Comparison of salpingectomy and tubal detorsion procedures after experimental ischemia-reperfusion injury in a rat fallopian tube model: biochemical and histopathological evaluation.

OBJECTIVE: To compare salpingectomy and detorsion procedures and investigate the biochemical and histopathological changes in the fallopian tubes in the experimentally isolated fallopian tube torsion model in rats. DESIGN: Experimental study. SETTING: Experimental surgery laboratory in a training and research hospital. ANIMAL(S): Twenty-seven Sprague-Dawley rats in the reproductive period. INTERVENTION(S): Group 1, control group (n = 6); group 2, bilateral total salpingectomy group after 4 hours of tubal ischemia (n = 7); group 3: 4 hours of bilateral tubal ischemia plus 1 week of reperfusion (n = 7); and group 4, 4-hour period of bilateral tubal ischemia plus 30 days of reperfusion (n = 7). A 22-gauge catheter was administered before and after surgery using methylene blue through the uterine horn of the rat to evaluate tubal patency. MAIN OUTCOME MEASURE(S): Preoperative and postoperative serum antimüllerian hormone (AMH) levels, histopathological examination of the rat tuba uterine and histopathological damage scores, antioxidant compounds (superoxide dismutase [SOD], catalase, and glutathione peroxidase [GSH-Px]), and oxidative stress end product levels (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]). RESULT(S): Although a significant difference was observed in the tissue SOD, GSH-Px, MDA, and 8-OHdG values, no significant difference was observed between the groups in serum samples. The tissue SOD and tissue GSH-Px levels in group 2 significantly decreased, and a significant increase was observed in the tissue MDA and 8-OHdG values in group 2. Among the histopathological parameters, epithelial changes, vascular congestion, and the total fallopian tube mean damage score of 4 showed a significant decrease in group 4. When the methylene blue transitions before and after ischemia-reperfusion injury were compared, the values of the methylene blue transition after ischemia-reperfusion injury in groups 2-4 significantly decreased. When the serum AMH levels were analyzed, the postoperative AMH value in group 2 significantly increased. CONCLUSION(S): This study reveals that biochemical and histopathological improvement is observed in the fallopian tube tissues gradually when the detorsion procedure is performed for the necrotized tubal tissue instead of salpingectomy. Although there is restoration of epithelial integrity after reperfusion, tubal passage remains absent. CLINICAL TRIAL REGISTRATION NUMBER: This study was approved by the Local Ethics Committee for Animal Experiments of the Health Sciences University, Istanbul Hamidiye Medicine Faculty (approval number 27.05.2022-9269). The study followed the ethics standards recommended by the Declaration of Helsinki.

The effect of mesenchymal stem cells administration on DNA repair gene expressions in critically ill COVID-19 patients: prospective controlled study.

When the studies are evaluated, immunomodulatory effect of MSCs, administration in critically ill patients, obstacle situations in use and side effects, pulmonary fibrosis prevention, which stem cells and their products, regeneration effect, administration route, and dosage are listed under the main heading like. The effect of MSC administration on DNA repair genes in COVID-19 infection is unknown. Our aim is to determine the effect of mesenchymal stem cells (MSCs) therapy applied in critically ill patients with coronavirus infection on DNA repair pathways and genes associated with those pathways. Patients (n = 30) divided into two equal groups. Group-1: Patients in a critically ill condition, Group-2: Patients in critically ill condition and transplanted MSCs. The mechanism was investigated in eleven genes of five different pathways; Base excision repair: PARP1, Nucleotide excision repair (NER): RAD23B and ERCC1, Homologous recombinational repair (HR): ATM, RAD51, RAD52 and WRN, Mismatch repair (MMR): MLH1, MSH2, and MSH6, Direct reversal repair pathway: MGMT. It was found that MSCs application had a significant effect on 6 genes located in 3 different DNA damage response pathways. These are NER pathway genes; RAD23 and ERCC1, HR pathway genes; ATM and RAD51, MMR pathway genes; MSH2 and MSH6 (p < 0.05). Two main points were shown. First, as a result of cellular damage in critical patients with COVID-19, DNA damage occurs and then DNA repair pathways and genes are activated in reaction to this situation. Second, administration of MSC to patients with COVID-19 infection plays a positive role by increasing the expression of DNA repair genes located in DNA damage pathways.

EFFECT OF DIET BEFORE BARIATRIC SURGERY ON GHRELIN LEVEL THROUGH DNA METHYLATION.

INTRODUCTION: The ghrelin system, which generates the appetite hormone, is harmed by obesity, a problem of worldwide public health. An efficient way to cure obesity is through bariatric surgery. This randomized controlled study's objective was to assess preoperative diet-related DNA methylation of Ghrelin (GHRL) levels in patients undergoing bariatric surgery. METHODS: The 50 patients who volunteered to participate in the trial were randomly divided into two groups. The study group followed the very low-calorie diet (VLCD) for two weeks. The control group did not follow any diet. The physiological parameters, weight, and DNA methylation levels of the patients were assessed. RESULTS: The percentage of excess weight loss (EWL) in the control and study groups was determined as 47.1% and 51.5%, respectively. The study group's GHRL percentage of methylated reference (PMR) was 76.8%, whereas the control group's was 67.3%. It was concluded that the EWL and GHRL gene DNA methylation of the diet-treated study group were significantly higher than the control group (p<0.05). CONCLUSION: According to the findings, the pre-op diet had a favorable effect on the patient's behavior modification. It has also been shown to increase post-operative weight loss and DNA methylation of the Ghrelin gene. The ghrelin gene has been muted by methylation, making hunger regulation more manageable.

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical and bi-genomic DNA findings of patients suspected to have mitochondrial diseases.

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed. Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents. Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides (AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG, and TK2) in 12 patients from nine families and four variants in genes encoding important for muscle structure (CAPN3, DYSF, and TCAP) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes (MT-ATP6 and MT-TL1). Nine variants in five genes are reported for the first time with disease association: (AARS2: c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2: c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1: c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6: c.479delA/p.(N162Ifs*27); and OXCT1: c.1370C>T/p.(T457I), c.1173-139G>T/p.(?). Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene.

Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

BACKGROUND: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. METHODS: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. RESULTS: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. CONCLUSIONS: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy.

OBJECTIVE: Alström syndrome (ALMS) is a rare autosomal recessive genetic disorder that is caused by homozygous or compound heterozygous mutation in the ALMS1 gene. Dilated cardiomyopathy (DCM) is one of the well-recognized features of the syndrome ranging from sudden-onset infantile DCM to adult-onset cardiomyopathy, sometimes of the restrictive hypertrophic form with a poor prognosis. We aimed to evaluate severe cardiomyopathy in Alström syndrome in infancy and display susceptible specific mutations of the disease, which may be linked to severe DCM. Secondarily we reviewed published mutations in ALMS1 with cardiomyopathies in the literature. METHOD: We represent new mutagenic alleles related to severe cardiomyopathy and cardiac outcome in this patient cohort. We evaluated echocardiographic studies of nine Turkish patients diagnosed with Alström syndrome (between 2014 and 2020, at age two weeks to twenty years). Thus, we examined the cardiac manifestations of a single-centre prospective series of nine children with specific ALMS mutations and multisystem involvement. All patients underwent genetic and biochemical testing, electrocardiograms, and echocardiographic imaging to evaluate systolic strain with speckle tracking. RESULTS: Four of the patients died from cardiomyopathy. Three patients (including three of the four fatalities) with the same mutation (c.7911dupC [p.Asn2638Glnfs*24]) had cardiomyopathy with intra-familial variability in the severity of cardiomyopathy. Global longitudinal strain, a measure of systolic contractile function, was abnormal in all patients that can be measured. CONCLUSION: Cardiac function in ALMS patients with infantile cardiomyopathy appears to have different clinical spectrums depending on the mutagenic allele. The c.7911dupC (p. Asn2638Glnfs*24) mutation can be related to severe cardiomyopathy. Parents can be informed and consulted about the progression of severe cardiomyopathy in a child carrying this mutagenic allele.

The Effect of Host miRNAs on Prognosis in COVID-19: miRNA-155 May Promote Severity via Targeting Suppressor of Cytokine Signaling 1 (SOCS1) Gene.

The epigenetic features contribute to variations in host susceptibility to SARS-CoV-2 infection and severity of symptoms. This study aimed to evaluate the relationship between the relative expression of microRNAs (miRNAs) and the severity of the disease in COVID-19 patients. The miRNA profiles were monitored during the different stages of the disease course using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of the selected 11 miRNAs were measured in the blood samples collected from 73 patients (moderate, n = 37; severe, n = 25; critically ill, n = 11, a total of 219 longitudinal samples) on hospitalization day and days 7 and 21. Expression changes were expressed as "fold change" compared to healthy controls (n = 10). Our study found that several miRNAs differed according to disease severity, with the miR-155-5p the most strongly upregulated (p = 0.0001). A statistically significant negative correlation was observed between the expression of miR-155-5p and its target gene, the suppressor of cytokine signaling 1 (SOCS1). The relative expression of miR-155-5p was significantly increased and SOCS1 was significantly decreased with the disease progression (r = -0.805 p = 0.0001, r = -0.940 p = 0.0001, r = -0.933 p = 0.0001 for admission, day 7, and day 21, respectively). The overexpression of miR-155-5p has significantly increased inflammatory cytokine production and promoted COVID-19 progression. We speculated that microRNA-155 facilitates immune inflammation via targeting SOCS1, thus establishing its association with disease prognosis.

Evaluation of HSP70 levels in ectopic pregnancy, abortus imminens and intrauterine pregnancy.

Aim: To assess the serum levels of HSP70 concentrations in ectopic pregnancy (EP) patients compared with abortus imminens (AI) patients and healthy controls. Materials & methods: Age-matched patients were divided into three groups, with 30 patients in each group: EP, AI and healthy intrauterine pregnancy groups. Blood samples were taken from the antecubital vein and kept for HSP70 analysis. Results: The HSP70 levels were higher in the EP group than in AI patients and healthy controls (p < 0.05). The area under the curve for the serum HSP70 assay reached a value of 0.81 for a cutoff point of 11.12 pg/ml, which identified women with EP. Conclusion: Serum HSP70 levels increased in women with EP compared with healthy controls and women with AI.

A pregnancy outside the uterus is called ectopic pregnancy. While diagnosing these patients, consecutive blood tests and serial vaginal examinations are used. Abortus imminens, which is in the differential diagnosis of ectopic pregnancy, means impending miscarriage or abortion. The aim of this study was to evaluate the relationship between HSP70 serum levels and pregnancies in which the exact location is unknown. Therefore, the study determined that HSP70 increased in ectopic pregnancy patients compared with abortus imminens and healthy patient groups.

Evaluation of Glycogen Storage Patients: Report of Twelve Novel Variants and New Clinical Findings in a Turkish Population.

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.

PROGRESS STUDY: Progression of chronic kidney disease in children and heat shock proteins.

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.

Role of soluble triggering receptor expressed in myeloid cells-1 in distinguishing SIRS, sepsis, and septic shock in the pediatric intensive care unit.

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.

Serum prolidase activity in patients with cardiac syndrome X.

OBJECTIVE: Although the underlying mechanism is not yet fully understood, Cardiac Syndrome X (CSX) is defined as microvascular dysfunction. Prolidase plays a role in collagen synthesis. Increased serum prolidase activity (SPA) has been shown to correlate with collagen turnover. Augmented collagen turn-over may be associated with vascular fibrosis and microvascular dysfunction. In this study, we assessed whether there was a correlation between CXS and prolidase activity. METHODS: This case-control study included 45 consecutive CSX patients (mean age 50.7±6.5 years, 27 women) and 40 healthy controls (mean age 51.2±6.5 years, 25 women). Prolidase activity was determined with the Human Xaa-Pro Dipeptidase/Prolidase enzyme-linked immunosorbent assay kit (Cusabio Biotech Co. Ltd, China). RESULTS: Mean prolidase activity was 898.8±639.1 mU/mL in the CSX group and 434.1±289.8 mU/mL in the control group (p<0.001). In ROC analysis, it was found that the SPA value above 350 mU/mL sympathizes with the diagnosis of CSX. CONCLUSION: Increased SPA in CXS patients may play an essential role in the pathophysiology of CSX, leading to augmented oxidative stress and vascular fibrosis, endothelial dysfunction, and increased microvascular resistance.

Endocan as a predictor of increased cardiovascular risk during the menopausal transition period.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.001, respectively). A positive correlation was found between body mass index (BMI), systolic blood pressure (SBP), abdominal circumference (AC), and CIMT and postmenopausal serum endocan levels. Serum endocan levels with a cutoff point of 141.14 ng/L identified women with significant CIMT levels with sensitivity of 73.8% and specificity of 77.3%. A positive correlation was found between CIMT and endocan and total MRS scores. CONCLUSION: Serum endocan levels were associated with CIMT during the menopausal transition period. Increased circulating endocan levels can be a predictor of cardiovascular risk in pre- and postmenopausal women.

Serum Levels and Urinary Excretion of Tenascin-C and TIMP-1 in Acute Kidney Injury.

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.

Visfatin Levels May be an Early Marker of Atherosclerosis in Patients with Acromegaly.

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<0.001 and p=0.007, respectively). There was no difference in visfatin between the active and controlled acromegaly groups, but HbA1c was higher in the active than the controlled acromegaly group (p<0.04). EFT, cIMT, and ABI were similar between the acromegaly and control groups and between the active and controlled acromegaly groups. Serum visfatin positively correlated with HbA1c, growth hormone (GH), and insulin-like growth factor-1 (IGF-1)/upper limit of normal ratio (r=0.245, p=0.024; r=0.259, p=0.017; and r=0.282, p=0.009, respectively). This study has revealed that a high visfatin level is associated with glycemic dysregulation and higher levels of GH and IGF-1 in acromegalic patients.

DNA damage effects of inhalation anesthetics in human bronchoalveolar cells.

BACKGROUND: The main objective was to evaluate and compare the local genotoxicity of sevoflurane and desflurane in bronchoalveolar cells, while the secondary outcome was to detect systemic oxidative DNA damage. To our knowledge, our study is the first one to evaluate the local effects of inhalation anesthetics in human bronchoalveolar cells in patients. METHODS: American Society of Anesthesiologists group I-II patients scheduled for lumbar discectomy surgery were enrolled in this randomized prospective study. Patients were randomized to sevoflurane or desflurane for anesthesia maintenance. Bronchoalveolar lavage samples and peripheral blood samples were taken at 2-time points: the first point (baseline, T1); and the second point (postexposure, T2). Final number of 48 samples were the sevoflurane (n = 22) and desflurane (n = 26) groups. Comet assay was applied to examine genotoxic properties. Oxidative DNA damage in plasma was measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: T2 values were higher than baseline values in both the desflurane group (tail-length: 66 ±â€Š24, %DNA in tail: 72 ±â€Š60, tail moment: 47.52 ±â€Š14.4; P = .001, P = .005, P = .001, respectively) and the sevoflurane group (tail-length: 58 ±â€Š33, %DNA in tail: 88 ±â€Š80, tail moment: 51.04 ±â€Š26.4; P = .001, P = .012, P = .001, respectively). T2 plasma 8-OHdG levels were also higher than baseline levels in the desflurane group (3.91 ±â€Š0.19 ng/ml vs 1.32 ±â€Š0.20 ng/ml, P = .001) and sevoflurane group (3.98 ±â€Š0.18 ng/ml vs 1.31 ±â€Š0.11 ng/ml, P = .001). There were no differences between the 2 groups in comet parameters and 8-OHdG levels. CONCLUSION: Our results indicate that both inhalation agents cause DNA damage in the bronchoalveolar cells. Also, we detected increases in plasma 8-OHdG concentrations. Local genotoxicity and systemic oxidized DNA damage were similar in both groups.

LDL Subclasses in Ischemic Stroke: A Risk Factor?

INTRODUCTION: Seven low-density lipoprotein (LDL) subclasses are identified, and smaller LDL particles are associated with an increased risk for cardiovascular events. However, there is limited data about the relationship between the acute ischemic stroke (AIS) subtypes and LDL subclasses. The aim of our study is to investigate the relationship between AIS subtypes and LDL subclasses. METHODS: This study consisted of 110 AIS patients and 60 healthy controls. Stroke patients were classified according to the TOAST classification system as cardioembolic infarct (CI), large artery atherosclerosis (LAA), and lacunar infarct (LI). LDL subclasses were distributed as seven bands (LDL-1 and-2 defined as large, and LDL-3 to-7 defined as small-LDL particle), using the LipoPrintª System. Control group and AIS subtypes were compared in terms of LDL subclasses; p<0.05 was considered statistically significant. RESULTS: AIS patients had higher LDL-2, LDL-3 and LDL-4 subclasses compared to the control groups, while LDL-1 was similar in two groups. In addition, LDL-2 and LDL-3 subclasses were significantly higher in each AIS subtype when compared to the control group. LDL-4 subclasses were significantly higher in LAA and LI subtypes than in the control group, but there was no relationship for CI subtypes. Smaller subclasses LDL-5 to LDL-7 were undetectable in both AIS patients and controls. Using regression analysis; age, LDL-2, LDL-3 and LDL-4 were found to be independent predictors of AIS development. CONCLUSION: Our study showed that examination of LDL subclasses may be important in management of AIS patients. LDL-2, LDL-3, and LDL-4 are independent predictors of AIS development. These findings should be supported by further large studies.

Serum Kisspeptin levels in unexplained infertility, polycystic ovary syndrome, and male factor infertility.

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.

Urine Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Children with Type 1 Diabetes Mellitus

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-ß1 (TGF-ß1) 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-ß1/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<0.05). Conclusion: Our findings suggest that urinary biomarkers of fibrosis do not show an increase in diabetic children without microalbuminuria. The results also indicate that the risk of early fibrosis may increase as age of onset of T1DM decreases.