Contents of endogenous brassinosteroids and the response to drought and/or exogenously applied 24-brassinolide in two different maize leaves.

Exogenously applied brassinosteroids (BRs) improve plant response to drought. However, many important aspects of this process, such as the potential differences caused by different developmental stages of analyzed organs at the beginning of drought, or by BR application before or during drought, remain still unexplored. The same applies for the response of different endogenous BRs belonging to the C, C-and C- structural groups to drought and/or exogenous BRs.

Prevalence of congenital hypothyroidism in North Macedonia: data from a newborn screening program conducted for twenty years.

Background: Congenital hypothyroidism (CH) is a common endocrine disorder that can be treated if timely detected by newborn screening, optimizing the developmental outcome in affected children. In the present study, we analyze the data of the national newborn thyroid screening program in North Macedonia collected over twenty years, including the CH prevalence as well as its geographical and ethnic variations.

Methods: The thyroid-stimulating hormone (TSH) was measured on a filter paper blood spot sample using the DELFIA fluoroimmunometric assay.

Age-period-cohort modelling of type 1 diabetes incidence rates among children included in the EURODIAB 25-year follow-up study.

Aims: Specific patterns in incidence may reveal environmental explanations for type 1 diabetes incidence. We aimed to study type 1 diabetes incidence in European childhood populations to assess whether an increase could be attributed to either period or cohort effects.

Methods: Nineteen EURODIAB centres provided single year incidence data for ages 0-14 in the 25-year period 1989-2013.

Characteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

Substantial research has been performed during the last decades on the clinical and genetic variability of congenital adrenal hyperplasia (CAH) and its most common form, 21-hydroxylase deficiency (21OHD). CAH is one of the most prevalent autosomal recessive diseases in humans, and it can be divided into classic-further subdivided into salt wasting (SW) and simple virilizing (SV)-and non-classic (NC) forms. Pathogenic variants of gene, encoding the 21-hydroxylase enzyme, have been reported with variable prevalence in different populations.

Current Status of Newborn Screening in Southeastern Europe.

Significant part of Southeastern Europe (with a population of 76 million) has newborn screening (NBS) programs non-harmonized with developed European countries. Initial survey was conducted in 2013/2014 among 11 countries from the region (Albania, Bulgaria, Bosnia and Herzegovina (BIH), Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, and Slovenia) to assess the main characteristics of their NBS programs and their future plans. Their cumulative population at that time was ~52,5 million.

Thyroid function and dysfunction in preterm infants-Challenges in evaluation, diagnosis and therapy.

Thyroid hormone levels have a crucial role for optimal brain development from gestation through the first 2 postnatal years. However, thyroid hormones vary with gestational age, and their levels vary between term and preterm infants. Preterm newborns are prone to thyroid dysfunction which is now more frequently observed with the advances of neonatal care and improved survival of extremely premature infants.

Genetic Spectrum of Neonatal Diabetes.

Neonatal diabetes (ND) appears during the first months of life and is caused by a single gene mutation. It is heterogenous and very different compared to other forms of multi-factorial or polygenic diabetes. Clinically, this form is extremely severe, however, early genetic diagnosis is pivotal for successful therapy.

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010.

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies.

A novel 9 bp deletion (c.1271_1279delGTGCCCGCG) in exon 10 of CYP21A2 gene causing severe congenital adrenal hyperplasia.

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of adrenal steroidogenesis with a broad spectrum of clinical presentations, ranging from the severe classical salt-wasting (SW) and simple-virilizing (SV) form, to the mild nonclassical form. A large variety of CYP21A2 genotypes in correlation with phenotype have been described.

Materials And Methods: DNA samples from a 14-day-old male newborn with clinical and laboratory signs of SW CAH and family members were subjected for molecular analysis of the nine most common point CYP21A2 mutations by ACRS/PCR method.

First insights into the genetics of 21-hydroxylase deficiency in the Roma population.

Background: 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder with an incidence of 1:10,000-1:20,000 and is the result of various mutations in the CYP21A2 gene. 21OHD has been described in many different populations, but it has not been studied in Roma individuals so far. The aim of the study was to analyse the genotype in Roma patients with 21OHD and the prevalence of the disease in the Roma population of North Macedonia.

Genetics of Gland- or Hypoplastic Congenital Hypothyroidism in Macedonia.

Neonatal screening in Macedonia detects congenital hypothyroidism (CH) with an incidence of 1 in 1,585, and more than 50% of cases exhibit a normally located gland- (GIS). Monogenic mutations causing dyshormonogenesis may underlie GIS CH; additionally, a small proportion of thyroid hypoplasia has a monogenic cause, such as and defects. The genetic architecture of Macedonian CH cases has not previously been studied.

Clinical outcomes and characteristics of P30L mutations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Despite numerous studies in the field of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, some clinical variability of the presentation and discrepancies in the genotype/phenotype correlation are still unexplained. Some, but not all, discordant phenotypes caused by mutations with known enzyme activity have been explained by in silico structural changes in the 21-hydroxylase protein. The incidence of P30L mutation varies in different populations and is most frequently found in several Central and Southeast European countries as well as Mexico.

Novel Genotype in Two Siblings with 5-α-reductase 2 Deficiency: Different Clinical Course due to the Time of Diagnosis.

Steroid 5-α-reductase-2 (5-ARD) deficiency is a result of mutations of the gene. It causes the disorder of sexual differentiation (DSD) in 46,XY individuals with a variable genital phenotype. We present two siblings with female external genitalia at birth and bilateral inguinal testes, raised as females.

The impact of CYP21A2 (P30L/I172N) genotype on female fertility in one family.

Background: The simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder usually caused by steroid 21-hydroxylase deficiency due to I172N missense mutation at the CYP21A2 gene. Clinical presentation encompasses virilization of external genitalia in newborn females and pseudoprecocious puberty in both sexes, due to reactive androgen overproduction. The aim of this study was to present two sisters with an SV form of CAH and distinctive genotype, detected and treated since childhood with a poor compliance and poor metabolic control hindering the fertility.

The Association between Asthma and Obesity in Children - Inflammatory and Mechanical Factors.

Background: Association of asthma and obesity has been demonstrated in numerous epidemiological studies. However, the underlying mechanisms of the association are not well understood. Both conditions are characterised by chronic tissue inflammation, which includes numerous different inflammatory markers, and possible atopy.

Therapeutic challenges in a patient with the simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) due to the P30L/I172N genotype.

Background Steroid 21-hydroxylase deficiency is an autosomal recessive disorder, present in 90-95% of all cases with congenital adrenal hyperplasia (CAH). The classical simple virilizing (SV) form of the disease causes virilization of the external genitalia in newborn females and pseudo-precocious puberty in both sexes, due to reactive androgen overproduction. Case presentation We describe a 3.

Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

Aims/hypothesis: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years.

Methods: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013.

Clinical Variability in Two Macedonian Families with Arterial Tortuosity Syndrome.

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder caused by mutations in the solute carrier family 2 member 10 () gene encoding a glucose/ascorbic acid transporter. The clinical features of ATS are mild-to-severe tortuosity of the large and medium arteries throughout the body, accompanied by dysmorphisms and joint laxity. Vascular changes in different parts of the body lead to stenosis and/or aneurysms requiring difficult surgical procedures.

Detection of Virus Herpes Simplex Type 1 in Patients with Chronic Periodontal Disease.

Background: Periodontal disease is an inflammatory-destructive condition of the supporting tissues of the teeth. Microorganisms found in the dental plaque were considered to be the primary local etiologic factor responsible for the periodontal destruction. It is also evident that herpes simplex viruses may have an impact in the etiopathogenesis of periodontal disease.

Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: A randomized trial.

Background: Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin.

Objective: To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D).

Subjects: Children and adolescents (aged 1 to <18 years) with T1D.

Old syndrome-new approach: Mauriac syndrome treated with continuous insulin delivery.

Mauriac syndrome has rarely been reported in children and adolescents with a poorly controlled diabetes mellitus type 1. However, it still occurs despite the worldwide improvements of metabolic control. The risks have not been elucidated.

Drought-tolerant and drought-sensitive genotypes of maize (Zea mays L.) differ in contents of endogenous brassinosteroids and their drought-induced changes.

The contents of endogenous brassinosteroids (BRs) together with various aspects of plant morphology, water management, photosynthesis and protection against cell damage were assessed in two maize genotypes that differed in their drought sensitivity. The presence of 28-norbrassinolide in rather high quantities (1-2 pg mg-1 fresh mass) in the leaves of monocot plants is reported for the first time. The intraspecific variability in the presence/content of the individual BRs in drought-stressed plants is also described for the first time.

Testicular adrenal rest tumors in boys with 21-hydroxylase deficiency, timely diagnosis and follow-up.

Background: Testicular adrenal rest tumors (TARTs) are found in 30-94% of adult males with congenital adrenal hyperplasia (CAH). We sought to explore TART appearance through yearly ultrasound examination of testes in young boys with CAH, and its association with metabolic control and genetic mutations.

Methods: Twenty-five boys with 21-hydroxylase deficiency in the age group 4-18 years diagnosed during the period 2001-2016 were included in the study.

Diagnostic re-evaluation of congenital hypothyroidism in Macedonia: predictors for transient or permanent hypothyroidism.

Background: Diagnostic re-evaluation is important for all patients with congenital hypothyroidism (CH) for determining the etiology and identifying transient CH cases. Our study is a first thyroxine therapy withdrawal study conducted in Macedonian CH patients for a diagnostic re-evaluation. We aimed to evaluate the etiology of CH, the prevalence of transient CH and identify predictive factors for distinguishing between permanent (PCH) and transient CH (TCH).