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We aimed to determine the relationship of Lyso-Gb1 levels, bone biomarkers, and mutation findings with bone marrow burden (BMB) scores.

Abstract Cystathionine beta-synthase deficiency (CBSD) is the most prevalent inherited disorder of homocysteine metabolism in the transsulphuration pathway. Research have suggested oxidative stress and inflammation as candidate pathogenic mechanisms in CBSD. This study aims to evaluate mitochondrial dysfunction and oxidative stress biomarkers in cystathionine beta-synthase deficiency (CBSD) patients, which may aid in understanding the pathogenesis of CBSD and improving treatment. The study group comprised 23 patients with a diagnosis of CBSD and healthy controls. We analysed serum levels of NAD+ and NADH by fluorometric assay, FGF-21 and GDF-15 by ELISA, mitochondrial DAMPs by real time qRT-PCR, total homocysteine levels in plasma by enzymatic test and compared the results in CBSD group with healthy controls. In patient group, a positive correlation was found between the total homocysteine level and both GDF-15 and NAD+/NADH levels. Furthermore, there was a negative correlation between total homocysteine levels and both total NAD++NADH and NADH levels. The alterations in NAD+, FGF-21, GDF-15 levels, and NAD+/NADH ratio in patients suggest that oxidative damage coexists with mitochondrial dysfunction in CBSD. Assessment of oxidative damage and addition of anti-oxidant therapy together with mitochondrial support may have additional benefits in reducing long-term morbidity in CBSD patients.

BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are defined as structural malformations of the kidney and/or urinary tract. Heat shock proteins (HSPs) are expressed in the kidney in response to cellular changes, such as thermal, hemodynamic, osmotic, inflammatory, and mechanical stresses. This study aimed to assess uHSP70 levels during acute urinary tract infections (UTI) and non-infection periods in patients with CAKUT, and to evaluate whether uHSP70 is elevated in CAKUT subtypes.MethodsAmong patients with CAKUT, 89 patients with UTI (CAKUT-A), 111 without UTI (CAKUT-B), and 74 healthy children were included in the study. uHSP70 levels were measured using enzyme-linked immunosorbent assay (ELISA).ResultsuHSP70 level was significantly higher in the CAKUT-A group than in the CAKUT-B and healthy control groups (p < 0.0001). Moreover, the level of uHSP70 was significantly higher in the CAKUT-B group than in the control group (p < 0.0001), but was not different between the CAKUT subtypes (p > 0.05).ConclusionUrine HSP70 can also be used to predict UTI in patients with CAKUT. Moreover, uHSP70 levels were higher in children with CAKUT during the non-infectious period than in healthy controls. This suggests that children with CAKUT are at risk of chronic non-infectious damage.

Abstract 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.

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.

Background: The purpose of the study, to determine whether exposure to nifedipine before delivery is associated with an increased risk of postpartum blood loss in patients with preterm labor. Methods: This was a retrospective study screening a total of 486 patients who were admitted due to preterm labor from 2012 to 2019. Patients who were given nifedipine for tocolysis before delivery were considered as the study group (n: 240), and the patients who gave birth without getting tocolysis were considered as the control group (n: 246). The dose of nifedipine used during the last 24 hours, 72 hours and 1 week before delivery, the total dose of nifedipine given and the duration from the last dose to the delivery were recorded separately. Hemoglobin and hematocrit and platelet values measured before and 6 hours after delivery were recorded and postpartum bleeding amount was calculated. Results: No significant difference is observed in terms of mean difference between pre/postpartum hemoglobin and hematocrit levels between control group and nifedipine group (p > 0.05). But when subgroups that are created according to the time of use of nifedipine before delivery, a positive correlation was observed between difference in hemoglobin and hematocrit levels between prepartum and postpartum and nifedipine dosage for the last 24 hours (r = 0.176, p = 0.006), (r = 0.139, p = 0.030), but not for 72 hours or one week. Conclusions: The use of nifedipine in patients with preterm labor for tocolysis may be associated with increase in postpartum blood loss in the last 24 hours before delivery.

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

Purpose: We investigated the optimal cut-off level for urinary neutrophil gelatinase-associated lipocalin (NGAL) in preeclamptic patients to confirm the diagnosis. Methods: Urinary NGAL concentrations were measured by specific enzyme-linked immunosorbent assay (ELISA). Results: Patients with preeclampsia had significantly higher urinary NGAL concentrations than controls (mean: 387 ng/ml vs. 188 ng/ml, respectively; P< 0.001). Using a cutoff value 252 ng/ml for urinary NGAL to confirm diagnosis of preeclampsia, sensitivity, and specificity were 92% and 91%, respectively. Conclusion: Urinary NGAL concentrations were significantly elevated in women with preeclampsia versus normotensive controls.

Objective: The present study aimed to define characteristics of the patients who were readmitted with the diagnosis of surgical site infections after gynecologic or obstetric procedures and management of these patients. We also reviewed the literature in this context. Study design: We examined 120 patients with surgical site infections that had been hospitalized and managed medically and/or surgically between April 2014 and April 2015. Characteristics of the patients were recorded and analyzed. Results: The mean age of the patients was 33.4±11.8 years. The patients were readmitted for surgical site infections on the mean of 9.6±5.4 days after the first operation. The most frequent procedures resulted with SSI were cesarean delivery, abdominal hysterectomy and vaginal birth. When patients were compared according to these procedures, there were statistically significant differences regarding age, gravida, parity, preoperative white blood cell count, postoperative white blood cell count and antibiotics usage. Conclusion: Combining evidence-based surgical site infections prevention practices and clinician and patient cooperation will result in reduction in surgical site infections incidence following obstetric and gynecologic procedures. Because of economic burden and threat to the physical and psychological health of the patients, these modifiable risks should be recognized and surgical site infections should be minimized. After surgical site infections occurred, diagnosis and proper management with antibiotics and wound care with debridement and secondary suturing is important.

Objectives: The aim of this study was to evaluate the relationship between the cervix and the threat of preterm labor in singleton pregnancies between gestational weeks less than 37 and greater than 37 weeks in correlation with utero‐cervical angle (UCA) and cervical length (CL) measurements. Materials and Methods: We conducted a prospective cohort study with UCA and CL measurements in patients with threatened preterm labor (TPL). Primary outcome was differences in UCA and CL measurements in relationship to maternal characteristics and perinatal outcome between groups. Secondary outcome evaluated measurement results and influencing factors for delivery within 7 days, between 1 and 4 weeks and beyond 4 weeks. Results: Overall 152 patients were divided into as study/preterm group (<37 weeks; n = 56) and the control/term group (≥37 weeks; n = 96). Mean gestational age at admission was similar in both groups (30.98 ± 2.83 vs. 30.36 ± 2.63 weeks, p = 0.149) with similar CL (33.9 ± 6.34 vs. 32.02 ± 8.88 mm, p = 0.132), but wider UCA in the preterm group (81.65 ± 16.81° vs. 99.21 ± 22.33°, p < 0.001). Multivariate logistic regression analysis for preterm delivery was significant for nulliparity and UCA measurement. The factor for delivering before 37 gestational weeks within 7 days was the gestational week at admission (p = 0.046). UCA and CL measurements were statistically significant for distinguishing patients for delivery within 7 days and beyond 4 weeks (p = 0.001 for CL and p = 0.0001 for UCA). NPV was found 92.5, 92.2, and 92.3 for UCA >105°, CL ≤30 mm, and Bishop score >3, respectively. Conclusion: Combined measurement of TV UCA and CL represents stronger predictors for sPTB ultrasonographically, demonstrating the uterocervical sub‐segment maturation before the active onset of labor. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Heat shock proteins (HSPs) are a multi-family group of proteins which are upregulated by the cell in response to exposure to hazardous (stress) factors, including infectious agents, to prevent changes in protein structure. The aim of our study was to assess whether urine levels of the 70-kDa family of HSPs (HSP70s) increase in children with urinary tract infection (UTI) and to determine the optimal urine (u) HSP70 cut-off level to predict UTI in children. Methods Forty patients with symptomatic UTI (UTI group), 30 healthy children (control group), 21 asymptomatic patients with proven bacterial contamination in their urine culture (contamination group) and 30 patients with fever caused by other infections (non-UTI infection group) were enrolled in the study. Random urine samples were obtained for measurement of HSP70 and creatinine (Cr) from all groups. Urine was collected prior to the treatment of UTI at the time of presentation and after treatment. Urine HSP70 levels were measured by enzyme-linked immunosorbent analysis. A dimercaptosuccinic acid (DMSA) scan was performed at 5-7 days after presentation in UTI group to distinguish patients with acute pyelonephritis from those with cystitis; based on this scan, no patients had acute pyelonephritis. Patients were classified with pyelonephritis in the presence of all of the following signs: axillary fever of [greater than or equal to]39 °C, leukocytosis and positivity for C-reactive protein. Results The mean urine HSP70:Cr ratio (uHSP70/Cr) prior to treatment was significantly higher in the UTI group (449.86 ± 194.33 pg/mg) than in the control, contamination and non-UTI infection groups (39.93 ± 47.61, 32.43 ± 9.09 and 45.14 ± 19.76, respectively; p = 0.0001). Using a cut-off of 158 pg/mg uHSP70/Cr for the prediction of UTI, the sensitivity and specificity of the assay were 100 and 100 %, respectively (area under the time-concentration curve = 1). The uHSP70/Cr was highest in the patients with clinical pyelonephritis (p = 0.001). Mean uHSP70/Cr after treatment decreased to 60.68 ± 51.11 pg/mg in UTI group (p = 0 .0001). Conclusions Our findings suggest that elevated uHSP70/Cr may be a useful biomarker for the prediction of UTI in children, with a high sensitivity and specificity, and that they may help to distinguish UTI from other infections as well as bacterial contamination of the urine., Author(s): Alev Yilmaz[sup.1] , Zeynep Yuruk Yildirim[sup.1] , Sevinc Emre[sup.1] , Asuman Gedikbasi[sup.2] , Tarik Yildirim[sup.3] , Ahmet Dirican[sup.4] , Evren Onay Ucar[sup.5] Author Affiliations: (1) Istanbul Faculty of Medicine, [...]