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The common fig (Ficus carica L.) is a tree species and is one of the oldest fruit trees cultivated in Turkey. The Western Anatolian region of Turkey produces nearly a quarter of the total dried fig production of the world. This region also harbours a rich fig germplasm. However, so far this germplasm has remained largely uncharacterised. In this study, using 14 simple sequence repeat (SSR) primer pairs, we analysed a total of 310 fig accessions from six different regions of Anatolia. In structure analyses, Western Anatolian accessions formed a group, which was correlated with their geographical distribution. In addition, 7 identical, 36 synonymous, and 22 homonymous fig accessions were identified. In multilocus lineages (MLLs) analysis a total of 54 accessions were matched to different accessions as clone assignment. The results will facilitate future germplasm management and breeding efforts in this economically important tree species by identifying genetic diversity, genetic relations and characterising the structure of studied populations and accessions.

Consanguineous marriages have a prevalence rate of 24% in Turkey. These carry an increased risk of autosomal recessive genetic conditions, leading to severe disability or premature death, with a significant health and economic burden. A definitive molecular diagnosis could not be achieved in these children previously, as infrastructures and access to sophisticated diagnostic options were limited. We studied the cause of neurogenetic disease in 246 children from 190 consanguineous families, recruited in three Turkish hospitals between 2016 and 2020. All patients underwent deep phenotyping and trio whole exome sequencing, and data were integrated in advanced international bioinformatics platforms. We detected causative variants in 119 known disease genes in 72% of families. Due to overlapping phenotypes 52% of the confirmed genetic diagnoses would have been missed on targeted diagnostic gene panels. Likely pathogenic variants in 27 novel genes in 14% of the families increased the diagnostic yield to 86%. Eighty-two% of causative variants (141/172) were homozygous, 11 of which were detected in genes previously only associated with autosomal dominant inheritance. Eight families carried two pathogenic variants in different disease genes. De novo (9.3%), X-linked recessive (5.2%) and compound heterozygous (3.5%) variants were less frequent compared to non-consanguineous populations. This cohort provided a unique opportunity to better understand the genetic characteristics of neurogenetic diseases in a consanguineous population. Contrary to what may be expected, causative variants were often not on the longest run of homozygosity and the diagnostic yield was lower in families with the highest degree of consanguinity, due to the high number of homozygous variants in these patients. Pathway analysis highlighted that protein synthesis/degradation defects and metabolic diseases are the most common pathways underlying paediatric neurogenetic disease. In our cohort 164 families (86%) received a diagnosis, enabling prevention of transmission and targeted treatments in 24 patients (10%). We generated an important body of genomic data with lasting impacts on the health and wellbeing of consanguineous families, and economic benefit for the healthcare system in Turkey and elsewhere. We demonstrate that an untargeted next generation sequencing approach is far superior to a more targeted gene panel approach, and can be performed without specialised bioinformatics knowledge by clinicians using established pipelines in populations with high rates of consanguinity. The project is supported by TUBITAK (The Scientific and Technological Research Council of Turkey) Project No. 216S771. YO is supported by the Turkish Academy of Sciences’ Young Investigator award, TÜBA-GEBİP (2017). PFC is a Wellcome Trust Principal Research Fellow (212219/Z/18/Z), and a UK NIHR Senior Investigator, who receives support from the Medical Research Council Mitochondrial Biology Unit (MC_UU_00015/9), the Leverhulme Trust (RPG-2018-408), an MRC research grant (MR/S035699/1), an Alzheimer's Society Project Grant (AS-PG-18b-022). This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). RH was supported by the European Research Council [309548], the Wellcome Investigator Award [109915/Z/15/Z]. the Medical Research Council (UK) [MR/N025431/1]; the Wellcome Trust Pathfinder Scheme [201064/Z/16/Z], the Newton Fund [UK/Turkey, MR/N027302/1], the Lily Foundation and the Evelyn Trust. HL receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). Sequencing and analysis were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141. Data was analysed using the RD-Connect Genome-Phenome Analysis platform developed under FP7/2007-2013 funded project (grant agreement nº 305444) and funding from EJP-RD and INB/ELIXIR-ES. The study was further supported by the Horizon 2020 research and innovation program via grant 779257 “Solve-RD” (RH, SB, AT and HL). RH, PFC and YO were supported by an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1

Introduction: Nitisinone used in alkaptonuria (AKU) can result in keratopathy due to strongly increased tyrosine levels. Methods: This study aimed to investigate nutritional status and changes in plasma tyrosine and phenylalanine and urinary homogentisic acid (u-HGA) levels in 8 adult AKU patients (mean age, 56.3 ± 4.7 years) who were on tyrosine/phenylalanine-restricted diet together with 2 mg/day nitisinone. Results: The treatment period was 23.4 ± 6.9 months. Daily dietary protein intake was restricted to 0.8–1.0 g/kg/day. Daily tyrosine intake was restricted to 260–450 mg/day for females and 330–550 mg/day for males. Tyrosine/phenylalanine-free amino acid supplements accounted for an average of 56.1% of daily protein intake. The following assessments were performed: anthropometric and plasma tyrosine level measurements every 2 months; ophthalmological examination every 6 months, and nutritional laboratory analyses and measurements of plasma amino acids and u-HGA once in a year. It was targeted to keep the plasma tyrosine level 700 μmol/L was detected. The u-HGA level before and after the 1st year of treatment was 1,429.3 ± 1,073.4 mmol/mol creatinine and 33.6 ± 9.5 mmol/mol creatinine, respectively. None of the patients developed keratopathy or experienced weight loss and protein or micronutrient deficiency. Conclusion: AKU patients should receive tyrosine/phenylalanine-restricted diet for reducing plasma tyrosine level to the safe range. Tyrosine/phenylalanine-free amino acid supplements can be safely used to enhance dietary compliance. Keratopathy and nutrient deficiency should be frequently monitored.

International audience; This article studies the distribution problem of brick-and-mortar retailers aiming to integrate the online channel into their operations. The article presents an integrated modeling approach addressing the online channel-driven distribution network deployment (e-DND) problem under uncertainty. The e-DND involves decisions on operating fulfillment platforms and on assigning a fulfillment mission to those platforms, while anticipating the revenues and costs induced by order fulfillment, replenishment, delivery, and inventory holding. To model this problem while taking into account the uncertain nature of multi-item online orders, store sales, and capacities, a two-stage stochastic program with mixed-integer recourse is developed. Two alternative deployment strategies, characterized by allocation of orders, inventory positioning, delivery schema, and inbound flow pattern decisions, are investigated using this model. The first deployment strategy investigates the ship-from stores practice where the on-hand inventory is used for all sales channels. The second deployment strategy additionally considers the advanced positioning of inventory at a fulfillment center in the urban area where the online orders are requested. To solve the two-stage stochastic model with integer recourse, an exact solution approach combining scenario sampling and the integer L-shaped method is proposed. Numerical results, inspired by the case of a European retailer, are provided to evaluate the performance of the deployment strategies and the efficiency of the proposed solution approach.

Intercellular adhesion is the key to multicellularity, and its malfunction plays an important role in various developmental and disease-related processes. Although it has been intensively studied by both biologists and physicists, a commonly accepted definition of cell-cell adhesion is still being debated. Cell-cell adhesion has been described at the molecular scale as a function of adhesion receptors controlling binding affinity, at the cellular scale as resistance to detachment forces or modulation of surface tension, and at the tissue scale as a regulator of cellular rearrangements and morphogenesis. In this review, we aim to summarize and discuss recent advances in the molecular, cellular, and theoretical description of cell-cell adhesion, ranging from biomimetic models to the complexity of cells and tissues in an organismal context. In particular, we will focus on cadherin-mediated cell-cell adhesion and the role of adhesion signaling and mechanosensation therein, two processes central for understanding the biological and physical basis of cell-cell adhesion.

Mentorship is experience and/or knowledge-based guidance. Mentors support, sponsor and advocate for mentees. Having one or more mentors when you seek advice can significantly influence and improve your research endeavours, well-being and career development. Positive mentee-mentor relationships are vital for maintaining work-life balance and success in careers. Early-career researchers (ECRs), in particular, can benefit from mentorship to navigate challenges in academic and nonacademic life and careers. Yet, strategies for selecting mentors and maintaining interactions with them are often underdiscussed within research environments. In this Words of Advice, we provide recommendations for ECRs to seek and manage mentorship interactions. Our article draws from our experiences as ECRs and published work, to provide suggestions for mentees to proactively promote beneficial mentorship interactions. The recommended practices highlight the importance of identifying mentorship needs, planning and selecting multiple and diverse mentors, setting goals, and maintaining constructive, and mutually beneficial working relationships with mentors.

Background Vitamin B12 deficiency frequently appears in phenylketonuria patients having a diet poor in natural protein. The aims of this study were to evaluate vitamin B12 status in phenylketonuria patients by using combined indicator of vitamin B12 status (cB12) as well as methylmalonic acid and homocysteine, more specific and sensitive markers, in comparison with healthy controls. Methods Fifty-three children and adolescents with phenylketonuria under dietary treatment and 30 healthy controls were assessed cross-sectionally. Serum vitamin B12 and folate concentrations were analysed by chemiluminescence immunoassay. Plasma methylmalonic acid and total homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry and liquid chromatography, respectively. cB12 was calculated by using a formula involving blood parameters. Results Methylmalonic acid and folate concentrations in phenylketonuria group were higher compared with controls. Methylmalonic acid concentrations were high in 56.5% of the patients and 26.7% of the controls with normal vitamin B12 concentrations. Based on cB12, a significant difference within the normal values was detected between the groups. However, although 24.5% of phenylketonuria patients and 13.3% of controls had decreased vitamin B12 status according to cB12, there was no significant difference. Conclusion Children and adolescents with phenylketonuria having a strict diet can be at risk of functional vitamin B12 deficiency. This deficiency can be accurately determined by measuring methylmalonic acid concentrations. Calculation of cB12 as a biochemical index did not provide additional information compared with the measurement of methylmalonic acid alone, but may be helpful for classification of some patients with increased methylmalonic acid as having adequate vitamin B12 status.

This paper presents a chemometrics-assisted optimization study to improve the separation of tocopherol (-T) and tocotrienol (-TT) homologues on a C30 stationary phase in reversed-phase HPLC. The HPLC settings were optimized using a central composite design and the response surface methodology. Flow rate, column temperature, and mobile phase composition were chosen as independent variables. Peak resolution (Rs), analysis time (tR), and peak symmetries of the tocopherol isomers were chosen as response variables. Optimum performance in terms of Rs was obtained at a flow rate of 0.31 mL min?1, a temperature of 8.70 °C, and % B content (methyl tert-butyl ether: methanol: water, 80:18:2, v/v/v) in the mobile phase of 38.12%. The analysis of variance and regression analysis gave adjusted R2 values of 0.9841 for Rs, 0.9850 for tR-(?-T), 0.9853 for tR-(?-T), and 0.9204 for the peak symmetry of ?-T. This confirms the good agreement of experimental data with predicted values. The close eluting peaks of ?-/?-tocol could be baseline separated at the optimized conditions at a minimized analysis time. Empirical second-order polynomial models were derived that gave statistically high significances (P < 0.0001). Hence, the models can be successfully employed to predict the optimum separation conditions of co-eluting peaks of ?-/?-tocols. The optimized method was successfully applied to determine the individual tocol homologues in various cold pressed edible oils. Total contents ranged from 15 to almost 2600 mg tocol kg?1 oil. 18-M-17 Acknowledgements This article is supported financially by the Scientific Research Project Center of Karamanoglu Mehmetbey University (Project number 18-M-17). The authors would also like to thank the Scientific and Technological Research Council of Turkey (TUBITAK) under the 2219 Research Fellowship Program for International Postdoctoral stays for providing the financial scholarship support to carry out this research work.

WOS:000560919000021 A fluorogenic probe based on a coumarin-derivative for Cu2+ sensing in CH3CN/H2O media (v/v, 95/5, 5.0 mu M) was developed and applied in real samples. 3-(4-chlorophenyl)-6,7-dihydroxy-coumarin (MCPC) probe was obtained by synthetic methodologies and identified by spectral techniques. The probe MCPC showed remarkable changes with a "turn-off" fluorogenic sensing approach for the monitoring of Cu2+ at 456 nm under an excitation wavelength of 366 nm. The response time of the probe MCPC was founded as only 1 min The detection limit of the probe MCPC was recorded to be 1.47 nM. The binding constant and possible stoichiometric ratio (1:1) values were determined by Benesi-Hildebrand and Job's plot systems, respectively. The mechanism of the probe MCPC with Cu2+ was further confirmed by ESI-MS and FT-IR analyses, as well as supported by theoretical calculations. Furthermore, the probe MCPC was successfully employed for the practical applications to sense Cu2+ in different herbal and black tea samples. The proposed sensing method was also verified by ICP-OES method This work was supported by the Karamanoglu Mehmetbey University (KMU) with the financial support to use Gaussian-09 and GaussView-5.0.8 software packages (KMU BAP-Grant Number: 30-M-16 and 13-YL-18) and by the Scientific and Technological Research and Council of Turkey (TUBIITAK) (Grant Number: 110T652).

Pozadina istraživanja. Upotreba pšeničnih klica i njihovog ulja ograničena je zbog velike aktivnosti enzima u klicama i prisutnosti nezasićenih masnih kiselina u ulju, što zahtijeva primjenu stabilizacijskih tehnika. Eksperimentalni pristup. U ovom su istraživanju procijenjeni učinci metoda stabilizacije (suho zagrijavanje u konvekcijskoj pećnici na 90 i 160 °C, mikrovalno zračenje na 180 i 360 W i uparavanje u autoklavu) na pšenične klice i njihovo ulje. Rezultati i zaključci. Uparavanje je prouzročilo najdramatičnije promjene aktivnosti lipoksigenaze, udjela slobodnih masnih kiselina, aktivnosti uklanjanja radikala DPPH i masenih udjela tokoferola i tokotrienola. Niži peroksidni broj izmjeren je u uzorcima ulja obrađenim konvekcijskim zagrijavanjem (160 °C) i parom na temperaturama iznad 100 °C. Međutim, vrijednosti p-anisidina u uzorcima tretiranim na višim temperaturama bile su znatno veće od onih u uzorcima stabiliziranim pri nižim temperaturama. Zagrijavanje u pećnici na 160 °C je nakon uparavanja bilo jedno od najučinkovitijih postupaka za inaktivaciju lipoksigenaze. Primjena pare bitno je smanjila maseni udjel ukupnih tokoferola, što je izravno povezano s povećanim gubitkom β-tokoferola. Suprotno tome, pronađeno je znatno više γ- i δ-tokoferola te homologa tokotrienola u uparenim uzorcima. Izomeri najotporniji na procese stabilizacije bili su α-tokoferol i γ-tokotrienol. Novina i znanstveni doprinos. Ovo istraživanje pokazuje da metoda zagrijavanja u pećnici na visokoj temperaturi, koja se često koristi u industriji za toplinsku stabilizaciju pšeničnih klica, ne poboljšava njihovu oksidacijsku stabilnost u usporedbi s obradom parom i mikrovalovima. Uparavanje odgađa oksidacijske procese u klici te inhibira aktivnost lipoksigenaze, a osim toga smanjuje gubitak tokotrienola. Za industrijsku se primjenu preporučuje uporaba mikrovalne pećnice male snage (180 umjesto 360 W) i zagrijavanje u pećnici na nižoj temperaturi (90 umjesto 160 °C)., Research background. Utilization of wheat germ and wheat germ oil is limited due to high enzymatic activity and the presence of unsaturated fatty acids, which require stabilization techniques to overcome this problem. Experimental approach. In this study, the effects of stabilization methods (dry convective oven heating at 90 and 160 °C, microwave radiation at 180 and 360 W, and autoclave steaming) on both wheat germ and its oil were evaluated. Results and conclusions. Steaming caused the most dramatic changes in lipoxygenase activity, free fatty acid content, DPPH radical scavenging activity, and mass fractions of tocopherols and tocotrienols. Lower peroxide values were measured in the oil samples treated with convectional heating (160 °C) and steaming at temperatures above 100 °C. However, p-anisidine values of samples treated at higher temperatures were considerably greater than those of samples stabilized at lower temperatures. Oven heating at 160 °C was also one of the most effective treatments, after steaming, for the inactivation of lipoxygenase. Steaming significantly reduced mass fraction of total tocopherols, which was directly associated with the greater loss of β-tocopherol content. On the contrary, γ- and δ-tocopherol and tocotrienol homologues were abundant with higher amounts in steamed samples. α-Tocopherol and γ-tocotrienol were the most resistant isomers to stabilization processes. Novelty and scientific contribution. This study shows that the high temperature oven heating method, which is widely used in the industry for thermal stabilization of wheat germ, does not provide an advantage in oxidative stability compared to steaming and microwave applications. Steaming delayed oxidation in the germ, while further inhibiting lipoxygenase activity. Moreover, tocotrienols were more conservable. In industrial application, low-power microwave (180 instead of 360 W) and oven heating at lower temperature (90 instead of 160 °C) would be preferable.

Here we report the comparison of ATR-FTIR and synchronous fluorescence (SyF) spectroscopy combined with multivariate data analysis to detect the authenticity of cold pressed black cumin seed oil (BCSO) and quantify adulterant levels of soybean oil (SBO). Forty pure oils, as well as ninety six oil blends, were analyzed using FTIR and SyF spectroscopy in combination with PCA, SIMCA and PLSR analysis. A SIMCA model of fluorescence data provided an excellent classification for pure BCSO and other vegetable oils, such as sunflower oils (SFOs), soybean oils (SBOs), hazelnut oils (HNOs), cotton seed oils (CSOs), grape seed oil (GSOs) and virgin olive oils (VOOs) from different brands and origins, with 99% significance level. The limit for detection of SBO adulteration in BCSO by fluorescence spectroscopy was also below 5%. In the optimum for both techniques, the plots of actual versus predicted values exhibited high linearity. R2 and RMSEC of the PLSR calibration model for FTIR spectra were between 0.9250–0.9998 and 0.1685–4.4762, respectively. R2 and RMSEC values of the PLSR calibration model for SyF spectra were between 0.9764–0.9975 and 0.8189–2.5122.

Two simplified methods based on manual thermally–assisted hydrolysis and methylation (THM) GC and GC × GC with flame ionization detection (FID) were developed for the detection of mycobacteria and Mycobacterium tuberculosis (MTB) in sputum. A central composite design was employed to optimize the THM derivatization conditions. For the detection of MTB the known mycobacterial markers tuberculostearic acid (TBSA) and hexacosanoic acid (C26), as well as three MTB specific markers, the mycocerosates, were evaluated. We found that the optimum conditions for THM release of TBSA and C26 differ from those for maximum release of the mycocerosates. Higher reagent volumes, higher temperatures and longer incubation increase the mycocerosates yield. Application of these conditions unfortunately resulted in unacceptable safety hazards. A GC × GC–FID method was developed that allowed accurate detection of mycocerosates even at poor conversion yields of the derivatization reaction. Using spiked sputum samples from non–TB patients, the detection limit of the method based on TBSA and C26 was found to be comparable to that of microscopy, i.e. 104–105 bacteria/mL sputum. To validate the new test, we compared the results we found for fifteen sputum samples from patients from South Africa suspected of having tuberculosis with those of culture, the gold standard method. Based on the presence of TBSA and C26, all eight microscopy and culture positive samples, and even two microscopy negative but culture positive samples were positive by THM–GC–FID. All five microscopy and culture negative sputum samples were also negative for THM–GC–FID, giving a specificity of 100%. Using GC × GC–FID we could detect mycocerosates, the specific markers for MTB in seven out of ten MTB culture positive sputum samples. The five culture negative cases were also negative for mycocerosates in manual THM–GC × GC–FID giving again 100% specificity. The results obtained indicate that the new methods hold great potential for the early diagnosis of TB in developing countries.

Introduction: Several case reports stress that high-dose biotin causes incorrect laboratory results. However, the extent of this interference in children is not systematically studied. Aim: To assess factors associated with biotin interference on thyroid function tests in subjects with biotinidase deficiency. Method: The study included 44 children who were treated with oral biotin (Group 1, median dose: 10 mg/day [25–75p; 10–10], age: 1.83 years [1.04–2.90]) and 30 healthy subjects (Group 2, age: 1.05 years [0.37–3.37]). Thyroid function tests were performed with two different assays, and streptavidin-coated particles were used in order to remove biotin from serum samples of cases with biotin interference. Results: The measurements were first performed with Beckman Coulter. In Group 1, remarkably high levels of fT3 and fT4 were found in 26 (59.1%) and 25 (56.8%) patients, respectively. Thyroid hormone functions were all normal in Group 2. Significantly higher serum biotin levels were detected in interference-positive children (p < 0.001). The serum biotin levels in Group 1 showed a strong positive correlation with fT3 (r = 0.867, p < 0.001) and fT4 levels (r = 0.905, p < 0.001). A serum biotin level of 80.35 µg/L was found to be the best cut-off value for predicting interference (sensitivity: 96.2% and specificity: 94.4%). When analyzed with Siemens Advia Centaur XP, all thyroid function tests were normal in both groups except in one patient (2.27%) with slightly elevated fT3 level in Group 1. Repeated tests with Beckman Coulter after neutralization of biotin with streptavidin magnetic particles in serum samples of the interference-positive cases revealed normal thyroid hormone levels. Conclusion: Interference is an important problem in thyroid function tests in nearly 60% of all children receiving biotin treatment for biotinidase deficiency. Serum levels of biotin rather than the dosage are the main determinant of interference, which can be eliminated by choosing appropriate laboratory methods.

WOS:000455514300006 This paper describes the feasibility of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy combined with multivariate data analyses for rapid determination of cold-pressed wheat germ oil (WGO) adulteration. Thirty-six pure edibleoils, as wellas 216 binary blends of WGO adulterated with cheaper refined oils, sunflower (SFO), and soybean oil (SBO) (1-50%) were analyzed by using ATR-FTIR spectroscopy in combination with PCA, LDA, SIMCA, and PLSR analyses. SIMCA models provide excellent classification for pure cold-pressed WGO and refined edible oil samples, with 95% significance level. The classification limits for detection of SFO and SBO adulterations in WGO were below 1%. Furthermore, a total of 100% of studied samples were correctly classified on the basis of their origin in calibration and in cross-validation by LDA models. Under the optimum conditions, the PLS-R plots of actual versus predicted values exhibited high linearity (R-2>0.9990). The content of SFO and SBO adulterants has been successively quantified using PLSR at levels

WOS:000468847900008 A new methodology is described herein that provides an experimentally simple, rapid, and cost-effective mass fingerprinting method for the assessment of edible oil authentication based on their fatty acid methyl ester (FAMEs). This analytical approach is based on the application of electron impact (EI) ionization-mass spectrometry (MS) without chromatographic separation, followed by the treatment of the spectral data via chemometrics analysis, linear discriminant analysis (LDA), principal component analysis (PCA), soft independent modeling of class analogies (SIMCA), and hierarchical cluster analysis (HCA). This fingerprinting analysis was applied by using a gas chromatography-mass spectroscopy instrument, without chromatographic column usage and ion identification; therefore, each measurement lasted about 1 min. All multivariate analyses provided excellent discriminations between the edible oil clusters with low classification error. LDA models constructed with six predictors and a total of 100% of edible oil samples from different brands were correctly classified. Furthermore, no misclassification was reported for the discriminant analysis in supervised SIMCA models with an accuracy of 95%. Thus, the present results pointed to the successful application of such methodology to detect, for the first time, authentication of the edible oils. Scientific Research Project Center of Karamanoglu Mehmetbey University [18-M-18]; Scientific Research Project Center of Ankara University; Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TUBITAK-116Z159]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) This study is supported financially by the Scientific Research Project Center of Karamanoglu Mehmetbey University (Project number 18-M-18). The authors would like to thank the Scientific Research Project Center of Ankara University and the Scientific and Technological Research Council of Turkey (TUBITAK) (Project number TUBITAK-116Z159) for providing the financial support to use the Unscrambler (R) X10.4 (CAMO software, Oslo, Norway) program. The authors would also like to thank TUBITAK under the 2219-Research Fellowship Program for International Postdoctoral for providing the financial support to carry out this research work.

Functional constipation is a clinical problem with an incompletely understood etiology. Functional bowel diseases have been shown to be related to inflammation in many studies in adults. In this study, we aimed to evaluate leukocytes, C-reactive protein, proinflammatory and anti-inflammatory cytokines, and neopterin levels in children with functional constipation. Seventy-six children with constipation and 71 healthy controls (mean age 7.12 ± 3.46 years and 7.32 ± 4.33 years, respectively, P = 0.991) were included in the study. Leukocytes, C-reactive protein, interleukin (IL)-1β, IL-6, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α) and neopterin levels were assessed in patients and healthy controls. Parameters were measured in the serum using enzyme-linked immunosorbent assay methods. Mean IL-6 (20.31 ± 12.05 vs. 16.2 ± 10.25 pg/mL, respectively, P = 0.003), IL-12 (181.42 ± 133.45 vs. 135.6 ± 83.67 pg/mL, respectively, P = 0.018) and neopterin levels (2.08 ± 1.12 vs. 1.52 ± 1.02 pg/mL, respectively, P = 0.001) were significantly higher in constipated children than healthy controls. Leukocyte and thrombocyte counts, C-reactive protein, and IL-1β, IL-10 and TNF-α levels did not show any difference between the two groups. In this study, IL-6, IL-12 and neopterin levels of constipated patients were found to be higher than those of controls. These results indicate the presence of subclinical inflammation in children with functional constipation.

Aims: To investigate the effect of ketogenic diet on motor function and daily living activities in children with epilepsy. Methods: A total of 62 children (median age 5.0 years) were enrolled. Motor function was assessed using the Gross Motor Function Measure (GMFM), and daily living activities and cognitive functions were assessed using the Functional Independence Measure (WeeFIM) before treatment and 3, 6, and 12 months after ketogenic diet treatment. Results: Significant improvement in total GMFM and WeeFIM scores ( P < .001) were found during the 12 months of ketogenic diet treatment. There was a positive correlation between total GMFM scores and WeeFIM scores at baseline (r= 0.792, P = .0001), and at 3 (r= 0.780, P = .0001), 6 (r= 0.744, P = .0001), and 12 months (r= 0.692, P = .0001) of treatment. Both the responder (50 patients, 80.7%) and nonresponder (12 patients, 19.3%) patient groups showed significantly higher GMFM and WeeFIM scores at 12 months of treatment compared to baseline values. A ≥50% reduction in seizure frequency was observed in 77.4%, 72.6%, and 80.7% of the patients after 3, 6, and 12 months of treatment, respectively. Conclusion: Ketogenic diet treatment improves motor functions and daily living activities in children with epilepsy during the 12 months of treatment.

Tay-Sachs disease is an autosomal recessive type of lysosomal storage disorder. The disease is very rare in Turkey, with an incidence of 0.54/100,000. The clinical manifestations of Tay-Sachs disease include progressive developmental delay, seizures, deafness, blindness, spasticity, and dystonia, which are caused by the accumulation of gangliosides in the central nervous system. To date, only one case indicating the association between Tay-Sachs disease and central precocious puberty has been reported. Although the mechanism of this association is not clear, it is thought to be due to ganglioside accumulation in the central nervous system or the inhibition of the hypothalamic inhibiting pathway. Herein, we report two patients with genetically proven Tay-Sachs disease who developed central precocious puberty during follow-up. Pubertal development in patients affected by Tay-Sachs disease should be carefully assessed.

WOS: 000442229500021, PubMed ID: 30101073, Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey (R) questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months. 53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, >= 26 weeks in 12% and < 17 weeks in 3%. Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development., Vitaflo, We thank Vitaflo for supporting the publication cost of this paper.

Objective: The aim of the present study was to evaluate the relationship between adipokines and perilipin (PLIN) polymorphisms with non-alcoholic fatty liver disease (NAFLD).

SummaryWhat is known and objective Carglumic acid is a structural analogue of human N-acetylglutamate, which has become an alternative therapeutic option for hyperammonaemia in organic acidaemias such as isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia, and it has been suggested in other urea cycle disorders such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase 1 deficiency. Case description A male newborn was diagnosed with citrullinemia after serum amino acid analyses revealed markedly elevated citrulline concentration together with homozygous p.Gly390Arg mutation in ASS1 gene. The ammonia concentration decreased and blood gas analysis normalized after peritoneal dialysis was performed for three days. Also, sodium benzoate, L-arginine and parenteral nutrition with glucose and lipid therapy were initiated. Until 1 year of age, low adherence to sodium benzoate therapy due to unpleasant taste caused hyperammonaemic episodes and obligated us to initiate carglumic acid (100 mg/kg/day) therapy. During treatment with carglumic acid, the median ammonia level was 45.6 µmol/L. The patient's treatment was switched from carglumic acid to sodium phenylbutyrate when he was 4.5 years old. Currently, the patient is 6.5 years old and remains under follow-up with sodium phenylbutyrate, L-arginine and protein-restricted diet. Plasma ornithine level was found to be significantly lower during the carglumic acid treatment compared to other treatments (P=.039). Also, glutamic acid was found to be higher during the sodium benzoate treatment period compared to other treatment periods (P=.024). What is new and conclusion To the best of our knowledge, this is the first report describing the long-term use of carglumic acid in a patient with argininosuccinate synthetase deficiency.

In the early years of phenylketonuria (PKU) treatment, mothers and healthcare professionals often decide to discontinue breastfeeding after the diagnosis of PKU in infants. It was believed to be the only effective way to monitor the infant's intake and allow for precise titration and measurement of the intake of phenylalanine (Phe). In the early 1980s, with the determination of low concentration of Phe in breast milk, breast milk supplemented with Phe-free formula has become an acceptable dietary treatment for infants with PKU. Today, breastfeeding is encouraged and well established in PKU patients. The aim of the present study is to investigate the prevalence and duration of breastfeeding, the effect of breastfeeding on serum Phe levels, and weight gain in infants with PKU.Data were collected from chart reviews. Medical records of 142 children with PKU diagnosed via the national neonatal screening program were analyzed retrospectively.Of the 41 infants with complete medical records, 40 (97.6%) were breastfed following delivery whereas only one (2.4%) was bottle fed. After the diagnosis, breastfeeding was continued in 25 (61%) infants with phenylalanine-free amino acid based protein substitute. The mean duration of breastfeeding was 7.4±4.0 (1-15) months. Serum Phe concentration of breastfed infants (280±163 μmol/L) was significantly lower than non-breastfed infants (490±199 μmol/L) (p0.001). Mean monthly weight gain in the first year of life was significantly higher in breastfed patients (493±159 g/month) compared to non-breastfed patients (399±116 g/month) (p=0.046).In the first year of life, weight gain and serum Phe levels were more favorable in breastfed infants with PKU compared to non-breastfed infants with PKU.

A combination of attenuated total reflectance–Fourier transform infrared (ATR–FTIR) spectroscopy and chemometric techniques was used to classify different trademarks of edible oils available on the Turkish markets. A total of 144 spectra of edible oil samples, including extra virgin olive oil (VOO), hazelnut oil (HNO), cottonseed oil (CSO), sunflower oil (SFO) and soybean oil (SBO), was recorded. The feasibility of ATR–FTIR with multivariate data analysis for discrimination of extra VOOs from other edible oils was also evaluated. Classification of edible oils was performed using principal components analysis (PCA), hierarchical cluster analysis (HCA), linear discriminant analysis (LDA) and soft independent modeling of class analogies (SIMCA). The spectra collected from wavelength region of 4000–650 cm-1 and 28 different wavelength ranges selected from full spectra were evaluated for optimal classification models. All multivariate analysis provided excellent discriminations between the edible oil classes with low classification error. LDA models constructed with five predictors, and a total of 100% of edible oil samples from different trademarks were correctly classified. Furthermore, no misclassification was reported for the discriminant analysis in supervised SIMCA models with an accuracy of 95%. Consequently, ATR–FTIR spectroscopy combined with multivariate data analyses provides excellent illustrations of the relative positions of the different brands of commercial edible oils according to their quality and purity.

WOS:000426367000024 The study deals with the optimization of reverse-phase HPLC separation of cis-/trans- isomers of long-chain unsaturated fatty acids by the assessment of the central composite design (CCD) of response surface methodology (RSM). The optimized conditions were also applied for the analysis of fatty acids in functional cold-pressed oils. The data obtained from experimental applications of CCD was used to model the parameters that significantly affect separations. The independent variables chosen were flow rate (X (1) ), column temperature (X (2) ), and acetonitrile content in mobile phase (X (3) ). A second-order polynomial model was used to estimate the impact of variables on separation efficiencies of the C30 and C18 stationary phases. The proposed CCD models were also validated with the ANOVA. The predicted values were in good agreement with experimental data, advising expert application of CCD as an option to obtain maximum information for the modeling of reverse-phase HPLC separation with little number of experiments. The optimal values of method parameters for the efficient C18 and C30 column separations as part of the k' response value were found to be flow rate of 1.10 and 0.42 mL min(-1), temperature of 3.6 and 9.4 A degrees C, and acetonitrile content in mobile phase of 100 and 77.4%, respectively. ANOVA test results also illustrate that the CCD models can be successfully used to predict the optimum method parameters. To maximize both sensitivity and precision of the methods, the validation procedure was also performed and the higher correlation coefficients (r = 0.9149-0.9993) were determined for all fatty acid methyl esters. Thus, the proposed experimental designs were shown to offer considerable advantages over traditional method optimization approaches. Karamanoglu Mehmetbey University (Karaman, Turkey) [14-M-16] The present study was supported by Karamanoglu Mehmetbey University (Karaman, Turkey) Scientific Research Project Centre with 14-M-16 project number.

Benefits of the ketogenic diet (KD) in epileptic patients are well known while less is known about the nutritional risks of the diet and its potential impacts on biochemical nutritional status. In this study, we aimed to evaluate the hematological parameters of patients who have drug-resistant epilepsy and are treated with KD. Fifty-three patients with drug-resistant epilepsy (mean age 7.4 +/- 4.4 years [2-18], 23 [43.4%] female) were included in the study. Demographic and laboratory data of the patients were retrospectively analyzed at baseline and Month 6 and Month 12 of the treatment. Repeated measures ANOVA (post hoc Bonferroni correction) and Friedman test were used to assess the changes in data during the treatment. Mean hemoglobin levels increased by 0.594 g/dL after 6 months (p = 0.001) and by 0.602 g/dL after 12 months of the treatment (p = 0.002). Mean hematocrit level was found to be significantly increased at Month 6 and 12 of the treatment compared to baseline [F(2,94) = 8.9, p < 0.0001]. An increase in MCV levels was determined with the KD treatment [F(2,94) = 19.7, p < 0.0001]. Mean level of vitamin B12 was found to be significantly increased in Month 12 of treatments compared to Month 6 [F(1.686,72.479) = 3.472, p = 0.035]. There was no significant effect of KD on other hematological parameters (red blood cell, white blood cell and platelet counts, serum iron, total iron-binding capacity, transferrin saturation, and ferritin and folic acid levels). We can conclude that KD increases levels of hemoglobin, hematocrit, MCV, and serum vitamin B12 in patients with intractable epilepsy. Prospective, multi-center, longitudinal studies are needed to confirm our results.

Background: Tandem MS analysis of dried blood spots is a widely used method for diagnosis of inborn errors of metabolism. Clinical laboratories performing this test for clinically suspected children at different ages are faced with the challenge of using appropriate reference ranges for the diagnostic markers. Objectives: Retrospective evaluation of laboratory data was performed to establish the disease spectrum and clinically relevant reference ranges for the diagnostic markers. Methods: The results of clinically suspected 4800 patients were extracted from laboratory information system and correlated with clinical data. Relevant reference ranges for the analytes in dried blood spots was determined using nonparametric statistical methods. Results: Forty four patients were diagnosed with 12 different inborn errors of metabolism. There were 23 patients with organic acid disorder, 13 patients with amino acid or urea cycle disorder and 8 patients with fatty acid oxidation disorder. The reference ranges were significantly different between the children under and over 1 year of age for some acylcarnitines (C0, C2, C3, C5OH, C14, C16 and C18) and amino acids (citrulline, arginine, tyrosine, valine and leucine). Conclusions: The interpretation of the Tandem MS analysis results showed that the difference in the reference ranges for children under or over one year of age did not affect the diagnosis for most frequent inborn errors of metabolism.

Haberle, Johannes/0000-0003-0635-091X WOS: 000406086600009 PubMed: 28132756 Objectives: Citrullinemia type 1 (CTLN1) is an autosomal recessive genetic disorder caused by mutations in the argininosuccinate synthetase 1 (ASST) gene, which encodes for the argininosuccinate synthetase enzyme. Here, we report genetic and clinical characterizations of 14 patients with citrullinemia type 1. Design & methods: The study group consisted of 14 patients (4 females, 10 males) diagnosed with citrullinemia type 1 from three centers in Turkey. Age of onset, clinical presentation, initial citrulline and ammonia levels, family history and molecular genetic analysis were retrospectively evaluated. Results: The mean age of the cohort and the mean age at the time of diagnosis were 483 +/- 36.5 months (min: 12 days, max: 10 years) and 11.6 +/- 26.2 months (min: 3 days, max: 8 years), respectively. In four patients, a homozygous p.Gly390Arg pathogenic variant was detected. All patients homozygous for p.Gly390Arg were diagnosed during the newborn period with the clinical presentation of classical citrullinemia. In each two patients, homozygous p.Arg86His, c.773 + 49C>T and p.Gly362Val pathogenic variants were detected. Clinical presentation was compatible with the mild form of the disease in patients homozygous for c.773 + 49C>T and for Gly362Val. Novel compound heterozygous genotypes (p.A1a164Pro/p.Gly390Arg; p.Leu290Pro/p.Gly390Arg; p.Thr389Pro/p.Gly390Arg) were identified in five patients. Of these, three siblings with CTLN1 were diagnosed with the compound heterozygous genotype p.A1a164Pro/p.Gly390Arg at the age of 4 days, 5 days and 2 years, respectively. The other two patients with novel compound heterozygous genotypes (p.Leu290Pro/p.Gly390Arg; p.Thr389Pro/p.Gly390Arg) were identified in the first month of life as neonatal onset form and were born to non-consanguineous parents. Conclusion: In our study, consistent with the literature, a correlation was found between homozygous p.Gly390Arg mutation and the classic neonatal onset form. Mild citrullinemia was detected in patients with c.773 + 49C>T or p.Gly362Val pathogenic variants. This study adds to our understanding of the molecular genetic background of patients with CTLN1, and allows to infer on the correlation between the genotype and phenotype of the disease. (C) 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Swiss National Science FoundationSwiss National Science Foundation (SNSF) [310030_153196] The study on urea cycle disorders is supported by the Swiss National Science Foundation (grant 310030_153196 to JH).

Aim: Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders caused by the deficiency of spesific lysosomal enzymes required to break down glycosaminoglycans. MPSs should be suspected in a child with coarse facial features, organomegaly, and bone disease (dysostosis multiplex), with central nervous system abnormalities. Early diagnosis and treatment can improve outcomes in MPS. The aim of this study was to evaluate the demographic characteristics and clinical findings of our MPS patients. Materials and Methods: This is a retrospective study which included 27 MPS patients who were diagnosed and treated in our center. Results: The mean age of the group was 112.3±52.5 months (36-196 months); the mean onset age of symptoms was 40.8±30.6 months (4-112 months), and the mean time from symptom onset to diagnosis was 16.3±21.4 months (0-80 months). MPS subgroups were Type III in 13 (48%) patients, Type II in seven (26%), Type VI in four (15%), Type I in two (7%) patients and Type IV in one patient. Nine (33.3%) patients received enzyme replacement therapy (ERT). The mean duration of ERT was 31.3±21.5 months (9-67 months). Conclusion: MPS Type III was found to be the most common subgroup in our center. We can speculate that the mean time from symptom onset to diagnosis was found too long for MPS in which early diagnosis improves the prognosis. Increasing awareness of the disease in physicians encountering these patients in different clinics will be an important factor in the early diagnosis of the disease.

Non-ketotic hyperglycinemia (NKH) is a rare inborn error of metabolism and is caused by a glycine cleavage system deficiency. Eighty-five percent of patients present with the neonatal type of NKH, the infants initially develop lethargy, seizures, and episodes of apnea, and most often death. Between 60-90% of cases are caused by mutations in the glycine decarboxylase (GLDC). We believed that more mutation reports especially for rare disease as NKH help to evaluate the genotype-phenotype relationship in patients with GLDC. In this study, we describe a case of a neonate admitted to intensive care unit with hypotonia, respiratory failure, lethargy, poor feeding. Due to the history of 2 non-ketotic hyperglycinemia diagnosed male siblings, molecular prenatal diagnosis in patient was performed and a novel c.2963G>A (Arg998Gln) homozygous mutation within the GLDC gene has been detected. We aimed to contribute to mutation knowledge pool of GLDC gene with a novel mutation.

B12 vitamin eksikliginin beslenme bozukluklarinin yani sira, en onemli nedenlerinden biri malabsorpsiyondur. Helicobacter pylori (HP) bazi calismalarda B12 eksikligi ile iliskili bulunmustur. Bu calismanin amaci, B12 eksikligi saptanan cocuklarda HP sikliginin arastirilmasidir. Calismaya 24 hasta (ortalama yas: 15.6 ± 1.3 yil) dâhil edildi. B12 vitamini duzeyi elektrokemiluminesens immunoassay yontemi ile olculdu. Tum hastalara ust gastrointestinal sistem endoskopisi yapilarak hizli ureaz testi yapildi ve histopatolojik inceleme yapildi. Hastalarin 15’i (%62.5) norolojik bulgular ile basvururken, 6 (%25.0) hastada halsizlik ve yorgunluk sikâyetleri mevcuttu. Uc (%12.5) hasta ise baska nedenlerle tetkik edilirken B12 vitamini eksikligi saptanmisti. Uc farkli tablo ile basvuran hastalarin B12 vitamini duzeyleri arasinda anlamli fark saptanmadi (p=0.224). Hastalarin 18’inde (%75) HP pozitif saptandi. HP pozitif hastalarin ortalama B12 vitamini duzeyi 108.6 ± 31.1 pg/mL iken, HP negatif hastalarda 113.5 ± 41.2 pg/mL saptandi (p=973). Sonuc olarak B12 vitamini eksikligi saptanan hastalarda, B12 vitamini eksikliginin onemli bir nedeni olan HP enfeksiyonu arastirilmali ve pozitif saptanan hastalar tedavi edilmelidir.

WOS: 000395169000020, Blending polyunsaturated oils with highly saturated or monounsaturated oils has been studied extensively; however, in literature there is negligible information available on the blending of refined cottonseed oil with palm olein oil. Blending could enhance the stability and quality of cottonseed oil during the frying process. In the present study, the effects of frying conditions on physicochemical properties of the palm olein-cottonseed oil blends (1:0, 3:2, 1:1, 2:3, and 0:1, w/w) were determined and compared to the pure oils. The frying process of frozen French fries was performed in duplicate at 170 +/- 5 degrees C for 10 h without interruption. The oil degradations were characterized during deep-frying applications; peroxide, free fatty acid, and iodine value by standardized methods, fatty acid profile by using a gas chromatography-flame ionization detector, polar and polymeric compounds by using the high-performance size exclusion chromatography/evaporative light scattering detector technique. The present study clearly indicated that the oxidative and frying performances of pure palm olein oil and cottonseed oil significantly improved by blending application. Results clearly indicated that the frying performance of cottonseed oil significantly improved by the blending with palm olein oil. Except that free fatty acid content, all the physicochemical variables were significantly influenced by type of pure and blend oils. By increasing the proportion of palm olein oil in cottonseed oil, the levels of polyunsaturated fatty acids decreased, while saturated fatty acid content increased. The progression of oxidation was basically followed by detecting polar and polymeric compounds. The fastest increments for polar and polymeric compounds were found as 6.30% level in pure cottonseed oil and as 7.07% level in 40% cottonseed oil:60% palm olein oil blend. The least increments were detected as 5.40% level in 40% cottonseed oil:60% palm olein oil blend and 2.27% level in 50% cottonseed oil:50% palm olein oil blend. These levels were considerably below the acceptable levels recommended by the official codex. Therefore, the present study suggested that blending of cottonseed oil with palm olein oil provided the oil blends (50% cottonseed oil:50% palm olein oil and 40% cottonseed oil:60% palm olein oil, w/w) with more desirable properties for human nutrition., Selcuk University Coordinators of Scientific Research ProjectSelcuk University [11401121], The research was supported by Selcuk University Coordinators of Scientific Research Project entitled "Development of The Frying Oil Production Technologies by Formation of the Blend Oils Based on The Palm/Cottonseed Oils" with 11401121 project number.

In this study, physicochemical characteristics, pesticide residues and aflatoxin contaminations of cold pressed pumpkin seed ( Cucurbita pepo L. ) oils cultivated in four different central Anatolia regions of Turkey, were investigated. Lab-scale screw press machine was used to produce cold pressed pumpkin seed oils and the oil contents were found between 42.8%−47.4% for naked seeds. The physicochemical characteristic ( refractive index, viscosity, color value, triglyceride profile analysis, peroxide value, iodine value, free fatty acid, saponification number, unsaponified matter, specific extinction values at 232 and 270 nm ) of cold pressed oils were determined by using different analytical techniques. The results showed that there was a non-significant difference between cold pressed pumpkin seed oils from different regions, in terms of physicochemical characteristics. The contents of pesticide residue and aflatoxin B 1 , B 2 , G 1 and G 2 contamination were determined by using validated UHPLC-MS/MS method. The chlorpyrifos pesticide residue was detected under the limit value declared by official authorities for the quality assessment of edible oils. Aflatoxins weren’t detected in any of studied pumpkin seed oils. Therefore, in food industry the positive effect of screw-pressing application could be useful for preservation of bioactive compounds during edible oil production and also enhancing of their functional properties.