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Key words: colchicine; hypernatraemia; polyuria [ABSTRACT FROM PUBLISHER]

Invertebrate iridescent virus 6 (IIV6) is a nucleocytoplasmic insect virus and a member of the family Iridoviridae. The IIV6 genome consists of 212,482 bp of linear dsDNA with 215 non-overlapping and putative protein-encoding ORFs. The IIV6 118L ORF is conserved in all sequenced members of the Iridoviridae and encodes a 515 amino acid protein with three predicted transmembrane domains and several N-glycosylation/N-myristoylation sites. In this study, we characterized the 118L ORF by both deleting it from the viral genome and silencing its expression with dsRNA in infected insect cells. The homologous recombination method was used to replace 118L ORF with the green fluorescent protein (gfp) gene. Virus mutants in which the 118L gene sequence had been replaced with gfp were identified by fluorescence microscopy but could not be propagated separately from the wild-type virus in insect cells. Unsuccessful attempts to isolate the mutant virus with the 118L gene deletion suggested that the protein is essential for virus replication. To support this result, we used dsRNA to target the 118L gene and showed that treatment resulted in a 99% reduction in virus titer. Subsequently, we demonstrated that 118L-specific antibodies produced against the 118L protein expressed in the baculovirus vector system were able to neutralize the virus infection. All these results indicate that 118L is a viral envelope protein that is required for the initiation of virus replication., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD., Competing Interests: MArici reports payment or honoraria for lectures, presentations, speakers bureaus, publication writing or educational events from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Menarini, MSD, Novo Nordisk, Sandoz, Sanofi, and participation on a Data Safety Monitoring Board or Advisory Board for Astra Zeneca, Bayer, Boehringer Ingelheim, and Novo Nordisk. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Arici, Altun, Araz, Atmaca, Demir, Ecder, Guz, Gogas Yavuz, Yildiz and Yilmaz.)

Everolimus is an orally administered mechanistic target of rapamycin inhibitor in solid-organ transplant patients. In addition to the common adverse side effects of this treatment, such as hyperlipidemia, rash, stomatitis, anorexia, diarrhea, anemia, thrombocytopenia, and leukopenia, pulmonary toxicity is also an important adverse side effect. Although pulmonary toxicity due to everolimus has been reported mostly as pneumonitis, cases of pleural effusion due to everolimus have also been reported rarely. Chylothorax is defined as the accumulation of lymphatic fluid in the pleural space. It may develop secondary to trauma or malignancy. In this case report, we present a patient with chylothorax after everolimus treatment.

Background: Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform., Methods: hBMMSC-Exos were isolated and characterized. Real-time impedance-based cell proliferation analysis (RTCA) determined the effective dose and treatment window for acute hypoxic PT injury. A 2-lane 3D gravity-driven microfluidic platform was set to mimic PT in vitro. ZO-1, acetylated α-tubulin immunolabelling, and permeability index assessed structural; cell proliferation by WST-1 measured functional integrity of PT., Results: hBMMSC-Exos induced PT proliferation with ED50 of 172,582 µg/ml at the 26th hour. Hypoxia significantly decreased ZO-1, increased permeability index, and decreased cell proliferation rate on 24-48 h in the microfluidic platform. hBMMSC-Exos reinforced polarity by a 1.72-fold increase in ZO-1, restored permeability by 20/45-fold against 20/155 kDa dextran and increased epithelial proliferation 3-fold compared to control., Conclusions: The real-time potency assay and 3D gravity-driven microfluidic acute hypoxic PT injury platform precisely demonstrated the therapeutic performance window of allogeneic hBMMSC-Exos on ischemic AKI based on structural and functional cellular data. The novel standardized, non-invasive two-step system validates the cell-based personalized theragnostic tool in a real-time physiological microenvironment prior to safe and efficient clinical usage in nephrology., (© 2024. The Author(s).)

Urinary omics has become a powerful tool for elucidating pathophysiology of glomerular diseases. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urine proteomic and metabolomic analysis between recently diagnosed renal AA amyloidosis (AA) and membranous nephropathy (MN) patients. Urine samples of 22 (8 AA, 8 MN and 6 healthy control) patients were analyzed with nLC-MS/MS and GC/MS for proteomic and metabolomic studies, respectively. Pathological specimens were scored for glomerulosclerosis and tubulointerstitial fibrosis grades. Functional enrichment analysis between AA and control groups showed enrichment in cell adhesion related sub-domains. Uromodulin (UMOD) was lower, whereas ribonuclease 1 (RNase1) and α-1-microglobulin/bikunin precursor (AMBP) were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03) and AMBP-eGFR (r = -0.69, p = 0.003) variables. Metabolomic analysis showed myo-inositol and urate were higher in AA compared to MN group. A positive correlation was detected between RNase1 and urate independent of eGFR values (r = 0.63, p = 0.01). Enrichment in cell adhesion related domains suggested a possible increased urinary shear stress due to amyloid fibrils. UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be related with systemic inflammation in AA amyloidosis. SIGNIFICANCE: Urinary omics studies have become a standard tool for biomarker studies. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urinary omics analysis between recently diagnosed renal AA amyloidosis (AA), membranous nephropathy (MN) patients and healthy controls. Pathological specimens were scored with glomerulosclerosis (G) and tubulointerstitial fibrosis (IF) grades to consolidate the results of the omics studies and correlation analyzes. Functional enrichment analysis showed enrichment in cell adhesion related sub-domains due to downregulation of cadherins; which could be related with increased urinary shear stress due to amyloid deposition and disruption of tissue micro-architecture. In comparative proteomic analyzes UMOD was lower, whereas RNase1 and AMBP were higher in AA compared to MN group. Whereas in metabolomic analyzes; myo-inositol, urate and maltose were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03), AMBP-eGFR (r = -0.69, p = 0.003) and between RNase1-Urate independent of eGFR values (r = 0.63, p = 0.01). This study is the first comprehensive urinary omics analysis focusing on renal AA Amyloidosis to the best of our knowledge. Based on physiologic roles and clinicopathologic correlations of the molecules; UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be increased with systemic inflammation and endothelial damage in AA amyloidosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Living kidney donors (LKD) may experience some untoward consequences following donation such as development of chronic kidney disease (CKD). In this study, we aimed to investigate the rate of development of CKD and factors affecting the development of CKD in LKDs during long-term follow-up from a center in Turkey., Methods: This study was a retrospective analysis of LKDs followed between January 2000 and December 2017. Pre-transplant and post-transplant clinical data of the 338 LKDs were recorded and compared. Factors affecting the development of stage 3 and later stages of CKD were analyzed., Results: Majority of the donors were females (64.2%), and the median age of all donors was 47 (39-54) years. Stage 3 CKD developed in 50 donors during the median follow-up of 71 months. Older age at the time of transplantation and a low pre-transplant estimated glomerular filtration rate (eGFR) were determined as the factors affecting the development of stage 3 CKD (p < 0.001, p < 0.001). The receiver operating characteristic analysis showed that the cut-off age for the development of stage 3 CKD was 50.5 years. Newly diagnosed hypertension was detected in 57 patients (16.8%) after the transplantation. While hypertension was seen at a rate of 42% in those with an eGFR <60 mL/min/1.73 m2, it was detected at 19.4% in the group with an eGFR >60 mL/min/1.73 m2 (p < 0.001)., Conclusion: These results reveal that being a LKD is associated with the development of CKD and hypertension. Age and eGFR values at the time of transplantation were the determinants for the development of CKD., (© 2023 S. Karger AG, Basel.)

Although epidemiological data on heart failure (HF) with preserved ejection fraction (HFpEF) are scarce in the Middle East, North Africa and Turkey (MENAT) region, Lancet Global Burden of Disease estimated the prevalence of HF in the MENAT region in 2019 to be 0.78%, versus 0.71% globally. There is also a high incidence of HFpEF risk factors and co-morbidities in the region, including coronary artery disease, diabetes, obesity, hypertension, anaemia and chronic kidney disease. For instance, 14.5-16.2% of adults in the region reportedly have diabetes, versus 7.0% in Europe. Together with increasing life expectancy, this may contribute towards a higher burden of HFpEF in the region than currently reported. This paper aims to describe the epidemiology and burden of HFpEF in the MENAT region, including unique risk factors and co-morbidities. It highlights challenges with diagnosing HFpEF, such as the prioritization of HF with reduced ejection fraction (HFrEF), the specific profile of HFpEF patients in the region and barriers to effective management associated with the healthcare system. Guidance is given on the diagnosis, prevention and management of HFpEF, including the emerging role of sodium-glucose co-transporter-2 inhibitors. Given the high burden of HFpEF coupled with the fact that its prevalence is likely to be underestimated, healthcare professionals need to be alert to its signs and symptoms and to manage patients accordingly. Historically, HFpEF treatments have focused on managing co-morbidities and symptoms, but new agents are now available with proven effects on outcomes in patients with HFpEF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Electrocardiography is used in the initial risk assessment of patients with non-ST-elevation myocardial infarction. The frontal QRS-T angle is an electrocardiography parameter that may be affected by the alterations in the coronary blood flow. This study aimed to explore the relationship of the frontal QRS-T angle with coronary flow grade and adverse events in non-ST-elevation myocardial infarction patients., Methods: A total of 191 non-ST-elevation myocardial infarction patients were divided into 2 groups based on the thrombolysis in myocardial infarction (TIMI) flow level on coronary angiography before revascularization, namely TIMI 0/1 and TIMI 2/3. The frontal QRS-T angle obtained before revascularization was compared between the groups and its relationship with adverse events was examined. In-hospital all-cause mortality, repeat target lesion revascular-ization, new-onset heart failure, ventricular arrhythmias, and atrial fibrillation were defined as adverse events., Results: Frontal QRS-T angle was wider in the patients with TIMI 0/1 flow compared to the patients with TIMI 2/3 flow (P  <  0.001). The frontal QRS-T angle was determined to be a predictor of TIMI flow grade 0/1 before revascularization in patients with non-ST-elevation myocardial infarction (odds ratio: 1.51; 95% CI: 1.30-1.75; P < 0.001). The frontal QRS-T angle was a predictor of the adverse events during hospitalization in the patients with non-ST-elevation myocardial infarction (odds ratio: 1.11; 95% CI: 1.04-1.19; P = 0.002). The cut-off values of the frontal QRS-T angle for TIMI flow grade and adverse events were determined to be 73.5°, based on receiver operating characteristic curve analysis., Conclusion: Increased frontal QRS-T angle may be a useful electrocardiography parameter for determining TIMI flow grade and the need for an early invasive strategy in patients with non-ST-elevation myocardial infarction.

Introduction: We aimed to investigate the effect of a standard hemodialysis prescription in hyponatremic patients requiring hemodialysis on the development of osmotic demyelination syndrome., Methods: Ninety-nine patients who were treated with hemodialysis for the first time and had a pre-dialysis sodium value of ≤125 meq/L included in the study. Standard hemodialysis treatment was applied to all patients. Biochemical data before, immediately after and 24 h after hemodialysis were recorded retrospectively. All patients followed up for 2 weeks and magnetic resonance imaging was performed in patients with neurological symptoms., Results: Eight patients had a sodium increase of more than 12 meq/L at 24-h after hemodialysis. Although hyponatremia was corrected rapidly with hemodialysis, none of the 99 azotemic patients developed osmotic demyelination syndrome., Conclusion: We did not observe osmotic demyelination syndrome in hyponatremic patients with azotemia treated with standard protocol hemodialysis. However, caution should still be exercised in high-risk patients for osmotic demyelination., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

Background: There is no human data regarding the exposure, metabolism and potential health effects of arsenic (As) contamination in drinking water in the Central Anatolian region of Turkey., Methods: Residents in ten villages with drinking water of total As (T-As) level >50 μg L -1 and 10-50 μg L -1 were selected as an exposed group (n = 420) and <10 μg L -1 as an unexposed group (n = 185). Time-weighted average-As (TWA-As) intake was calculated from T-As analysis of drinking water samples. Concentrations of T-As in urine and hair samples, urinary As species [i.e., As(III), As(V), MMA(V) and DMA(V], and some micronutrients in serum samples of residents of the study area were determined. Primary and secondary methylation indices (PMI and SMI, respectively) were assessed from urinary As species concentrations and the presence of skin lesion was examined., Results: TWA-As intake was found as 75 μg L -1 in the exposed group. Urinary and hair T-As and urinary As species concentrations were significantly higher in the exposed group (P < 0.05). The PMI and SMI values revealed that methylation capacities of the residents were efficient and that there was no saturation in As metabolism. No significant increase was observed in the frequency of skin lesions (hyperpigmentation, hypopigmentation, keratosis) of the exposed group (P > 0.05). Only frequency of keratosis either at the hand or foot was higher in individuals with hair As concentration >1 μg g -1 (P < 0.05)., Conclusions: Individuals living in the study area were chronically exposed to low-to-moderate As due to geological contamination in drinking water. No significant increase was observed in the frequency of skin lesions. Because of the controversy surrounding the health risks of low-to-moderate As exposure, it is critical to initiate long-term follow-up studies on health effects in this region., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim: The effect of hypertension (HT) and antihypertensive therapies such as renin-angiotensin-aldosterone system (RAAS) blockers on the disease course in COVID-19 patients is controversial. The purpose of this study was to evaluate the effect of HT and antihypertensive therapies on the course of COVID-19 disease., Method: The age, sex, comorbid diseases, and antihypertensive therapies of 132,790 patients with positive COVID-19 real-time transcriptase polymerase chain reaction (RT-PCR) tests in the Turkish Health Ministry National COVID-19 database between 11 March and 31 May 2020, were examined and analyzed., Results: Forty-one percent of the 132,790 patients in this study (median age: 40, 47.3% female) were hospitalized for treatment, and 4.5% were followed-up in the intensive care unit (ICU). The most frequent comorbid disease, at 19.5%, was HT (n = 25,863). Mortality was determined in 4.9% of HT patients and 1.9% of non-HT patients (p < .001). HT, age, and male gender emerged as independent predictors of hospitalization and admission to the ICU, while HT was not a predictor of mortality. In addition, no adverse effect of any antihypertensive treatment, including RAAS inhibitors, on mortality was detected., Conclusion: Based on Turkish national data, HT is common in COVID-19 patients, but does not appear to be an independent predictor of mortality, and no adverse effect of RAAS inhibitors on COVID-19-related mortality was observed.

Background: Renal parenchymal fibrosis is the most important determinant of kidney disease progression and it is determined via biopsy. The aim of this study is to evaluate the renal stiffness noninvasively by magnetic resonance elastography (MRE) and to compare it with clinicopathologic parameters in glomerulonephritis and AA amyloidosis patients., Methods: Thirty-four patients with glomerular filtration rate (GFR) over 20 ml/min/1.73m 2 had non-contrast MRE prospectively. Kidney stiffness values were obtained from whole kidney, cortex, and medulla. Values were correlated with GFR, albuminuria, proteinuria, and degree of fibrosis that are assessed via renal biopsy. Patients were grouped clinicopathologically to assess the relation between stiffness and chronicity., Results: Mean whole kidney, cortex, and medulla stiffnesses were 3.78 (± 1.26), 3.63 (± 1.25), and 4.77 (± 2.03) kPa, respectively. Mean global glomerulosclerosis was 22% (± 18%) and median segmental glomerulosclerosis was 4% (min-max: 0%-100%). Extent of tubulointerstitial fibrosis was less than 25% in 26 of the patients (76.5%), 25%-50% in 6 of the patients (17.6%), and higher than 50% in 2 of the patients (5.9%). Fourteen patients were defined to have chronic renal parenchymal injury. MRE-derived stiffness values correlated negatively with parameters of fibrosis. Lower stiffness values were observed in patients with chronic renal injury compared to those without (P < 0.05 for whole kidney and medulla MRE-derived stiffness)., Conclusion: MRE-derived stiffness values were lower in patients with chronic injury. Stiffness decreases as glomerulosclerosis and tubulointerstitial fibrosis progresses in patients with primary glomerulonephritis and AA amyloidosis. With future studies, there may be a role for MRE to assess renal function in concert with conventional markers., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Galactose-deficient IgA1 (Gd-IgA1) has an increased tendency to form immunocomplexes with IgG in the serum, contributing to IgAN pathogenesis by accumulating in the glomerular mesangium. Several studies showed that glomerular IgG deposition in IgAN is an important cause of mesangial proliferation and glomerular damage. This study aims to determine the association of the positivity of IgG and the intensity of IgG staining with a poor renal prognosis., Methods: A total of 943 IgAN patients were included in the study. Glomerular IgG staining negative and positive patients were compared using Oxford classification scores, histopathological evaluations, proteinuria, eGFR, albumin, blood pressures. IgG positive patients were classified as (+), (++), (+++) based on their staining intensity, and the association with the prognostic criteria was also evaluated., Results: 81% (n = 764) of the patients were detected as IgG negative, while 19% (n = 179) were positive. Age, gender, body mass index, blood pressure, proteinuria, eGFR, uric acid values were similar in IgG positive and negative patients who underwent biopsy (p > 0.05). Intensity of glomerular IgG positivity was not found to be associated with diastolic and systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p > 0.05 for all, r = - 0.084, r = - 0.102, r = - 0.006, r = 0.062, r = 0.014, r = - 0.044, r = - 0.061, r = - 0.066, r = 0.150, respectively). There was no difference for histopathological findings between IgG (+), IgG (++), IgG (+++) groups (for all, p > 0.05)., Conclusion: Glomerular IgG negativity and positivity detected by routine IFM in IgAN patients is not associated with poor renal prognostic risk factors., (© 2021. The Author(s).)

Background: Diarrhea is a common adverse effect of mycophenolate treatment in renal transplant recipients. In patients with mycophenolate-induced diarrhea, one option is to switch to mycophenolate to azathioprine. In this study, we aimed to define the safety and efficacy of switching from mycophenolate to azathioprine for mycophenolate-related diarrhea in renal transplant recipients., Methods: A total of 177 patients, 59 of whom were switched to azathioprine because of diarrhea and 118 of whom comprised a matched control group without diarrhea and continued mycophenolate treatment participated in this study. We analyzed the effect of switching to azathioprine from mycophenolate on amelioration of diarrhea and graft survival., Results: We observed that 89.8% of patients who switched to azathioprine because of diarrhea had improved diarrhea complaints. Patients switched to azathioprine because of diarrhea had lower glomerular filtration rates (P < .001) and higher proteinuria (P < .001) compared with the control group before the switch. Patients switched to azathioprine compared with a subgroup of 59 control patients were matched to patients switched to azathioprine in terms of baseline renal function and proteinuria in addition to demographic parameters had higher 10-year graft loss compared with patients who continued mycophenolate (P = .03). Particularly in patients with a glomerular filtration rate <30 mL/min at the time of conversion, the risk of early graft loss was high., Conclusions: Although switching from mycophenolate to azathioprine was an effective approach to improve diarrhea, this approach is associated with increased risk of graft loss., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country., Methods: Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded., Results: Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001)., Conclusion: This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

Tissue-mimicking materials (TMMs) play a key role in the quality assurance of ultrasound diagnostic equipment and should have acoustic properties similar to human tissues. We propose a method to quantify the acoustic properties of TMM samples through the use of an 80 MHz Scanning Acoustic Microscopy (SAM), which provides micrometer resolution and fast data recording. We produced breast TMM samples in varying compositions that resulted in acoustic impedance values in the range of 1.373 ± 0.031 and 1.707 ± 0.036 MRayl. Additionally, liver TMM and blood mimicking fluid (BMF) samples were prepared that had acoustic impedance values of 1.693 ± 0.085 MRayl and 1.624 ± 0.006 MRayl, respectively. The characterization of the TMMs by SAM may provide reproducible and uniform acoustic reference data for tissue substitutes in a single-run microscopy experiment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cystic fibrosis (CF) is a hereditary, multisystemic disease caused by different mutations in the CFTR gene encoding CF transmembrane conductance regulator. CF is mainly characterized by pulmonary dysfunction as a result of deterioration in the mucociliary clearance and anion transport of airways. Mortality is mostly caused by bronchiectasis, bronchiole obstruction, and progressive respiratory dysfunction in the early years of life. Over the last decade, new therapeutic strategies rather than symptomatic treatment have been proposed, such as the small molecule approach, ion channel therapy, and pulmonary gene therapy. Due to considerable progress in the treatment options, CF has become an adult disease rather than a pediatric disease in recent years. Pulmonary gene therapy has gained special attention due to its mutation type independent aspect, therefore being applicable to all CF patients. On the other hand, the major obstacle for CF treatment is to predict the drug response of patients due to genetic complexity and heterogeneity. The advancement of 3D culture systems has made it possible to extrapolate the disease modeling and individual drug response in vitro by producing mini adult organs called "organoids" obtained from rectal cell biopsies. In this review, we summarize the advances in the novel therapeutic approaches, clinical interventions, and precision medicine concept for CF.

Vancomycin-resistant enterococcus (VRE) is a global threat to public health. Knowledge about the occurrence of vanA-carrying enterococci in broiler and environmental samples is important as antibiotic resistance can be transferred to human bacteria. The aim of this study was to investigate the presence of VRE in broiler cloacal and environmental (house) samples and to genotype the isolates. In this study, 350 swabs were collected from broiler farms. All samples were plated onto enterococcus selective agar containing 6 mg/L vancomycin and 64 mg/L ceftazidime. Minimum inhibitory concentration (MIC) values were determined for vancomycin and teicoplanin. Vancomycin-resistant Enterococcus faecium (VREfm) was isolated from 6 out of 300 (2%) broiler cloacal samples and 13 out of 50 (26%) house samples. All E. faecium isolates had vanA genes. All VREfm isolates (19 isolates) were confirmed to be 95% similar to each other. In conclusion, although 20 years have passed since the ban on avoparcin in Turkey, the present study shows that VREfm isolates are still present in broiler production and especially in broiler houses, and most importantly, a major VREfm clone was isolated from broiler cloacal and house samples.

Escherichia coli ST131 clone and H30-R/H30-Rx subclones are the most common multidrug-resistant high-risk clones in UTIs. Antimicrobial susceptibility of fosfomycin was compared to five other agents in consecutively collected 299 urinary isolates using the agar dilution method. Prevalence of the ST131 clone and the occurrence of blaCTX-M were also investigated. Overall resistance to fosfomycin, cefuroxime, and ceftriaxone were 2.7%, 35.4%, and 30.1% respectively. fosA, fosA3, and fosC2 genes were not detected. In isolates resistant to ciprofloxacin (34.7%), the prevalence of ST131 clone was 31.7%, of which 81.8% belonged to H30-R and 66.7% to H30-Rx subclones. None of the isolates of the ST131 clone were resistant to fosfomycin. However, bla CTX-M occurred in 57.6% of the isolates among this clone, 62.9% in H30-R and 68.2% in H30-Rx subclones. The results of this study suggest that fosfomycin resistance is not prevalent in urinary isolates, however, bla CTX-M positive ST131 clone is quite common., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: It is not known whether there are any differences in dialysis outcomes of hemodialysis patients on Monday, Wednesday and Friday (MWF) schedule and patients on Tuesday, Thursday and Saturday (TTS) schedules. Patients on TTS schedule who receive one of the treatments on weekends may have worse outcomes compared with patients on MWF schedule as a result of weekend effect. In this study we compared the mortality and clinical performance measures for hemodialysis care, between patients on these two different hemodialysis schedules., Methods: This single center study was conducted on chronic hemodialysis patients above 18 years of age at the time of initiation of hemodialysis who were under thrice weekly hemodialysis treatment for at least 12 months. Mortality and hemodialysis related quality indices were retrospectively compared between patients on MWF or TTS schedules., Results: A total of 188 patients (114 male and 74 female) were included. The mean age of the patients at the start of dialysis was 50.9 ± 18.4 years and median hemodialysis vintage was 60.5 (12 to 369) months. Ninety-nine patients were on MWF schedule and 89 patients were on TTS schedule. More patients on MWF schedule reached the target laboratory values and patients on MWF schedule had a survival advantage compared with patients on TTS schedule., Conclusion: Hemodialysis patients on MWF schedule may receive higher quality of care and may have better outcomes compared with patients on TTS schedule.

Synthetic cathinones are new designer drugs that possess hallucinogenic and psychostimulant properties, and are designed to mimic the effects of illegal substances such as cocaine, amphetamines, and 3.4-methylenedioxymethamphetamine (ecstasy) and to produce rewarding effects, circumventing existing laws and penalties. Synthetic cathinones, also referred to as 'bath salts', have become popular particularly among young people since the mid-2000s. Similar to other psychomotor stimulants, synthetic cathinones have the potential to increase monoamine concentration in the synaptic cleft by targeting the plasma membrane transporters of dopamine, norepinephrine, and serotonin. Because of their structural similarities to amphetamines, it has been suggested that synthetic cathinones may have a neurotoxicity profile similar to that of their amphetamine congeners. Therefore, it has been hypothesized that synthetic cathinones may induce neurotoxicity on monoamine nerve endings in the striatum, hippocampus, and cortex. To date, with regard to synthetic cathinone neurotoxicity, parameters such as monoamine depletion, biosynthetic enzyme inhibition, cytotoxicity, generation of reactive oxygen species, pro-oxidation status, and the ability to induce neuroinflammation were investigated in both in vitro and in vivo experimental studies. Compared with amphetamines, synthetic cathinones appear to have more moderate effects than their amphetamine congeners in terms of neurotoxic effects. However, many synthetic cathinone users take these substances simultaneously with other substances such as benzodiazepines, amphetamines, ecstasy, tetrahydrocannabinol, and ethanol and this abuse can modify their neurotoxic effects. Hence, it is important to understand the underlying mechanism of early neurotoxic effects in case of polysubstance use. In this review, we aimed to present up-to-date information on the abuse potential of synthetic cathinones, their legal status, mechanism of action, and particularly their neurotoxic effects., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2020 Turk J Pharm Sci, Published by Galenos Publishing House.)

Lactobacilli are part of the microbiota and are also used as probiotics. However, in recent years they have been associated with invasive infections, especially bacteremia. Lactobacillus spp. are usually susceptible to penicillins, macrolides, and carbapenems, but Lactobacillus rhamnosus is intrinsically resistant to glycopeptides. The aim of this study was to determine the antimicrobial susceptibility profile and resistance mechanism of a clinical isolate of L. rhamnosus isolated from 10 sets of blood cultures of the same patient. The isolate was identified by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (Bruker Daltonics; BD, Bremen, Germany) and 16S rRNA gene sequencing. In vitro susceptibilities to penicillin, ampicillin, imipenem, vancomycin, erythromycin, clindamycin, and linezolid were determined with gradient test strips (bioMérieux, France) on Mueller-Hinton agar plates supplemented with 5% defibrinated horse blood and 20 mg/L β-NAD. The isolate was resistant to vancomycin and imipenem. Polymerase chain reaction test was positive for bla OXA-48 and the presence of this carbapenemase was confirmed by gene sequencing. Although plasmid analysis suggested that the bla OXA-48 is chromosomal in this isolate, it is still an alarming finding for potential transmission of antibiotic resistance genes to other bacteria in the gut. To our knowledge, this is the first report of the presence of bla OXA-48 in a Lactobacillus spp. and has utmost importance as these bacteria are used as probiotics. The isolation of these bacteria from sterile body sites should not go unnoticed.

Viridans streptococci are still under investigation concerning epidemiology, pathogenesis and clinical presentations. We aimed to investigate the clinical presentations and outcomes of pediatric patients infected with Streptococcus mitis/oralis. Based on the accumulation of bloodstream infections (BSI) caused by S. mitis/oralis in 4 patients in our Hematology and Bone Marrow Transplantation Department at a particular time, a review of the medical and microbiological records of pediatric patients with positive blood cultures for S. mitis/oralis in the entire hospital was performed. In addition, a retrospective case-control study was conducted. Pulsed-field gel electrophoresis of S. mitis/oralis in 4 patients displayed unrelatedness of the strains. A total of 53 BSI (42 BSI and 11 catheter-related BSI) were analyzed. Thirty-four percent of patients with BSI caused by S. mitis/oralis had febrile neutropenia. Clinical and microbiological outcomes were favorable and infection-related mortality was not observed. Although not significant, previous antibiotic use and trimethoprim-sulfamethoxazole prophylaxis were more common in the case group. S. mitis/oralis seems likely an important agent in bacteremic children who are particularly neutropenic because of the underlying hematologic and oncologic diseases. Prompt management of infections with appropriate antimicrobials, regarding antibiotic susceptibilities of organisms, may facilitate favorable outcomes.

We demonstrate selective labeling of cell surface proteins using fluorogen-activating proteins (FAPs) conjugated to standard immunoglobulins (IgGs). Conjugation was achieved with a polypeptide reagent comprised of an N-terminal photoactivatable Fc-binding domain and a C-terminal FAP domain. The resulting FAP-antibody conjugates were effective agents for protein detection and cell ablation in cultured mammalian cells and for visualizing cell-cell contacts using a tethered fluorogen assay. Because our approach allows FAP-antibody conjugates to be generated for most currently available IgGs, it should have broad utility for experimental and therapeutic applications.

Background/aims: Refugee dialysis is a worldwide growing dilemma with limited experience. This report presents the largest hemodialysis (HD) patient registry data of Syrian refugees in Turkey., Methods: Demographic, clinical, laboratory, and dialysis practice data of 345 Syrian HD patients during one year were collected and analyzed., Results: There were 345 prevalent Syrian HD patients at the end of 2016. Majority of the patients were placed in the Southeast Anatolian Region. The majority of the patients (74.8%) are in the age range of 20-64 years. Dialysis vintage in Turkey is less than 12 months in 20.8% and less than one month in 29.3% of patients. The vascular access was arteriovenous fistula in the majority of patients (72.5%). Kt/V is over 1.7 in 57%, serum albumin is above 35 g/L in 65.8% and hemoglobin level is more than 100 g/L in %65.2 of the patients. The ratio of patients with serum phosphorus level of 1.13-1.77 mmol/L was 56.2%. Twenty Syrian HD patients (14 male, 6 female) died within the year 2016 and annual mortality rate was 5.7%., Conclusion: This study with the largest number of Syrian refugees undergoing maintenance hemodialysis showed good dialysis practices, acceptable values for dialysis adequacy and biochemical parameters along with lower mortality compared to native HD population of Turkey. Longer follow up will enrich the knowledge related to care of refugee population in all over the world., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

Single nucleotide polymorphisms (SNPs), the most common genetic variations in human genome, can manage the predisposition of certain complex diseases or situations such as obesity. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to being overweight or obese and developing related chronic complications such as hypertension, coronary heart disease, diabetes and cancer. The present study comprised of 193 unrelated healthy volunteers (120 females and 73 males) with Turkish origin. Only female adolescents (n = 110) were divided into 2 categories according to their BMI values as overweight (BMI ≥ 25) and normal (18.5 < BMI < 25) according to WHO classification. Genomic DNA was isolated from venous blood samples and genotyping of DENND1A rs10818854 and CYP19A1 rs2414096 variants was performed on Roche Light Cycler 2.0 Real-Time PCR platform. Serum hormone levels were analyzed by Electrochemiluminescent Immunoassay (ECLIA; Roche diagnostics). The genotype distributions were consistent with the Hardy-Weinberg equilibrium for both SNPs in the studied population (p > 0.05). The genotype distribution of DENND1A rs10818854 was determined for the first time in Turkish population and the variant allele frequency was found as 0.095. According to reduced sex hormone-binding globulin levels and increased free androgen index in the present study, obesity was linked with hyperandrogenism in female subjects. Both polymorphisms were investigated as potential genetic susceptibility markers for obesity and neither DENND1A nor CYP19A1 showed any associations.

Recently, it has been shown that amphiphilic dyes such as Indocyanine Green (ICG) and Protoporphyrin IX (PpIX) can solubilize hydrophobic colloids and/or drugs by driving the formation of stable nanoemulsions. These nanoemulsions are unique in that they can be composed entirely of functional and clinically used materials; however, they lack bio-orthogonal chemical handles for the facile attachment of targeting ligands. The ability to target nanoparticles is desirable because it can lead to improved specificity and reduced side effects. Here, we describe variants of ICG and PpIX with azide handles that can be readily incorporated into dye-stabilized nanoemulsions and facilitate the attachment of targeting ligands via click-chemistry in a simple, scalable, and reproducible reaction. As a model system, an anti-Her2 affibody was site-specifically attached to both ICG and PpIX-stabilized nanoemulsions with encapsulated superparamagnetic iron oxide nanoparticles.

Objective: Cardiovascular risc factors may show significant changes over the years. A systematic review and meta-analysis of epidemiological studies conducted in Turkey was performed to assess the latest profile and temporal changes in cardiovascular risk factors. Presented here are the data on hypertension (HT) and blood pressure (BP)., Methods: Ovid Medline, the Web of Science Core Collection, and the Turkish Academic Network and Information Center (ULAKBIM) were searched for epidemiological studies conducted in Turkey during the last 15 years. In addition, the web pages of the Ministry of Health, the Turkish Statistical Institute, and associations of cardiology, nephrology, and endocrinology were searched for appropriate studies. Regional studies were excluded. The studies included were assessed with a bias score developed by our team, then categorized as having a low risk or a high risk of bias. The crude values of HT prevalence and BP were pooled using a random effects model. Meta-regression was performed to explain heterogeneity and to assess temporal changes., Results: The agreement between the 2 authors on the selection and bias scoring of the studies was perfect (Kappa ≥0.95). There were 7 (n=73218) studies providing HT prevalence data, and 8 (n=75879) studies with BP data. The heterogeneity between the studies was high. Meta-analysis of the studies with a low risk of bias indicated that the crude prevalence of HT is higher in women, but that BP levels were similar in both sexes. The HT prevalence and BP value decreased between 2003 and 2012; however, the number of hypertensives stabilized at approximately 15 million, and the number of uncontrolled hypertensives, despite some decrease, was around 11 million., Conclusion: Despite some improvement, HT is still an important public health problem in Turkey.

Cardiovascular disease is one of the most frequent causes of mortality and morbidity worldwide. Several variables have been identified as risk factors for cardiovascular disease. Recently, the role of receptor activator of nuclear factor kappa B, receptor activator of nuclear factor kappa B ligand, and the osteoprotegerin system has been recognized as more important in the pathogenesis of cardiovascular disease. Besides their roles in the regulation of bone resorption, these molecules have been reported to be associated with the pathophysiology of cardiovascular disease. There are conflicting data regarding the impact of osteoprotegerin, a glycoprotein with a regulatory role in the cardiovascular system. The aim of this review is to discuss the current knowledge and the role of osteoprotegerin in cardiovascular disease.

Genetic incorporation of biologically orthogonal functional groups into macromolecules has the potential to yield efficient, controlled, reproducible, site-specific conjugation of affinity ligands, contrast agents, or therapeutic cargoes. Here, we applied this approach to ferritin, a ubiquitous iron-storage protein that self-assembles into multimeric nanocages with remarkable stability, size uniformity (12 nm), and endogenous capacity for loading and transport of a variety of inorganic and organic cargoes. The unnatural amino acid, 4-azidophenylalanine (4-AzF), was incorporated at different sites in the human ferritin light chain (hFTL) to allow site-specific conjugation of alkyne-containing small molecules or affinity ligands to the exterior surface of the nanocage. The optimal positioning of the 4-AzF residue was evaluated by screening a library of variants for the efficiency of copper-free click conjugation. One of the engineered ferritins, hFTL-5X, was found to accommodate ∼14 small-molecule fluorophores (AlexaFluor 488) and 3-4 IgG molecules per nanocage. Intravascular injection in mice of radiolabeled hFTL-5X carrying antibody to cell adhesion molecule ICAM-1, but not control IgG, enabled specific targeting to the lung due to high basal expression of ICAM-1 (43.3 ± 6.99 vs 3.48 ± 0.14%ID/g for Ab vs IgG). Treatment of mice with endotoxin known to stimulate inflammatory ICAM-1 overexpression resulted in 2-fold enhancement of pulmonary targeting (84.4 ± 12.89 vs 43.3 ± 6.99%ID/g). Likewise, injection of fluorescent, ICAM-targeted hFTL-5X nanocages revealed the effect of endotoxin by enhancement of near-infrared signal, indicating potential utility of this approach for both vascular targeting and imaging.

Granulocyte colony-stimulating factor (G-CSF) is a well-known hematopoietic stem cell (HSC)-mobilizing agent used in both allogeneic and autologous transplantation. However, a proportion of patients or healthy donors fail to mobilize a sufficient number of cells. New mobilization agents are therefore needed. Endocannabinoids (eCBs) are endogenous lipid mediators generated in the brain and peripheral tissues and activate the cannabinoid receptors CB1 and CB2. We suggest that eCBs may act as mobilizers of HSCs from the bone marrow (BM) under stress conditions as beta-adrenergic receptors (Adrβ). This study demonstrates that BM mesenchymal stem cells (MSCs) secrete anandamide (AEA) and 2-arachidonylglycerol (2-AG) and the peripheral blood (PB) and BM microenvironment contain AEA and 2-AG. 2-AG levels are significantly higher in PB of the G-CSF-treated group compared with BM plasma. BM mononuclear cells (MNCs) and CD34 + HSCs express CB1, CB2, and Adrβ subtypes. CD34 + HSCs had higher CB1 and CB2 receptor expression in G-CSF-untreated and G-CSF-treated groups compared with MSCs. MNCs but not MSCs expressed CB1 and CB2 receptors based on qRT-PCR and flow cytometry. AEA- and 2-AG-stimulated HSC migration was blocked by eCB receptor antagonists in an in vitro migration assay. In conclusion, components of the eCB system and their interaction with Adrβ subtypes were demonstrated on HSCs and MSCs of G-CSF-treated and G-CSF-untreated healthy donors in vitro, revealing that eCBs might be potential candidates to enhance or facilitate G-CSF-mediated HSC migration under stress conditions in a clinical setting., (Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Previous research has shown daily salt intakes in Turkey to be far above the recommended limits. Knowing the sources of dietary salt could form a basis for preventive strategies aimed towards salt reduction. This study aimed to investigate dietary sources of salt in Turkey. A sub-group ( n = 657) was selected from the PatenT2 study population, which represented the urban and rural areas of 4 major cities (Ankara, Istanbul, Izmir, and Konya). A questionnaire inquiring about sociodemographic characteristics, medical histories, detailed histories of diet, and salt consumption was completed. Participants were asked to collect a 24-h urine sample and to record their food intake (dietary recall) on the same day. Of 925 participants selected, 657 (71%) provided accurate 24-h urine collections, based on creatinine excretion data. The mean daily 24-h urinary sodium excretion was 252.0 ± 92.2 mmol/day, equal to daily salt intake of 14.8 ± 5.4 g. Of the 657 participants with accurate 24-h urine collections, 464 (70%) provided fully completed dietary recalls. Among these 464 participants, there was a significant difference between the 24-h urinary sodium excretion-based salt intake estimation (14.5 ± 5.1 g/day) and the dietary recall-based salt intake estimation (12.0 ± 7.0 g/day) ( p < 0.001). On the other hand, a positive correlation was obtained between the dietary recall-based daily salt intake and 24-h urinary sodium excretion-based daily salt intake ( r = 0.277, p < 0.001). Bread was the main source of salt (34%) followed by salt added during cooking and preparing food before serving (30%), salt from various processed foods (21%), and salt added at the table during food consumption (11%). Conclusively, this study confirmed a very high salt intake of the adult population in four major cities in Turkey. The present findings support the emerging salt reduction strategy in Turkey by promoting lower salt content in baked bread, and less salt use in habitual food preparation and during food consumption in the home.

Introduction: HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied., Methods: 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined., Findings: Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6)., Discussion: Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation., (© 2017 International Society for Hemodialysis.)

Protein bioconjugation has been a crucial tool for studying biological processes and developing therapeutics. Sortase A (SrtA), a bacterial transpeptidase, has become widely used for its ability to site-specifically label proteins with diverse functional moieties, but a significant limitation is its poor reaction kinetics. In this work, we address this by developing proximity-based sortase-mediated ligation (PBSL), which improves the ligation efficiency to over 95 % by linking the target protein to SrtA using the SpyTag-SpyCatcher peptide-protein pair. By expressing the target protein with SpyTag C-terminal to the SrtA recognition motif, it can be covalently captured by an immobilized SpyCatcher-SrtA fusion protein during purification. Following the ligation reaction, SpyTag is cleaved off, rendering PBSL traceless, and only the labeled protein is released, simplifying target protein purification and labeling to a single step., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)