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Purpose: There is no consensus in the literature on nonoperative treatment of displaced and multipart fractures of proximal humerus as those are normally treated operatively. Our aim was to compare the functional results of nonoperative management and open reduction internal fixation with the proximal humerus internal locking system of 2-, 3-, and 4-part proximal humerus fractures, among themselves and with a healthy control group., Methods: Between 2014 and 2018, 92 proximal humerus fractures constituting a nonoperative group ( n = 47) and an operative group ( n = 45) together with healthy control subjects ( n = 45) were analyzed in a tertiary care referral center. The American Shoulder and Elbow Surgeons (ASES) shoulder score and visual analog scale (VAS) pain score were used for subjective functional analysis. Range of motion and muscle strength were analyzed objectively for all patients and healthy control subjects., Results: In 2-part fractures, VAS scores and hand grip strength were determined as lower in the nonoperative group ( p = 0.033 and p = 0.034, respectively). In 3- and 4-part fractures, there was no difference between the two groups in terms of ASES and VAS scores. Patients who underwent surgery had more muscle strength than those in the nonoperative group, but only arm extensor and forearm flexor muscle strengths were statistically significant for 3-part fractures. In cases of 4-part fractures, objective functional results were similar between the two groups., Conclusions: With insufficient functional results and high complication rates in surgery, nonoperative management is still the preferred choice for proximal humerus fractures, especially in case of multipart fractures.

Introduction: Repetitive pulmonary infections are the main cause of morbidity and mortality in cystic fibrosis (CF) patients. In recent years, non-culture dependent metagenomic studies showed complex dynamics of the pulmonary environment of CF patients and pointed out the importance of anaerobic bacteria. Molecular-based studies indicate that anaerobic bacteria can be found more than aerobic or facultative anaerobic bacteria in CF lung environment. However, limited number of studies are far away to clarify the importance of anaerobic bacteria in CF pulmonary disease., Materials and Methods: The aim of this study was to evaluate the role of anaerobic bacteria in CF patients admitted to Hacettepe University, Pediatric Respiratory Diseases Department, by using quantitative culture method for both aerobic and anaerobic bacteria. Anaerobic bacteria were identified by conventional and semi-automated methods. Antibiotic susceptibilities were performed by agar dilution method., Result: Seventy-seven anaerobic bacteria were isolated from 35 (81.4%) of 43 patients. The total count of anaerobes and facultative bacteria (mean 16 x 106), was higher than aerobes and facultative bacteria (mean 14.1 x 106). If anaerobe culture were not performed merely 63.65% of all species could be obtained. In patients whose samples yielded intermediate or high numbers of PMNLs, significantly more obligate anaerobic bacteria were isolated (p= 0.046). Patients older than 18 years were colonized with higher number of anaerobic bacteria. Susceptibilities of 72 isolates out of 77, against ampicillin, sulbactam-ampicillin, piperacillin, piperacillin-tazobactam, moxifloxacin, metronidazole, imipenem, and clindamycin were also evaluated. Clindamycin was found to be the least effective antibiotic among all. None of the isolates was resistant to imipenem., Conclusions: This is the first study to show the role and importance of anaerobic bacteria in CF patients in our country. The resistance rates in anaerobic bacteria isolated from CF patients is concerning. Therefore, intermittent anaerobic culture and follow-up of resistance rates will be helpful in the follow-up of these patients.

Background: The purpose of this study is to evaluate serum levels of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), tumor necrosis factor alpha (TNF-α), and progranulin in patients with gastric cancer (GC) and precancerous lesions (PCL) and to determine the usefulness of these markers as diagnostic biomarkers in these diseases., Method: A total of 32 GC patients, 35 PCL patients, and 23 healthy controls participated in the study. The serum levels of VEGF, PEDF, TNF-α, and progranulin were measured by enzyme-linked immunosorbent assay (ELISA)., Results: The mean serum VEGF levels were 30.6 ± 12.98 pg/mL in GC, 18.2 ± 5.72 pg/mL in PCL, and 17.5 ± 5.59 pg/mL in controls. GC VEGF levels were significantly higher than both PCL and control groups (p < 0.001). The mean serum PEDF levels were 1516.1 ± 993.8 pg/mL in GC, 1039.1 ± 1002.3 pg/mL in PCL, and 767.5 ± 661.5 pg/mL in controls. The serum PEDF level in the GC group was significantly higher than that in both PCL and control groups (p = 0.004 and p = 0.038, respectively). The mean serum TNF-α levels were 46.7 ± 14.82 pg/mL in GC, 38.4 ± 11.89 pg/mL in PCL, and 33.8 ± 12.77 pg/mL in controls. There was a significant difference between GC and controls (p = 0.022) in TNF-α levels. The mean serum progranulin levels in GC were 2496.6 ± 737.8 pg/mL, 2332.0 ± 482.1 pg/mL in PCL, and 1288.7 ± 830.9 pg/mL in controls. Progranulin levels in both GC and PCL groups were significantly higher than that in the control group (p < 0.001 for both)., Conclusion: There were significant differences among patients with GC and PCL and healthy controls in terms of serum VEGF, PEDF, TNF-α, and progranulin levels.

Objectives: This study investigated the antifungal resistance rates of isolates from candidaemia patients in 12 tertiary-care centres in Turkey., Methods: A total of 1991 Candida spp. isolates from 12 centres isolated from 1997-2017 were included in the study. Species/species complex (SC) identification was performed using conventional methods in all centres, occasionally accompanied by MALDI-TOF/MS. Antifungal susceptibility testing was performed for amphotericin B, fluconazole, itraconazole, posaconazole, voriconazole and micafungin (as echinocandin class representative) using the CLSI microdilution method. Resistance rates were determined according to CLSI clinical breakpoints (CBPs). For drugs and species with undetermined CBPs, epidemiological cut-off values were used for wild-type (WT)/non-WT categorisation., Results: No or low rates of resistance were detected in general for tested Candida spp. isolates. Specifically, overall resistance to fluconazole in isolates of Candida parapsilosis SC and Candida glabrata SC were 7.7% and 0.9%, respectively. Resistance rates for C. parapsilosis SC varied extensively from one center to other (0-47.1%). Importantly, no echinocandin resistance was detected. Rates of non-WT isolates were also generally low: fluconazole against Candida lusitaniae, 4.3%; posaconazole against C. parapsilosis SC, 3.5%; posaconazole against Candida krusei, 1.9%; and voriconazole against C. glabrata SC, 0.5%., Conclusion: This is the first multicentre report of antifungal resistance rates among candidaemia isolates in Turkey, suggesting low resistance rates in general. Due to varying rates of fluconazole resistance in C. parapsilosis SC isolates that was detected at remarkably high levels in some centres, further studies are warranted to explore the source, clonal relatedness and resistance mechanisms of the isolates., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells in the lungs, skin, and intestinal mucosa and is involved in several physiological and pathological processes. In this study, we evaluated serum TSLP levels in patients with celiac disease (CD). The prospective study was conducted at a gastroenterology outpatient clinic between March 2018 and August 2018. Eighty-nine participants aged between 18 and 75 years were classified into following groups: 22 patients with newly diagnosed CD; 20 patients with CD who were compliant with a gluten-free diet (GFD); 32 patients with CD who were not compliant with a GFD; and 15 healthy controls. Demographic characteristics, disease duration, and selected biochemical and hematologic parameters were recorded and compared between groups. Median serum TSLP levels were 1193.65 pg/mL (range: 480.1-1547.1) in newly diagnosed CD patients, 110.25 pg/mL (range: 60.3-216.7) in CD patients who were compliant with a GFD, 113.1 pg/mL (range: 76.3-303.4) in CD patients who were not compliant with a GFD, and 57 pg/mL (range: 49-67.8) in healthy controls. Overall, there was a significant difference in serum TSLP levels between groups (p = 0.001). Patients with newly diagnosed CD had the highest serum TSLP levels. There was no significant difference in serum TSLP levels between patients with CD who were and were not compliant with a GFD. TSLP appears to be involved in the pathogenesis of CD. Further studies are required to determine if the TSLP signaling pathway can be used in the treatment of CD.

Objective: Angiotensin II promotes growth and angiogenesis via type 1 receptors (AGTR1) in certain tumors. In this study, we examine the bone marrow AGTR1 expression in multiple myeloma (MM) and its relationship with the regulation of angiogenesis and prognostic factors., Materials and Methods: Bone marrow AGTR1 mRNA levels of 39 MM patients and 15 healthy controls were analyzed with quantitative RT-PCR. Immunohistochemical staining of the tissue vascular endothelial growth factor (VEGF), CD34, and factor VIIIrAg (fVIIIrAg) was used to assess bone marrow angiogenesis., Results: Bone marrow samples of the patients showed increased VEGF, fVIIIrAg, and CD34 staining and higher AGTR1 expression levels when compared to controls. Patients with severe-diffuse bone marrow infiltration showed higher bone marrow VEGF, fVIIIrAg, CD34, and AGTR1 mRNA levels when compared to other patients., Conclusion: AGTR1 expression was found positively correlated with plasma β2-microglobulin level and patients with increased AGTR1 expression showed increased bone marrow CD34 levels.

Objective: Valproic acid (VPA)-induced hyperammonemia (VIH), is an increase in blood ammonia levels without any alteration of hepatic enzymes, which can occur during VPA treatment. We aimed to determine the prevalence rate and the risk factors for VIH and its association with cognitive functions., Method: A prospective, cross-sectional study was conducted. Patients aged between 18 and 64 who were on VPA treatment and who diagnosed with mood disorders or epilepsy were enrolled in this study (n = 107). For cognitive assessment, Serial 7's and Subjective Memory Complaints Questionnaire (SMCQ) were used. Blood samples were collected for blood VPA and ammonia levels along with other laboratory tests., Results: 55,3% of the sample were considered as VIH. Blood ammonia level significantly correlates with VPA blood levels, total daily dose of VPA and total number of medications concurrently used, but no significant correlation was found between blood ammonia level and cognitive test scores. Gender, body weight, blood VPA levels and the total number of medications concurrently used significantly predicted blood ammonia levels (F(4,81) = 2670, p = 0,038, R 2  = 0,116)., Conclusion: VIH is relatively high in our sample. There is a dose-dependent association between VPA and blood ammonia level. No association was found between cognitive functions and hyperammonemia however with some limitations. Future, prospective cohort studies are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ophthalmo-acromelic syndrome is a rare autosomal recessive disorder characterized by ocular and skeletal abnormalities. Ocular findings present as a wide spectrum, ranging from mild microphthalmia to true anophthalmia. Short 5th finger, synostosis of 4th and 5th metacarpals, and oligodactyly in feet are frequent limb malformations. Homozygous variants in the SMOC1 gene (SPARC-related modular calcium-binding protein 1 gene) were identified as causative for the syndrome. A 9-month-old female patient is presented herein, who was diagnosed with ophthalmo-acromelic syndrome and had a homozygous nonsense mutation (p.Arg75Ter) in SMOC1, along with a review of the literature., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background and Aims: The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam., Method: LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0., Results: Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group., Conclusion: We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hyperphosphatasia with mental retardation syndrome (HPMRS) (OMIM # 239300), is an autosomal recessive disease with phenotypic variability, ranging from mild nonsyndromic intellectual disability to syndromic form with severe intellectual disability, seizures, elevated alkaline phosphatase, brachytelephalangy and facial dysmorphism, Six subgroups of HPMRS were defined in which pathogenic mutations affect genes involved in either synthesis or remodeling of the anchor proteins. Among these, PGAP3 mutations are associated with HPMRS type 4. We report two siblings with a novel homozygous variant in PGAP3 expanding both the phenotypic findings and the mutational spectrum of HPMRS type 4. Developmental delay, hypotonia, facial dysmorphism were the consistent findings with HPMRS in our patients. Large anterior fontanel size, gum hypertrophy, pes equinovarus, concentric ventricle hypertrophy, frontoparietal atrophy and dysphagia were the findings of our patients that have been reported for the first time in this syndrome. Although there is an extensive list of differential diagnoses in patients with developmental delay and hypotonia, the recognizable pattern of facial features, parental consanguinity and mild to moderate serum ALP elevation should be sufficiently suggestive of HPMRS type 4., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To assess the nasal functions, nasal resistance, olfactory function, and quality of life in different surgical techniques for nasal septum deviation STUDY DESIGN:: Randomized controlled trial., Methods: This prospective controlled study was carried out on patients who underwent septoplasty. Patients participating in the study were divided into 2 groups; group 1: classic septoplasty (n: 25) and group 2: extracorporeal septoplasty (n: 14). The sinonasal outcome test-22 (SNOT-22), peak nasal flowmetry, and Connecticut Chemosensory Clinical Research Center test were applied to all patients before and 8 weeks after surgery. Surgical outcomes also assessed to evaluate complications 6 months after surgery., Result: In total, 39 (27 males, 12 females) patients diagnosed with nasal septum deviation were included in this study. A septoplasty was performed in all patients: 25 of them (18 males, 7 females; mean age = 29.4 [range, 23-50] years) underwent classic septoplasties and 14 (9 males, 5 females; mean age = 31.3 [range, 23-50] years) underwent extracorporeal septoplasties. Airway openness was achieved in all patients. As a result, the SNOT-22 scores, peak nasal inspiratory flowmeter results, and smell function scores showed significant improvements (P < 0.001)., Conclusion: All corrective surgical methods for a septum deviation have positive effects on nasal airflow, quality of life, and olfaction. The rates of complications were not significantly different between 2 treatment groups.

The Pamphilioidea represents a small superfamily of the phytophagous suborder Symphyta (Hymenoptera). Here, nearly complete mitochondrial genomes (mitogenomes) of three pamphilioid species: Chinolyda flagellicornis (Pamphiliidae), Megalodontes spiraeae and M. cephalotes (Megalodontesidae) were newly sequenced using next generation sequencing and comparatively analysed with the previously reported symphytan mitogenomes. A positive AT skew (0.013) and a negative GC skew (-0.194) were found in pamphilioid mitogenome, and a deviation from strand asymmetry was also observed in the PCGs encoded on both strands. Several gene rearrangement events were observed in four tRNA gene clusters (WCY, IQM, ARNS1EF and TP clusters), which have not been reported from symphytan mitogenomes to date. As the most parsimonious explanation, compared with the inferred insect ancestral mitogenome architecture, the occurrence of gene rearrangements in pamphilioid mitogenomes requires totally five evolutionary steps, including four transpositions and one inversion. The predicted secondary structures of tRNAs, rrnS and rrnL genes are mostly consistent with reported hymenopteran species. Phylogenetic analyses recovered the monophyly of superfamily Pamphilioidea and indicated the relationship Tenthredinoidea + (Pamphilioidea + (Cephoidea + (Orussoidea + Apocrita))) with strong nodal supports., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Interleukin-35 (IL-35) is a newly defined potent anti-inflammatory cytokine that is predominantly produced by regulatory T cells, and pentraxin-3 belongs to the acute-phase proteins., Aim: To measure the serum IL-35 and pentraxin-3 levels in the early phase of mild acute pancreatitis (AP)., Material and Methods: Eighty-three patients with mild AP and 30 healthy controls were included in the study. The serum levels of IL-35 and pentraxin-3 were measured by enzyme-linked immunosorbent assay upon admission and at the 48 th hour after diagnosis., Results: The mean value of serum IL-35 levels in patients with mild acute pancreatitis at admission was 5.91 ng/ml (4.21-7.90) and was significantly lower than those in healthy controls (25.53 ng/ml (12.79-54.73, p < 0.001)) and 48-hour value were (6.79 ng/ml (4.42-9.62) ( p = 0.015)). The mean value of serum pentraxin-3 levels in patients at the time of admission was 6.75 ng/ml (4.42-9.62) and there was no significant difference from healthy controls, at 7.64 ng/ml (6.58-8.62, p > 0.05). Also there was no significant difference between the mean value at admission and the mean value at 48-hour, 6.75 ng/ml (4.74-9.06, p > 0.05)., Conclusions: Interleukin-35 can be used in diagnosis and follow-up in patients with mild AP., Competing Interests: The authors declare no conflict of interest.

Background/aim: Discrimination of pleural effusion etiology is not always easy in clinical practice. Pentraxin-3 (PTX-3) is a new acute- phase protein. The aim of this study was to investigate the role of PTX-3 in the differential diagnosis of pleural effusions., Materials and Methods: This prospective study enrolled all consecutive patients from two tertiary hospitals who underwent diagnostic or therapeutic thoracentesis. In a cohort of 149 subjects with pleural effusion, including transudates and malignant (MPE), tuberculous (TPE), and parapneumonic effusion (PPE), serum and pleural effusion PTX-3 concentration measurements were performed using ELISA. Serum and pleural effusion protein, lactate dehydrogenase, C-reactive protein (CRP), and adenosine deaminase levels were also assessed., Results: Of these patients, 34 had transudates, 29 had PPE, 63 had MPE, and 23 had TPE. There was a weak correlation between pleural effusion PTX-3 level and serum CRP (P < 0.01). There was a significant difference in pleural PTX-3 levels between the exudative effusion groups (P < 0.01). The median pleural effusion PTX-3 was significantly higher in patients with PPE (11.2 ng/mL, 2–17.8) than MPE (4.7 ng/mL, 1.8–13.9) and TPE (3.1 ng/mL, 2.0–4.1). At a cut-off point of 5.89 ng/mL, PTX-3 had the best discriminatory power for PPE versus other exudative effusions (sensitivity: 86.2%, specificity: 87.7%). The exudative effusion group had a significantly different pleural effusion/serum PTX-3 ratio (P = 0.03)., Conclusion: PTX-3 concentration in pleural effusion was elevated without a significant correlation with serum PTX-3 in PPE. These results may suggest that PTX-3 is a local acute-phase reactant and may allow discrimination of PPE from other exudative effusions., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

B cells may contribute to the pathogenesis of myasthenia gravis with anti-acetylcholine antibodies (AChR+ MG) by co-stimulation or selection of T cells. In this study, we investigated costimulatory molecules on B cells in the blood and in the thymus as well as by TLR9 and IL-21 stimulations in AChR+ MG patients with or without immunosuppressive treatment and controls. CD80 and CD86 expression on B cells was increased in the peripheral blood and in the thymus of untreated patients. CD86 was further amplified by IL-21. A role for activated B cells, active thymic environment and IL-21 is implicated in MG., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, is a rare autosomal recessive disorder of the skeleton characterized by disproportionate short stature with narrow chest and dysmorphic facial features. The skeletal manifestations include platyspondyly, short flared ribs, short tubular bones with abnormal metaphyses and epiphyses, severe brachydactyly, and premature stippled calcifications in the cartilage. The abnormal calcifications are so distinctive as to point to the definitive diagnosis. However, they may be too subtle to attract diagnostic attention in infancy. Homozygous variants in DDR2 cause this disorder. We report on a 5-year-old girl with the classic phenotype of SMED, SL-AC in whom a novel homozygous nonsense mutation in DDR2 was detected using exome sequencing.

Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on susceptibility testing is not yet standardised. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. A CLSI M38-A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48 hours, 72 hours and 96 hours. MIC-0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC-2 endpoint (~50% inhibition compared to growth control) was used. Both MIC-0 and MIC-1 (~80% inhibition compared to growth control) results were analysed for terbinafine to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48 hours for all isolates except two Exophiala dermatitidis strains. At 72 hours, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala., (© 2018 Blackwell Verlag GmbH.)

Backround: The relationship between maternal zinc level and birth weight, birth week, delivery type, garvida, maternal age, etc., contribute to diagnosis and clinical follow-up., Method: Multivariate investigated for data of 275 patients were obtained during their pregnancy periods until birth. 3 cc blood samples were centrifuged for 15 minutes at 2500 g within a period of 30 minutes and were stored at -80°C until the time of analysis. The zinc levels of the patients were found to be within the range of 49-129 μg/dL. Patients were divided into 8 groups according to their zinc levels (49-59, 60-69, …, 120-129) and the relationships of zinc level with the parameters related to the mode of delivery, week of delivery, birth weight, age, early membrane rupture, live-stillbirth, and gravid were statistically analyzed to determine differences between the groups., Results: There was a significant difference between the live births and stillbirths with a 95% confidence level regarding the zinc level. The zinc level affected the live-stillbirth status; patients with a zinc level of 49-59 μg/dL had stillbirths, the live birth rate for 59-69 μg/dL was approximately 50%, whereas it was approximately 88% for in the patients with a zinc level of 109-119 μg/dL. All patients with a zinc level of 119 μg/dL and above had live births., Conclusion: Based on the results of this study, it is suggested that zinc supplementation may be an appropriate treatment for the pregnant women with low zinc levels to provide the realization of live births., (© 2018 Wiley Periodicals, Inc.)

Objective:  Trisomies 13 and 18 are among the most common autosomal aneuploidies associated with high mortality rates. Conventional management strategies offer to limit interventional support; however, some of the recent studies suggest that intervention does make a difference in terms of survival., Study Design:  A retrospective cohort study was performed between January 1996 and January 2016, covering all cases with such trisomies. A total of 69 cases were reviewed for clinical aspects, outcome, and management strategies., Results:  In almost all pregnancies with follow-up, at least one indication present for invasive testing (54/55). Invasive testing was not performed in 18.5% of such cases. All parents opted for termination in cases with prenatal diagnosis. None of the liveborns had prenatal diagnoses, thus, neonatal resuscitation and intensive care unit admission were not withheld in such infants. Major intervention was done in only one patient with full trisomy 13. Median survival for infants with full trisomies 13 and 18 was 36 and 60 days, respectively. Almost half the patients died within 1 month., Conclusion:  To which extent the major interventions should be withheld is an issue of debate in managing such infants; however, current approaches are subject to change, given the technological advances., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To determine frequency of fragile X associated premature ovarian insufficiency (FXPOI) among Turkish premutation carriers., Study Design: FMR1 premutation is the single most common genetic cause of POI (FXPOI). Fragile X Registry at Hacettepe University has been reviewed for the frequency of FXPOI among female premutation carriers. Since 1991 when FMR1 testing was available, 760 individuals from 243 families have been registered. Actual data on menstrual status of female premutation carriers were gathered and analysed., Results: Among 314 premutation-bearing females in the cohort, 268 could be reached for an update of their menstrual history; 107 adults were 40 or younger and 156 were older than 40 years of age, whereas the remaining 5 patients were prepubertal. Among 263 postpubertal females with premutations, 90 women stopped menstruating before or at 40 years of age (premature ovarian failure - POF), constituting 34.2% of our cohort. Additionally, one carrier of a gray zone allele experienced FXPOI. History of twinning was present once in 18 women (5.7%) and twice in two women (0.6%), one of the latter interestingly bearing a full-mutation., Conclusions: FXPOI rates in the present cohort are higher than those reported in other populations. Higher FXPOI rates in Turkish premutation carriers might be a reflection of younger mean menopause age and higher POI rates in otherwise healthy Turkish women. Since POI is much more frequent among premutation carriers than in general population, testing for CGG repeat expansions in FMR1 should be included in the work-up., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Progranulin is a novel growth factor that has several physiological and pathological roles such as cell growth, tumourigenesis, embryogenesis, wound healing, and inflammation., Aim: To compare the pre-treatment and post-treatment serum levels of the angiogenic factor vascular endothelial growth factor (VEGF), pro-inflammatory cytokine tumor necrosis factor α (TNF-α), and progranulin in peptic ulcer (PU) patients with a healthy control group., Material and Methods: Serum VEGF, TNF-α, and progranulin levels were studied with ELISA in 42 PU patients (antral ulcer (AU): 22, duodenal ulcer (DU): 20) and 15 healthy controls., Results: The serum progranulin levels before treatment were 4237.35 ±1091.30 pg/ml in the patients with AU, 4682.64 ±1501.46 pg/ml in the patients with DU, 3055.66 ±626.88 pg/ml in the control group, and 4460 ±1315 pg/ml in the ulcer (AU and DU) group. The serum progranulin levels were 3607.7 ±869.4 pg/ml in the AU group, 4286.5 ±1208.78 pg/ml in the DU group, and 3947.1 ±1094.64 pg/ml in the ulcer group after the treatment. When comparing pre-treatment serum progranulin levels of the AU group, DU group, and ulcer group with the control group there were statistically significant differences ( p < 0.001, p < 0.0001, p < 0.0001, respectively)., Conclusions: The disappearance of the difference in terms of post-treatment serum levels of progranulin between the AU group and the control group suggests that serum levels of progranulin can be used as a biomarker of gastric ulcer healing.

Akgün-Doğan Ö, Şimsek-Kiper PÖ, Utine GE, Boduroğlu K. Anauxetic dysplasia: A rare clinical entity. Turk J Pediatr 2018; 60: 89-93. Cartilage hair hypoplasia and anauxetic dysplasia spectrum constitute a group of autosomal recessive disorders characterized by variable extent of metaphyseal to spondylometaepiphyseal involvement and various additional clinical features. Within this group, anauxetic dysplasia represents the severe end of the skeletal spectrum. However, extraskeletal features including immunodeficiency, hematological abnormalities, and hair hypoplasia are absent, despite the severe skeletal involvement. This disorder is caused by mutations in the gene encoding ribonuclease mitochondrial RNA-processing complex. We herein report on a patient with anauxetic dysplasia, who presented with severe roto-scoliosis and skeletal findings requiring surgical intervention, and in whom a homozygous RMRP mutation was detected.

The Cimbicidae is a small family of the primitive and relatively less diverse suborder Symphyta (Hymenoptera). Here, nearly complete mitochondrial genome (mitogenome) of hairy sawfly, Corynis lateralis (Hymenoptera: Cimbicidae) was sequenced using next generation sequencing and comparatively analysed with the mitogenome of Trichiosoma anthracinum. The sequenced length of C. lateralis mitogenome was 14,899 bp with an A+T content of 80.60%. All protein coding genes (PCGs) are initiated by ATN codons and all are terminated with TAR or T- stop codon. All tRNA genes preferred usual anticodons. Compared with the inferred insect ancestral mitogenome, two tRNA rearrangements were observed in the IQM and ARNS1EF gene clusters, representing a new event not previously reported in Symphyta. An illicit priming of replication and/or intra/inter-mitochondrial recombination and TDRL seem to be responsible mechanisms for the rearrangement events in these gene clusters. Phylogenetic analyses confirmed the position of Corynis within Cimbicidae and recovered a relationship of Tenthredinoidea + (Cephoidea + Orussoidea) in Symphyta.

Overexpression of DEK oncogene is associated with increased proliferation of carcinoma cells and it is observed in several solid tumors due to the amplification of the 6p22.3 chromosomal region where DEK locates. Although the same chromosomal amplification occurs in multiple myeloma (MM), a plasma cell neoplasm, whether the expression and the copy number of the DEK gene are affected in MM remains elusive. We show that despite the increased copy number in CD138positive MM cells (4 out of 41 MM samples), DEK mRNA expression was down-regulated compared with that in CD138negative bone marrow (BM) cells of the same patients (P<0.0001). DEK protein was not detectable by immunohistochemistry (IHC) in CD138positive normal plasma cells or in malignant plasma cells of MM patients (n = 56) whereas it was widely expressed in normal and neoplastic B-cells. Stable knockdown or overexpression of DEK in CD138positive MM cell lines did not affect the proliferation and viability of the cells profoundly in the presence or absence of chemotherapeutic agent melphalan whereas knockdown of DEK moderately but significantly increased the expression level of CD138 (p<0.01). Decreased DEK expression in plasma cells suggests a potential role of this gene in plasma cell development and lack of detectable DEK protein by IHC could be used as a biomarker for normal and malignant plasma cells.

Early antifungal therapy has a major influence on survival in candidemia. Rapid identification of the species has importance for the treatment, prediction of the species-specific primary resistance and variable antifungal susceptibility. Recently, molecular-based methods attempt to reduce the time between the positive signal of a blood culture and identification of the fungus. PNA-FISH (Peptide nucleic acid fluorescence in situ hybridization) assay distinguishes a number of frequently isolated Candida species in groups following the growth in blood culture. The aim of this study was to investigate the correlation of the species identified by PNA-FISH with conventional identification methods in yeast positive blood cultures and its influence on the selection of antifungal therapy. Specimens of adult patients diagnosed as yeast with Gram stain in signal-positive blood cultures between August to December 2013, were included in the study. The strains were concomitantly cultivated by subculturing from the blood culture bottles onto solid media and identified by conventional methods (germ tube test, ID32C and morphology on cornmeal Tween 80 agar). Rapid species identification was performed by Yeast Traffic Light PNA-FISH, which generates green flourescence for Candida albicans and Candida parapsilosis, yellow for Candida tropicalis, and red for Candida krusei and Candida glabrata. C.tropicalis was identified as a single species whereas the others were identified in pairs. The time points when the yeast positive blood culture bottle was received by the mycology laboratory and reporting of the species identification results by PNA-FISH and the conventional methods were recorded. Seven C.albicans, six C.glabrata, three C.parapsilosis, one C.tropicalis, one C.krusei, one Cryptococcus neoformans, one Saprochaete capitata (Blastoschizomyces capitatus), one C.albicans and Candida dubliniensis, one C.krusei and C.dubliniensis, and one C.glabrata and C.parapsilosis were identified by conventional methods in 23 specimens. Results of PNA-FISH and conventional methods were in full agreement in 19 of the 23 specimens (82.6%). Two specimens were negative by PNA-FISH and yielded S.capitata and C.neoformans which were not included in the test panel. In three specimens that were infected with multiple species, PNA-FISH detected only one of the species. On the other hand and in one specimen, PNA-FISH detected a second species (C.glabrata or C.krusei) that could not be isolated and identified conventionally. Species identification were obtained 72 hours (mean) earlier with PNA-FISH. PNA-FISH provided accurate species identification that were consistent with conventional methods. However and expectedly, it failed to detect species that were not included in the test panel. During the study period, 13 of the 23 patients have passed away. Apart from six patients died prior to blood culture positivity and the one that could not get any antifungal therapy during hospital stay, 16 patients received antifungal treatment. Of sixteen patients who received antifungal therapy, initial antifungal treatment was fluconazole for five and echinocandin for 10 patients. Fluconazole and amphotericin B combination was preferred for one patient. In this study, PNA-FISH result had an influence on the modification of the antifungal treatment of only for one patient in accordance with the clinical findings. We conclude that the utility of PNA-FISH method appeared to be limited in our center since the assay cannot differentiate C.albicans and C.parapsilosis, the two commonly isolated species among our candidemia isolates. However, advantages of the assay might be more pronounced for the centers where C.glabrata is a relatively more frequent species.

Objective: It is widely known that myocardial damage is not immediately terminated after the elimination of epicardial occlusion in cases of myocardial infarction. In situ thrombosis during epicardial occlusion might contribute to poor myocardial perfusion after reperfusion of an occluded epicardial artery. In the current study, we sought to determine the effects of ischemia and reperfusion on microvascular thrombotic occlusion., Methods: Thirty male Wistar rats were included in the study. After the rats had been anesthetized and thoracotomized, the left coronary artery was occluded for 30 minutes in the first group, and it was occluded for 30 minutes and reperfused for an additional 20 minutes in the second group. Ten rats were used as a sham-operated control group. After completion of the study protocol, excised heart preparations were analyzed by immunohistochemistry and electron microscopy., Results: A significant difference was found between the infarction plus reperfusion group and the other 2 groups, with respect to microvascular fibrin and thrombocyte deposition in immunohistochemistry analysis. These results were confirmed by morphological examination with electron microscopy., Conclusion: In situ fibrin formation accompanies microvascular obstruction in acute myocardial infarction. Our results indicate that additional therapeutic approaches are needed in order to achieve better tissue perfusion in contemporary treatment of acute myocardial infarction after successful reopening of the infarct-related artery.

Alginate is a natural biopolymer composed of mannuronic and guluronic acid monomers. It is produced by algae and some species of Azotobacter and Pseudomonas. This study aims to investigate the effect of dissolved oxygen tension (DOT) and growth medium substrate and calcium concentrations on the monomeric composition of alginate produced by Azotobacter vinelandii ATCC® 9046 in a fermenter. Results showed that alginate production increased with increasing DOT from 1 to 5 %. The highest alginate production was obtained as 4.51 g/L under 20 g/L of sucrose and 50 mg/L of calcium at 5 % DOT. At these conditions, alginate was rich in mannuronic acid (up to 61 %) and it was particularly high at low calcium concentration. On the other hand, at extreme conditions such as high DOT level (10 % DOT) and low sucrose concentration (10 g/L), guluronic acid was dominant (ranging between 65 and 100 %).

Our aim was to investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody Bevacizumab on endometrial explants and on apoptotic gene expression levels in the rat endometriosis model. Endometriotic implants were surgically formed, and rats treated with (i) 1 mg/kg single subcutaneous injection of depot leuprolide acetate; (ii) 2.5 mg/kg of single intaperitoneal injection of bevacizumab; (iii) intraperitoneal injection of saline. Histopathologic scores and adhesion scores of endometriotic foci and levels of Bcl-2-associated X protein (Bax), Cytochrome c (Cyt-c), B-cell lymphoma/leukemia 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) mRNA gene expressions of endometriotic foci. Bevacizumab treatment decreased the endometriotic explant size compared with control. Bevacizumab-treated rats had lower total adhesion scores when compared with the control group. Semi-quantitative evaluation of the persistence of endometrial epithelial cells in the explants showed a lower score in gonadotropin-releasing hormone (GnRH) agonist-treated rats compared with control rats. In Bevacizumab increased expression of Bax 3.1-fold, Cyt-c 1.3-fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold compared with the control group. The GnRH agonist increased expression of Bax 3.0 fold, Cyt-c 1.3 fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold, compared with the control group. This study suggests that a novel angiogenesis inhibitor, anti-VEGF antibody bevacizumab is as effective as GnRH agonist in the regression of the endometriotic lesions in rat endometriosis model. One possible mechanism of this effect is the induction of apoptosis.

Two nearly complete mitochondrial genomes (mitogenomes) of wheat stem borers, Cephus pygmeus and Cephus sareptanus (Hymenoptera: Cephidae), were sequenced, characterised and compared with the previously known mitogenome of Cephus cinctus. The gene orders are mostly conserved, except for translocation of trnM and swapped position of trnI and trnQ. An A+T bias was found, but a deviation from strand asymmetry was also detected on the J strand. All protein coding genes (PCGs) are initiated by ATN codons, except for nad1, nad2 and atp8, and all are terminated with TAA, TA- or T- as a stop codon. The predicted secondary structures of rrnS and rrnL genes are mostly consistent with reported hymenopteran species. However, an unusual elongation in rrnS, not know elsewhere in the order, was discovered in Cephus species. Three autonomous sequences detected in domains I and II are mainly responsible for the length expansions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Osteoporosis, osteosclerosis, and lytic bone lesions have been observed in patients with systemic mastocytosis (SM). We examined bone mineral density (BMD) biochemical turnover markers and serum tryptase levels in SM, which is considered a rare disease., Materials and Methods: Seventeen adult patients (5 females, 12 males; median age: 33 years, range: 20-64) with mastocytosis were included in this study. We investigated the value of quantitative ultrasound (QUS) of the calcaneus in the assessment of BMD in SM patients, as well as BMD of the lumbar spine (L1-L4), femoral neck, and distal radius using dual energy x-ray absorptiometry (DXA) and plasma tryptase levels, biochemical markers of bone turnover., Results: At lumbar spine L1-L4, the femoral neck, and the distal radius or as calcaneus stiffness, 12 of 17 patients had T-scores of less than -1 at least at 1 site, reflecting osteopenia. Three of 17 patients had T-scores showing osteoporosis (T-score <-2.5). There was no relationship between DXA and bone lesion severity. We also found a significant positive correlation between tryptase levels and disease severity, as well as between disease severity and pyridinoline (p<0.01 by Spearman's test)., Conclusion: DXA and calcaneal QUS may not be appropriate techniques to assess bone involvement in SM patients because of the effects of osteosclerosis. This study further shows that the osteoclastic marker pyridinoline is helpful in patients with severe disease activity and sclerotic bone lesions to show bone demineralization.

Background: Concurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) in patients with inoperable stage III NSCLC followed in our oncology clinic., Material and Methods: Medical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system., Results: Our study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39-75) and 87 (89.7%) of the patients were men. ECOG performance score was 0-1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3-4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity., Conclusions: The results of this study suggest that split-dose cisplatin may offer fewer grade III-IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.

Soft tissue sarcomas (STS) are a group of rare mesenchymal cancers that include approximately 50 histological types and account for 1% of all adult cancers. The standard curative treatment option for localized disease is surgical resection and, if a surgically removed tumor exhibits high-risk characteristics, adjuvant chemotherapy and radiotherapy may be administered. Sarcoma presenting at an advanced stage has a dismal prognosis and survival has not markedly improved over the last 20 years. The standard first-line treatment for advanced STS, other than gastrointestinal stromal tumors, is cytotoxic chemotherapy. Therapies targeting pro-angiogenic factors have been a focus of drug development for STS over the last few years. Pazopanib, a multitargeted tyrosine kinase inhibitor, is a novel treatment option for patients with metastatic STS in the second-line setting. This is a presentation of 2 case reports of patients with metastatic STS who responded well to treatment with pazopanib.

Gastric cancer, with one million new cases observed annually, and its dismal prognosis, is one of the leading causes of cancer-related mortalities. Systemic chemotherapy is the main treatment modality in advanced gastric cancer patients. We aim to evaluate the predictive role of tumor localization and histopathology on choosing three or two-drug combination regimens. Consecutive 110 metastatic gastric adenocarcinoma patients who were admitted to the Baskent University Department of Medical Oncology and the Van Research and Training Hospital were included in the study. Data of patients were analyzed retrospectively. Median age of patients was 58 years (range 30-80). Proximal intestinal, distal intestinal, and diffuse gastric cancers were found in 35 (32 %), 64 (58 %), and 11 (10 %) patients, respectively. 5-fluoracil and platinum (PF) and PFtax were administered to 47 (43 %) and 63 (57 %) patients, respectively. Median progression-free survival (PFS) was 4.0 (95 % CI 2.5-5.6) and 7.4 months (95 % CI 6.0-8.7) for PF and PFtax groups, (p = 0.034). When we used tumor localization as strata in the PFS survival curve, PFtax produced significantly higher PFS rates only in distal intestinal-type gastric cancer, compared with PF (p = 0.03). Median overall survival (OS) was 9.0 (95 % CI 5.2-12.3) and 17.3 months (95 % CI 7.8-27) for PF and PFtax groups, (p = 0.010). When we used tumor localization as strata in the OS survival curve, PFtax produced significantly higher OS rates only in distal intestinal-type gastric cancer compared with PF (p = 0.015). Pathology and tumor location in gastric cancers may affect the outcome, the addition of taxanes as a third drug may significantly increase PFS and OS rate purely in distal intestinal-type gastric cancer but not in patients with proximal and diffuse-type gastric cancers.

Isolated central nervous system (CNS) relapse of non-Hodgkin lymphoma (NHL) is very rare. We report a five-year-old boy with T-cell lymphoblastic lymphoma (T-LBL), who developed CNS relapse under treatment when the primary tumor was in complete remission. The patient presented initially with persistent cough and an anterior mediastinal mass and had no bone marrow or CNS involvement at diagnosis. During re-induction treatment, a routine lumbar puncture revealed blasts in the cerebrospinal fluid (CSF). The patient developed neurological signs and symptoms consequently. Craniospinal radiotherapy followed by BFM (Berlin-Frankfurt-Münster) high-risk chemotherapy protocol was initiated. Despite complete response after three courses, the patient experienced CNS relapse and expired due to disease progression. In the treatment of a NHL patient, routine CSF analysis should be done for tumor cells even when the primary disease is in complete remission.

A set of new aziridinyl phosphonates (4a-g) were synthesized by using the Gabriel-Cromwell reaction and its modified version developed in this study and their structures confirmed by HRMS, IR, and NMR spectra. All the compounds were screened for their antibacterial activity. They all showed comparable moderate to good growth inhibitory activity in reference to ampicillin and streptomycin., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The involvement of the gut by Langerhans cell histiocytosis (LCH) is very rare in adults; however this is usually observed with a disseminated disease in children. We report a 75-year-old male patient who underwent right hemicolectomy for a complicated intestinal diverticular disease. The surgical specimen revealed LCH-like proliferative lesion associated with diverticulitis. The overall morphological and immunohistochemical findings are indistinguishable from LCH. Systemic scans and subsequently performed bone marrow biopsies were free of disease. Although the HUMARA clonality assay cannot be assessed, the lack of evidence of LCH progression or disease elsewhere in the whole body strongly supported the possibility of an atypical reactive phenomenon probably due to the underlying intestinal diverticular disease. Therefore, it is important to avoid diagnosing such a unifocal Langerhans cell proliferation as LCH in patients with underlying pathologies in the absence of systemic involvement. Therefore, without knowledge of clonal status of a unifocal Langerhans cell proliferation, we recommend using the terminology of LCH-like lesion.

Immunosuppression is a risk factor for the development of posttransplant lymphoproliferative disorder. This type of malignancy developed in an immunocompromised man. The patient presented with focal convulsion starting from right face and right arm followed by two generalized convulsions with one minute interval. Diagnosis was made by computed tomographic (CT) scan of the cranium following oral and intravenous administration of contrast dyes which revealedmass leisons in the frontotemporal lobe and by stereotaxic biopsy. Tissue sections showed a malignant tumor cell infiltration with large areas of necrosis and many mitoses. Many tumor cells were positive for CD 20 and CD 10. These findings were consistent with large B-cell lymphoma. Central nervous system radiation with a dose of 56 Gy was given with clinical and radiological improvement. The patient died due to multiorgan failure. Finally, the immunocompromised patients should be closely followed for the development of lymphoproliferative disorder.