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Aim: To evaluate the effect of timing of antimicrobial therapy on clinical progress of patients with septic shock., Materials and Method: We included 204 adult patients diagnosed with septic shock according to Sepsis-3 criteria between March 2016 and April 2021. One-month survival was evaluated using univariate and logistic regression analysis., Results: Antibiotic treatment was initiated within 1 h of the vasopressors in 26.4 % of patients. One-month mortality did not differ significantly between patients with and without empirical therapy coverage on etiological agents. Univariate factors that significantly affected one-month survival were starting antibiotics at the first hour, the unit where the case was diagnosed with septic shock, SOFA scores, qSOFA scores, and lactate level. In multivariate analysis, diagnosis of septic shock in the Emergency Service, SOFA score ≥11, qSOFA score of three and lactate level ≥4 were significantly associated with one-month mortality., Conclusion: Training programs should be designed to increase the awareness of septic shock diagnosis and treatment in the Emergency Service and other hospital units. Additionally, electronic patient files should have warning systems for earlier diagnosis and consultation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Wastewater treatment facility location selection and network design issues have become attractive topics in the field of wastewater management due to increasing human population, resource scarcity, environmental concerns, and rise of necessity for sustainable solutions for future policy designs. Especially in areas where the demand for wastewater treatment increases dramatically over the years because of reasons such as high migration levels, rapid industrialization, and tourism activities, the problem turns out to be more critical and dynamic. The existing studies try to deal with the issue through mathematical modeling approaches based on optimization perspectives, which require significant computational effort. In this study, an alternative approach based on system dynamics (SD) method is proposed to examine the complex dynamic and nonlinear structure of wastewater treatment facility location selection and network design problems. The proposed SD simulation model is designed for a densely populated industrial and tourism spot, the city of Antalya, located on the Mediterranean coast of Turkey. The model is capable of determining where and when to build a new wastewater treatment facility as well as generating the generic wastewater network structure to be built for the five districts situated in the city center based on cost issues for 2015-2040 period. In addition, the impacts of demand level changes for wastewater treatment due to population variations are analyzed via several scenarios to help decision makers to develop sustainable and cost-efficient management policies. Although SD is a frequently utilized approach in the water/wastewater management arena, to the best of our knowledge, this study is the first attempt to examine the complex and dynamic nature of wastewater treatment facility location selection and network design problems through SD approach., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: To interpret test results correctly, understanding of the variations that affect test results is essential. The aim of this study is: 1) to evaluate the clinicians' knowledge and opinion concerning biological variation (BV), and 2) to investigate if clinicians use BV in the interpretation of test results., Materials and Methods: This study uses a questionnaire comprising open-ended and close-ended questions. Questions were selected from the real-life numerical examples of interpretation of test results, the knowledge about main sources of variations in laboratories and the opinion of clinicians on BV. A total of 399 clinicians were interviewed, and the answers were evaluated using a scoring system ranked from A (clinician has the highest level of knowledge and the ability of using BV data) to D (clinician has no knowledge about variations in laboratory). The results were presented as number (N) and percentage (%)., Results: Altogether, 60.4% of clinicians have knowledge of pre-analytical and analytical variations; but only 3.5% of them have knowledge related to BV. The number of clinicians using BV data or reference change value (RCV) to interpret measurements results was zero, while 79.4% of clinicians accepted that the difference between two measurements results located within the reference interval may be significant., Conclusions: Clinicians do not use BV data or tools derived from BV such as RCV to interpret test results. It is recommended that BV should be included in the medical school curriculum, and clinicians should be encouraged to use BV data for safe and valid interpretation of test results., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Background: Providing medical students with opportunities for research experience is challenging for medical schools in developing countries. The Research Training Program (RTP), which is carried out in Ege University Faculty of Medicine (EUFM) parallel to the core curriculum, aims to improve the scientific competencies of the highly motivated students and to provide them with the opportunity to conduct a research. The purpose of this project is to evaluate RTP through the perspectives of students and faculty members., Methods: This phenomenological study included two groups; students of RTP and faculty members who contributed to the program. Interviews were conducted with the research group whose selection was determined by maximum variation technique. Interviews with new individuals continued until data saturation was reached. Interpretative data analysis started with close reading of the transcripts and generating a list of codes. Coding by two independently, developing categories and themes were the following steps., Results: Twenty-one RTP students and 14 faculty members were interviewed. The main motivation for students to participate was the desire to learn how to do research. The introduction course providing the students with the basic competencies needs to be improved in terms of practical activities. It was reported that during the project process students needed intensive guidance especially in finding a research topic and a mentor. The students' lack of time, deficit of enough mentoring and the fact that conducting a research does not provide a competitive advantage for residency are important obstacles to the completion of the program. The most frequently mentioned achievement of the students is to learn all the stages of the research as well as getting acquainted with critical thinking., Conclusions: This research showed that it was realistic to implement research programs for highly motivated students in medical schools with conditions like those in EUFM. The solution of mentor shortage emerged in this study is dependent on the adoption of student research as a national policy. Getting acquainted with the interrogative thinking style, conducting research, and making lifelong learning a core value are more important outcomes of research programs than the number of completed projects.

Background Recently, urinary excretion of the tetrasaccharide 6-α-D-glucopyranosyl-maltotriose (Glc4) has been proposed as a marker for the diagnosis and monitoring of Pompe disease (PD). We aimed to determine the reference intervals and reliable decision-making levels of urine tetrasaccharide concentrations for the diagnosis of infantile- and late-onset Pompe patients in the Turkish population. Methods In this study, nine patients with PD (five of them with late-onset PD [LOPD]) and 226 healthy individuals (aged 0-64 years) were included. Urine Glc4 concentrations were determined using the ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method. Results Our data showed that the urine tetrasaccharide levels decreased with age in healthy individuals (p < 0.001, r = -0.256). It was higher especially during the first year of life compared to that in the elder subjects. The tetrasaccharide level of Pompe patients was higher compared to that of healthy controls of the same age: 99 ± 68 mmol/mol creatinine for infantile onset vs. 4.0 ± 3.0 mmol/mol creatinine for healthy controls of the same age group and 12.1 ± 17.4 mmol/mol creatinine for late onset vs. 1.7±1.2 mmol/mol creatinine for healthy controls of the same age group. Conclusions The results of this study showed that the reference intervals of tetrasaccharide in urine changed over time; therefore, it is critically important to define age-based decision levels for the diagnosis of LOPD.

Cystinosis is an autosomal recessive disorder characterized by the accumulation of cystine in lysosomes, causing irreversible damage to organs, especially the kidneys. Intracellular leukocyte cystine concentrations are used to diagnose cystinosis and to monitor cysteamine treatment. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method without derivatization capable of measuring leukocyte intracellular cystine concentrations. During development, the effects of using three different protein precipitation agents were evaluated in terms of sensitivity and the matrix effect, with 12% trichloroacetic acid providing the highest sensitivity. The effects of different blood collection tubes were also assessed in terms of recovery, matrix effect, and protein content. Compared to other methods, our method was quicker (run time of 3 min), was linear over the range 0.078-100 μM, and had lower limits of detection (0.0192 μM) and quantification (0.0582 μM). The intra-day and inter-day reproducibility %CVs were ≤10%. and the method had excellent recovery rates (94%-106%). Other parameters including matrix selectivity, injection carryover, leukocyte lysate stability were also validated and met the acceptance criterias of European Medicines Agency (EMA) Guideline. The assay was successfully applied to quantify cystine leukocyte concentration in healthy and cystinosis patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In recent years, natural products gained popularity with their anti-inflammatory and antioxidant effects mediated by chemical compounds within their composition. Study results offering them as palliative therapy options in cancer or as anticancer agents with high levels of cytotoxicity brought a new approach to combine cancer treatment protocols with these products. From a different perspective, edible types of these products are suggested in daily diets due to their potential cancer preventive effects. Our preliminary work was on blueberry extracts ( Vaccinium myrtillus ) as a main representative of these natural products, and the contents of the extracts were analyzed with liquid chromatography tandem mass spectrometry (LC MS/MS) to reveal the composition and distribution of polyphenolic compounds within. The most abundant polyphenols detected in V. myrtillus extracts were quercetin, kaempferol, and a phenolic acid, gentisic acid (GA). The compounds were further evaluated on treated HCT-116 cells for their potential anticancer effects by measuring total antioxidant status, total oxidant status, and 8-hydroxydeoxyguanosine levels for evaluation of oxidative stress and through protein array analysis and flow cytometric analysis for evaluation of apoptosis. In analysis of oxidative stress parameters, reduced total oxidant levels and reduced oxidative stress index levels were found in cells treated with the compounds in comparison with untreated cells. In apoptosis-related protein profiles, at least twofold reduction in various apoptotic proteins was observed after quercetin and kaempferol treatment, whereas a different profile was observed for GA. Overall, results of this study showed that quercetin and kaempferol have strong cytotoxic, antioxidant, and apoptotic effects, although GA is mostly effective as an antioxidant polyphenol on HCT-116 cells.

The lysosomal storage diseases (LDSs) are a heterogeneous group of inherited genetic disorders caused by defects of lysosomal proteins. The accumulation of undigested substrates from different catabolic pathways leads to cellular dysfunction. LSDs generally presents during early childhood and have a devastating impact on the families and on public health. Over the years, approaches for treatment of some LSDs have been developed with different strategies. Increasing availability of treatments of these diseases has accelerated the development of new methods and techniques for rapid diagnosis in patients with clinical indication.The use of dried blood spot (DBS) test has been proposed as a first tier test to identify patients with Gaucher, Pompe, and Fabry diseases. DBS usage is advantageous for the purpose of screening as it is non-invasive, sensitive, has low-cost and fast turnaround time compared to measurements in leucocyte and/or fibroblast culture. This chapter focuses on the activity measurement of three lysosomal enzymes (α-glucosidase, β-glucosidase, and α galactosidase) in DBS samples by using fluorescent substrates and by the LC-MS/MS (liquid chromatography-mass spectrometry) method. All steps of the methods, from preparation of the solutions to calculation of the enzyme activity, will be explained in detail.

Study Objective: To investigate the relationship between both insulin resistance and fertility and the oxidant/antioxidant system in young, non-obese patients diagnosed with polycystic ovary syndrome (PCOS)., Design: Case-control study., Setting: Department of Obstetrics and Gynecology, Ege University, Izmir, Turkey., Participants: PCOS patients without insulin resistance (IR-) (n = 33), PCOS patients with insulin resistance (IR+) (n = 27), and healthy controls (n = 30). Patients with PCOS and regular sexual intercourse were further divided into infertile (n = 14) and fertile (n = 15) groups., Main Outcome Measures: The malondialdehyde (MDA) and thiol levels as well as the catalase (CAT) and superoxide dismutase (SOD) enzyme activities., Results: Both IR+ and IR- PCOS patients had higher MDA levels and lower thiol levels when compared to the controls (each P < .001). However, only IR- patients had significantly higher SOD (3700.81 ± 410.13 vs 2614.19 ± 611.80 U/g Hb; P < .001) and CAT (7565.06 ± 628.27 vs 6819.61 ± 539.2 U/g Hb; P < .001) activities when compared to the controls. Infertile PCOS patients had significantly higher MDA levels (347.5 ± 22.8 vs 278.6 ± 42.6 nmol/g Hb, P < .001) and lower thiol levels (498.5 ± 56.2 vs 568.5 ± 38.6 μmol/l, P = .001) when compared to fertile patients., Conclusions: The results of this study demonstrated an imbalance in the oxidative-antioxidative system of PCOS patients. This imbalance was worse in IR+ and infertile PCOS patients., (Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)