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Objective: To define the relationship of tumor size with surgico-pathological factors and oncological outcome in FIGO 2014 stage IB cervical cancer., Methods: This study retrospectively evaluated 384 FIGO 2014 Stage IB cervical cancer patients who underwent radical hysterectomy and lymphadenectomy. Tumor size was stratified according to 2 cm (≤ 2cm, 2-≤4 cm, >4 cm) and 4 cm (≤4 cm, >4 cm), and the relationship with poor prognostic factors, and the effects on survival were examined. The distribution of prognostic factors was compared between three subgroups: ≤2 cm vs. 2-≤4 cm; 2-≤4 cm vs. > 4 cm and ≤ 2 cm vs. > 4 cm. Survival rate was evaluated using the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was performed using Cox proportional-hazards regression., Results: Stratification of tumor size according to 4 cm was found to better determine pelvic lymph node determination. Parametrial involvement, uterine involvement and deep cervical stromal invasion were correlated with increasing tumor size. Lymph node involvement and uterine involvement were an independent prognostic risk factor for recurrence and cancer-specific survival. Tumor size showed no association with prognosis., Conclusion: There is no meaningful cut-off value for tumor size determining all surgico-pathological factors. There was also seen to be no association between tumor size and recurrence or disease-related mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This study aimed to evaluate neoadjuvant chemotherapy (NACT) for locally advanced stage cervical carcinoma., Materials and Methods: Data of 43 patients with locally advanced cervical carcinoma who had NACT were reviewed. NACT protocols implemented included cisplatin/5-fluorauracil, cisplatin/UFT, and carboplatin/paclitaxel. After NACT, the patients were re-examined, and patients who had a tumor size ≤40 mm underwent Piver-Rutledge type III radical hysterectomy, while other patients received radiotherapy. Following NACT, clinical responses were assessed according to the criteria of the World Health Organization., Results: The mean age of the patients was 49.4 years, and the median follow-up duration was 48 (range, 5-228) months. The median tumor sizes were 50 and 30 mm before and after NACT, respectively. Complete clinical response was observed in 4 (9.3%) patients, partial clinical response in 8 (18.6%), and pathologic complete response in 3 (6.9%). Stable disease was noted in 30 (69.9%) patients and progression in 1 (2.3%) patient. After NACT, 31 patients have undergone radical surgical procedures. The 5-year disease-free survival rate was 72%, and the 5-year disease-specific survival rate was 91%. Age, International Federation of Gynaecology and Obstetrics 2009 stage, histopathologic type, NACT protocol, rate of decrease in tumor size after NACT, clinical response, number of courses, tumor size before NACT, tumor size after NACT, and lymph node metastasis were not associated with disease-free survival., Conclusion: Following NACT, a significant reduction in tumor dimension was observed, and the probability of radical surgery is increased. However, clinical response was not predictive of survival.

Disorders of intracellular trafficking are a group of inherited disorders, which often display multisystem phenotypes. Vacuolar protein sorting (VPS) subunit C, composed of VPS11, VPS18, VPS16, and VPS33A proteins, is involved in tethering of endosomes, lysosomes, and autophagosomes. Our group and others have previously described patients with a specific homozygous missense VPS33A variant, exhibiting a storage disease phenotype resembling mucopolysaccharidosis (MPS), termed "MPS-plus syndrome." Here, we report two siblings from a consanguineous Turkish-Arabic family, who have overlapping features of MPS and intracellular trafficking disorders, including short stature, coarse facies, developmental delay, peripheral neuropathy, splenomegaly, spondylar dysplasia, congenital neutropenia, and high-normal glycosaminoglycan excretion. Whole exome sequencing and familial segregation analyses led to the homozygous NM_022575.3:c.540G>T; p.Trp180Cys variant in VPS16 in both siblings. Multiple bioinformatic methods supported the pathogenicity of this variant. Different monoallelic null VPS16 variants and a homozygous missense VPS16 variant had been previously associated with dystonia. A biallelic intronic, probably splice-altering variant in VPS16, causing an MPS-plus syndrome-like disease has been very recently reported in two individuals. The siblings presented herein display no dystonia, but have features of a multisystem storage disorder, representing a novel MPS-plus syndrome-like disease, associated for the first time with VPS16 missense variants., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Prediction and time estimation are all but required for motor function in everyday life. In the context of eye movements, for instance, they allow predictive saccades and eye re-acceleration in anticipation of a target re-appearance. While the neural pathways involved are not fully understood, it is known that the frontal lobe plays an important role. As such, neurological disorders that affect it, such as frontotemporal (FTD) dementia, are likely to induce deficits in such movements. In this work, we study the performances of frontotemporal dementia patients in an oculomotor task designed to elicit predictive saccades at different rates, and compare them to young and older adults. Clear deficits in the production of predictive saccades were found in patients, in particular when the time between saccades was short (~500 ms). Furthermore, one asymptomatic C9ORF72 mutation bearer showed patterns of oculomotor behavior similar to FTD patients. He exhibited FTD symptoms within 3 years post-measure, suggesting that an impairment of oculomotor function could be an early clinical sign. Taken together, these results argue in favor of a role of the frontal lobe in predictive movements timing over short timescales, and suggest that predictive saccades in FTD patients warrant further investigation to fully assess their potential as a diagnostic aid., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Nonketotic hyperglycinemia is an autosomal recessive inborn error of glycine metabolism, characterized by deficient activity of the glycine cleavage enzyme system. Classic nonketotic hyperglycinemia is caused by mutations or genomic changes in genes that encode the protein components of the glycine cleavage enzyme system. We aimed to investigate clinical, biochemical, radiological findings and molecular genetic data in ten Turkish patients with classic nonketotic hyperglycinemia. Ten Turkish patients who were diagnosed with classic nonketotic hyperglycinemia in a single center from 2013 to 2019 were included in this study. Their clinical, radiological, electrophysiological and laboratory data were collected retrospectively. Sixty percent of the patients were in neonatal group, while 40 % of the patients were infantile. There were no late-onset patients. 90 % of the patients had the severe form. All patients had developmental delay and seizures. Mortality ratio was 30 % in all groups and 50 % in the neonatal group, while no mortality was seen in infantile group. Median (range) values of cerebrospinal fluid (CSF) glycine levels, plasma glycine levels and CSF/plasma glycine ratios were 148 (15-320) µmol/L, 896 (87-1910) µmol/L, 0.17 (0.09-0.21) respectively. Diffuse hypomyelination and corpus callosum anomaly were the most common cranial MRI findings and multifocal epileptic activity and burst supression pattern were the most common electroencephalographic findings. Six patients had variants in GLDC gene and four in AMT gene; five novel variants including AMT gene deletion were detected. Prognosis was poor and treatment was not effective, especially in the severe form. Classic nonketotic hyperglycinemia causes high morbidity and mortality. Neonatal-onset disease was more common and severe than infantile-onset disease. The ratio of AMT gene variants might be higher in Turkey than other countries. AMT gene deletion also plays a role in the etiology of classic nonketotic hyperglycinemia., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study analyzed the characteristics of pursuit and assessed the influence of prior and visual information on eye velocity and saccades in amblyopic and control children, in comparison to adults. Eye movements of 41 children (21 amblyopes and 20 controls) were compared to eye movements of 55 adults (18 amblyopes and 37 controls). Participants were asked to pursue a target moving at a constant velocity. The target was either a 'standard' target, with a uniform color intensity, or a 'noisy' target, with blurry edges, to mimic the blurriness of an amblyopic eye. Analysis of pursuit patterns showed that the onset was delayed, and the gain was decreased in control children with a noisy target in comparison to amblyopic or control children with a standard target. Furthermore, a significant effect of prior and visual information on pursuit velocity and saccades was found across all participants. Moreover, the modulation of the effect of visual information on the pursuit velocity by group, that is amblyopes or controls with a standard target, and controls with a noisy target, was more limited in children. In other words, the effect of visual information was higher in control adults with a standard target compared to control children with the same target. However, in the case of a blurry target, either in control participants with a noisy target or in amblyopic participants with a standard target, the effect of visual information was larger in children., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: X-linked adrenoleukodystrophy (X-ALD), is a peroxisomal inborn error of metabolism caused due to the loss of function variants of ABCD1 gene that leads to accumulation of very long chain fatty acids (VLCFAs) in several tissues including the neurological system. Childhood cerebral X-ALD (CCALD) is the most common and severe form of X-ALD, if left untreated. Allogenic hematopoietic stem cell transplantation (HSCT) is the only available therapy that halts neurological deterioration in CCALD. We present 12 patients with several subtypes of X-ALD that were followed-up in a single center., Methods: Data of 12 patients diagnosed with X-ALD were documented retrospectively. Demographics, age of onset, initial symptoms, endocrine and neurological findings, VLCFA levels, neuroimaging data, molecular genetic analysis of ABCD1 gene, and disease progress were documented., Results: Mean age of initiation of symptoms was 7.9 years and mean age of diagnosis was 10.45 years. Eight patients had the CCALD subtype, while two had the cerebral form of AMN, one had the adult form of cerebral ALD, and one patient had the Addison only phenotype. The most common initial symptoms involved the neurological system. Loes scores varied between 0 and 12. Seven patients with CCALD underwent HSCT, among them three patients died. The overall mortality rate was 25%., Conclusions: Patients with X-ALD should be carefully followed up for cerebral findings and progression, since there is no genotype-phenotype correlation, and the clinical course cannot be predicted by family history. HSCT is the only available treatment option for patients with neurological deterioration., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Leiomyomas are mostly located in the uterus.Retroperitoneal presentation of leiomyomas are rare and have a greater diagnostic challenge.Because retroperinoteal tumours are quite rare and mostly malignant. Therefore, differantial diagnosis is difficult.We report a rare case of retroperitoneal leiomyomatosis, in which there were concurrent leiomyomas in uterus, pelvic and paraaortic regions that are adjacent to pelvic and paraaortic vascular structures.The patient underwent type 1 hysterectomy and bilateral salpingo-oophorectomy and had a total excision of the myomas from adjacent structures. Histological examination of the surgical specimen revealed that leiomyoma. She has been disease -free for 24 months now., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background/aim: To investigate the risk factors for evisceration in a gynecological oncology population. The secondary aim was to evaluate the impact of evisceration on survival., Materials and Methods: Inclusion criteria consisted of having had an elective surgery performed through a xiphoidopubic incision in our institution and having a gynecological malignancy based on pathology. A total of 198 patients were evaluated, 54 with evisceration and 144 without evisceration. Due to the widely varied prognosis of female genital cancers, the survival was analyzed on a homogenized group, including only 62 patients with primary advanced stage epithelial ovarian-tubal-peritoneal cancer., Results: The preoperative factors associated with evisceration in the univariate analysis were old age, high body mass index (BMI), hypertension, smoking, comorbidities, high American Society of Anesthesiologist (ASA) score (3 and 4), and low preoperative albumin level. The associated intraoperative factors were bleeding volume, receiving more than two units of erythrocyte suspension or fresh frozen plasma, and having had a major operation. The associated postoperative factors were the albumin transfusion and the antibiotic use in the early postoperative period. In the multivariate analysis, smoking, low levels of preoperative albumin, high BMIs, and high ASA scores (3 and 4) were independent prognostic factors for evisceration. Evisceration was not associated with recurrence and survival in the patients with primary advanced stage epithelial ovarian-tubal-peritoneal cancer., Conclusion: Smoking, preoperative hypoalbuminemia, obesity, and high ASA scores (3and 4) were the prognostic factors for evisceration. Short-term modifiable factors such as smoking cessation and improved nutritional status should be considered in elective gynecological oncology surgeries. Evisceration had no impact on survival and recurrence in the patients with primary advanced stage epithelial ovarian-tubal-peritoneal cancer., Competing Interests: none declared., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background/aim: Acute necrotizing encephalopathy is a rare type of acute encephalopathy characterized by multi-ocal brain lesions and associated severe neurological findings and various organ dysfunctions may accompany it., Materials and Methods: Patients with acute necrotizing encephalopathy of childhood diagnosed by pediatric neurology and pediatric intensive care at Sami Ulus Maternity, Child Health and Diseases Training and Research Hospital between 2007 and 2020 were included in this study., Results: Nine patients (six females, three males) with a mean age of 4.05 ± 1.94 years (age range 1–6.5) were included in this study. The interval range between fever and encephalopathy in patients was 1–4 days. Influenza A (3H1N1, one untyped) was detected in four patients, influenza B in three patients, and no cause was found in two patients. Major clinical findings other than febrile encephalopathy in all patients were a hemodynamic shock in seven patients, seizures in six patients, vomiting in five patients, dystonia in three patients, and flaccid paralysis in the upper extremity in one patient. Despite all our treatment approaches, including plasmapheresis, moderate to severe neurological sequelae was observed in all of our patients, who survived even with significant radiological improvement. Three patients for whom we could not perform plasmapheresis died., Conclusion: Our study revealed that thalamic involvement increased as the interval shortened, and brainstem involvement increased in patients over four years of age. The presence of persistent vomiting accompanying encephalopathy during the parainfectious period and plasmapheresis treatment being a treatment option that could prevent mortality were cautionary for our study., Competing Interests: None of the authors has any conflict of interest to disclose., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Pediatric-onset systemic lupus erythematosus is among the prototypic systemic autoimmune diseases seen in children. Although the neuropsychiatric involvement rate varies during the course of the disease, it is an important cause of morbidity and mortality. The clinical picture of neuropsychiatric SLE (NPSLE) is highly variable, and neurological features can precede systemic findings, leading to some diagnostic difficulties. NPSLE requires early and aggressive immunosuppressive therapy. Some patients can be resistant to immunosuppressive therapy. Chorea is a rare manifestation that occurs in 1.2%-2% of SLE patients and can result from an immunologically mediated mechanism, antiphospholipid autoantibodies or ischemia. Herein we present the first case of pediatric-onset SLE diagnosed with central nervous system involvement and treated with Zipper method. The Zipper method is a new immunomodulation treatment. The clinical findings of the patient, which were resistant to corticosteroids and cyclophosphamide, resolved by this novel treatment.

Background: Symptoms and findings called orange or red flags may indicate the etiology of pediatric headaches and may point to a life-threatening situation requiring urgent treatment and thus can alter patient management. These findings can be either misleading or prognostic for clinicians. We aimed to identify the etiology and prognostic value of orange/red flags in pediatric patients., Methods: This study included 810 children with headaches who underwent neuroimaging due to the existence of orange/red flags. Their hospital records were examined to obtain demographical, clinical, laboratory data, and re-classify the headaches and determine orange/red flags on admission., Results: Secondary causes were identified in 17.0% (n: 138) of patients, however, those who were diagnosed with a life-threatening headache that required emergency treatment were 5.2% of all patients and 30.4% of the patients diagnosed with a secondary headache. Those with secondary headaches and with life threatening secondary headaches which required urgent treatment were younger (p = 0,018, p = 0,022), had more emergency department visits (p < 0,001), and acute onsets (p < 0,001). Red flags, like systemic symptoms (p < 0,001), sudden onset (p = 0,023, p = 0.039), papilledema (p < 0,001), and progressive headaches (p = 0,048, p = 0.006), were more common with secondary headaches and its subgroup, while headache awakening from sleep (p = 0.009) and family history of primary headache (P > 0,001) were more common in primary headaches. No correlation existed between the number of red flags and etiology. However, older age (p = 0,001) and a shorter duration between symptoms and admission (p = 0,032), and the number of emergency service visits (p = 0,020) increased with increasing red flags., Conclusions: Physicians always look for flags when they encounter patients with headaches, which is a common symptom, so as not to overlook anything. However, red flags do not always mean that the underlying cause requires emergency treatment and the severity of the cause is not correlated with the number of flags., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

The prostate-specific membrane antigen (PSMA) represents an ideal biomarker for molecular imaging. Various PSMA-targeted radioligands are available for prostate cancer imaging. In this study, labeling of PSMA I&T with 68 Ga, as well as validation of the radiochemical purity of the synthesis product by reverse phase radio high-performance liquid chromatography (HPLC) method are intended. Since the standard procedure for the quality control (QC) was not available, definition of chemical and radiochemical purity of 68 Ga-PSMA I&T was carried out according to the Q2 (R1) ICH guideline. The standard QC tests were analyzed with Scintomics 8100 radio-HPLC system equipped with a radioactivity detector. The method was evaluated in terms of linearity, precision and accuracy, LOQ, robustness parameters, and specificity. To assess the radiochemical and chemical purity of 68 Ga-PSMA I&T, the developed method was validated to apply safely to patients. An excellent linearity was found between 1μg/mL and 30 μg/mL, with a limit of detection and limit of quantitation of 0.286 μg/mL and 0.866 μg/mL, respectively for 68 Ga-PSMA I&T. The recovery was 96.8 ± 3.8%. The quality control of the final product was performed many times with validated radio-HPLC method and was found to comply with ICH requirements, thus demonstrating the accuracy and robustness of the method for routine clinical practice., Competing Interests: CONFLICT OF INTEREST: none declared, (Copyright © 2021 The Author(s).)

Objectives: Germanium-68/gallium-68 ( 68 Ge/ 68 Ga) generator eluate contains a number of metal cations that can compete with 68 GaCl 3 , reducing specific radioactivity. The first step in peptide labeling with 68 GaCl 3 is to remove 68 Ge and several other metals with a long half-life. In this purification step, the elution residue that is passed through the cartridge is collected in glass waste bottles. Waste management is included in good production practices, and in particular, the activity of long half-life 68 Ge (270.95 days) and other toxic metal levels need to be examined. Our objective in this study is to determine the 68 Ge activity in liquid waste produced by the generation of 68 Ga and heavy metal concentrations from the generator column materials and to assess whether it can be disposed of as normal waste., Methods: Liquid wastes produced by passing the 68 Ge/ 68 Ga generator eluate of 2 different identities via PSH+ cartridge have been analyzed with the inductively coupled plasma mass spectrometry device in the advanced technology application and research center of our university., Results: The average of the 68 Ge radioactive pollution was estimated to be 0.142 ppm (μg.mL -1 ) in the liquid waste analysis after passing through the PSH+ cartridge in the pre-elution in the GalluGEN brand generator. While there was no tin (Sn) impurity, it was determined that the average zinc (Zn) was 1.95 ppm (μg.mL -1 ) and the average aluminum (Al) impurity was 10.95 ppm (μg.mL -1 ). While no 68 Ge radioactive pollution was determined in the iThemba LABS brand generator, the average Sn was 0.098 ppm (μg.mL -1 ), average Zn 48.6 ppm (μg.mL -1 ), and average Al impurity 4.135 ppm (μg.mL -1 )., Conclusion: All 68 Ge/ 68 Ga generators produced have their own certificates. Metallic contamination in the postmarking waste of 68 Ge/ 68 Ga generators can be different. It would be a safe method to keep these wastes in place until they are dumped into the sewage systems, given their half-lives in terms of long half-life radioactive metallic contamination.

Purpose: This study aimed to describe the electroclinical spectrum and neurocognitive outcome in children with epileptic encephalopathy with status epilepticus during sleep (ESES) according to the EEG patterns., Methods: Records of 48 (19 males, 29 females) patients with ESES/CSWS syndrome were retrospectively evaluated for data on sleep and awake EEGs, psychometric tests, and brain MRI. Patients with a spike-wave index (SWI) of at least 50 % in the NREM sleep EEG were included in the study. Electrophysiologic findings were separated into two groups based on SWI: SWI>85-100 % (typical ESES) and SWI < 85 % (atypical ESES). The neurocognitive prognosis was also evaluated in two groups; favorable and unfavorable., Results: The median age at the onset of ESES was 6 years and 5 months and ranged from 3 to 13 years. The median duration of follow-up after the ESES diagnosis was 57 months (range 24-150 months). Etiology was evaluated in three groups: symptomatic/structural, idiopathic, and unknown (cryptogenic). Twenty-seven (56.25 %) patients had atypical ESES patterns and 21 patients (43.75 %) had typical ESES patterns. Twenty-eight patients (58.3 %) had cognitive deterioration. Long term neurocognitive outcome was unfavorable in half of the patients. Symptomatic/structural etiology was more common in patients with unfavorable (p < 0.001) outcomes. The median age at the diagnosis of ESES (p < 0.001) was significantly earlier in the patients with unfavorable neurocognitive outcomes. The longer duration of ESES(p < 0.001), and the longer time between the onset of epilepsy and ESES (p = 0.039) was significantly associated with unfavorable outcomes. We found that patients with typical ESES had a higher risk for poor neurocognitive outcomes than patients with atypical ESES (OR: 31.096 [1.565-617.696])., Conclusion: The long-term outcome of ESES is exceedingly variable. An unfavorable neurocognitive outcome seems to be related to ESES with a long-duration and early-onset epileptic activity, SWI ≥ 85 %, and etiology., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background/aim: Especially suitable for PET due to its nuclear physical and radiochemical properties, the positron emitter Gallium-68 (Ga) occurs by electron capture from Germanium-68 (Ge). In such a radionuclide generator, the germanium is bound to an insoluble, inert column matrix and forms a secular radioactive balance with 68Ga obtained in the hour. As a result of the limited radiochemical selectivity of the elution process, the eluate obtained is basically contaminated with the main nuclide traces, so that the eluate becomes a mixture of Ga and Ge radionuclides. Also, the generator eluate contains a number to metal cations that reduce specific radioactivity and can compete with 68Ga. The presence of toxic metal that can be found in the eluate carries the risks of contamination at every step from the production of generators to radiopharmaceutical production., Materials and Method: In our study, by collecting the eluate of the Ge/Ga generators used with different identities in different centers in Turkey, we report comparative analysis of metal contamination in the generator eluate. The eluates of 68Ge/68Ga generators to five different identities were collected. Eluates were analyzed by inductively coupled plasma-mass spectrometry., Results and Conclusion: As a result, each generator contains metallic impurities different from its certificate.

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.

Purpose: To describe the vision screening procedures in the three Belgian linguistic communities and present Belgian screening results., Methods: Analyses were carried out on 636 260 Belgian children between 2009 and 2016. Pre-school children were tested once or twice, while schoolchildren were tested seven or eight times., Results: 57-83% of Belgian pre-school children and close to 100% of school children were tested. Proportions of referrals varied between 9% and 15% for pre-school children and 6-18% for school children. Proportions of failed or doubtful examinations (i.e., incomplete examinations or those with unreliable results) decreased from 1% to 10% in pre-school to 1-4% in school children. Proportions of true positive referrals (36-83%) at the pre-school level varied between linguistic communities. Estimated costs of pre-school screening appeared to be lower in the Flemish community. However, the cost of the ophthalmologist's time per pre-school child with a confirmed diagnostic was probably lower in the French community, as a result of a higher proportion of true referrals., Conclusion: Compared to screening programs in 10 developed countries, at the pre-school level, population coverage was lower in the French community, and comparable in the other communities. Proportions of referred children were similar. True positive referrals were comparable in the French community, but below results in other countries in the other communities. At the school level, population coverages were in the higher range of results compared to other countries. Proportions of referrals were below the results of other countries in the Flemish community, and comparable in the rest of the country.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

Objective: Acute appendicitis (AA) is a common urgent surgical situation of the gastrointestinal tract. Gallium-68 ( 68 Ga)-citrate has been recently investigated as a radiopharmaceutical for infection and inflammation imaging. Aim of the study was to determine the effectiveness of 68 Ga-citrate positron emission tomography/computed tomography (PET/CT) imaging in rabbits with experimentally induced AA., Materials and Methods: In the AA group (n=6), the appendices of the rabbits were surgically ligated. The sham group (n=6) was used as control. Gallium-68-citrate was synthesized. All rabbits were imaged using 68 Ga-citrate PET/CT at 36 th following the establishment of experimental models, and at 36 th h, all rabbits were appendectomised. Appendices were examined histopathologically. Blood samples were drawn from all rabbits at the beginning and end of the experimental process. Interleukin-6 (IL-6) and procalcitonin (Pct) levels were measured. Acute appendicitis was confirmed histopathologically and biochemically., Results: Gallium-68-citrate PET/CT showed acute appendicitis in all rabbits. The sensitivity, specificity and accuracy of 68 Ga-citrate PET/CT in AA were 100%, 83.3% and 91.7%, respectively., Conclusion: Acute appendicitis is accurately imaged in an experimental rabbit model by using 68 Ga-citrate with PET/CT.

This study was designed to evaluate the accuracy of detecting pulmonary embolism (PE) using the Technegas SPECT/CT combined with 68 Ga PET/CT in a rabbit model. One hour after artificial PE ( n  = 6) and sham ( n  = 6) models were created, Technegas SPECT/CT ventilation and 68 Ga-MAA PET/CT perfusion scan (V/Q scan) were performed. Ventilation imaging was performed first on all cases. Technegas SPECT/CT and 68 Ga-MAA PET/CT images were evaluated by a nuclear medicine physician who recorded the presence, number, and location of PE on a per-lobe basis. The sensitivity, specificity, and accuracy of Technegas SPECT/CT and 68 Ga-MAA PET/CT for detecting PE were calculated using a histopathological evaluation as a reference standard. A total of 60 lung lobes were evaluated in 12 rabbits, and PE was detected in 20 lobes in V/Q scans and histopathological analysis. The overall sensitivity, specificity, and accuracy were 100%, 100%, and 100%, respectively, for both the Technegas SPECT/CT and 68 Ga-MAA PET/CT V/Q scans. Technegas/ 68 Ga-MAA V/Q scans have good sensitivity, specificity, and accuracy in the detection of PE in this animal model study., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Aziz Gültekin et al.)

Purpose: To assess the extent to which strabismus in children was associated with motor difficulties and to examine which parameters of strabismus were most closely associated with motor development., Methods: The motor skills of children who were suffering from strabismus, were tested binocularly using the Movement Assessment Battery for Children, Second Edition (MABC-2) and compared with the motor performance of monocularly tested healthy controls without any ophthalmologic disease., Results: A total of 40 children with strabismus (mean, 7.25 ± 3.83 years; 19 females) and 18 controls (mean age, 8.33 ± 5.42 years; 6 females) were tested. According to the MABC-2 test, of the 40, 19 had no motor disability, and 21 were at risk of or already presented significant motor disabilities. Results of the MABC-2 were significantly lower for strabismic children without binocularity compared to those with binocularity (P = 0.002). Lack of binocularity was associated with significantly lower performance for static balance (P = 0.003) as well as for catching tasks (P = 0.042)., Conclusions: Lack of binocularity and stereopsis in children is associated with significant motor skills impairment, in particular for static balance and catching tasks. These results should be confirmed with a larger sample, including older patients, to assess the compensation mechanisms that develop with age and the actual effects of strabismus on overall motor performance., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Introduction: Febrile convulsion (FC) is the most common neurological disorder in childhood. The aim of this study was to determine the risk factors for recurrence and the development of epilepsy from the demographic data of these patients., Methods: A retrospective study was made of 680 patients with FC who presented to our hospital. Patients with only FC were defined as group 1 and those who developed epilepsy after FC as group 2. Comparisons were made between the 2 groups of the demographic parameters, parental consanguinity, familial history of FCs or epilepsy, criteria for starting prophylactic treatment, response to treatment, risk factors for recurrence, and results of electroencephalogram., Results: The study included a total of 680 patients comprising 399 males (59%) and 281 females (41%). A diagnosis of FC was made in 652 cases (95.8%, group 1), and epilepsy was diagnosed in 28 (4.2%, group 2). A positive familial history of FCs was determined statistically significantly higher in group 1. On the other hand, a history of pathological birth and parental consanguinity was found higher in group 2. Prophylactic treatment was administered to 89.3% of group 2 and 40.3% of group 1., Conclusions: Febrile convulsions create fear and panic in the family and are a significant health problem in Turkey. The conclusion that has been reached is that the unnecessary administration of prophylactic treatment could be prevented with education of the families on the subject of fever and correct identification of patients at risk of developing epilepsy.

Subacute sclerosing panencephalitis (SSPE) is a rare neurodegenerative disorder caused by a persistent infection with aberrant measles virus. Indoleamine-2, 3-dioxygenase (IDO) initiates the increased production of kynurenine pathway (KP) metabolites quinolinic acid (QUIN), which has an excitotoxic effect for neurons. We measured serum IDO activity and cerebrospinal fluid (CSF) levels of QUIN. The CSF QUIN levels were significantly higher in SSPE patients than in controls, and increased according as neurological disability in a patient studied. Elevation of CSF QUIN and progression of SSPE indicate a pathological role of KP metabolism in the inflammatory neurodestruction., (Copyright © 2019. Published by Elsevier B.V.)

Background Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation. Case presentation A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9. A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage. Conclusions We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.

Background/aim: The objective of this work was to assess the value of 68Ga-DOTAGA-(3-iodo-y)fk(Sub-KuE) positron emission tomography (68Ga-PSMA-I/T PET-CT) and multiparametric magnetic resonance imaging (mp-MRI) for preoperative staging in prostate cancer (PCa) patients who underwent radical prostatectomy (RP) by validating with postoperative histopathology data., Materials and Methods: We prospectively investigated 30 consecutive PCa patients who had both mp-MRI and 68Ga-PSMA-I/T PET-CT before laparoscopic RP. The seminal vesicle invasion (SVI), lymph node metastasis (LNM), bladder neck invasion (BNI), and extracapsular extension (ECE) were investigated separately. The diagnostic performances of mp-MRI and 68Ga-PSMA-I/T PET-CT were assessed using histopathological results., Results: Both mp-MRI and 68Ga-PSMA-I/T PET-CT were not statistically significant in the evaluation of SVI, BNI, and ECE preoperatively but had statistically significant results in the assessment of LNM. mp-MRI had higher overall sensitivity for ECE, overall specificity for SVI, ECE, and BNI, and positive predictive value for ECE, SVI, BNI. 68Ga-PSMA-I/T PET-CT had higher overall sensitivity for BNI, and negative predictive value for BNI and LNM., Conclusion: mp-MRI has superior specificity, sensitivity, and accuracy for assessing ECE and SVI. Both imaging modalities had similar specificity, sensitivity, and accuracy for determining BNI. However, both imaging modalities had low diagnostic accuracy for LNM on histopathology., (© 2020 S. Karger AG, Basel.)

Objectives: The use of Ga-prostate-specific membrane antigen positron emission tomography/computed tomography is spreading due to its clinical benefits. In this study, we aim to determine the intra- and interobserver agreement levels of Ga- prostate-specific membrane antigen-I&T positron emission tomography/computed tomography according to molecular imaging tumor-lymph node-metastases reporting system., Materials and Methods: Eighty prostate cancer patients and underwent Ga- prostate-specific membrane antigen positron emission tomography/computed tomography were blindly evaluated twice by four nuclear medicine specialists at intervals of 4 weeks. The evaluations were performed according to molecular imaging tumour-lymph node-metastases (miTNM) classification. We used Cohen's Kappa and Fleiss' Kappa analysis to analyse intra- and interobserver agreements., Results: When Ga-prostate-specific membrane antigen positron emission tomography/computed tomography findings were evaluated according to miTNM classification, the obtained kappa values were as follows. The intraobserver Cohen's kappa coefficient was found to be 0.79 (substantial agreement), 0.93 (almost perfect agreement), and 0.94 (almost perfect agreement) for miT, miN, and miM, respectively. During interobserver evaluation between the four observers, the kappa coefficient was 0.52 (moderate agreement) for miT, 0.74 (substantial agreement) for miN, and 0.84 (almost perfect agreement) for miM., Conclusion: There is no research on the intraobserver agreement analysis of Ga-prostate-specific membrane antigen positron emission tomography/computed tomography in the literature. Our findings are the first ones. The intraobserver agreement was almost perfect. Moreover, although Ga-prostate-specific membrane antigen I&T positron emission tomography/computed tomography had moderate interobserver evaluation compliance of the primary tumour, it had excellent interobserver agreement levels in local lymph node metastasis and distant metastasis evaluation.4012501255.

Objective: To present the clinical, surgical, and pathologic features of bone recurrence in patients who underwent radical hysterectomy for early-stage uterine cervical cancer., Materials and Methods: Data of 412 patients who underwent type III radical hysterectomy and pelvic ± paraaortic lymphadenectomy for stage 1B-2A epithelial cervical cancer were reviewed. Seven (1.7%) patients with bone recurrence in the first recurrence were included in the study., Results: The median follow-up of the main cohort (n=412) was 46 (range=1-300) months. In this period, recurrence developed in 53 (12.9%) patients and recurrence was observed in bone in 13.2% (7 of 53) of these recurrences. Time to recurrence ranged from 9 to 45 months. Of the recurrences, five were in the axial skeleton and two were in the appendicular skeleton. Recurrence was observed in lumbar vertebrae in three patients, thoracic vertebrae in one patient, sacral vertebrae in one patient, lumbosacral vertebrae in one patient, and the left femur in two patients. Four patients had multiple recurrence in 3 patients despite isolated bone recurrence. Patients with multiple recurrences died within 6-25 months. All isolated bone recurrences were in the axial skeleton. Complete clinical response with salvage therapy was achieved in two patients with isolated bone recurrence., Conclusion: Complete clinical response and long postoperative survival can be achieved with salvage treatment when bone recurrence is solitary in cervical cancers., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2019 by Turkish Society of Obstetrics and Gynecology | Turkish Journal of Obstetrics and Gynecology published by Galenos Publishing House.)

Objective: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects., Methods: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T 1 -weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1., Results: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset., Conclusions: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.

Objective: To evaluate uncommon types of borderline ovarian tumors (BOT) and define the clinical, surgical, and pathologic features., Material and Methods: Seventeen patients who were treated in our hospital between 1990 and 2017 were identified. Patients’ data were collected from the gynecologic oncology clinic electronic database, patients’ files, and pathology reports. Conservative surgery was defined as preservation of the uterus and at least part of one ovary., Results: The mean age was 47 (range, 22-70) years. Based on histopathologic tumor type, there was mixed tumor in five (29.4%) patients, endometrioid-type in nine (52.9%), seromusinous-type in two (11.8%), and Brenner-type in one (5.9%). Conservative surgery was performed in 4 patients. Two patients with endometrioid BOT had synchronous endometrial pathology, including one (11%) patient with endometrial cancer, one (11%) with endometrial hyperplasia without atypia, and 3 (33%) patients had endometriosis. The median follow-up was 19 (range, 1-137) months. No recurrence was observed during the follow-up period., Conclusion: In our small volume case series, it could be said that non-serous/non-mucinous BOT has excellent prognosis. However, endometrial pathology should be checked in endometrioid type.

Background/aim: We aimed to define the effect of tumor size on recurrence and survival rates in patients with stage I–II endometrioid-type endometrial cancer., Materials and Methods: A total of 550 patients who had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic-paraaortic lymphadenectomy were included. Patients with extrauterine spread, sarcomatous components, or synchronized tumor and those who did not undergo lymphadenectomy or did not have data on tumor size were excluded., Results: The median tumor size was 35 mm (range: 3–335 mm). According to the 2009 International Federation of Obstetrics and Gynecology (FIGO) criteria, 245 cases were defined as stage IA, 271 as stage IB, and 34 as stage II. The 5-year disease-free survival (DFS) rate was 92% and the 5-year disease-specific survival (DSS) rate was 99%. The effects of prognostic factors on DFS were evaluated. Older age, stage II disease, deep myometrial invasion, and receiving adjuvant radiotherapy were associated with decreased DFS. There was no statistically significant association between tumor size and DFS. The 5-year DFS for patients with a tumor diameter of <35 mm, which was the median tumor size of the entire group, was 94%, while it was 89% for patients having a tumor diameter of >35 mm (P = 0.128)., Conclusion: Tumor size was not a risk factor predicting recurrence in patients with stage I or II endometrioid-type endometrial cancer who had lymphadenectomy., Competing Interests: none declared, (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background: This study aims to evaluate the effect of quantitative volumetric metabolic measurements in F-18 fluorodeoxyglucose positron emission tomographycomputed tomography to distinguish benign and malignant solitary pulmonary nodules., Methods: We retrospectively reviewed 78 patients (56 males; 22 females; mean age 61±11.9 years; range, 32 to 82 years) with solitary pulmonary nodules who underwent F-18 fluorodeoxyglucose positron emission tomography-computed tomography. Patients were classified as benign, malignant and metastatic lesions according to pathology results. Metabolic volume, maximum standardized uptake value, mean standardized uptake value, maximum metabolic index and mean metabolic index were measured. Mean, median and standard error values were calculated for each group. Nonparametric tests were used for the comparison of each group. Partial correlation analysis was used for the relationship between parameters. For all parameters, cut-off values were obtained with receiver operating characteristic analysis., Results: Of 78 lesions, 10 were benign (12.8%), 38 were primary lung carcinoma (48.7%) and 30 were metastatic lung nodules (38.5%). There was a significant difference between benign lesions and primary lung cancer and between primary lung cancer and metastatic groups in all parameters (p<0.05). We determined highly significant positive correlation between maximum standardized uptake value and maximum metabolic index (r=0.73; p<0.05), and moderate positive correlation between mean standardized uptake value and mean metabolic index (r=0.56; p<0.05). In receiver operating characteristic analysis, maximum standardized uptake value and mean standardized uptake value were found to be the most sensitive and specific methods for benign/malignant discrimination. In the cut-off value=2.59, the sensitivity and specificity for maximum standardized uptake value were 98.0% and 91.7%, respectively. In the cut-off value=1.65, the sensitivity and specificity for mean standardized uptake value were 94.0% and 91.7%, respectively., Conclusion: Maximum metabolic index value is highly correlated with maximum standardized uptake value in benign/malignant solitary pulmonary nodules discrimination by F-18 fluorodeoxyglucose positron emission tomographycomputed tomography. Maximum metabolic index can also be used for discrimination of primary/metastatic malignant lesions., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2019, Turkish Society of Cardiovascular Surgery.)

18 F-FDG PET/CT scanning was performed for the primary staging of a 47-year-old man with urothelial carcinoma. The patient underwent biopsy by ureteroscopy 15 days ago and the PET images revealed 18 F-FDG accumulation in the right retroperitenal region, compatible with an “urinoma”.

Objective: To evaluate the necessity of adjuvant therapy and other prognostic factors in high-grade uterine corpus-confined endometrial cancer (EC) with lymphadenectomy performed., Materials and Methods: This study included 120 patients who had endometrioid-type grade 3, serous-type, clear cell-type, and undifferentiated-type EC and underwent lymphadenectomy., Results: Patients with high-grade uterine corpus-confined EC who underwent lymphadenectomy were evaluated. The modality of adjuvant therapy performed was not a predictor for the site of recurrence. The loco-regional recurrence rate decreased from 9.5% to 3.8% in patients who received radiotherapy. However, this difference was not statistically significant (p=0.206). In addition, performing adjuvant chemotherapy did not alter the risk of extrapelvic recurrence. Only International Federation of Gynecology and Obstetrics 2009 stage was significant in the univariate analysis. On the other hand, age, tumor type, number of removed lymph nodes, presence of myometrial and lymphovascular space invasion, tumor size and adjuvant therapy modality were not related with disease-free survival., Conclusion: Performing adjuvant therapy and therapy modality does not improve oncologic outcomes in intermediate and high-risk patients. However, radiotherapy reduced the risk of local recurrence by more than 50%. Vaginal brachytherapy was efficient as external beam radiotherapy. Therefore, vaginal brachytherapy should be used for these patients in order to reduce loco-regional recurrence even if it is not reported to be effective on disease-free survival., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2019 by Turkish Society of Obstetrics and Gynecology | Turkish Journal of Obstetrics and Gynecology published by Galenos Publishing House.)

Objectives: Patients with head and neck cancer (HNC) have a high risk of sarcopenia, which is associated with poor prognosis. Skeletal-muscle area and index at the third lumbar (L3) vertebra level (L3MA and L3MI) are recommended for the detection of sarcopenia. However, L3 level is not included in many imaging protocols and there are no data for optimal levels and cutoffs for the diagnosis of sarcopenia in head and neck computed tomography (HNCT) scans. Our aim was to assess the relationship between cervical paravertebral muscle values and L3MI and to investigate optimal level to diagnose sarcopenia on HNCTs., Methods: Patients with HNC (n=159) who underwent positron emission tomography-CT for tumor staging were retrospectively analyzed. On CT images, paravertebral and sternocleidomastoid muscle areas at second (C2), third (C3), and fourth (C4) cervical vertebrae levels (C2MA, C3MA, C4MA, SCMA) and L3MA were measured. Cross-sectional areas were normalized for stature (muscle area/height square) and muscle index (C2MI, C3MI, C4MI, SCMI, L3MI) values were obtained. Spearman correlation and linear regression analyses were used for assessing correlations. To calculate the diagnostic performance of SCMI, C2MI, C3MI, and C4MI for the diagnosis of sarcopenia with respect to the cutoffs of L3MI, receiver operating characteristic (ROC) analysis was used., Results: Males had significantly higher muscle areas than females. Although C2MI, C3MI, C4MI, and SCMI values all showed very strong and significant correlation with L3MI (P<0.001). According to the ROC analysis, the best discriminative for sarcopenia was C3MI in males (area under curve [AUC], 0.967) and SCMI in females (AUC, 0.898)., Conclusion: C2MI, C3MI, C4MI, and SCMI values can be used as alternatives for the diagnosis of sarcopenia in routine HNCT examinations.

Aim: To evaluate the clinical characteristics and outcome of ovarian Sertoli-Leydig cell tumors (SLCTs) managed at a single institution., Methods: The hospital records of 17 patients with the diagnosis of ovarian SLCT between 1994 and 2018 were reviewed retrospectively., Results: The median age of the patients was 30 years (range, 18-67 years). All the patients had unilateral tumors. All of the 17 were stage 1 tumors. Two (11.8%) patients were stage 1C1 and two (11.8%) patients were stage 1C2. Thirteen (76.5%) patients were stage 1A. Three (17.6%) of the tumors were well differentiated, 11 (64.7%) were intermediately differentiated, 1 (5.9%) was poorly differentiated, and the degree of the differentiation was not identified for 2 (11.8%) patients. One showed retiform pattern and one had heterologous elements at the histopathologic evaluation. Among the 17 patients, we identified structural/vascular renal and ureteral anomalies in 3 (17.6%) patients. Eight patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, seven underwent unilateral salpingo-oophorectomy or oophorectomy and two underwent cystectomy with or without additional surgical staging procedures. Four patients received adjuvant chemotherapy. All the 17 patients were alive and free of disease for 1-287 months after the diagnosis. Median follow-up time was 78 months. None of the patients recurred., Conclusion: Sertoli-Leydig cell tumors are rare ovarian malignancies with low recurrence rates and have a favorable outcome compared to malignant epithelial tumors of the ovary. Main treatment is surgical resection and it is appropriate to prefer fertility sparing conservative surgeries for young patients., (© 2019 Japan Society of Obstetrics and Gynecology.)

Objective: Learning and memory performance have been reported to be impaired in patients with Major Depressive Disorder (MDD). Impairments are associated with diminished psychosocial functioning. Based on the processing-speed theory, we aimed to examine whether processing speed mediates the relationship between depression status and verbal, visuo-spatial and working memory impairment., Methods: A neuropsychological test-battery was administered to 106 patients with current MDD, 119 patients with remitted MDD and 120 healthy controls to assess processing speed, learning and memory performance. To examine the impact of diagnosis status and processing speed on learning and memory performance, simple mediation models were computed., Results: Currently depressed patients with MDD showed partially slowed processing speed, impaired short-term verbal and visuo-spatial memory performance compared to healthy controls. A basic deficit in processing speed mediated the relationship between depression status and verbal, visuo-spatial, and working memory impairment. However, there was no processing speed or memory impairment in patients with remitted MDD., Conclusion: Processing speed is an important factor regarding learning and memory impairment in patients with current MDD. Thereby, our results highlight novel targets for treatment of diminished learning and memory performance via enhancement of processing speed using pharmacological as well as therapeutic interventions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Schizotypy is a multidimensional risk phenotype distributed in the general population, constituting of subclinical, psychotic-like symptoms. It is associated with psychosis proneness, and several risk genes for psychosis are associated with schizotypy in non-clinical populations. Schizotypy might also modulate cognitive abilities as it is associated with attentional deficits in healthy subjects. In this study, we tested the hypothesis that established genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737 are associated with psychometric schizotypy and that schizotypy mediates their effect on attention or vice versa. In 615 healthy subjects from the FOR2107 cohort study, we analysed the genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737, psychometric schizotypy (schizotypal personality questionnaire-brief SPQB), and a neuropsychological measure of sustained and selective attention (d2 test). ZNF804A rs1344706 C (non-risk) alleles were significantly associated with higher SPQ-B Cognitive-Perceptual subscores in women and with attention deficits in both sexes. This schizotypy dimension also mediated the effect of ZNF804A on attention in women, but not in men. CACNA1C rs1006737-A showed a significant sex-modulated negative association with Interpersonal schizotypy only in men, and no effect on attention. Our multivariate model demonstrates differential genetic contributions of two psychosis risk genes to dimensions of schizotypy and, partly, to attention. This supports a model of shared genetic influence between schizotypy and cognitive functions impaired in schizophrenia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Theoretical background: The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age onward changes are detectable and if alterations may interact with cognitive deficits in major depressive disorder (MDD). The current work investigated the effect of APOE ε4 homozygosity on visuospatial working memory (vWM) capacity, and on hippocampal morphometry. Furthermore, potential moderating roles of age and MDD were assessed. Methods: A sample of n = 31 homozygous ε4 carriers was contrasted with n = 31 non-ε4 carriers in a cross-sectional design. The sample consisted of non-demented, young to mid-age participants (mean age = 34.47; SD = 13.48; 51.6% female). Among them were n = 12 homozygous ε4 carriers and n = 12 non-ε4 carriers suffering from MDD (39%). VWM was assessed using the Corsi block-tapping task. Region of interest analyses of hippocampal gray matter density and volume were conducted using voxel-based morphometry (CAT12), and Freesurfer, respectively. Results: Homozygous ε4 carriers showed significantly lower Corsi span capacity than non-ε4 carriers did, and Corsi span capacity was associated with higher gray matter density of the hippocampus. APOE group differences in hippocampal volume could be detected but were no longer present when controlling for total intracranial volume. Hippocampal gray matter density did not differ between APOE groups. We did not find any interaction effects of age and MDD diagnosis on hippocampal morphometry. Conclusion: Our results point toward a negative association of homozygous ε4 allele status with vWM capacity already during mid-adulthood, which emerges independently of MDD diagnosis and age. APOE genotype seems to be associated with global brain structural rather than hippocampus specific alterations in young- to mid-age participants.

Combination of signals based on their reliability is an increasingly popular model for sensorimotor processing. However, how reliability is estimated, or how such estimation is affected by prolonged exposure to noisy inputs, is still unknown. In this study, we compare patients with unilateral functional amblyopia with control subjects tracking either a reliable target, or a blurry, unreliable target, in a task of repeated, sustained smooth pursuit. We provide evidence for a lower weight of visual information during smooth pursuit in amblyopic and control subjects tracking a blurry target, with no significant difference of prior information weight. In contrast, we found no evidence of lower visual information weight in the catch-up saccades of amblyopic subjects. We conclude that oculomotor performance in unilateral amblyopia mostly lays within the continuum between our control groups, without significant differences in the relative weights of prior and visual information. However, smooth pursuit exhibits additional deficits that might result from abnormal visual development., (© 2019 Elsevier B.V. All rights reserved.)

Background: Nonketotic hyperglycinemia (NKH) is an autosomal recessive severe life-threatening catostrophic metabolic disorder., Materials and Methods: The present study was conducted in a tertiary reference center in Turkey for six years period. The accurate diagnosis of six NKH patients was based on clinical history of the patients, neurological examinations, seizure semiology, serial electroencephalography (EEG) recordings, neuroimaging findings, metabolic tests and genetic analysis., Results: The common clinical findings were hypotonia with severe head lag, poor feeding, poor sucking, and intractable seizures. The starting age of the symptoms was between birth and 45 days of age (median: 8 days). The starting age of the seizures was between 30 min of age and 45 days of age (median: 18 days). The age of accurate diagnosis was between 1 month of age and 5.5 months of age (mean: 3.75 ± 1.69 months). The cerebrospinal fluid (CSF) to plasma GLY ratio of the patients was between 0.031 and 0.21 (median: 0.16). The EEG patterns of the patients were suppression-burst, hypsarrhythmia, multifocal epileptic activity, and right centro-occipital epileptic activity on admission. The neuroimaging findings were diffuse hypomyelination, corpus callosum (CC) hypoplasia, CC agenesis and brainstem hypoplasia on the magnetic resonance imaging and glycine peak was evidenced on magnetic resonance spectroscopy. Four of the patients were mutation-positive., Conclusions: If a child is encephalopathic and/or hypotonic with severe head lag, early evaluation of the EEG records should be made even without a history of clinical seizures. The disease has a heterogenous course and the clinical outcome depends on the mutation type., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years. The Cat12 toolbox was used to analyze longitudinal data (p < 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; > 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.

Objectives: During mid-trimester, it is necessary to terminate pregnancy due to some fetal anomalies and intrauterine death. Therefore, in this study, we aimed to compare abortion induction methods and combined use retrospectively., Methods: About 112 out of 223 pregnant patients were included in the study. The groups were determined as follows: Group 1 including pregnant patients who were administered misoprostol only (50 patients), Group 2 including pregnant patients who were administered single dose misoprostol (according to FIGO) and subsequently received cervical Foley catheter (30 patients), and Group 3 including pregnant patients who received Foley catheter only (32 patients). These three groups were compared in terms of effectiveness of the method, side effects, and complications as well as their characteristics., Results: In terms of characteristic of the groups, the average age of the women in the Group 1 was significantly higher than other two groups ( p  < 0.001). In terms of effectiveness of the method, the termination period in Groups 1 and 2 was significantly lower than Group 3 ( p  < 0.001). However, in terms of complications, it was observed that uterine rupture was developed in Group 1., Conclusions: Although medical methods may seem to be more effective in the process of termination, mechanical methods seem more reliable in terms of reliability. Especially combined methods can be used to increase effectiveness and also to reduce complications.

Schizophrenia is a disorder with a high heritability. Patients as well as their first degree relatives display lower levels of performance in a number of cognitive domains compared to subjects without genetic risk. Several studies could link these aberrations to single genetic variants, however, only recently, polygenic risk scores as proxies for genetic risk have been associated with cognitive domains and their neural correlates. In the present study, a sample of healthy subjects (n=137) performed a letter version of the n-back task while scanned with 3-T fMRI. All subjects were genotyped with the PsychChip and polygenic risk scores were calculated based on the PGC2 schizophrenia GWAS results. Polygenic risk for schizophrenia was associated with a lower degree of brain activation in prefrontal areas during the 3-back compared to the 0-back baseline condition. Furthermore, polygenic risk was associated with lower levels of brain activation in the right inferior frontal gyrus during the 3-back compared to a 2-back condition. Polygenic risk leads to a shift in the underlying activation pattern to the left side, thus resembling results reported in patients with schizophrenia. The data may point to polygenic risk for schizophrenia being associated with brain function in a cognitive task known to be impaired in patients and their relatives., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Patients suffering from major depressive disorder (MDD) show deficits in working memory (WM) performance accompanied by bilateral fronto-parietal BOLD signal changes. It is unclear whether patients with a first depressive episode (FDE) exhibit the same signal changes as patients with recurrent depressive episodes (RDE)., Methods: We investigated seventy-four MDD inpatients (48 RDE, 26 FDE) and 74 healthy control (HC) subjects performing an n-back WM task (0-back, 2-back, 3-back condition) in a 3T-fMRI., Results: FMRI analyses revealed deviating BOLD signal in MDD in the thalamus (0-back vs. 2-back), the angular gyrus (0-back vs. 3-back), and the superior frontal gyrus (2-back vs. 3-back). Further effects were observed between RDE vs. FDE. Thus, RDE displayed differing neural activation in the middle frontal gyrus (2-back vs. 3-back), the inferior frontal gyrus, and the precentral gyrus (0-back vs. 2-back). In addition, both HC and FDE indicated a linear activation trend depending on task complexity., Conclusions: Although we failed to find behavioral differences between the groups, results suggest differing BOLD signal in fronto-parietal brain regions in MDD vs. HC, and in RDE vs. FDE. Moreover, both HC and FDE show similar trends in activation shapes. This indicates a link between levels of complexity-dependent activation in fronto-parietal brain regions and the stage of MDD. We therefore assume that load-dependent BOLD signal during WM is impaired in MDD, and that it is particularly affected in RDE. We also suspect neurobiological compensatory mechanisms of the reported brain regions in (working) memory functioning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Major depressive disorder (MDD) patients show impairments of cognitive functioning such as working memory (WM), and furthermore alterations during WM-fMRI tasks especially in frontal and parietal brain regions. The calculation of a polygenic risk score (PRS) can be used to describe the genetic influence on MDD, hence imaging genetic studies aspire to combine both genetics and neuroimaging data to identify the influence of genetic factors on brain functioning. We aimed to detect the effect of MDD-PRS on brain activation during a WM task measured with fMRI and expect healthy individuals with a higher PRS to be more resembling to MDD patients., Method: In total, n=137 (80 men, 57 women, aged 34.5, SD=10.4years) healthy subjects performed a WM n-back task [0-back (baseline), 2-back and 3-back condition] in a 3T-MRI-tomograph. The sample was genotyped using the Infinium PsychArray BeadChip and a polygenic risk score was calculated for MDD using PGC MDD GWAS results., Results: A lower MDD risk score was associated with increased activation in the bilateral middle occipital gyri (MOG), the bilateral middle frontal gyri (MFG) and the right precentral gyrus (PCG) during the 2-back vs. baseline condition. Moreover, a lower PRS was associated with increased brain activation during the 3-back vs. baseline condition in the bilateral cerebellum, the right MFG and the left inferior parietal lobule. A higher polygenic risk score was associated with hyperactivation in brain regions comprising the right MFG and the right supplementary motor area during the 3-back vs. 2-back condition., Discussion: The results suggest that part of the WM-related brain activation patterns might be explained by genetic variants captured by the MDD-PRS. Furthermore we were able to detect MDD-associated activation patterns in healthy individuals depending on the MDD-PRS and the task complexity. Additional gene loci could contribute to these task-dependent brain activation patterns., (Copyright © 2017 Elsevier Inc. All rights reserved.)

MRPS22 gene defect is a very rare newly discovered mitochondrial disorder. We report a 4-month-old severely affected male infant with MRPS22 mutation. Whole exome sequencing revealed a novel homozygous splicing mutation c.339 + 5 G > A in MRPS22 gene. He has mild dysmorphism, hypotonia, developmental delay but not hypertrophic cardiomyopathy and tubulopathy which differ from other majority of reported patients. Therefore, hypertrophic cardiomyopathy and tubulopathy may not be considered as constant features of MRPS22. With this case report, we also present first symmetrical bilateral brainstem and medial thalamic lesions, and cerebellar and cerebral atrophy on a brain MR imaging follow-up of ten months.

Various typical and atypical neurological manifestations can be seen as the initial symptoms of celiac disease (CD). We suggest that gluten toxicity is the most suspicious triggering risk factor for probable pathophysiological pathways of neurological involvement in atypical CD. The medical charts of 117 patients diagnosed with atypical CD were retrieved from a tertiary center in Ankara, Turkey. Eight patients reported as having neurologic manifestations as initiating symptoms were evaluated in detail. The initial neurological manifestations of CD in our study included atypical absence, which was reported first in this study, generalized tonic-clonic seizures, complex partial seizures, severe axial hypotonia and down phenotype, multifocal leukoencephalopathy, mild optic neuritis, attention deficit hyperactivity disorder, and short duration headaches. Seizures mostly emphasizing atypical absence could be the initial presentation manifestation of CD, first described in this literature. Gluten toxicity could be one of the most powerful triggering factors for developing epilepsy in CD. Learning disorders such as attention deficit hyperactivity disorder, short duration headaches, mild optic neuritis, encephalopathy, and DS could also be the initial neurological manifestations of atypical CD. A gluten-restricted diet may improve neurological complaints, epileptic discharges, and neuropsychiatric symptoms. All we found may be a small part of the full range of neurological disorders of unknown origin related to CD. Clinical suspicion should be the rule for accurate diagnosis of the disease.