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INTRODUCTION: Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of pituitary hormone deficiencies, suggesting a potential role for the PROK2 pathway in pituitary development, in addition to its role in gonadotropin releasing hormone-expressing neuron development. Here, we present the clinical and molecular findings of four patients with PROKR2 mutations. METHODS: Next-generation targeted sequencing was used to screen 25 genes in 59 unrelated patients with multiple pituitary hormone deficiency (MPHD), isolated growth hormone (GH) deficiency, or idiopathic short stature. RESULTS: Two different, very rare PROKR2 missense alterations classified as pathogenic (NM_144773.4: c.518T>G; NP_658986.1: p. (Leu173Arg)) and likely pathogenic (NM_144773.4: c.254G>A; NP_658986.1: p.(Arg85His)) were identified in four patients in heterozygous form. Patient 1 and Patient 2 presented with short stature and were diagnosed as GH deficiency. Patient 3 and Patient 4 presented with central hypothyroidism and cryptorchidism and were diagnosed as MPHD. No other pathogenic alterations were detected in the remaining 24 genes related to short stature, MPHD, and hypogonadotropic hypogonadism. Segregation analysis revealed asymptomatic or mildly affected carriers in the families. DISCUSSION AND CONCLUSION: PROKR2 dominance should be kept in mind as a very rare cause of GH deficiency and MPHD. Expressional variation or lack of penetrance may imply oligogenic inheritance or other environmental modifiers in individuals who are heterozygous carriers.

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed.Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents.Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides (AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG, and TK2) in 12 patients from nine families and four variants in genes encoding important for muscle structure (CAPN3, DYSF, and TCAP) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes (MT-ATP6 and MT-TL1). Nine variants in five genes are reported for the first time with disease association: (AARS2: c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2: c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1: c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6: c.479delA/p.(N162Ifs*27); and OXCT1: c.1370C>T/p.(T457I), c.1173-139G>T/p.(?).Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene.

For the first time, sol-gel spin coating was used to fabricate thin films of NiO doped with lutetium. The films were characterized to determine their crystalline structure, surface morphology, and optical properties as a function of Lu doping concentration. The investigations revealed that the Lu-doped NiO films consisted of nano-polycrystalline particles with a cubic bunsenite structure and (200) preferential orientation. Optical studies indicated that the optical band gap of pure NiO widened with low levels of Lu incorporation before narrowing with higher concentrations. The Urbach energy value for pure NiO initially decreased with 1 at. % Lu-content, from 224 meV to 190 meV, and then continuously increased to 380 meV with more Lu-level. To investigate the effects of Lu doping on the electronics, magnetic, and optical properties of NiO, first-principle computations were performed. The results showed that bulk magnetization underwent significant modifications due to a high hybridization between the Lu-f/d and Ni-d states. This study suggests that NiO doped with lutetium could be used for spin-polarized transport devices and other spin-dependent applications.

INTRODUCTION: Objective: Androgen insensivity syndrome (AIS) and 5α-reductase deficiency (5α-RD) present with indistinguishable phenotypes among the 46,XY disorders of sexual development (DSD) that usually necessitate molecular analyses for the definitive diagnosis in the prepubertal period. The aim was to evaluate the clinical, hormonal and genetic findings of 46,XY DSD patients who were diagnosed as AIS or 5α-RD. METHODS: Methods: Patients diagnosed as AIS or 5α-RD according to clinical and hormonal evaluations were investigated. Sequence variants of steroid 5-α-reductase type 2 were analyzed in cases with testosterone/dihydrotestosterone (T/DHT) ratio of ≥20, whereas the androgen receptor (AR) gene was screened when the ratio was T, p.Glu32*, c.330G>C, p.Leu110=; c.2084C>T, p.Pro695Leu, c.2585_2592delAGCTCCTG, p.(Lys862Argfs*16), of these c.330G>C with silent status remained undefined in terms of its causative effects. DISCUSSION AND CONCLUSION: Conclusion: T/DHT ratio is an important hormonal criterion, but in some cases, T/DHT ratio may lead to diagnostic confusion. Molecular diagnosis is important for the robust diagnosis of 46,XY DSD patients. Four novel AR variants were identified in our study.

Aim:Breast cancer is the most prevalent cancer diagnosed in women. Screening programs to diagnose breast anomalies increase the likelihood of early diagnosis and survival. This study describes the most extensive breast cancer screening program in Istanbul/Turkey between 2018 and 2019 and offers recommendations for nationwide programs.Methods:We collected data from the Istanbul Health Directorate’s cancer surveillance database from May 2018 to December 2019. We analyzed data on patients referred for further investigation due to suspicion of possible tumors in their screening radiography. The database included socio-demographic information and further examination details (tests, outcomes, and planned treatment).Results:The mean age of the 3,577 women who were invited for further examination was 52.3 [standard deviation (SD): 7.5]. The age group with the highest percentage of further investigation invitations was between 50 and 54. The mean time between the results of screening mammography was 16.2 days (SD: 15.3). 5.1% of the women referred were diagnosed with some sort of cancer. Women who went to the place of scheduled appointments, instead of getting an appointment in another place of their choosing, were diagnosed and treated earlier.Conclusion:For a breast screening program to reach the entirety of the target population, a comprehensive approach to every step of the process (screening, diagnosis, treatment) needs to be considered together.

Objective: Most lacunar strokes are sporadic, and hypertension, diabetes, smoking, and cardiovascular diseases are among its main risk factors. Strokes caused by small vessel diseases are generally associated with single-gene disorders with familial dominant and recessive inheritance. The most common condition is cerebral autosomal dominant arteriopathy, with subcortical infarcts and leukoencephalopathy (CADASIL), associated with the NOTCH3 gene. An infrequent form of this disease is the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), revealed with pathogenic HTRA1 gene variants related to distinct molecular pathways. The neurological and cranial magnetic resonance imaging (MRI) findings are very similar to CADASIL; however, earlier than expected onset of common alopecia in man, low back pain, and more severe memory impairment are the differences in terms of clinical presentations. Clinical findings of 22 patients from 16 families with widespread white matter lesions in the periventricular field in the brain were investigated with molecular genetic findings. Materials and Methods: Clinical examination results and cranial MRI findings are reported, and NOTCH3 and HTRA1 genes are sequenced stepwise by Sanger and next-generation sequencing techniques. Results: Missense changes in epidermal growth factor (EGF)-like domain in the NOTCH3 are found in 18 cases from 14 families. Two different homozygous pathogenic missense and non-sense variants, in the HTRA1 gene, were detected in four patients from two families. The disease onset age was approximately 16 years earlier in cases carrying pathogenic variants located in the encoding region of EGF-like domains 1-6 of NOTCH3. Conclusion: In the NOTCH3 gene with c.382T>C (p.C128R), c.555T>G (p.C185W), and c.1903C>T (p.R635C) and in the HTRA1 gene c.235C>T (p.Q79*) are presented for the first time in this study. Molecular genetic investigation of CADASIL and CARASIL is important to support the clinical diagnosis, determine the inheritance model, provide patient and family counseling, manage disease process, and evaluate possible treatment strategies.

The aim of this paper is to determine neutronic performances of the light water reactor (LWR) spent fuel mixed with fertile thorium fuel in a FFHR. Time dependent three dimensional calculations for major technical data, such as blanket energy multiplication, tritium breeding ratio, cumulative fissile fuel enrichment and burnup have been performed by using Monte Carlo Neutron-Particle Transport code MCNP5 1.4, coupled with a novel interface code MCNPAS, which is developed by our research group. A self-sustaining tritium breeding ratio (TBR>1.05) has been kept throughout the calculations. The study has shown that the fissile fuel quality will be improved in the course of the transmutation of the LWR spent in the FFHR. The latter has gained the reusable fuel enrichment level conventional LWRs between one and two years. Furthermore, LWR spent fuel - thorium mixture provides higher burn-up values than in light water reactors. Keywords: LWR spent fuel, Thorium, Time dependent neutronic analysis, Fusion-fission hybrid reactor

Abstract Background Pallister Killian syndrome (PKS, OMIM 601803) is a rare genetic disorder with a distinct phenotype caused by tissue- limited mosaicism tetrasomy of the short arm of chromosome 12, which usually cytogenetically presents as an extra isochromosome 12p. Wide phenotypic variability in PKS has been reported, ranging from pre-to perinatal death due to multiple congenital anomalies, especially diaphragmatic hernia, and classic phenotypes including seizures, severe developmental delay, macrosomia at birth, deafness, and distinct dysmorphic features, such as coarse face, temporal alopecia, a small nose with anteverted nostrils, long philtrum, and hypo−/hyper- pigmented streaks on the skin. Results Karyotypes obtained from cultured peripheral lymphocytes of 13 cases, who were diagnosed as PKS, were normal, while karyotypes obtained from cultured skin samples and buccal mucosa revealed the supernumerary mosaic i(12p). Mosaic karyotype was found in both fibroblast and buccal mucosa in 14 of 15 patients in our series, whereas in one stillbirth, following the clinical diagnosis of PKS, skin and buccal smear samples were taken, and all karyotypes from cultured fibroblasts revealed a supernumerary i(12p), while I-FISH study showed 60% mosaicism in mucosal cells. Conclusions We here share the clinical, cytogenetic and molecular cytogenetic findings of 15 cases with PKS phenotype and the parental origin of seven i(12p) identified by molecular analyses. To our knowledge, this is the largest series of PKS patients with parental origin study from a single center. We believe that our study makes a significant contribution to the literature because we specifically found no differences in the phenotypes of cases with either a maternal or paternal origin of the extra element and differential imprinting appeared not to be a factor.

Abstract Background Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in other genetic loci should be considered, particularly in malignant course patients. Case presentations Three patients were admitted into hospital due to recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively; moreover all three patients had congenital sensorineural hearing-loss. Their electrocardiograms showed markedly prolonged QT interval. Implantable defibrillator was implanted and left cardiac sympathetic denervation was performed due to the progressive disease in case 1. She had countless ventricular fibrillation and appropriate shock while using an implantable defibrillator. The DNA sequencing analysis of the KCNQ1 gene disclosed a homozygous c.728G > A (p.Arg243His) missense mutation in case1. Further targeted next generation sequencing of cardiac panel comprising 68 gene revealed a heterozygous c.1346 T > G (p.Ile449Arg) variant in RYR2 gene and a heterozygous c.809G > A (p.Cys270Tyr) variant in NKX2–5 gene in the same patient. Additional gene alterations in RYR2 and NKX2–5 genes were thought to be responsible for progressive and malignant course of the disease. As a result of DNA sequencing analysis of KCNQ1 and KCNE1 genes, a compound heterozygosity for two mutations had been detected in KCNQ1 gene in case 2: a maternally derived c.477 + 1G > A splice site mutation and a paternally derived c.520C > T (p.Arg174Cys) missense mutation. Sanger sequencing of KCNQ1 and KCNE1 genes displayed a homozygous c.1097G > A (p.Arg366Gln) mutation in KCNQ1 gene in case 3. β-blocker therapy was initiated to all the index subjects. Conclusions Three families of JLNS who presented with long QT and deafness and who carry homozygous, or compound heterozygous mutation in KCNQ1 gene were presented in this report. It was emphasized that broad targeted cardiac panels may be useful to predict the outcome especially in patients with unexplained phenotype-genotype correlation. Clinical presentations and molecular findings will be discussed further to clarify the phenotype genotype associations.

In this investigation, Al/PEDOT/C/p-Si structure has been fabricated by synthesizing PEDOT/C composites on the p-Si substrate. The thickness and surface morphology of PEDOT/C on p-Si have been investigated by using the scanning electron microscope. The optical characterization of PEDOT/C solution indicated a strong optical absorbance peak located at 267 nm. The electrical characterization of Al/PEDOT/C/p-Si structure was made under dark and illumination conditions at the room temperature. The ideality factor, and barrier height were identified to be 1.28, 1.12 and 0.80 eV, 0.83 eV from current–voltage (I–V) measurements for dark and illuminated conditions, respectively. The results show that the Al/PEDOT/C/p-Si structure may be utilized to be a photodiode in optoelectronic implementations. Keywords: Polymeric composites, Electrical properties, Contacts

This study aims to examine the studies regarding In doped ZnO published in the Web of Science database. A total of 777 articles were reached (31 March 2020). The articles were downloaded for the bibliometric analysis and collected in a file. The file was uploaded to VOSViewer programme in order to reveal the most used keywords, words in the abstracts, citation analyses, co-citation and co-authorship and countries analyses of the articles. The results showed that the most used keywords were “ZnO”, “photoluminescence”, “optical properties”, “thin films” and “doping”. These results indicate that the articles mostly focus on some characteristics of In doped ZnO thin films such as structural, optical and electrical features. When the distribution of the number of articles using the keywords by year was searched, it was found that recent articles focus mainly on synthesis of In doped ZnO film via chemical routes such as sol-gel and hydrothermal syntheses, and on ZnO-based device applications such as solar cells and gas sensors. The most used keywords were also found to be films, X-ray, glass substrate, X-ray Diffraction (XRD), spectra and layer. These results indicate that the studies mostly focus on In doped ZnO thin films as transparent conductive oxide (TCO) material used in device applications like solar cells. In this context, it was found that structural, topographical, optical, electrical and magnetic properties of In doped ZnO films were characterized in terms of defected structure or defect type, substrate temperature, film thickness and In doping content. When the distribution of these words is shown on a year-by-year basis, it is evident that more recent articles tend to focus both on efficiency and performance of In doped ZnO films as TCO in solar cells, diodes and photoluminescence applications both on nanostructures, such as nanoparticles, and nanorods for gas sensor applications. The results also indicated that Maldonado and Asomoza were the most cited authors in this field. In addition, Major, Minami and Ozgur were the most cited (co-citation) authors in this field. The most cited journals were found to be Thin Solid Films, Journal of Materials Science Materials in Electronics and Journal of Applied Physics and, more recently, Energy, Ceramics International, Applied Physics-A, Optik, Material Research Express, ACS Applied Materials and Interfaces and Optical Materials. The most co-cited journals were Applied Physics Letters, Thin Solid Films, Journal of Applied Physics, Physical Review B, and Applied Surface Science. Lastly, the countries with the highest number of documents were China, India, South Korea, USA and Japan. Consequently, it is suggested that future research needs to focus more on synthesis and characterization with different growth techniques which make In doped ZnO suitable for device applications, such as solar cells and diodes. In this context, this study may provide valuable information to researchers for future studies on the topic.

Tungsten (VI) oxide (WO3) nanoparticles (NPs) are used for many industrial purposes in everyday life. However, their effects on human health have not been sufficiently evaluated. Therefore, the present study was designed to investigate the toxicity potentials of various concentrations (0 to 1000 ppm) of WO3NPs (

PURPOSEWe aimed to describe the technical aspects and outcomes of the retrograde tibial approach and balloon predilation for recanalization of complex infrainguinal arterial occlusions and determine the efficacy of this approach in minimizing failure rates. MATERIALS AND METHODSBetween September 2006 and April 2011, antegrade revascularization failed in 22 limbs with complex total occlusions within the infrainguinal arterial territory. For each of these antegrade failure cases in 22 patients, a retrograde tibial puncture had been attempted. Percutaneous recanalization and predilation were initially performed through tibial access, and final balloon dilatation or stent placement was performed from antegrade femoral access. The patients were followed up for functionality and wound healing. RESULTSAccess from the tibial artery was successfully obtained for all patients (100%). Successful recanalization was obtained in 18 patients (82%). Retrograde access was performed from the anterior tibial/dorsalis pedis artery in 12 patients and posterior tibial artery in 10 patients. One major and one minor complications were documented. CONCLUSIONRetrograde tibial recanalization technique in the infrainguinal complex arterial occlusion safely increases the success rates of percutaneous recanalization in the failed traditional approach and is a feasible endovascular option to avoid more invasive, time-consuming, and high-risk procedures.

A 23-year-old primigravida was referred to our clinic for evaluation of high blood pressure (BP) in her 16th week of gestation. She had an operation to repair congenital aortic coarctation and patent ductus arteriosus 8 years ago. On physical examination the blood pressure in upper extremity was 155/95 and in lower extremity was 90/55 mmHg, and heart rate was 93 beats/min. Transthoracic echocardiography showed narrowing of the descending aorta, the diameter of the aortic arch was 10.60 mm and an echocardiographic gradient was 96 mmHg. During the pregnancy (from 16 weeks to 38 weeks) BP was regulated with metoprolol. Cesarean section delivery was applied at 38 weeks of gestation. There was no complication in postpartum period. Spinal anesthesia application was used for caesarean section intervention and healthy female baby was delivered with the APGAR scores of 10/10. Herein the diagnosis of aortic coarctation is reviewed and the management when found during pregnancy is discussed.