High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with NLRP7 Pathogenic Variations.

Objective: Pathogenic variations of the NLRP7 and KHDC3L genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies. Material and Methods: Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of NLRP7 and KHDC3L genes. Results: NLRP7 pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the KHDC3L gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans. Conclusions: We found that defects of the NLRP7 gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.

EVALUATION OF THE ASSOCIATION OF PLASMA PENTRAXIN-3 LEVELS WITH CAROTID INTIMA-MEDIA THICKNESS AND HIGH-SENSITIVE CRP IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM.

Context: Inflammation-related markers may predict cardiovascular diseases. Objective: In this study, it was aimed to assess pentraxin-3 (PTX-3) levels and its relationship with carotid intima-media thickness (CIMT) and high-sensitive C-reactive protein (hsCRP) in patients with subclinical hypothyroidism. Design: Prospective cross-sectional study. Methods: This study included 60 patients (aged 30-60 years) with subclinical hypothyroidism and 30 healthy volunteers as controls. The demographic characteristics and anthropometric measurements were performed in all patients and controls. In addition, sonographic carotid artery examination, thyroid functional tests, lipid profile, hsCRP, and PTX-3 levels of the participants were investigated. Results: The PTX-3, hsCRP levels and CIMT were higher in patients with subclinical hypothyroidism when compared to controls (p=0.008, p=0.001, p<0.001, respectively). The PTX-3 level was strongly correlated with hsCRP (r=0.865; p<0.001), but no such correlation was detected with CIMT (r=-0.255; p=0.50). In binominal logistic regression analysis, it was found that CIMT and serum uric acid levels were independent parameters associated with subclinical hypothyroidism. In ROC analysis, a cut-off value of >3.75 ng/mL for serum PTX-3 level predicted subclinical hypothyroidism with a sensitivity of 60% and specificity of 60.7% (AUC: 0.672, p=0.004). Conclusion: Showing inflammation and endothelial dysfunction, the PTX-3 may be a helpful marker in patients with subclinical hypothyroidism associated with increased risk for cardiovascular disease.

Molecular epidemiology, antifungal susceptibility and virulence factors of Candida glabrata complex strains in Kayseri/Turkey.

BACKGROUND: Candida nivariensis and Candida bracarensis are included in Candida glabrata complex, which are usually misidentified as C. glabrata based on phenotypic identification methods. It was aimed to identify C. glabrata complex isolated from various clinical samples in Kayseri/Turkey to the species level and to determine antifungal susceptibilities, virulence factors, and molecular epidemiology. METHODS: Eighty three C. glabrata complex strains were studied in this study. Strains were phenotypically and molecularly identified. Phylogenetic analysis was done by the neighbor-joining method. Proteinase, phospholipase, esterase enzyme activity, and biofilm formation of strains were determined phenotypically. Antifungal susceptibility of strains were determined according to M60-Ed2 recommendations. RESULTS: All the 83 strains identified as C. glabrata complex by phenotypic tests were confirmed as C. glabrata sensu stricto (C. glabrata) by PCR amplification and sequence analysis, but other complex members C. nivariensis and C. bracarensis were not detected. Phylogenetic analysis results revealed 19 different genotypes. No clonal relationship was detected among the strains. Biofilm formation in 75.9% of strains and esterase activity in 7.2% were found positive. Antifungal resistance rates of strains were determined as 9.2% for fluconazole and 45.8% for itraconazole; 43.4% of the strains for voriconazole were determined as non-wild type. CONCLUSION: It was determined that biofilm and esterase activity might play an active role in the virulence of C. glabrata. In addition, high resistance rates to azoles in C. glabrata strains isolated in our hospital at Kayseri/Turkey emphasized the significance of epidemiological studies.

Molecular identification, virulence factors and antifungal susceptibility patterns of Candida parapsilosis complex species isolated from clinical samples.

AIMS: The aim of this study was to identify C. parapsilosis complex strains isolated from various clinical samples by sequence analysis and to investigate whether there are any differences between the species in terms of virulence factors and antifungal susceptibility. METHODS: The study included a total of 42 isolates identified as C. parapsilosis complex based on the color they formed in chromogenic medium, colony morphology, and microscopic appearance in Corn Meal-Tween 80 Agar and they were confirmed with API 20 C AUX. For the DNA sequence analysis of clinical isolates, V9G forward and LS reverse primers were used as well as internal transcribed spacers (ITS1 and ITS4). Biofilm formation, esterase, phospholipase, and protease activities were evaluated as virulence factors. Antifungal susceptibility was investigated via colorimetric microdilution method. RESULTS: A total of 75 non-C. albicans isolates were obtained from various clinical samples between 2016 and 2017 in a Turkish Tertiary Care Hospital. Of them, 42 were identified as members of the C. parapsilosis complex. Of the 42 strains, 41 were identified as C. parapsilosis sensu stricto (CpSS), while only one was identified as C. orthopsilosis. Of the CpSS strains, 31 (75.6%) were biofilm-positive, six (14.6%) were esterase-positive, nine (21.9%) were positive for phospholipase activity, and 31 (75.6%) were positive for protease formation, whereas all virulence factors of C. orthopsilosis strain were found to be negative. All CpSS strains were found susceptible to amphotericin B, echinocandins, and flucytosine. CONCLUSIONS: It has been concluded that the use of molecular methods to identify CpSS would not be effective in routine laboratory practices as it is the most commonly isolated species from the C. parapsilosis complex and there are no significant differences between species in terms of antifungal susceptibility.

Hemoptysis and massive focal alveolar hemorrhage after successful biventricular pacemaker implantation.

During and after cardiac resynchronization therapy (CRT) implantation, many adverse events may occur. We present an interesting and important patient with hemoptysis and massive focal alveolar hemorrhage in a patient after a successful CRT implantation. CRT implantation was completed without any problems. In the follow-up, complaints of cough and hemoptysis began 1 h after the procedure. On the PA chest X-ray, a ground glass image was found in the left upper zone. Thorax CT revealed focal alveolar hemorrhage in the left upper lobe anterior segmental lung parenchyma. The patient was followed up with medical treatment and discharged in good health.

Lung ultrasound and computed tomographic findings in pregnant woman with COVID-19.

Imaging modalities play a crucial role in the management of suspected COVID-19 patients. Before reverse transcription polymerase chain reaction (RT-PCR) test results are positive, 60-93% of patients have positive chest computed tomographic (CT) findings consistent with COVID-19. We report a case of positive lung ultrasound findings consistent with COVID-19 in a woman with an initially negative RT-PCR result. The lung ultrasound-imaging findings were present between the negative and subsequent positive RT-PCR tests and correlated with CT findings. The point-of-care lung-ultrasound examination was easy to perform and, as such, could play an important role in the triage of women with suspected COVID-19. The neonatal swabs, cord blood and placental swab RT-PCR tests were negative for SARS-CoV-2, a finding consistent with the published literature suggesting no vertical transmission of this virus in pregnant women. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

[tRNA Wobble Base Modifications and Boric Acid Resistance in Yeast: Boron-Resistant Deletion Mutants Induce the General Amino Acid Control Mechanism and Activate Boron Efflux].

Boric acid is essential for plants and has many vital roles in animals and microorganisms. However, its high doses are toxic to all organisms. We previously screened yeast deletion collections to identify boric acid-resistant and susceptible mutants to identify genes that play a role in boron tolerance. Here, we analyzed boron resistant mutants (elplΔ, elp3Δ, elp6Δ, ncs2Δ, ncs6Δ and ktil2Δ) for their abilities to modulate the general amino acid control system (GAAC) and to induce boron efflux pump ATR1. The mutants analyzed in this study lack the genes that play roles in tRNA Wobble base modifications. We found that all of the boron resistant mutants activated Gcn4-dependent reporter gene activity and increased the transcript level of the ATR1 gene. Additionally, boron resistant cells accumulated less boric acid in their cytoplasm compared to the wild type cells upon boron exposure. Thus, our findings suggested that loss of wobble base modifications in tRNA leads to GAAC activation and ATR1 induction, which in turn reduced intracellular boron levels and caused boron resistance.

[Distribution of Yeast Species Isolated from Blood Cultures for a Six Year Period in Turkey: a Multicentre Study]. / Türkiye'de Alti Yillik Zaman Dilimi Içerisinde Kan Kültürlerinden Soyutlanan Maya Mantarlarinin Tür Dagilimi: Çok Merkezli Bir Çalisma.

Bloodstream infections due to yeast species especially Candida spp. have been reported to be important healthcare associated infections with high mortality and morbidity rates. Candidemia causes prolonged hospital stays as well as increased cost. In order to prevent or treat these life-threatening bloodstream infections successfully, nationwide epidemiological data should be available about the etiological agents of these infections. Multi-centre national epidemiological data on yeast bloodstream infections in Turkey is lacking. A retrospective study was designed and data from six different centres in Turkey between 2011 and 2016 years were gathered and analysed for the distribution and frequency of yeast species in order to assist clinicians in their choice of early and appropriate antifungal therapy. All laboratories used automated blood culture systems for the isolation of blood strains. All the participating centres performed the identification of their own isolates by conventional methods using germ tube test, morphology on corn meal agar with tween 80 and chromogenic media and the identification was confirmed by API 20C AUX, API ID 32C or matrix-assisted laser desorption/ionization time of flight mass spectrophotometry (MALDI-TOF MS) systems. The analysis of the results was performed on the basis of intensive care units (ICUs), other inpatient clinics (OICs) and totally all clinics (ACs). Totally 2547 yeast isolates were determined from six participating centres during six years. According to the total ACs results, Candida albicans was the most prevalent species (43.1%), followed by Candida parapsilosis complex (29.1%), Candida glabrata (10.1%), Candida tropicalis (7.5%), Candida krusei (2.4%) and Candida kefyr (1.6%) and the remaining (6.2%) of them consisted of other yeast species. The distribution of the Candida species did not show statistically significant difference between the years, however the increase of C.parapsilosis complex in 2016 was statistically significant, (p= 0.02). During the study period, totally 1054 yeast isolates were obtained from the ICUs of the centres. C.albicans predominated with 476 (45.2%) isolates and C.parapsilosis complex (28.7%), C.glabrata (10.7%) and C.tropicalis (7.3%) were the other leading species in ICUs. Among 1493 isolates of the OICs of six centres participated in the study, C.albicans was the most prevalent species with 622 (41.7%) isolates. The other frequent species of OICs were C.parapsilosis complex (29.5%), C.glabrata (9.6%) and C.tropicalis (7.6%) resembling ICU results. It can be concluded that C.albicans is still the leading cause of bloodstream infections in the six different centres located in various geographical areas of Turkey.

Experiences in microarray-based evaluation of developmental disabilities and congenital anomalies.

BACKGROUND: Chromosomal microarray analysis is the first-tier test for the evaluation of developmental disabilities and congenital anomalies. In this report, we present CMA results of 971 patient and 301 parent samples. MATERIALS AND METHODS: Among 971 patient samples, 133 (13.6%) had pathogenic variants. RESULTS: While analyzing, an "in-house" variant database was also used besides other databases. Owing to this, we have found chance to report the most frequent benign variants in Turkish population. CONCLUSION: With the additional data we acquired in this study, we also emphasized the high potential of CMA in revealing single gene disorders and novel gene-phenotype associations as well as copy number variations.

Assessing the risk of false positive serum galactomannan among patients receiving piperacillin/tazobactam for febrile neutropenia.

Galactomannan (GM) assay is commonly used as an early diagnostic tool for invasive fungal infection (IFI) in high-risk hematology patients. False positivity is frequently observed in GM with the use of piperacillin/tazobactam. The usage of generic drugs over the original brand has a significant cost advantage. The aim of this study was to assess the performance of GM test among patients receiving original and generic piperacillin/tazobactam formulations. The study included 85 adult patients; 62.4% were male with hematological malignancy currently receiving piperacillin/tazobactam. The study group was divided into two groups: patients receiving original and generic piperacillin/tazobactam. Serum GM index was positive in one of 35 patients receiving original piperacillin/tazobactam, whereas it was positive in 46 out of 50 patients receiving generic piperacillin/tazobactam (P < .001). However, the patients receiving generic piperacillin/tazobactam underwent computed tomography (CT) scans more frequently than those receiving original piperacillin/tazobactam (P = .047). In addition, in vitro analysis of GM was performed in two generics and one original piperacillin/tazobactam vials. One generic piperacillin/tazobactam vial included high GM level. False positivity of serum GM with generic formulations of piperacillin/tazobactam is still an ongoing issue in hematology patients. A high rate of serum GM index false positivity may unexpectedly lead to a higher rate of CT scan. Selected piperacillin/tazobactam vials in each batch should be checked for GM to identify a false positivity of GM before purchase.

Identification and molecular epidemiology of dermatophyte isolates by repetitive-sequence-PCR-based DNA fingerprinting using the DiversiLab system in Turkey.

Dermatophyte species, isolation and identification in clinical samples are still difficult and take a long time. The identification and molecular epidemiology of dermatophytes commonly isolated in a clinical laboratory in Turkey by repetitive sequence-based PCR (rep-PCR) were assessed by comparing the results with those of reference identification. A total of 44 dermatophytes isolated from various clinical specimens of 20 patients with superficial mycoses in Kayseri and 24 patients in Hatay were studied. The identification of dermatophyte isolates was based on the reference identification and rep-PCR using the DiversiLab System (BioMerieux). The genotyping of dermatophyte isolates from different patients was determined by rep-PCR. In the identification of dermatophyte isolates, agreement between rep-PCR and conventional methods was 87.8 % ( 36 of 41). The dermatophyte strains belonged to four clones (A -D) which were determined by the use of rep-PCR. The dermatophyte strains in Clone B, D showed identical patterns with respect to the region. In conclusion, rep-PCR appears to be useful for evaluation of the identification and clonal relationships between Trichophyton rubrum species complex and Trichophyton mentagrophytes species complex isolates. The similarity and diversity of these isolates may be assessed according to different regions by rep-PCR.

Can serums be replaced by Mueller-Hinton agar in germ tube test?

BACKGROUND: The germ tube test (GTT) is inexpensive, easy, and well-defined test that differentiates Candida albicans (excluding Candida dubliniensis and Candida africana) from other species. The aim of this study was to evaluate various serums (i.e., human, rabbit, horse, and fetal bovine serum) used in the GTT and Mueller-Hinton agar (MHA). MATERIALS AND METHODS: Fifty species isolated from various clinical samples that were defined as C. albicans by both conventional and DNA sequence analysis methods were included in the study. One to two colonies of C. albicans were mixed into 0.5-1 ml of fetal bovine serum, horse serum, rabbit serum, and human serum. Serums and MHA were incubated at 37°C for GTT. They were removed from the incubator and evaluated after 30 min, 1 h, 2 h, and 3 h of incubation. The GTT was accepted to be positive only if germ tube was 1/2 the width and 3 times the length of the parent yeast cell and with no constriction at the point of origin. RESULTS: When the use of serums and MHA for GTT was statistically evaluated, according to the positive scoring, the best results were obtained with MHA and with rabbit, horse, and fetal bovine serum, respectively. The best definition over time statistically was the third hour. CONCLUSION: It is suggested that inexpensive MHA is a fast, appropriate, and reliable medium for the probable diagnosis of GTT and C. albicans; however, additional studies are still needed to define other Candida species.

Optical Writing of Magnetic Properties by Remanent Photostriction.

We present an optically induced remanent photostriction in BiFeO_{3}, resulting from the photovoltaic effect, which is used to modify the ferromagnetism of Ni film in a hybrid BiFeO_{3}/Ni structure. The 75% change in coercivity in the Ni film is achieved via optical and nonvolatile control. This photoferromagnetic effect can be reversed by static or ac electric depolarization of BiFeO_{3}. Hence, the strain dependent changes in magnetic properties are written optically, and erased electrically. Light-mediated straintronics is therefore a possible approach for low-power multistate control of magnetic elements relevant for memory and spintronic applications.

Comparison of effects of digital vaginal examination with transperineal ultrasound during labor on pain and anxiety levels: a randomized controlled trial.

OBJECTIVE: To evaluate whether routine vaginal examination during labor is associated with increased levels of anxiety and pain compared with transperineal ultrasound assessment. METHODS: This was a single-blinded, parallel, randomized controlled trial conducted in a tertiary care facility. Parous pregnant women without a known psychiatric condition who were seen at the care facility between November 2015 and March 2016 were included in the trial. Participants had an uneventful pregnancy and were assigned randomly to routine digital vaginal examination or transperineal ultrasound assessment during labor. Psychological distress levels, measured by the Symptom Checklist-90-Revised, and anxiety levels, measured by State-Trait Anxiety Inventory (STAI), were recorded before admission, and pain, measured using a visual analog scale, and anxiety were recorded during the latent phase of labor, the beginning of active labor and the postpartum period. A sample size of 45 women per group (n = 90) was planned to compare methods of assessment. RESULTS: Ninety women were randomized (1:1 allocation) to one or other of the interventions. Preadmission psychological distress and anxiety levels were similar between the two groups (P = 0.93 and 0.65, respectively). Most of the studied characteristics were similar in each group including duration of labor, number of examinations, analgesic administration during labor, episiotomy rate and interval between deliveries. Visual analog scale scores revealed that pain perception was reduced during latent (mean difference, -1.5 (95% CI, -2.51 to -0.57); P < 0.01) and active (mean difference, -1.2 (95% CI, -2.45 to -0.09); P = 0.03) stages of labor and during the postpartum period (mean difference, -0.5 (95% CI, -1.02 to -0.06); P = 0.02) in participants who had a transperineal ultrasound assessment compared with participants who had a digital vaginal examination. STAI scores revealed that anxiety levels were similar between the two groups during the latent and active phases of labor and during the postpartum period (P = 0.07, P = 0.38 and P = 0.13, respectively). CONCLUSIONS: The perception of pain was significantly reduced with the use of a transperineal ultrasound assessment compared with routine digital vaginal examination. However, only during the latent stage of labor was the magnitude of the observed effect sufficiently great to be considered clinically significant. Our results indicate that transperineal ultrasound assessment could be preferred to digital examination for the evaluation of progression of labor during this phase. Digital examination has no clinically relevant effects on state anxiety levels, as measured by the STAI. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Immunohistochemical investigation of endometrial leukocytes in implantation period in rats with streptozotosin-induced diabetes.

Our first aim was to determine the total leukocyte profile in implantation. Second aim was to detect the changes in uterine leukocyte profile in diabetes, a common accompanying disease. For this purpose 4 groups are formed with Wistar albino rats weighing 250-300 g. Two of the groups were non-diabetic and two of them were diabetic. One of the diabetic and one of the non-diabetic groups were left pregnant. Then uterus tissues of pregnant animals were removed in the 5th and 7th days of pregnancy together with tissues of other two non-pregnant groups. Tissues were analyzed immunohistochemically with antibodies CD45, CD3, CD4, CD8, CD56, CD68 and CD79a. It was revealed that pregnancy increased immune staining of CD68, CD3, CD45 and CD56 in endometrium. In addition it was observed that immune staining density of CD68, CD45 and CD56 decreased in diabetes. In the histopathological examination, significant degeneration was detected in the endometrium of diabetic rats. Diabetes could decrease leukocyte proportions in decidua in early pregnancy periods. Therefore immune cell therapies could be administrated in diabetes related problems of pregnancy.

Association of NFKB1 and NFKBIA polymorphisms in relation to susceptibility of Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory autoimmune disease. Although raised levels of proinflammatory cytokines in BD have been reported, the pathogenesis is still unknown. The aim of this study was to investigate the association of NFKB1 and NFKBIA polymorphisms and their single and combined analysis effects on susceptibility of BD in Turkish population. We analysed the distribution of NFKB1 -94 ins/del ATTG (rs28362491) and NFKBIA 3' UTR A→G (rs696) polymorphisms using PCR-RFLP method in 89 patients with BD and 190 controls in this population. Statistical analysis of the results was performed by calculating OR, and 95% CI via χ(2) test and using Bonferroni correction. According to the significant results of both single and combined genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were significantly higher in patients with BD (Pc = 0.003, 0.004, respectively). Also, higher frequencies of the rs696 variant containing AA genotype was found in patients with BD (Pc = 0.0033), whereas no statistical significant differences in distribution of the alleles of rs696 polymorphism in patients and controls. In addition, according to the combined genotype analysis, the wild type of both rs28362491 and rs696 polymorphisms (ins/ins/AA genotype) was also significantly higher in BD cases (Pc = 0.044). Our findings prove that both single and combined genotype analysis of rs28362491 and rs696 polymorphisms indicate that the wild genotypes of both two SNPs (ins/ins and AA genotypes) and ins/ins/AA combined genotype are strongly associated with enhanced risk of BD in a Turkish population.

Cell free fetal DNA in the plasma of pregnant women with preeclampsia.

OBJECTIVE: Insufficient cytotrophoblast invasion to the myometrium is associated with preeclampsia, especially with the early-onset preeclampsia (before 34 gestational weeks). Several investigations have marked changes in the concentration of cell free fetal DNA in the maternal circulation of women with preeclampsia. However, these studies were not performed for early or late preeclampsia subgroups individually. The present authors planned to determine the levels of the cell free both fetal and maternal DNA in the maternal circulation in early preeclampsia subgroup and compare it with normotensive control cohort. MATERIALS AND METHODS: A total of 16 women; eight of these with preeclampsia and eight normotensive control cohorts with singleton male pregnancy between 28 and 32 gestational weeks were included in the study. Real-time PCR analysis was performed for determining the circulating cell free DNA levels. RESULTS: Cell free fetal DNA concentrations were higher in early preeclamptic women than control subjects. The authors found no statistically significant difference in each levels of maternal and total DNA between hypertensive and normotensive groups. CONCLUSIONS: The present findings suggest that the levels of cell free fetal DNA in maternal circulation were higher in pregnancies which are complicated with early preeclampsia than normotensive controls.

Investigation of possible virulence factors in Candida strains isolated from blood cultures.

BACKGROUND: The Candida species, which are one of the most common causes of nosocomial bloodstream infections, present with high mortality and morbidity rates. This study aims to investigate the production of esterase, phospholipase, proteinase, and biofilm formation ability of the Candida strains isolated from the blood cultures. MATERIALS AND METHODS: Between June 2011 and July 2012, the Candida strains, which were isolated from blood cultures of a total of 50 patients, were studied. The esterase activity was analyzed in the Tween-80 agar, while phospholipase activity was studied in the egg yolk agar. The proteinase activity and biofilm formation were identified by using the petri dish method and microplate method, respectively. RESULTS: Of 50 specimens obtained from individual patients, 17 (34%) were identified as C. albicans, 14 (28%) as C. glabrata, 9 (18%) as C. parapsilosis, 5 (10%) as C. krusei, 4 (8%) as C. kefyr, and 1 (2%) as C. tropicalis. The rate of proteinase, phospholipase, and esterase positivity was higher in the C. albicans isolates. Biofilm formation was the highest in the C. parapsilosis strains. CONCLUSIONS: Higher rate of virulence factors in the most commonly isolated Candida species than other species indicates that these virulence factors play a crucial role in the pathogenesis.