Explore the vast range of titles available.

Kisspeptin and neurokinin B stimulate gonadotropin-releasing hormone. The authors describe an inactivating mutation in the human kisspeptin gene KISS1 leading to failure of pubertal progression. It is still unknown how puberty in humans, occurring during the early years of the second decade of life, is initiated. 1 The hallmark of puberty is increased secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which act in concert to stimulate the gonads to drive sex-hormone secretion and gametogenesis. The production of gonadotropins from pituitary gonadotropic cells is controlled by the pulsatile delivery of GnRH. Inactivating mutations in the genes encoding GNRH1 2 or the GNRH receptor (GNRHR) 3 give rise to normosmic idiopathic hypogonadotropic hypogonadism in humans. 4 However, GnRH neurons lack sex-steroid receptors. This suggests the . . .

This study is aimed at developing an achievement test on quadrilaterals for seventh-grade students. The concept of the atom can be visualized in different ways in the mind due to its structure, which the naked eye cannot see. Augmented reality (AR) is one of the applications that can be used to teach such concepts. This study aimed to investigate students' views on the use of AR applications in teaching. Phenomenological design, one of the qualitative research designs, was used in the study. The study group consisted of 26 -graders in a public secondary school. AR application was organized to teach the structure of the atom. Within the scope of the study, an interview form consisting of four open-ended questions prepared by the researchers and submitted to expert opinion for content validity was used as a data collection tool. When the students' answers to the questions were examined, it was determined that they had positive opinions that AR application could be used in other courses and different subjects, that this application was more instructive because it concretized the subject, that it caused a better understanding of the subject it was used in, and that it increased participation in the lesson due to the possibilities of providing three-dimensional images. Suggestions were made based on the results.

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. We screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. We identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. SEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.

Metabolism has a role in determining the time of pubertal development and fertility. Nonetheless, molecular/cellular pathways linking metabolism/body weight to puberty/reproduction are unknown. The KNDy (Kisspeptin/Neurokinin B/Dynorphin) neurons in the arcuate nucleus of the hypothalamus constitute the GnRH (gonadotropin-releasing hormone) pulse generator. We previously created a mouse model with a whole-body targeted deletion of nescient helix-loop-helix 2 (Nhlh2; N2KO), a class II member of the basic helix-loop-helix family of transcription factors. As this mouse model features pubertal failure and late-onset obesity, we wanted to study whether NHLH2 represents a candidate molecule to link metabolism and puberty in the hypothalamus. Exome sequencing of a large Idiopathic Hypogonadotropic Hypogonadism cohort revealed obese patients with rare sequence variants in NHLH2, which were characterized by in-silico protein analysis, chromatin immunoprecipitation, and luciferase reporter assays. In vitro heterologous expression studies demonstrated that the variant p.R79C impairs Nhlh2 binding to the Mc4r promoter. Furthermore, p.R79C and other variants show impaired transactivation of the human KISS1 promoter. These are the first inactivating human variants that support NHLH2’s critical role in human puberty and body weight control. Failure to carry out this function results in the absence of pubertal development and late-onset obesity in humans.

Inappropriate antidiuretic hormone syndrome (SIADH) may develop after intracranial surgery. SIADH in the pediatric age group is usually encountered in patients with an intracranial mass both before and after surgery. Fluid restriction is the standard therapy in SIADH. However, a resistant, hyponatremic pattern may be encountered in some cases. Vaptans have been recently introduced for treatment of hyponatremia due to SIADH. There is inadequate data concerning tolvaptan treatment in pediatric patients. We present a 13 year-old female with SIADH of triphasic episode who was transferred to our clinic after surgery for craniopharyngioma. Resistant hyponatremia did not resolve despite fluid restriction and hypertonic saline support. The patient responded rapidly to a single dose of tolvaptan, with no adverse effect, which resulted in successful control of her SIADH.

Background/Objectives: To evaluate pancreatic size and echogenicity using ultrasonography in newly diagnosed pediatric Type 1 Diabetes Mellitus patients within five days of diagnosis, and compare early childhood (<7 years) and adolescent (≥13 years) endotypes with clinical and laboratory findings. Methods: This prospective, cross-sectional, case–control study included 69 pediatric patients with newly diagnosed type 1 diabetes mellitus, aged 1–18 years, and 78 age- and sex-matched healthy controls. Patients with chronic conditions (e.g., pancreatitis or cystic fibrosis), other forms of diabetes, or medications affecting glucose metabolism were excluded. Ultrasonography was performed within five days of diagnosis, after metabolic stabilization, to assess pancreatic dimensions and echogenicity. Laboratory analyses included measurements of C-peptide, HbA1c, and autoantibodies (anti-GAD, islet cell antibody, and insulin antibody). Results: Pancreatic dimensions were significantly smaller in type 1 diabetes mellitus patients (p < 0.001), with greater reductions in adolescents (head: 21%, body: 26.7%) vs. young children (head: 14.4%, body: 15.5%). Isoechoic pancreases were more common in young patients (80% vs. 40.9%; p = 0.033). C-peptide and HgbA1c were higher in adolescents (p < 0.05), with no echogenicity–autoantibody association. Conclusions: This first early-post-diagnosis ultrasonography study reveals age-specific pancreatic atrophy and echogenicity changes in children, more severe in adolescents, reflecting type 1 diabetes mellitus endotypes. Ultrasonography offers a practical noninvasive tool for early detection and endotype stratification, informing personalized diabetes care.

Mutations of genes encoding transcription factors which play important roles in pituitary morphogenesis, differentiation and maturation lead to combined pituitary hormone deficiency (CPHD). gene mutations are reported as the most frequent genetic aetiology of CHPD. The aim of this study is to describe phenotype of Turkish CPHD patients and define frequency of mutations. Fifty-seven CPHD patients from 50 families were screened for mutations. The patients were affected by growth hormone and additional anterior pituitary hormone deficiencies. All patients had GH deficiency, 98,2% had central hypothyroidism, 45,6% had hypogonadotropic hypogonadism, 43,8% had ACTH deficiency and 7,1% had prolactin deficiency. Parental consanguinity rate was 50.9%. 14 cases were familial. Mean height standard deviation score (SDS) and weight SDS were -3,8 (±1,4) and -3,1 (±2,0), respectively. Of 53 patients with available pituitary imaging, 32 showed abnormalities. None had extra-pituitary abnormalities. 8 index patients had gene mutations. Five sporadic patients had homozygous c.301_302delAG (p.Leu102CysfsTer8) mutation, two siblings had exon 2 deletion, two siblings had complete gene deletion and two siblings had homozygous, novel c.353A>G (p.Q118R) mutation. Phenotype of patients regarding hormonal deficiencies, pituitary morphology, presence of extra-pituitary findings, family history of CPHD and parental consanguinity are important to decide which pituitary transcription factor deficiency should be investigated. The frequency of the mutations was 16% in our cohort. Mutation rate was higher in familial cases compared to sporadic cases (42,8% vs. 11,6%). mutation frequencies vary in different populations and its prevalence is high in Turkish CPHD patients.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder that causes systemic autoimmunity resulting from a mutation of the forkhead box protein 3 gene (FOXP3). A 2-year-old boy, was referred to the hospital due to vomiting and fever when he was 21 days old. On physical examination the patient was severely dehydrated, and his laboratory test results showed hyperglycemia and metabolic acidosis. Upon the continuance of the hyperglycemia which caused the patient to receive permanent insulin treatment, the patient was diagnosed with neonatal diabetes mellitus. Here, we report a 2-year-old boy with early-onset IPEX syndrome due to a c.1040G > A (p.R347H) mutation in exon 11 of the FOXP3 gene. Although the patient had missense mutation in his FOXP3 gene, he did not have other immunodysregulation symptoms. IPEX syndrome should be kept in mind in all the cases of associated neonatal diabetes mellitus in male neonates or infants.

Zinc transporter 8 protein (ZnT8A) is a transmembrane protein which functions to transfer zinc to insulin vesicles. Antibodies formed against ZnT8A (ZnT8A) are regarded as an independent autoimmunity demonstrator in type 1 diabetes (T1D). The aim of this study was to investigate the prevalence of ZnT8A in Turkish children with new onset T1D. Eighty four patients between 1-18 years of age diagnosed with T1D between February 2015-March 2016 and the control group consisting of 50 healthy children without any autoimmune diseases were included in the study. Serum samples for ZnT8A testing were taken from the patient group within a week of diagnosis. A ZnT8A enzyme-linked immunosorbent assay was used in the analyses. ZnT8A positivity was detected in 58% of the patients with new onset T1D and 8% of the control group. ZnT8A were demonstrated in 5 of 11 patients with negative results for classical diabetes antibodies [insulinoma antigen-2 antibody (IA-2A), glutamic acid decarboxylase (GAD) or insulin autoantibodies]. No association was found between ZnT8A positivity and age, gender, presence or degree of ketoacidosis at presentation, hemoglobin A1c, insulin or C-peptide concentration, or the presence of either thyroid or celiac antibodies. ZnT8A prevalence in children with T1D in Turkey was compatible with the literature. The ratio of patients who are clinically considered to have T1D but have negative routine diabetes auto-antibodies were observed to decrease nearly by 50% when ZnT8 antibodies were added to the panel. ZnT8 measurement should be more widespread for clarifying the etiology in T1D.

Dear Editor, Wolcott-Rallison syndrome (WRS; Online Mendelian Inheritance in Man 226980) is an autosomal recessively inherited disorder characterized by neonatal insulin-dependent diabetes mellitus, skeletal dysplasia (epiphyseal dysplasia), acute hepatic and/or renal dysfunction, exocrine pancreatic insufficiency, neutropenia, developmental delay, and growth retardation (1,2). This syndrome is caused by mutations in the gene encoding eukaryotic translation initiation factor 2a kinase 3 (EIF2AK3), and to date, more than 60 cases have been reported (2,3). A female Kurdish infant at 4 months of age had been diagnosed to have neonatal diabetes when admitted with an episode of diabetic ketoacidosis. Her parents were first-degree cousins. At diagnosis, laboratory findings (reference ranges) were as follows: glucose 492 mg/dL (70-105), C-peptide 0.001 ng/mL (0.9-4.3), insulin 0.2 µIU/mL (1.9-23), and HbA1c 15.2% (4.8-6.0). Her liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], thyroid stimulating hormone, thyroxine, blood urea nitrogen, and creatinine levels, and neutrophil count were in normal ranges. Type 1 diabetes-associated autoantibodies (islet cell antibody and glutamic acid decarboxylase antibody) were negative. At the age of eight months, the patient was admitted because of acute hepatic failure (on treatment with a regimen of insulin detemir and insulin lispro injected three times a day). ALT and AST levels (822 U/L and 1559 U/L, respectively) were elevated with no hepatomegaly. Viral hepatitis markers were negative. Additionally, she had neutropenia. During follow-up, with supportive treatment, liver enzymes and absolute neutrophil count returned to normal. No clinical or biochemical evidence of exocrine pancreas insufficiency was observed. At a routine visit at the age of 3 years and 5 months, her height was 90.9 cm (-1.53 standard deviation score) and weight was 11.3 kg (-2.45 standard deviation score). Her HbA1c was 8.69% while taking insulin detemir once a day and insulin lispro three times a day, with a total daily dose of insulin of 1.2 UI/kg. An X-ray survey showed osteopenia, generalized (proximal tibia, distal femur, and proximal phalanges) epiphyseal dysplasia, and tubulation deformities in the carpal bones and phalanges, but there were no abnormal findings in vertebral and pelvic bones (Figure 1). A clinical diagnosis of WRS was corrected by the identification of a novel homozygous nonsense mutation (p.Q333) in exon 5 of the EIF2AK3 gene. [University of Exeter Medical School (United Kingdom) with funding from the Wellcome Trust to Professors Andrew Hattersley and Sian Ellard]. We name all our EIF2AK3 mutations according to the sequence reference AF110146.1. Patient's parents were heterozygous for this mutation (Figure 2). Hepatic dysfunction is a typical feature of this syndrome presenting with hepatomegaly, elevated hepatic enzymes, and recurrent acute liver failure (4). Our patient had one temporary acute hepatic attack, and it has not recurred. Although developmental delay has been reported in this syndrome, our patient's development was normal. The skeletal abnormalities of WRS are stated as progressive osteoporosis, osteopenia, and epiphyseal dysplasia (5). In our patient, osteopenia and generalized epiphyseal dysplasia were present. In summary, the diagnosis of WRS should be considered in a neonatal or early infantile case of insulin-dependent diabetes mellitus with any of the accompanying features such as skeletal dysplasia, acute hepatic and/or renal failure, and neutropenia. Ethics Peer-review: Externally peer-reviewed. Authorship Contributions Concept: Fatih Gürbüz, Bilgin Yüksel, Ali Kemal Topaloglu, Design: Fatih Gürbüz, Data Collection and Processing: Fatih Gürbüz, Bilgin Yüksel, Ali Kemal Topaloglu, Analysis and Interpretation: University of Exeter Medical School (UK), Fatih Gürbüz, Bilgin Yüksel, Ali Kemal Topaloglu,Literature Research: Fatih Gürbüz, Bilgin Yüksel, Ali Kemal Topaloglu, Writing: Fatih Gürbüz, Bilgin Yüksel, Ali Kemal Topaloglu. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study received no financial support. References 1. Wolcott CD, Rallison ML. Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia. J Pediatr 1972;80:292-297. 2. Mihci E, Turkkahraman D, Ellard S, Akcurin S, Bircan I. Wolcott-Rallison syndrome due to a novel mutation (R491X) in EIF2AK3 gene. J Clin Res Pediatr Endocrinol 2012;4:101-103. 3. Ozbek MN, Senee V, Aydemir S, Kotan LD, Mungan NO, Yuksel B, Julier C, Topaloglu AK. Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. Pediatr Diabetes 2010;11:279-285. Epub 2010 Feb 25. 4. Julier C, Nicolino M. Wolcott-Rallison syndrome. Orphanet J Rare Dis 2010;5:29. 5. Juneja A, Sultan A, Bhatnagar S. Wolcott-Rallison syndrome. J Indian Soc Pedod Prev Dent 2012;30:250-253.