The relationship between Nuclear Factor-Kappa B and Inhibitor-Kappa B parameters with clinical course in COVID-19 patients.

BACKGROUND: We aimed to investigate the serum Nuclear Factor Kappa B (NF-κB) p105, NF-κB p65 and Inhibitor Kappa B Alpha (IκBα) levels in patients with mild/moderate Coronavirus Disease 2019 (COVID-19) and their association with the course of the disease. MATERIALS AND METHODS: Blood was drawn from 35 COVID-19 patients who applied to the Department of Emergency Medicine of Istanbul University-Cerrahpasa at the time of diagnosis and from 35 healthy individuals. The patients were evaluated to have mild/moderate degree of disease according to National Early Warning Score 2 (NEWS2) scoring and computed tomography (CT) findings. The markers were studied in the obtained serum samples, using enzyme-linked immunoassay (ELISA). Receiver Operating Characteristic (ROC) analysis was performed. Statistical significance was evaluated to be p < 0.05. RESULTS: NF-κB p105 levels were significantly higher in the COVID-19 group compared to the control group. C-reactive protein (CRP), D-dimer, ferritin levels of the patients were significantly higher (p < 0.001) compared to the control group, while the lymphocyte count was found lower (p = 0.001). IκBα and NF-κB p65 levels are similar in both groups. Threshold value for NF-κB p105 was above 0.78 ng/mL, sensitivity was 71.4% and specificity was 97.1% (p < 0.05). NF-κB p105 levels at the time of diagnosis of the patients who required supplemental oxygen (O2), were significantly higher (p < 0.01). CONCLUSIONS: The rise in serum NF-κB p105 levels during the early stages of infection holds diagnostic value. Besides its relation with severity might have a prognostic feature to foresee the requirement for supplemental O2 that occurs during hospitalization.

Clinical and subclinical acute kidney injury in children with mild-to-moderate COVID-19.

BACKGROUND: Our aim was to identify acute kidney injury (AKI) and subacute kidney injury using both KDIGO criteria and urinary biomarkers in children with mild/moderate COVID-19. METHODS: This cross-sectional study included 71 children who were hospitalized with a diagnosis of COVID-19 from 3 centers in Istanbul and 75 healthy children. We used a combination of functional (serum creatinine) and damage (NGAL, KIM-1, and IL-18) markers for the definition of AKI and subclinical AKI. Clinical and laboratory features were evaluated as predictors of AKI and subclinical AKI. RESULTS: Patients had significantly higher levels of urinary biomarkers and urine albumin-creatinine ratio than healthy controls (p < 0.001). Twelve patients (16.9%) developed AKI based on KDIGO criteria, and 22 patients (31%) had subclinical AKI. AKI group had significantly higher values of neutrophil count on admission than both subclinical AKI and non-AKI groups (p < 0.05 for all). Neutrophil count was independently associated with the presence of AKI (p = 0.014). CONCLUSIONS: This study reveals that even children with a mild or moderate disease course are at risk for AKI. Association between neutrophil count and AKI may point out the role of inflammation in the development of AKI. IMPACT: The key message of our article is that not only children with severe disease but also children with mild or moderate disease have an increased risk for kidney injury due to COVID-19. Urinary biomarkers enable the diagnosis of a significant number of patients with subclinical AKI in patients without elevation in serum creatinine. Our findings reveal that patients with high neutrophil count may be more prone to develop AKI and should be followed up carefully. We conclude that even children with mild or moderate COVID-19 disease courses should be evaluated for AKI and subclinical AKI, which may improve patient outcomes.

Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19.

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

Increased risk for kidney sequelae surrogates in survivors of Wilms tumor.

BACKGROUND: There is evidence of increased risk of hypertension, albuminuria, and development of chronic kidney disease (CKD) in long-term follow-up of survivors of Wilms tumor (WT). However, most studies were conducted in heterogeneous groups, including patients with solitary kidney. In addition, little is known about tubular dysfunction. This study aimed to investigate kidney sequelae, including CKD development, hypertension, and glomerular and tubular damage in WT survivors. METHODS: This cross-sectional, single-center study included 61 patients treated for WT. Surrogates for kidney sequelae were defined as presence of at least one of the following: decrease in GFR for CKD, hypertension detected by ambulatory blood pressure monitoring, albuminuria (albumin-to-creatinine ratio [ACR] > 30 mg/g), or increase in at least one tubular biomarker (beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, kidney injury marker-1, and liver fatty acid-binding protein) in 24-h urine. RESULTS: Median age of patients was 11.7 years, with median follow-up of 8.8 years. Thirty-eight patients (62%) had at least one surrogate for kidney sequelae. Twenty-four patients (39%) had CKD, 14 patients (23%) had albuminuria, 12 patients (21%) had hypertension, and 11 patients (18%) had tubular damage. Urine ACR was significantly higher in patients with advanced tumor stage and patients with nephrotoxic therapy than their counterparts (p < 0.05), but neither eGFR nor tubular biomarkers showed any association with tumor- or treatment-related factors. CONCLUSIONS: A considerable number of patients with WT have kidney sequelae, especially early-stage CKD with a high prevalence. Albuminuria emerges as a marker associated with tumor stages and nephrotoxic treatment. A higher resolution version of the Graphical abstract is available as Supplementary information.

Fluctuations in Interleukin-6 Levels during Hemodialysis Sessions with Medium Cutoff Membranes: An Analysis on COVID-19 Case Series.

INTRODUCTION: Interleukin-6 (IL-6) is one of the most important mediators of inflammation. It is also the culprit for a severe disease course in COVID-19. While COVID-19 has higher mortality in hemodialysis (HD) patients, medium cutoff (MCO) membranes were previously suggested as promising tools for better patient outcomes by purging inflammatory mediators. The aim of this study was to analyze changes in IL-6 levels of HD patients who were dialyzed via MCO membranes during their COVID-19 treatments. METHODS: This is an observational study on a group of HD patients who were admitted with COVID-19 diagnosis in a university hospital and intermittently dialyzed using MCO membranes during their hospital stay. IL-6 levels of the patients were measured before and after consecutive dialysis sessions by a commercial kit. Measurements were interpreted together with the clinical data. RESULTS: Nine patients with a total of 54 measurements were evaluated. IL-6 levels were significantly higher in patients who died (median and interquartile ranges [IQRs] of IL-6 levels for patients who died and survived were 112.0 pg/mL [48.3-399.4] and 5.3 pg/mL [2.2-27.4], respectively; p < 0.001). In the comparison of changes in IL-6 levels with dialysis sessions, patients who survived had lower post-dialysis levels (median: 4.5 pg/mL; IQR: 2.2-7.6). However, IL-6 levels had a tendency to increase with dialysis sessions in patients who could not survive COVID-19 (median: 237.0 pg/mL; IQR: 53.8-418.2). CONCLUSION: This study describes over time variations in IL-6 levels of COVID-19 patients undergoing HD with MCO membranes. The trend for the changes of IL-6 levels during dialysis sessions was not uniform for all patients. Surviving patients had decreasing levels of IL-6 with consecutive dialysis sessions, while nonsurvivors had an increasing trend.

Serum kisspeptin levels along reproductive period in women: is it a marker for aging?

OBJECTIVE: To demonstrate the change in serum kisspeptin levels during the reproductive period in healthy women and to investigate the relationship with other reproductive hormones. METHODS: One hundred thirty-one healthy women with normal menstrual history were included and serum kisspeptin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), estradiol (E2), and anti-Müllerian hormone (AMH) levels were determined on cycle day 3. The data were analyzed in 5-year age groups. RESULTS: Serum kisspeptin levels of all women were found to be significantly and negatively correlated with age (r= -0.458). The kisspeptin levels were the highest in the group of women aged between 20 and 24 years compared to other age groups above 25 years (p < .01, p < .001, p < .0005, p < .0005). There was not any significant correlation between serum kisspeptin levels and AMH, FSH, LH, TSH, E2, and body-mass index (BMI), respectively. The Scatter and Violin plots showed that most of the women over 35 years of age had serum kisspeptin levels under the level of 500 pg/ml. The kisspeptin levels of women over 35 years of age clustered closely as opposed to the kisspeptin levels of those below the age of 35, which were scattered. The median serum kisspeptin levels were found to be high in women below the age of 35 (p < .0005). CONCLUSION: In healthy women, serum kisspeptin level is the highest in the group of women aged between 20 and 24 years and declines with age. It tends to be below the level of 500 pg/ml in women over the age of 35.

Importance of oxidative stress in the evaluation of acute pulmonary embolism severity.

BACKGROUND: Pulmonary embolism (PE) is a common and potentially life-threatening disorder. Our study was aimed to investigate whether oxidative stress markers can be used as clinical markers in the evaluation of acute PE (APE) severity. METHODS: 47 patients with objectively documented diagnosis of APE were recorded. Of these patients, 14 had low-risk PE, 16 had moderate-risk PE, and 17 had high-risk PE. 21 healthy subjects were also enrolled in this study. Ischemia-modified albumin (IMA), prooxidants-antioxidants balance (PAB), advanced protein oxidation products (AOPPs), and ferric reducing antioxidant power (FRAP) were measured as oxidative stress parameters to evaluate the role of oxidative stress. RESULTS: In the low-risk and moderate-risk APE groups, AOPPs and PAB levels were significantly higher and FRAP levels were significantly lower than those in the control group. AOPPs and IMA levels in the patients with high-risk PE were significantly higher than those in both the low-risk and moderate-risk APE patients. There was a significant correlation between levels of AOPPs and the levels of both IMA (r: 0.462, p < 0.001) and PAB (r:0.378, p < 0.005). Serum FRAP levels were negatively correlated with PAB (r:- 0.683, p < 0.001) and AOPPs levels (r:- 0,384, p < 0.001). There was also a significant positive correlation between the serum IMA and PAB levels. CONCLUSIONS: We clearly demonstrated that reactive oxygen species formation is significantly enhanced in APE. IMA and AOPPs may be used as clinical markers in the evaluation of APE severity in clinical practice. However, further studies with larger patient populations and longer follow-up periods are required to confirm the mechanisms underlying these findings.

Assessment of the role of neutrophil extracellular traps in SARS-CoV-2 pneumonia.

BACKGROUND: Abnormal neutrophil extracellular traps are associated with lung diseases, thrombosis, increased mucosal secretion in the airways. The aim of this study is to evaluate the possible place of the most specific NETosis marker Cit-H3 protein in diagnostic algorithms by revealing its relationship with the severity, mortality and prognosis of SARS-CoV-2 pneumonia. PATIENTS AND METHODS: Patients (n = 78) who applied to the Emergency Department between March 11, 2020 and June 10, 2020, with positive SARS-CoV-2 polymerase chain reaction (PCR) test and lung involvement were included in the prospective study. Serum Cit-H3 levels and critical laboratory parameters were measured at baseline on the day of clinical deterioration and before recovery/discharge/death. Cit-C3 levels were determined by enzyme immunassay method. RESULTS: Cit-H3 levels in patients with SARS-CoV-2 pneumonia during their first admission to the hospital were significantly higher compared to the healthy control group (p < 0.05). Repeated measurements of Cit-H3 levels of the patients significantly correlated with D-dimer, procalcitonin, Neutrophil/ Lymphocyte ratio, lymphocyte, CRP, and oxygen saturation. Cit-H3 levels of the patients who died were significantly higher than that of those who survived (p < 0.05). Cit-H3 levels were found to be statistically significantly higher in patients who developed acute respiratory distress syndrome, were admitted to the intensive care unit, and had mortality (p < 0.05). CONCLUSIONS: Cit-H3 plays a role in inflammatory processes in SARS-CoV-2 pneumonia, and changes in serum Cit-H3 levels of these patients can be used to determine prognosis and mortality (Tab. 5, Fig. 1, Ref. 21).

Efficacy of Serum Angiotensin II Levels in Prognosis of Patients With Coronavirus Disease 2019.

OBJECTIVES: We aimed to determine serum angiotensin II levels in patients with coronavirus disease 2019 infection and to investigate the effect of these levels on the prognosis of the disease. DESIGN: The study was planned prospectively and observationally. SETTING: The study was conducted in a tertiary university hospital. PATIENTS: Coronavirus disease 2019 patients older than 18 years old, polymerase chain reaction test positive, with signs of pneumonia on tomography, and hospitalized were included in the study. ICU need, development of acute respiratory distress syndrome, and in-hospital mortality were considered as primary endpoints. INTERVENTIONS: Blood samples were taken from patients three times for angiotensin II levels. MEASUREMENTS AND MAIN RESULTS: Angiotensin II levels were studied by enzyme-linked immunosorbent assay method. The SPSS 24.0 program (Statistics Program for Social Scientists, SPSS, Chicago, IL) was used to analyze the data. A total of 112 patients were included in the study, of which 63.4% of the patients were men. The serum angiotensin II levels were statistically significantly lower in the patients with coronavirus disease 2019 compared with the healthy control group (p < 0.001). There was no statistical significance between the serum angiotensin II levels measured at three different times (p > 0.05). The serum angiotensin II levels of the patients with acute respiratory distress syndrome were found to be statistically significantly lower than those without acute respiratory distress syndrome in three samples collected at different clinical periods (p < 0.05). The angiotensin II levels of the patients who required admission to the ICU at all three times of blood sample collection were found to be statistically significantly lower than those who did not (p < 0.05). Although the serum angiotensin II levels of the patients who died were low, there was no statistically significant difference in mortality at all three times (p > 0.05). CONCLUSIONS: The serum angiotensin II levels decrease significantly in patients with coronavirus disease 2019, and this decrease is correlated with lung damage.

An easy-to-use nomogram for predicting in-hospital mortality risk in COVID-19: a retrospective cohort study in a university hospital.

BACKGROUND: One-fifth of COVID-19 patients are seriously and critically ill cases and have a worse prognosis than non-severe cases. Although there is no specific treatment available for COVID-19, early recognition and supportive treatment may reduce the mortality. The aim of this study is to develop a functional nomogram that can be used by clinicians to estimate the risk of in-hospital mortality in patients hospitalized and treated for COVID-19 disease, and to compare the accuracy of model predictions with previous nomograms. METHODS: This retrospective study enrolled 709 patients who were over 18 years old and received inpatient treatment for COVID-19 disease. Multivariable Logistic Regression analysis was performed to assess the possible predictors of a fatal outcome. A nomogram was developed with the possible predictors and total point were calculated. RESULTS: Of the 709 patients treated for COVID-19, 75 (11%) died and 634 survived. The elder age, certain comorbidities (cancer, heart failure, chronic renal failure), dyspnea, lower levels of oxygen saturation and hematocrit, higher levels of C-reactive protein, aspartate aminotransferase and ferritin were independent risk factors for mortality. The prediction ability of total points was excellent (Area Under Curve = 0.922). CONCLUSIONS: The nomogram developed in this study can be used by clinicians as a practical and effective tool in mortality risk estimation. So that with early diagnosis and intervention mortality in COVID-19 patients may be reduced.

Factors influencing blood pressure and microalbuminuria in children with type 1 diabetes mellitus: salt or sugar?

BACKGROUND: The aim of the study is to identify the effect of salt intake and diabetes itself on blood pressure (BP) profile and microalbuminuria in children with type one diabetes mellitus (T1DM). Our hypothesis is that higher amount of salt consumption and/or hyperglycemia may impair blood pressure pattern in children with T1DM. METHODS: This cross-sectional study included 84 children and adolescents with T1DM (62% females, age 13.9 ± 3.2 years, disease duration 7.3 ± 3.1 years, 43% poorly controlled diabetes) and 54 aged- and sex-matched healthy children with an adequately collected 24-h urine samples. Urine sodium, creatinine, and microalbumin were measured and salt intake was assessed on the basis of sodium excretion in 24-h urine. Blood pressure profile of the children with T1DM was evaluated with 24-h ambulatory blood pressure monitoring. RESULTS: Compared to the children with well-controlled diabetes, children with poorly controlled diabetes had significantly higher standard deviation scores (SDS) of nighttime systolic BP (0.22 ± 1.28 vs - 0.87 ± 0.76, p = 0.003) and lower dipping in diastole (13.4 ± 5.9 vs 18.4 ± 8.1, p = 0.046). Among T1DM group, children with the highest quartile of salt intake had higher nighttime systolic and diastolic BP-SDS (0.53 ± 1.25 vs - 0.55 ± 0.73, p = 0.002 and 0.89 ± 1.19 vs 0.25 ± 0.63, p = 0.038, respectively) and lower dipping in systole compared to their counterparts (7.7 ± 5.0 vs 11.5 ± 6.1, p = 0.040). High averaged HbA1c was independently associated with higher both daytime and nighttime systolic BP-SDS (p = 0.010, p < 0.001) and nighttime diastolic BP-SDS (p = 0.001), and lower diastolic dipping (p = 0.001). High salt intake was independently associated with higher nighttime systolic BP-SDS (p = 0.002) and lower systolic dipping (p = 0.019). A 24-h MAP-SDS was the only independent risk factor for microalbuminuria (p = 0.035). CONCLUSION: Beside poor diabetic control, high salt consumption appears to be an important modifiable risk factor for impaired BP pattern, which contributes to the development of diabetic kidney disease in children with T1DM.

Effects of Cigarette Smoke on Fat Graft Survival in an Experimental Rat Model.

INTRODUCTION: A fat graft is the closest thing to being the ideal soft tissue filler. Although it has many advantages, reliability of late-term survival is a never-ending debate. Although there are observational studies that research the effect of cigarette smoke on fat graft take in clinical setting, there has not been an objective experimental animal study on the affect of smoking on fat graft survival. The aim of our study is to search if smoking has an affect on fat grafts. MATERIALS AND METHODS: Twenty-two Sprague-Dawley type rats were used. Exposure was maintained via a passive smoke exposure system. Rats were divided into three groups regarding their exposure period. At the end of the study, transferred fat grafts were extracted and weighed with a precision scale, an arterial blood sample was taken for biochemical analysis, and grafts were sent to the pathology laboratory for immunohistochemical assessment. RESULTS: There were meaningful differences between the control group and the other two groups in graft weight loss, serum cotinine, tissue MDA, adipose tissue/fibrosis ratio, stem cell counts, perilipin positive cell density and inflammation density. Furthermore, we detected meaningful correlations between serum cotinine, tissue MDA and graft weight loss. CONCLUSION: Fat graft takes with the same mechanisms as a wound heals. So like wound healing, cigarette smoke has a negative affect on fat graft survival. A fat graft is by its nature an elective procedure so to improve our late-term success, cigarette smoke exposure should be kept to a minimum for increased reliability. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Plasma Betatrophin Levels of Subjects Classified with Normal, Impaired, and Diabetic Glucose Tolerance, and Subjects with Impaired Fasting Glucose.

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n=220) with a body mass index (BMI)<27 kg/m2. Subjects were categorized as normoglycemic (n=55), IFG (n=50), IGT (n=60), and DM (n=55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p<0.005), IFG (p<0.004), and IGT (p<0.001). Male subjects have significantly higher betatrophin levels than female subjects (p<0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p<0.04), IFG (p<0.01), and IGT (p<0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages.

Glucagon-like peptide-1 levels and dipeptidyl peptidase-4 activity in type 2 diabetes.

PURPOSE: Hyperglycemia is the major risk factor for microvascular complications in type 2 diabetes mellitus (T2DM) patients. This randomized controlled clinical trial aimed to investigate T2DM patients with microvascular complications with regard to possible relations among serum clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) activities. METHODS: Subject groups were defined as follows: T2DM without complications (n=25, F/M=9/16, age 53.9±11.1 years); T2DM+Retinopathy (n=25, F/M=13/12, age 63.8±7.1 years); T2DM+Nephropathy (n=25, F/M=13/12, age 58.7±14.4 years); T2DM+Neuropathy (n=25, F/M=15/10, age 63.2±9.6 years); and healthy control subjects (HC) (n=25). CLU, amylin, SFRP-4, DPP-4 and GLP-1 (total and active) activities were measured and compared in blood samples from type 2 diabetic patients with and without microvascular complications. RESULTS: Significantly lower levels of DPP-4 and GLP-1total (P.

Endothelial Dysfunction and Hypertension.

In the past, endothelium was thought to be only a mechanical barrier. Today, endothelium is known to be a tissue regulating vascular tone, cell growth and the interaction between the leukocytes, thrombocytes and the vessel wall. It also synthesizes growth factors and thrombo-regulatory molecules and responds to physical and chemical signals. Even though the term "endothelial dysfunction" is generally used for deterioration of endothelium-dependent vasodilatation; the term also includes the abnormalities between endothelium and leukocytes, thrombocytes and regulatory molecules and conditions resulting in aberrant endothelium activation. Healthy endothelium is essential for cardiovascular control. Thus, it plays an important role in pathogenesis of many diseases and cardiovascular problems such as atherosclerosis, systemic and pulmonary hypertension, cardiomyopathies and vasculitides. The aim of this chapter is to explain endothelial dysfunction and the circulating molecules of endothelial cells as they become potential targets of therapeutic approach for hypertension. This chapter reviews the roles of endothelial dysfunction in hypertension by addressing (1) the nature of endothelial function, (2) mechanisms of endothelial dysfunction and its relationship with the diseases (3) also endothelial function testing (4) the role of endothelial dysfunction and hypertension and (4) the effects of antihypertensive therapeutic options on the endothelial dysfunction. In addition to these, the role of endothelial dysfunction in white coat hypertension has been discussed. The key connections between hypertension and endothelial dysfunction are vitally important for future studies to permit new interventions to be designed and released.

Cardiovascular alterations do exist in children with stage-2 chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is an important complication of chronic kidney disease (CKD) in children. However, it is not well known when and how cardiovascular alterations start. METHODS: This cross-sectional, controlled study consisted of 25 patients and 28 healthy controls. 24-h ambulatory blood pressure monitoring, aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT) and carotid distensibility (distensibility coefficient and ß stiffness index), and echocardiography were assessed to evaluate CVD. Routine biochemical parameters, fibroblast growth factor-23 (FGF23) and high sensitive C- reactive protein were measured to determine cardiovascular risk factors. RESULTS: Hypertension was found in 12 patients (48 %). Patients had higher FGF23 levels and aPWV-standard deviation score (SDS) as compared to the controls (p = 0.003 and p = 0.002, respectively). Aortic PWV-SDS was predicted by increased daytime systolic blood pressure load (ß = 0.512, p = 0.009, R 2 = 0.262). Neither cIMT nor distensibility differed between the groups; however, older age and high level of FGF23 were independent predictors of ß stiffness index in patients (ß = 0.507, p = 0.005, R 2 = 0.461 and ß = 0.502, p = 0.005, R 2 = 0.461, respectively). As compared to controls, patients had worse left ventricular diastolic function [lower E/A ratio p = 0.006) and increased left atrial dimension (p < 0.001)]. CONCLUSIONS: Cardiovascular deteriorations appear in children with stage-2 CKD. Good control of BP and decreasing the level of FGF23 may be useful to slow down the progression of cardiovascular complications.

The impact of depression and ghrelin on body weight in migraineurs.

BACKGROUND: Comorbidity of migraine with anxiety and depression may play a role in the link between migraine and obesity. We examined the moderating and mediating roles of ghrelin in the relationship between depression (and anxiety) and body weight in newly diagnosed migraineurs. METHODS: Participants were 63 newly diagnosed migraine patients (using the ICHD-II criteria) and 42 healthy volunteers. Body mass index (BMI) was calculated by measuring height and weight. Ghrelin was assessed at fasting. Depression was assessed with the Hamilton Depression scale, and anxiety with the Hamilton Anxiety scale. RESULTS: The data did not support the mediating role of ghrelin in the relationship between depression (or anxiety) and BMI for either the migraine or the control group. The interaction between ghrelin and depression as well as anxiety was significant for the migraine group, but not for the control group. Depressed (or anxious) migraineurs had a positive association between ghrelin and BMI, whereas for the non-depressed (or non-anxious) migraineurs this association was negative. CONCLUSIONS: Depression and anxiety moderated the effect of ghrelin on BMI for migraineurs. Management of anxiety and depression might be regarded as part of migraine treatment.

Zinc Alpha-2 Glycoprotein, Acylated Ghrelin, and Zinc Levels in Prediabetics.

BACKGROUND/AIM: Prediabetic stages of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) exhibit differences in the sites of insulin resistance. Serum Zinc α-2 glycoprotein (ZAG), acylated ghrelin (AG), and zinc (Zn) levels can affect IFG, IGT, and diabetic glucose tolerance (DGT) differently. This study examined the importance of ZAG, AG, and serum Zn levels in prediabetic individuals with IFG, IGT, and DGT, compared to those with normal glucose levels. PATIENTS AND METHODS: The study was conducted at Istanbul University Cerrahpasa-Cerrahpasa Faculty of Medicine. A total of n=151 volunteers were classified according to the WHO criteria for diabetes after undergoing an oral glucose tolerance test. Plasma and serum samples were measured by Inductively Coupled Plasma Optical Emission Spectroscopy, ELISA, and immunoassay. RESULTS: Prediabetic conditions became more prominent with the decrease in ZAG levels. ZAG levels showed a negative correlation with acylated ghrelin and Homeostatic Model Assessment for assessing beta-cell function and insulin resistance. Zinc levels were significantly lower in DGT. CONCLUSION: ZAG levels have regulatory effects on insulin resistance and plasma glucose levels are mediated by zinc and acylated ghrelin.

Plasma Biomarkers in Neurodegenerative Dementias: Unrevealing the Potential of Serum Oxytocin, BDNF, NPTX1, TREM2, TNF-alpha, IL-1, and Prolactin.

BACKGROUND: Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases. OBJECTIVE: This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1), and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD), and healthy controls. METHODS: Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units, and 22 healthy controls. Diagnostic evaluations followed established criteria, and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods. RESULTS: Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha, and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls. CONCLUSION: The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.

Comparative analysis of effects of conditioned mediums obtained from 2D or 3D cultured mesenchymal stem cells on kidney functions of diabetic rats: Early intervention could potentiate transdifferentiation of parietal epithelial cell into podocyte precursors.

AIM: The secretome of mesenchymal stem cells (MSCs) could be a potential therapeutic intervention for diabetes and associated complications like nephropathy. This study aims to evaluate the effects of conditioned mediums (CMs) collected from umbilical cord-derived MSCs incubated under 2-dimensional (2D) or 3D culture conditions on kidney functions of rats with type-I diabetes (T1D). MAIN METHODS: Sprague-Dawley rats were treated with 20 mg/kg streptozocin for 5 consecutive days to induce T1D, and 12 doses of CMs were applied intraperitoneally for 4 weeks. The therapeutic effects of CMs were comparatively investigated by biochemical, physical, histopathological, and immunohistochemical analysis. KEY FINDINGS: 3D-CM had significantly higher total protein concentration than the 2D-CM Albumin/creatinine ratios of both treatment groups were significantly improved in comparison to diabetes. Light microscopic evaluations showed that glomerular and cortical tubular damages were significantly ameliorated in only the 3D-CM applied group compared to the diabetes group, which were correlated with transmission electron microscopic observations. The nephrin and synaptopodin expressions increased in both treatment groups compared to diabetes. The WT1, Ki-67, and active caspase-3 expressions in glomeruli and parietal layers of the treatment groups suggest that both types of CMs suppress apoptosis and promote possible parietal epithelial cells' (PECs') transdifferentiation towards podocyte precursor cells by switching on WT1 expression in parietal layer rather than inducing new cell proliferation. SIGNIFICANCE: 3D-CM was found to be more effective in improving kidney functions than 2D-CM by ameliorating glomerular damage through the possible mechanism of transdifferentiation of PECs into podocyte precursors and suppressing glomerular apoptosis.