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Background Research into new markers has been intensified for early diagnosis, prognosis, and differentiation of SIRS, sepsis, and septic shock in recent years. This study aimed to investigate the role of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) and interleukin (IL)-6 in distinguishing between systemic inflammatory response syndrome (SIRS), sepsis, and septic shock in pediatric intensive care unit (PICU) patients. Methods Between June 2014 and July 2015, 90 consecutive patients who were treated in the PICU were included in this prospective observational study. Patients were divided into four groups: control (n = 23), SIRS (n = 22), sepsis (n = 23), and septic shock (n = 22). All patients were evaluated for white blood cell (WBC), serum C-reactive protein (CRP), procalcitonin (PCT), IL-6, and sTREM-1 levels at 0, 24, and 72 h of admission. The prognostic evaluations were made using the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores. Patients were evaluated in terms of age, gender, prognosis, pathogen growth in culture, PRISM III and PELOD score, WBC, CRP, PCT, IL-6, and sTREM-1 levels and a comparison was made between groups. Results There was no significant difference between all groups in terms of the 0-, 24-, and 72-h sTREM-1 values (p = 0.761, p = 0.360, and p = 0.822, respectively). CRP and PCT values did not differ between the septic shock, sepsis, and SIRS groups at 0, 24, and 72 h. In the septic shock group, the 0-h IL-6 value was significantly higher than that of the SIRS group (p = 0.025). The 24-h IL-6 value in the septic shock group was significantly higher than the values of the sepsis and SIRS groups (p = 0.048 and p = 0.043, respectively). No significant difference was detected between the septic shock, sepsis, and SIRS groups in terms of IL-6 values at 72 h. Conclusion sTREM-1 is not useful for the diagnosis of infection and for distinguishing between sepsis, septic shock, and SIRS since it does not offer a clear diagnostic value for PICU patients, unlike other reliable markers such as WBC, CRP, and PCT. Elevated IL-6 levels may indicate septic shock in PICU patients. More research on sTREM-1 is needed in this setting.

Our aim was to investigate the serum endocan levels and carotid artery intima-media thickness (CIMT) measurements of pre- and postmenopausal patients to clarify the relationship between the menopausal transition and endothelial injury. This cross-sectional study was conducted on women who were premenopausal and postmenopausal between January 2019 and June 2019. The patients were divided into two groups according to premenopausal (n = 32) and postmenopausal (n = 32) status. Serum endocan levels were assessed by enzyme-linked immunosorbent assay (ELISA). CIMT ultrasonographic measurements were determined. Hormonal and biochemical parameters were measured. The validated Menopause Rating Scale (MRS) questionnaire was used on all women. Serum endocan levels were significantly higher in the postmenopausal group than in the premenopausal group (222.90 ± 121.00 ng/L and 146.62 ± 41.88 ng/L, p = 0.033, respectively). The mean CIMT was significantly higher in the postmenopausal group than in the premenopausal cohort (0.70 ± 0.14 mm and 0.58 ± 0.11 mm, p

Glycogen storage diseases (GSDs) are clinically and genetically heterogeneous disorders that disturb glycogen synthesis or utilization. Although it is one of the oldest inherited metabolic disorders, new genetic methods and long-time patient follow-ups provide us with unique insight into the genotype–phenotype correlations. The aim of this study was to share the phenotypic features and molecular diagnostic results that include new pathogenic variants in our GSD cases. Twenty-six GSD patients were evaluated retrospectively. Demographic data, initial laboratory and imaging features, and current findings of the patients were recorded. Molecular analysis results were classified as novel or previously defined variants. Novel variants were analyzed with pathogenicity prediction tools according to American College of Medical Genetics and Genomics (ACGM) criteria. Twelve novel and rare variants in six different genes were associated with the disease. Hearing impairment in two patients with GSD I, early peripheral neuropathy after liver transplantation in one patient with GSD IV, epilepsy and neuromotor retardation in three patients with GSD IXA were determined. We characterized a heterogeneous group of all diagnosed GSDs over a 5-year period in our institution, and identified novel variants and new clinical findings. It is still difficult to establish a genotype–phenotype correlation in GSDs.

Various molecular and cellular processes are involved in renal fibrosis, such as oxidative stress, inflammation, endothelial cell injury, and apoptosis. Heat shock proteins (HSPs) are implicated in the progression of chronic kidney disease (CKD). Our aim was to evaluate changes in urine and serum HSP levels over time and their relationships with the clinical parameters of CKD in children. In total, 117 children with CKD and 56 healthy children were examined. The CKD group was followed up prospectively for 24 months. Serum and urine HSP27, HSP40, HSP47, HSP60, HSP70, HSP72, and HSP90 levels and serum anti-HSP60 and anti-HSP70 levels were measured by ELISA at baseline, 12 months, and 24 months. The urine levels of all HSPs and the serum levels of HSP40, HSP47, HSP60, HSP70, anti-HSP60, and anti-HSP70 were higher at baseline in the CKD group than in the control group. Over the months, serum HSP47 and HSP60 levels steadily decreased, whereas HSP90 and anti-HSP60 levels steadily increased. Urine HSP levels were elevated in children with CKD; however, with the exception of HSP90, they decreased over time. In conclusion, our study demonstrates that CKD progression is a complicated process that involves HSPs, but they do not predict CKD progression. The protective role of HSPs against CKD may weaken over time, and HSP90 may have a detrimental effect on the disease course. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12192-021-01239-9.

Objective: Histopathological changes in the kidney in type 1 diabetes mellitus (T1DM) begin before detection of microalbuminuria. Therefore, there is interest in finding a better biomarker for the early detection of diabetic kidney injury. The aim of this present study was to determine whether urinary indicators of fibrosis are detectable early in the development of T1DM in children and if they may predict progressive renal injury. Methods: Urinary matrix metalloproteinase 2 and 9 (MMP2 and MMP9), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2) and transforming growth factor-β1 (TGF-β1) were assessed in 33 patients with T1DM with normal renal functions and in 24 healthy controls. Microalbuminuria was not present in the patient group with the exception of three patients. The results were adjusted to urine creatinine (Cr) and the differences between patients and controls were evaluated. These measurements were repeated after one year and the results were compared with the first year results. Results: Urine MMP2/Cr, MMP9/Cr, TIMP1/Cr, TIMP2/Cr, TGF-β1/Cr were not different between the patient and control groups (p>0.05). There were also no significant differences between the first and second year results for these biomarkers (p>0.05). None of these parameters were correlated with hemoglobin A1c, body mass index and duration of T1DM. Interestingly, all parameters were negatively correlated to age of onset of T1DM (p

Kisspeptin (KP), a hypothalamic peptide, is known as an important marker for neuroendocrine regulation during the human reproduction process. The unexplained infertility (UI) group comprised 30 patients, polycystic ovary syndrome (PCOS) group comprised 29 patients and the male factor infertility (MFI) group comprised 27 patients. An observational cohort study was conducted. The basic characteristics of the study population, BMI, and serum FSH, LH, E2, AMH, KP, TSH, and PRL levels and antral follicle count (AFC) on the 3rd menstruation day were evaluated. The mean KP level was 281.98 ± 73.9 ng/ml in the UI group, 525.49 ± 164.17 ng/ml in the PCOS group, and 354.313 ± 111.38 ng/ml in the MFI group (p < .001). KP levels were significantly higher in the PCOS group than in the UI and MFI groups (p < .001 for both). AUC was 83% (95% CI: 73%-93%), with 375.15 (pg/ml) as the cutoff value in the PCOS group with 83% sensitivity and 79% specificity. UI may be treated by KP injection therapies and higher levels of KP may be a reliable marker for AFC and diagnosis of PCOS. Clinical Trials registration number: NCT03018314.

Aim: The aims of this study are to evaluate the serum levels of paraoxonase (PON) and arylesterase (ARE) in breast cancer (BC) patients; to determine their relationship with chemotherapy requirements in BC; and to find a cut-off value to assess subjects with a higher risk of BC. Subjects and Methods: A total of 40 BC patients and 33 age-matched healthy women were included in this study. Beside other biochemical parameters, participants' serum PON and ARE levels were determined and analyzed. Results: Serum PON and ARE levels were found decreased in sera of the patients (96.44 ± 21 and 159.75 ± 15.75 U/L, respectively)compared to controls (158.39 ± 23.04 and 239.33 ± 32.98 U/L, respectively) (P = 0.001 for both). Subgroup analysis of the BC patients revealed that both serum PON and ARE levels were lower in patients who needed neoadjuvant chemotherapy (NAC), compared to those who did not (P = 0.024 and 0.02, respectively). We determined a cut-off value of PON according to the receiver operating characteristic curve analysis as 131.2 U/L (sensitivity 97.5% and specificity 93.9%). Conclusion: BC patients have lower serum PON and ARE levels than healthy controls. Also, serum ARE levels (but not PON) were negatively correlated with body mass index in BC patients. Both serum PON and ARE levels were lower in patients who needed NAC than in patients who did not need such therapy.

The objective of this study was to establish reference intervals for growth arrest-specific 6 (GAS6), a vitamin K-dependent protein, in human adult plasma according to the Guideline of Clinical and Laboratory Standards Institute (CLSI) C28-A3. Blood samples were collected from 308 healthy volunteers aged 18-72 (157 female, 151 male). A non-parametric approach was used to calculate the reference interval. The plasma GAS6 reference interval was determined, with 90% confidence interval: the lower limit (2.5 percentile) was 2.5 (1.9-3.1) μg/L and the upper limit (97.5 percentile) = 18.8 (18.0-22.3) μg/L. Harris-Boyd's test did not suggest partitioning by age or gender: medians for males [7.8 (5.8-10.7) μg/L] and females [9.9 (7.1-13.5) μg/L]. Three age-subgroups were tested: 18-29 years (n = 168); 30-44 years (n = 73); 45-72 years (n = 67). The intra- and inter-assay variations were 12.6% (mean, 5.2 ± 0.7 μg/L) and 14.0% (mean, 9.2 ± 1.3 μg/L), respectively. The mean recovery was 104%. This study reports plasma GAS6 reference intervals established first according to the guideline of CLSI C28-A3.

Background Both the extracellular matrix molecule tenascin-C (Tn-C) and tissue inhibitors of metalloproteinases (TIMPs) have a role in tissue injury, inflammation, and remodeling. In this pilot study, we tried to evaluate the role of these markers in acute kidney injury (AKI). Methods A total of 52 subjects were enrolled in this study. Group 1 consisted of 27 patients with AKI (stage 1, 2, and 3), and Group 2 consisted of 25 age- and gender-matched healthy subjects. Serum and urine samples (to determine Tn-C and TIMP-1) were obtained from the participants at the beginning of the study. Second samples were obtained from Group 1 patients when renal function improved (at discharge). Results Serum TIMP-1 concentrations (admission and discharge) were higher in Group 1 than Group 2 (p = 0.0001 for both comparisons). Tn-C excretion in spot urine was significantly higher in healthy controls than at the admission levels of the patient group (p = 0.036). However, TIMP-1 excretion in spot urine was lower in healthy controls than in admission and discharge levels of the patient group (p = 0.0001 for both comparisons). Conclusions Our results show that these biomarkers (especially TIMP-1) may have a role in the pathophysiology of AKI. Further studies are needed in this field.

The purpose of the study was to compare serum visfatin levels between patients with acromegaly and healthy controls and to evaluate the relationships between visfatin levels and epicardial fat thickness (EFT), carotid intima media thickness (cIMT), and ankle brachial index (ABI). We conducted a cross-sectional case-control study of 54 patients with acromegaly (37 females and 17 males) and 34 healthy controls (22 females and 12 males). Serum visfatin was measured by ELISA. Acromegalic and control participants and those with active or controlled acromegaly were compared with respect to their serum visfatin, clinical and metabolic parameters, EFT, cIMT, and ABI. Linear correlation was used to identify associations between these parameters and visfatin in all participants. Serum visfatin and glycated hemoglobin (HbA1c) were higher in the acromegaly group than in the control group (p

Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12 ± 217.64 versus 270.02 ± 136.83 pg/mgCr; uHSP40/Cr 180.89 ± 118.59 versus 99.44 ± 62.49 pg/mgCr; uHSP60/Cr 114.40 ± 64.91 versus 70.50 ± 43.70 pg/mgCr; uHSP70/Cr 41.17 ± 28.42 versus 16.47 ± 7.32 pg/mgCr; uHSP90/Cr 175.64 ± 102.22 versus 107.61 ± 75.85 pg/mgCr) (p 0.05). In 2013, uHSP70/Cr level increased significantly (51.08 ± 27.72 pg/mgCr; p = 0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p 0.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59 pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children.

Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55. Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. Our study aimed to compare the effects of PON1 192, PON1 55 polymorphisms, and PON1 activity in patients with urolithiasis and controls.PON1's arylesterase/paraoxonase activities and phenotype were determined in 158 stone forming cases (Group 1) and 138 non-stone forming controls (Group 2). The PON1 192 and PON1 55 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism.Paraoxonase activity was significantly lower in Group 1 than Group 2 (112 ± 31.8 vs. 208 ± 53.1 IU/L) (p 0.001). The PON1 L55M polymorphism was significantly higher in Group 1. The "M" allele coding for PON1 was higher in Group 1 (p 0.001). PON1 192 RR homozygotes had significantly higher PON1 activity than QR and QQ genotypes among all the patients (p 0.001).The results of our study demonstrate that the PON1 55 gene "M" allele is associated with renal stone disease. Individuals possessing the "M" allele have a higher incidence of urolithiasis. The results of this study provide genetic evidence that the PON1 gene may play a role in stone formation. PON1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis.

Objective There is some evidence indicating that histopathological changes in type 1 diabetes mellitus (T1DM) emerge before onset of microalbuminuria. The aim of our study was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) levels can be considered as an early sign of diabetic kidney injury. Methods Urine NGAL (uNGAL) levels and urinary NGAL/creatinine ratio (uNGAL/Cr) were assessed in 76 patients with T1DM and compared with the findings of 35 healthy individuals. The relationship of uNGAL levels with diabetes duration, body mass index (BMI), serum lipids, HbA1c, and microalbuminuria was also evaluated. Results Mean uNGAL (100.16±108.28 ng/mL) and uNGAL/Cr (118.93-117.97 ng/mg) levels in both microalbuminuric and non-microalbuminuric diabetic patients were found to be higher than those in the control group (uNGAL: 21.46±18.59 ng/mL and uNGAL/Cr: 32.1±51.48 ng/mg) (p=0.0001). Conclusion Urine NGAL level increases in the very early phase of T1DM before microalbuminuria develops. The patients with T1DM should be considered to have diabetic kidney injury from the time of diagnosis on and preventive interventions need to be initiated at an early stage to preclude the progression to end-stage renal disease.

Background The most frequent cause of cancer deaths throughout the world is breast cancer (BC). Therefore, preventing, diagnosing and treating BC has gained importance. S100 protein probably plays an important role in carcinogenesis, cancer development, and metastasis. In this study, we aimed at diagnostic and clinic-pathological importance of serum levels of S100A9 and S100A12 with known cytokine-like pro-inflammatory effects in BC. Material and method Serum samples were collected with BC and the control group consisting of healthy individuals. All the samples were analyzed with enzyme-linked immunosorbent assay for serum S100A9 and S100A12 levels before starting the systemic chemotherapy. Clinicopathological characteristics of BC and other blood parameters were compared in relation with serum S100A9 and S100A12 levels. Results While the serum S100A9 levels were found significantly higher as compared to healthy individuals (190.85 ± 32.29 and 92.72 ± 54, respectively) (p = 0.001), it was observed that there were no differences in S100A12 (120.50 ± 15.78 and 112.21 ± 10.46, respectively) (p = 0.056) levels. As regards the subgroup analysis in BC patients, no statistically significant results were found in body mass index (BMI), smoking, menopause status, histopathologic type, grade, and biological subtype of BC, tumor size, presence of lymph node metastases, lymphovascular invasion (LVI), perineural invasion (PNI) and stage. As regards the blood parameters and serum S100 A9, while only statistically significant results were found with anemia (209.05 ± 33.12 and 181.75 ± 28.21, respectively) (p = 0.005), no statistically significant results were found with leukocytosis, thrombocytosis and tumor markers. Conclusion In this study, while we found the level of S100A9, which has a potential cytokine-like function in inflammation, significantly higher, we could not find any increase in S100A12 level. Therefore, it is possible that S100A9 can play a key role in inflammation-related BC. Despite of there are no significance relationship between S100A9 and S100A12 clinicopathological features of BC, the determination of S100A9 levels contributes to diagnosis the of BC patients. In future, we suggest that serum S100A9 is investigated as a diagnostic tool even the target marker in BC to suppress inflammation in treatment.

Background/Aims: To identify the role of serum caspase 3, Annexin A2 (ANXA2), and Soluble Fas Ligand (sFasL) levels in the prediction of endometriosis severity. Methods: The study was performed on 90 women who were candidates for laparoscopic surgery due to endometrioma or any other benign ovarian cysts detected by ultrasound examination, pelvic pain, or infertility. The control group comprised 29 patients. The second group comprised 29 patients with stage I–II endometriosis and the third group comprised 30 patients with stage III–IV endometriosis. Results: Significant differences were detected between the control and stage III–IV endometriosis groups and between stage I–II and stage III–IV endometriosis groups in terms of caspase-3 levels (both, p < 0.001), ANXA2 levels (p = 0.007 and p = 0.002), and sFasL levels (p = 0.022 and p = 0.044). After receiver operating characteristic analysis, the area under curve was 93% (95% CI 57–82) at 10.7 ng/mL cut-off level for caspase-3 with 90% sensitivity and 87% specificity. Conclusion: Serum caspase-3 level may be a reliable predictor of endometriosis severity.

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3–p22.3, 5q13–q22, and 11p15) have been mapped to autosomes and one gene ( SOS1 ) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor ( REST ) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the HGF phenotype.

Altered paraoxonase (PON) and arylesterase (ARE) activities have been shown in anemic chronic kidney disease (CKD) patients and in iron deficiency anemia (IDA) patients. Whether accompanying anemia alone is responsible for this diminished PON and ARE activities in CKD patients or an additive factor for this is not well studied. Therefore, we tried to clarify this issue here.A total of 82 subjects that consisted of 19 patients with IDA (group 1), 23 anemic CKD patients (group 2), and 40 age and sex matched healthy subjects (group 3) were enrolled. Carotid intima media thickness (CIMT), serum total thiol (-SH), PON, and ARE activities of the participants were analyzed.Group 2 patients had significantly lowest serum levels of Total -SH, PON and ARE. Further comparison showed that total -SH, PON and ARE levels were lower in group 1 than group 3 (p = 0.0001 in both). Regarding comparison of group 1 and 2, only serum ARE levels were significantly lower in group 2 (p = 0.001). PON activity was not different between group 1 and group 2 whereas ARE activity was lower in group 2 than groups 1 and 3. In addition, correlation analysis showed that CIMT was negatively correlated with PON and ARE.This markedly decreased ARE activity in CKD patients, which could not be explained by the anemia alone, may have a role in the pathogenesis of increased atherosclerosis in such patients. Still further studies are needed to certain this.

In colorectal cancer (CRC), as in most of other malignancies, heat shock proteins (HSPs) are overexpressed and are associated with apoptosis, cancer cell proliferation, differentiation, invasion, and metastasis. HSP70 is one of the HSPs and has a promising future in cancer studies for both diagnostic and therapeutic applications. In this study, we tried to evaluate the serum levels of HSP70 in CRC patients, and to evaluate its predictive value of detecting CRC.This prospective study was consisted of 33 patients diagnosed with CRC and 31 healthy subjects who were matched for age. Enzyme-linked immunosorbent assays (ELISA) were used to evaluate the serum levels of HSP70 in patients with CRC and in the healthy control group. A cut-off value for HSP70 was also determined using receiver operating characteristic (ROC) curve analysis.Patients with CRC had significantly higher HSP70 concentrations compared with the control group (4.52 ± 1.83 vs 1.22 ± 0.48 ng/ml, p=0.001), the cut-off value was ≥2.25 ng/ml (95% CI 0.993-1.003, p0.001). The sensitivity and specificity of elevated serum HSP70 in the CRC group were 96.77 and 96.96%, respectively. Also, HSP70 levels were significantly higher with rectal disease localization (p=0.01).This study shows that the serum level of HSP70 is elevated in patients with CRC. HSP70 may be utilized as an adjunct to other diagnostic or screening tests.

AIMS Endothelin-1 (ET-1) contributes to renal fibrogenesis in several manners such as increasing collagen synthesis in mesangium, decreasing extracellular matrix (ECM) degradation by mesangial cells and stimulating mesangial contraction. The aim of our study was to investigate whether urine level of ET-1 (uET-1) could represent a useful biomarker of renal scarring and if so, to determine the optimal cutoff level for uET-1 to predict a renal scar. METHODS 44 children with renal scarring and 32 children without renal scarring were enrolled in the study. Urine ET-1 was measured by enzyme-linked immunosorbent assay. RESULTS Mean uET-1 level was significantly higher in the scar group than in controls (2.75 ± 1.35 fmol/ml vs. 0.68 ± 0.41 fmol/ml, p = 0.001). The optimal cut-off level was 1.064 fmol/ml for uET-1 to predict renal scarring. Using this cut-off point, sensitivity and specificity were 97.73% and 93.91%, respectively. AUC was found 0.975 (95% CI 0.917 - 0.996) for uET-1. Mean urine Endothelin-1/Creatinine ratio (uET-1/Cr) was also significantly higher in the scar group than in the control group (4.04 ± 2.29 fmol/mg Cr vs. 1.09 ± 0.67 fmol/mg Cr, p = 0.0001). Using 1.67 fmol/mgCr as optimal cut-off level, sensitivity and specificity were 95.45% and 84.09%, respectively. AUC was 0.945 (95% CI 0.875 - 0.982) for uET-1/Cr. CONCLUSION Our study suggests that both uET-1 and uET-1/Cr can be used for prediction of renal scarring in children with normal renal function. Measuring urine level of ET-1 can help us to avoid unnecessary DMSA studies if the patient's uET-1 level is found to be under the determined cut-off point.

To determine the changes in cervical collagen during the first trimester of pregnancy and to evaluate the collagen deficit in cases with a previous diagnosis of cervical insufficiency (CI).Cervical punch biopsies were obtained from 66 patients divided into three groups: patients with recurrent abortions due to CI (CI group; n = 8); first-trimester abortion group (study group; n = 37), subdivided into three groups according their gestational week (7, 7-9 and 9-12 weeks), and patients with cervical biopsy due to gynecologic reasons (control group; n = 12). Collagen quantity was determined by a biochemical method that measured the levels of hydroxyproline (HOP) in dry cervix tissue.The HOP concentrations were significantly higher at lower gestational ages (p = 0.001). Collagen quantity was lowest in the CI group compared with other groups (p 0.001).This study shows collagen component of cervix decreases as pregnancy advances through the first trimester. Cervical collagen concentration is lower in women with a history of CI compared to controls who has not a history of CI.

The aim of this study was to investigate whether urine levels of matrix metalloproteinase 9 (uMMP9) and tissue inhibitor of metalloproteinase 1 (uTIMP1) are novel biomarkers of vesicoureteral reflux (VUR) and to determine the optimal cut-off levels of these enzymes to predict VUR in children. The study group consisted of 67 children with VUR and 20 healthy children. Urine MMP9 and TIMP1 levels were measured by an enzyme-linked immunosorbent assay. Children with VUR had significantly higher uMMP9 (1,539.8 vs. 256.4 pg/mL; p = 0.0001) and uTIMP1 (182 vs. 32.6 pg/mL; p = 0.0001) levels than healthy children. For the prediction of VUR, the sensitivity of uMMP9 was 67%, with a specificity of 85% [cut-off value 1,054 pg/mL; area under the curve (AUC) 0.77], and the sensitivity of uTIMP1 was 74%, with a specificity of 65% (cut-off value 18.7 pg/mL; AUC 0.73). Both uMMP9 and uTIMP1 levels were significantly higher in patients with renal scar (uMMP9: 3,117.3 vs. 1,234.15 pg/mL; p = 0.0001; uTIMP1: 551.05 vs. 128.64 pg/mL; p = 0.0001). Urine MMP9 levels had a sensitivity of 81.2%, with a specificity of 85% to predict renal scar in the VUR group (cut-off 1,054 pg/mL; AUC 0.88). The sensitivity of uTIMP1 was 75%, with a specificity of 90% to predict renal scar (cut-off 243.7 pg/mL; AUC 0.82). Based on these results, we suggest that uTIMP1 may be a useful marker to predict renal scarring with a different cut-off value from VUR and a high specificity at this cut-off point. Although uMMP9 seemingly cannot distinguish renal scar from VUR, the simultaneous increase in the level of both markers may indicate ongoing renal injury due to VUR.

The matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase associated lipocalin (NGAL) are shown to increase in an inflammatory situation. Based on our previous reports that NGAL can be detected in the urine of children with urinary tract infection (UTI), we also asked whether MMP-9/NGAL complex could be detected in the urine of children with UTI. This multicenter, prospective study was conducted between October 2009 and October 2010. Seventy-one patients with symptomatic culture proven UTI, 37 asymptomatic children with contaminated urine and 37 healthy children were recruited. Mean uMMP-9/NGAL/Cr levels were significantly higher in the UTI group than in the control group (p < 0.0001). According to ROC analysis, the optimal cut-off level was 0.08 ng/mg to predict UTI. Using a cut-off value, sensitivity and specificity were 98.6 and 97.3%, respectively. The mean levels of uMMP-9/NGAL/cr in the UTI group were also significantly higher than those in the contamination group (p < 0.0001). There was no statistically significant difference between contamination group and the control group (p = 0.21). The mean uMMP-9/NGAL/Cr in the UTI group were significantly higher before treatment than after treatment (p < 0.0001). The area under the curve was 0.997 (SE: 0.002, 95% CI: 0.993 to 1.001) for uMMP-9/NGAL/Cr. Urinary MMP-9/NGAL/Cr level was also correlated with positive urine nitrite test, positive urine leukocyte esterase reaction and renal scarring (p = 0.0001, p = 0.0001, p = 0.04, respectively) whereas was not correlated to leukocytosis and positive CRP level in serum. Urine MMP-9/NGAL/cr can be used as a diagnostic biomarker for UTI in children. Identification of NGAL-MMP-9/cr levels in the urine of suspected UTI patients may also be useful to differentiate between contamination and infection and for monitoring of treatment response in children.

Neutrophil gelatinase associated lipocalin (NGAL) is a protein identified in human neutrophil granules. The aim of the study was to assess whether urine level of NGAL (uNGAL) could represent a novel, reliable marker of urinary tract infection (UTI) and to determine the optimal cutoff level for uNGAL to predict UTI in children. Sixty patients with symptomatic UTI and 29 healthy controls were enrolled the study. Urine NGAL was measured by enzyme-linked immunosorbent assay. A dimercaptosuccinic acid (DMSA) radionuclide scan was performed within 7 days in the patients with UTI in an attempt to distinguish pyelonephritis from cystitis. Mean uNGAL level was significantly higher in the UTI group than in the controls (91.02 ng/ml vs 14.29 ng/ml, p = 0.0001) and using a cutoff 20 ng/ml for uNGAL for diagnosis of UTI, sensitivity, and specificity were 97% and 76%, respectively [area under the curve (AUC): 0.979]. Mean uNGAL/creatinine ratio (uNGAL/Cr) was also significantly higher in the UTI group [201.81 ng/mg creatinine (Cr) vs 18.08 ng/mg Cr; p = 0.0001], and using a cutoff 30 ng/mg Cr for uNGAL/Cr for diagnosis of UTI, sensitivity and specificity were 98% and 76%, respectively (AUC: 0.992). In conclusion, both uNGAL and uNGAL/Cr can be used as a novel, sensitive marker for early prediction of UTI in the absence of acute kidney injury and chronic kidney disease, and the optimal cutoff value for prediction of UTI is lower than the values determined for acute kidney injury. Further investigations with larger patient groups are required to confirm our results.

The aim of this study is to evaluate the correlation between epicardial adipose tissue thickness and oxidative stress parameters in patients with polycystic ovarian syndrome.The study included 35 patients with PCOS and 35 healthy women. Transthoracic echocardiography was used to measure the epicardial adipose tissue thickness (EATT) of all patients. For all patients, serum TOS, TAS, hs-CRP, and insulin levels were measured according to the literature, and the HOMA-IR values were calculated. Independent samples t-test, Pearson's correlation analysis, multivariate logistic regression analysis, and receiver operator characteristic curve (ROC) analysis were used in the statistical analysis.Between the patient group and the control group, EATT was significantly higher in the PCOS group compared to the control group (5.4 ± 1.4 mm and 3.9 ± 1.6 mm, respectively; p 0.001). Similarly, TOS, TAS, and hs-CRP levels were significantly higher in the PCOS group compared to the control group (p 0.01 for all). The correlation analysis showed a significant positive correlation between EATT and TAS and hs-CRP (r = 0.349, p 0.01 and r = 0.352, p 0.01, respectively). Multivariate regression analysis showed a significant correlation between PCOS and EATT, TAS, and diastolic blood pressure (p 0.05 for all).Epicardial adipose tissue may play a major role in PCOS pathogenesis by leading to an increase in oxidative stress.

Breast cancer (BC) is the most frequent cause of cancer death in women throughout the world. Thus, it is necessary to establish sensitive screening, diagnosis and treatment methods for BC. Heat shock protein 70 (HSP70) is an important cellular stress response protein that protects cells from apoptosis. Recent studies have shown that serum HSP70 levels may provide clinically important information in various types of cancer. HSP70 is also overexpressed in BC, which is known to be associated with cancer progression, apoptosis and cell proliferation. However, the serum level of HSP70 and its diagnostic and prognostic potential in BC have not been investigated yet. The aim of this study was to determine the usefulness of serum HSP70 level as a diagnostic test and its predictive value in patients with BC. This prospective study consisted of 45 female patients diagnosed with BC and 16 healthy women who were matched for age and body mass index (BMI). Enzyme-linked immunosorbent assay (ELISA) technique was used to measure the serum level of HSP70. The serum level of HSP70 was significantly higher in patients with BC than in the healthy control group (5.98 ± 2.05 vs. 1.49 ± 0.47 ng/ml, p = 0.001). HSP70 level > 2.41 ng/ml was the best cutoff value to predict BC (97.78% sensitivity and 93.75% specificity). This study shows that HSP70 can be used as an adjunct to other diagnostic tests for BC and may be helpful for identifying patients at increased risk of BC.

Background Despite improved surgical techniques and materials, anastomotic leakage is a big problem for surgeons. The most frequently used laboratory parameters is leukocyte (white blood cell) and C-reactive protein (CRP). Availability of plasma calprotectin with CRP to detect anastomotic leakage was studied. Methods In this prospective study of 41 (male/female 18/23) patients in the anastomosis group, 30 (male/female 20/10) patients were included in the control group. The anastomosis groups viewed in preoperatively day and postoperatively 1st, 3rd, and 5th day of CRP, white blood cell, and plasma calprotectin values. Results Anastomosis group with complications and without complications were studied. Statistically significant similarities between plasma calprotectin and CRP levels in the postoperative period were observed. Conclusion Plasma calprotectin in monitoring the integrity of the anastomosis can be used with a marker CRP.

BACKGROUND & AIMS: Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. METHODS: We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. RESULTS: We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. CONCLUSIONS: Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons. Background Aims Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. Methods We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. Results We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. Conclusions Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons.

Patients with angiographically normal coronary arteries sometimes exhibit delayed clearance of contrast medium. This contrast layering (CL) was tested with intravascular ultrasound (IVUS) and markers of endothelial dysfunction and oxidative stress. The study group (n = 26) consisted of patients with CL and the control group (n = 32) comprised patients with normal coronary arteries despite angina symptoms. The CL was observed in 36 coronary arteries of 26 patients in the study group. Total antioxidant status and nitric oxide levels were significantly lower; total oxidant status, malondialdehyde plasma levels, and oxidative stress index were significantly higher in patients with CL than in controls. The IVUS studies revealed that atherosclerotic plaque burden, fibrous tissue, dense calcific tissue, and necrotic core ratios were significantly higher in the coronary segments with CL compared with adjacent normal segments. These results support the concept of CL as a new angiographic appearance of early atherosclerosis.

The aim of this study was to evaluate the serum soluble CD40 ligand (sCD40L) levels, serum uroten- sin II levels, and serum leptin levels as an indirect indicator of endothelial dysfunction, inflammation, and atherosclerosis at the microvascular level, and the comparison of those values with those of the control group with a nor- mal coronary flow pattern.The study included 35 consecutive patients (17 women, 18 men; average age: 51.20 ± 10.93 years) in our hospital who underwent coronary angiography due to objective myocardial ischemia and in whom slow coronary flow was detected. The control group included 34 consecutive patients with normal coronary flow pattern (18 women, 16 men; average age: 54.59 ± 12.40 years). The coronary flow rates of all patients and control subjects were documented by the thrombolysis in myocardial infarction (TIMI) frame count. Serum sCD40L concentrations, serum urotensin II concentrations and serum leptin concentrations were measured by an enzyme-linked immunosorbent assay method using commercially available kits.The corrected TIMI frame count for LAD, Cx, RCA, and mean TIMI frame count were significantly higher in patients with slow coronary flow (SCF), compared to subjects with normal coronary flow (43.8 ± 1.7 vs. 17.7 ± 4.7, p0.001; 27.9 ± 6.9 vs. 11.9 ± 4.8, p0.001; 25.4 ± 8.4 vs. 11.1 ± 3.1, p0.001; and 32.3 ± 6.4 vs. 13.7 ± 5, p0.001, respectively). The serum soluble CD40 ligand and serum urotensin II levels were significantly higher in the slow coronary flow group compared to the control group (12.00 ± 5.43 ng/mL--6.49 ± 5.03 ng/mL, p0.001; and 50.94 ± 34.28 pg/mL--26.91 ± 11.52 pg/mL, p0.001, respectively). In addition, there was no statistically significant difference between the slow coronary flow group and the control group with regard to serum leptin levels and hs-CRP levels (both p0.05).This study suggests that soluble CD40 ligand and urotensin II likely play a role in the pathogenesis of slow coronary flow.

Decreased collagen biosynthesis and increased collagenolysis may induce aneurysmal progress in arterial walls. Prolidase plays a role in collagen synthesis. In this study, we sought to evaluate whether there is a correlation between nonatherosclerotic coronary artery aneurysms (CAAs) and prolidase activity. A total of 174 CAAs were diagnosed in 144 (2.1%) patients among 6845 coronary angiographies performed between 2009 and 2012. In all, 23 (15.9%) patients had nonatherosclerotic aneurysms. Prolidase activity was compared to the results of 19 healthy volunteers with normal coronary arteries. Demographic parameters were similar between the groups. Mean prolidase activity was 241.6 ± 54.4 mU/mL in the coronary aneurysm group and 730.3 ± 243.1 mU/mL in the control group ( P < .001). The incidence of CAAs ranges between 0.3% and 5.3% in the general population. Decreased prolidase activity may reduce collagen biosynthesis that may contribute to aneurysm formation.

Objective: To compare the serum adiponectin levels together with metabolic and hormonal parameters among teenage girls at the early onset of polycystic ovary syndrome (PCOS) and hyperandrogenism with controls. Design: Prospective study. Settings: Education and research hospital, outpatient gynecological endocrinology clinic. Participants: Four hundred seventy-nine teenage girls from a school of nursing were interviewed for the signs and symptoms of PCOS. Among them, 42 cases who had a definitive diagnosis of PCOS with hyperandrogenism based on Rotterdam diagnostic criteria were recruited for the study and other causes of hyperandrogenemia had been excluded. The controls were recruited from regularly cycling healthy teenage girls from the same high school of nursing; none of those who agreed to join the study met any of the diagnostic criteria for PCOS (n 5 44). Interventions: Cases were selected as group I: PCOS with body mass index (BMI) !25 kg/m 2 (n 5 20), group II: PCOS with BMI O25 kg/m 2 (n 5 22), group III: Controls with BMI !25 kg/m 2 (n 5 21) and group IV: Controls with BMI O25 kg/m 2 (n 5 23). Serum adiponectin, metabolic and hormonal parameters were compared in PCOS patients with BMI matched controls. Main Outcome Measures: Difference of serum adiponectin levels, metabolic and hormonal parameters between teenage girls with PCOS and controls. Results: Serum adiponectin levels were not significantly different in group I and group II. Serum adiponectin levels were significantly decreased in group I and group II compared with both control groups (III and IV). Conclusion: Serum adiponectin levels were lower in teenage girls with PCOS and this reduction was independent from BMI.

Macrophage migration inhibitory factor (MIF) plays an essential pathophysiological role in inflammatory reactions. The aim of this study was to investigate the clinical utility of urine MIF (uMIF) level in predicting urinary tract infections (UTI). This multicenter, prospective study was conducted over a 1-year period between March 2008 and March 2009. Sixty patients with symptomatic culture-proven UTI and 29 healthy children were recruited. Urine MIF was measured by enzyme-linked immunosorbent assay. The mean MIF level was found to be significantly higher in the UTI group than in the control group (1082.82 vs. 211.45 pg/ml, p = 0.0001). Receiver operating characteristic (ROC) analysis revealed that the optimal cut-off uMIF level was 295 pg/ml for uMIF to predict UTI. The sensitivity and specificity of this cut-off level were 91.7% and 69%, respectively. Mean uMIF/creatinine (Cr) was also significantly higher in the UTI group than in the control group (2400.69 vs. 267.56 pg/mgCr, p = 0.0001). At a cut-off of 815 pg/mgCr for uMIF/Cr, the sensitivity and specificity were 95 and 79%, respectively. The area under curve (AUC) was 0.848 (standard error 0.040, 95% confidence interval 0.756–0.915) for uMIF and 0.889 (0.034, 0.805–0.946) for uMIF/Cr. Urine MIF/Cr was significantly higher in the patients with a positive leukocyte esterase reaction in the urine (p = 0.047), leukocytosis (p = 0.0001) and positive C-reactive protein level in serum (p = 0.003). The uMIF level was not related to leukocytosis, positive CRP level in serum and leukocyte esterase reaction in the urine. Neither uMIF nor uMIF/Cr were correlated to the positive urine nitrite test, pyuria, urine pH and specific gravity (p > 0.05). These results suggest that urine MIF and uMIF/Cr can be used for the early prediction of UTI in children.