrane Library, Web of Science, Scopus and Embase was conducted up to March 2023. Inclusion criteria: studies in which adult patients with schizophrenia treated with antipsychotic medication received ECT therapy and had the BDNF level measured before and after ECT treatment. Exclusion criteria: animal and in vitro studies or studies not involving complete information about the treatment and concentration of BDNF in plasma. The risk of bias was assessed using Egger's regression-based test for meta-analysis with continuous outcomes. Six studies comprising 248 individuals with schizophrenia were included. A statistically significant increase in BDNF levels after ECT treatment was observed only in two studies (p < 0.001 and p < 0.027, respectively), whereas in four other studies, an upward trend without statistical significance was noticed. The estimated overall size effect revealed that ECT therapy caused a slight change in the BDNF level but without statistical significance (ES = -0.328). Different numbers of ECT procedures (4-10), final measurement of the BDNF level made at a different time point, using bilateral or unilateral electrode positioning during ECT and treatment with different combinations of typical or atypical antipsychotic medications may be potential reasons for the lack of statistical significance in the changes in BDNF levels after treatment. Data regarding the measurement of BDNF levels pre and post ECT therapy in patients with schizophrenia are very limited without an extended follow-up period and evaluation of mental health change. Our meta-analysis showed that treatment with ECT therapy and antipsychotic medication increases serum BDNF levels in patients with drug-resistant schizophrenia compared to patients treated with medication only; however, this effect is not statistically significant.

Disparities in Cisplatin-Induced Cytotoxicity-A Meta-Analysis of Selected Cancer Cell Lines.

Cisplatin is a classic anticancer drug widely used as a reference drug to test new metal complex drug candidates. We found an unexpected diversity in cisplatin-related cytotoxicity values, expressed as IC50 (the half-maximal inhibitory concentration) in tumour cell lines, such as MCF-7, HepG2 and HeLa. We reviewed the data published from 2018 to 2022. A total of 41 articles based on 56 in vitro experiments met our eligibility criteria. Using a meta-analysis based on a random effect model, we evaluated the cytotoxicity of cisplatin (IC50) after 48- or 72-h cell exposure. We found large differences between studies using a particular cell line. According to the random effect model, the 95% confidence intervals for IC50 were extremely wide. The heterogeneity of cisplatin IC50, as measured by the I2 index for all cancer cell lines, was over 99.7% at culture times of 48 or 72 h. Therefore, the variability between studies is due to experimental heterogeneity rather than chance. Despite the higher IC50 values after 48 h than after 72 h, the heterogeneity between the two culture periods did not differ significantly. This indicates that the duration of cultivation is not the main cause of heterogeneity. Therefore, the available data is diverse and not useful as a reference. We discuss possible reasons for the IC50 heterogeneity and advise researchers to conduct preliminary testing before starting experiments and not to solely rely on the published data. We hope that this systematic meta-analysis will provide valuable information for researchers searching for new cancer drugs using cisplatin as a reference drug.

Genetic relatedness, virulence, and drug susceptibility of Campylobacter isolated from water and wild birds.

Introduction: This study aimed to identify the characteristics of Campylobacter isolated from wild birds (Black-headed gulls Chroicocephalus ridibundus and Great tits Parus major) and collect surface water samples (from rivers, ponds, ornamental lakes, freshwater beaches). Research material included 33 Campylobacter isolates. All the strains were isolated by different monitoring and surveillance plans. Methods: The prevalence of selected genes (flaA, cadF, iam, cdtB, wlaN, sodB, tet0) encoding virulence factors and resistance among Campylobacter spp. was assessed by the PCR method. The genetic similarities of isolates were determined by Pulsed-Field Gel Electrophoresis (PFGE). The susceptibility of Campylobacter isolates to clinically important antimicrobials: erythromycin, tetracycline, and ciprofloxacin, previously assessed by E-test, was presented in the form of drug susceptibility profiles depending on the origin of the isolates. Results: The cadF, flaA, cdtB, and sodB genes exhibited the highest detection rate. Statistically significant differences between the presence of wlaN virulence genes were noted among different species of the isolates. No genetically identical isolates were found. The most numerous antibiotic susceptibility profile included strains susceptible to all antibiotics studied (profile A-33.3%). The second most common were the tetracycline - and ciprofloxacin-resistant (profile B-27.2%), and tetracycline-resistant profile (C-24.2%) respectively. Discussion: The study revealed the virulent properties of Campylobacter isolated from water samples, and wild birds, and high resistance rates to tetracycline, and fluoroquinolones. The lack of genetic relatedness among strains isolated from water, and birds may indicate other sources of surface water contamination with Campylobacter bacteria than birds. The presence of Campylobacter spp. in wild birds could also have other environmental origins.

Association of FSH with metabolic syndrome in postmenopausal women: a comparison with CRP, adiponectin and leptin.

AIM: The aim of this study was to evaluate the usefulness of follicle-stimulating hormone (FSH) determination in the postmenopausal women with metabolic syndrome (MetS) in a comparative analysis with biomarkers such as C-reactive protein (CRP), adiponectin, leptin and leptin-to-adiponectin ratio (L/A). MATERIAL & METHODS: 135 postmenopausal women with MetS and 153 without MetS were subjected to examinations. RESULTS: The increase in the probability of MetS, when the value of the marker concentration decreased or increased by 1 standard deviation, was two times higher for FSH-based models than for models including CRP and leptin, and was similar to models including adiponectin and L/A. The areas under the ROC curves were 0.78 for FSH, 0.68 for CRP, 0.72 for leptin, 0.76 for adiponectin and 0.80 for L/A. CONCLUSIONS: Our results suggest that the FSH concentration assesses the probability of MetS similarly to L/A or adiponectin and better than CRP or leptin in postmenopausal women.

Association of follicle-stimulating hormone and sex hormone binding globulin with the metabolic syndrome in postmenopausal women.

OBJECTIVES: We compared the association of follicle-stimulating hormone (FSH) and sex hormone binding globulin (SHBG) with metabolic syndrome (MetS). DESIGN AND METHODS: We examined 320 postmenopausal women (148 with MetS and 172 without MetS). RESULTS: FSH was more strongly associated with MetS probability in the logistic regression model compared to SHBG. Receiver operating characteristic (ROC) curves comparison showed greater areas under the curve for FSH than SHBG concentrations. CONCLUSIONS: FSH exhibited a stronger coherence to MetS than SHBG in postmenopausal women.

Comparison between C-reactive protein and adipocyte fatty acid-binding protein as a component of metabolic syndrome in middle-aged women.

OBJECTIVES: We compared the diagnostic accuracy of CRP and adipocyte fatty acid-binding protein (A-FABP) for the metabolic syndrome (MS). DESIGN AND METHODS: We examined 310 middle-aged Caucasian women. RESULTS: CRP and AFABP values were significantly associated with the MS probability in the logistic regression model. Operating characteristic curves comparison showed similar areas under the curve. CONCLUSIONS: Measurement of A-FABP is equivalent to CRP in the diagnostic utility of the MS.

[The study of the prevalence of depressive disorders in primary care patients in Poland]. / Badanie rozpowszechnienia zaburzen depresyjnych u pacjentów podstawowej opieki zdrowotnej w Polsce.

UNLABELLED: Studies performed in recent years in different countries suggest a considerable prevalence of depressive disorders in primary care patients. The aim of our study was the assessment of depressive disorders among primary care patients in Poland. MATERIAL AND METHODS: Three-hundred thirty-three randomly chosen private and public primary care clinics from the whole country took part in the study. In each centre, 20 or 25 patients aged 18-65 years coming for a regular visit were asked to participate in the study. All patients filled in the Beck Depression Inventory (BDI). Additionally, basic demographic data and information on the presence of chronic somatic diseases were collected. Those patients who scored 12 or more points on BDI (cut-offpoint for depression in Poland) were evaluated by a primary care physician for presence of a depressive disorder upon the ICD-10 criteria and subsequently referred for a psychiatric consultation to the nearest psychiatric outpatient clinic for establishing plausible diagnosis of depression. RESULTS: Out of 7360 patients approached, 7289 (95.5%) agreed to participate. The mean age of the sample was 43.3 +/- 13.2 and 71% were females. Forty one percent of patients (2985) had 12 or more points on the BDI and were referred for a psychiatric evaluation. Only half of them came for a psychiatric consultation. Depressive disorder was recognised in 906 patients. Estimated prevalence of depressive disorders in the whole sample was 23.3%. The patients in whom depressive disorders were confirmed by psychiatric assessment had significantly more often hypertension, ischaemic heart disease, anaemia, stroke and hypothyroidism. CONCLUSIONS: The results obtained show that depressive disorders' prevalence in primary care patients in Poland is significant. The patients who had depressive disorders significantly more often than patients without depression suffered from some somatic diseases. In light of the results, both recognition and adequate treatment of depressive disorders in primary care patients should be regarded as equally important as the recognition and treatment of cardiovascular diseases or other common somatic illnesses.

[Antithrombin and protein C activity in the blood of premature newborns with intrauterine growth retardation]. / Aktywnosc inhibitorów ukladu krzepniecia -- antytrombiny i bialka C we krwi obwodowej noworodków urodzonych przedwczesnie z cechami wewnatrzmacicznego zahamowania wzrastania.

UNLABELLED: Intrauterine growth retardation (IUGR) and prematurity are often correlated with higher mortality and morbidity in the first days of life especially due to complications such as: hypoglycemia, polycythemia, necrotizing enterocolitis, meconium aspiration syndrome. Disturbances in the haemostatic system could be responsible for poor outcome of these complications. AIM: To determine the activity of main inhibitor of coagulation-antithrombin, level of protein C, concentration of thrombin-antithrombin (TAT) complexes and fibrinogen in the blood of premature infants with intrauterine growth retardation (IUGR) in comparison with premature infants without IUGR. MATERIAL: 33 premature infants with symptoms of intrauterine growth retardation (IUGR) and 146 premature infants without IUGR were included in our trial. RESULTS: There were no statistical differences between the analyzed groups in the level of protein C, concentration of TAT and fibrinogen. Activity of antithrombin was higher within 1 hour after birth and lower on the third day of life in the group of children with IUGR. CONCLUSIONS: Higher activity of antithrombin after birth in the group of newborns with IUGR prevents excessive activation of coagulation. On the third or fourth day of life the activity of antithrombin decreases due to its higher consumption in the blood of newborns with IUGR.

Effect on peripheral blood natural killer cytotoxic cell activity in rats after intraperitoneal implantation of double veloured polyester (Dacron) prosthesis.

INTRODUCTION: The aim of this study was to assess the changes affecting natural killer cytotoxic cell (NKCC) activity following intraperitoneal implantation of a double veloured polyester prosthesis in a rat model. MATERIAL/METHODS: Blood samples were taken by cardiac puncture 1 h before (base line) and 14, 28, 100 and 180 days post-implantation. Peripheral blood mononuclear cells were separated from heparinized blood by density centrifugation. A standard, 4 h (51)Cr-release assay against YAC-1 target cells at effector to target ratios of 12:1; 25:1 and 50:1 was performed and the number of total leukocytes, lymphocytes, granulocytes, monocytes, and large granular lymphocytes (LGLs), as well as serum corticosterone levels (radioimmunoassay method) were determined. RESULTS: Comparative analysis of the results obtained from animals with implants, baseline samples, and a control group (laparotomy only) revealed lower NKCC, LGL, leukocyte and lymphocyte counts and elevated plasma corticosterone levels in animals receiving the implant on the 14th day post-implantation. CONCLUSIONS: Our findings indicate that the polyester implant can transiently modulate immune system activities. Since NK cells are important in the control of viral infection and carcinogenesis in humans, it is possible that the stress generated by polyester prostheses can exacerbate the surgical stress and put patients at a higher risk for viral infection and/or metastases.