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Introduction Hashimoto’s thyroiditis (HT) is a common autoimmune disease influenced by genetic predisposition and environmental factors. Single-nucleotide polymorphisms (SNPs) in immune-related genes have been implicated n the genetic susceptibility to autoimmune diseases. The SNP rs791903 in the IP6K3 gene (chromosome 6p21; G/C, with C as the minor allele) has been linked to several autoimmune and inflammatory conditions. However, data in non-Caucasian populations, particularly regarding HT, remain limited. Objective To investigate the association between IP6K3 SNP rs791903 and Hashimoto’s thyroiditis in an Egyptian cohort. Materials and methods One hundred participants were enrolled: 50 patients with HT and 50 age- and sex-matched healthy controls. Genomic DNA was extracted from EDTA whole-blood samples using the QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany). Genotyping of SNP rs791903 (G/C) was performed using a TaqMan allelic discrimination assay on a real-time PCR platform. Results Genotype distribution of SNP rs791903 differed significantly between patients and controls. The CC genotype was more frequent among patients with HT than among controls. Conclusion The CC genotype of IP6K3 SNP rs791903 was more frequent among patients with HT and was associated with elevated serum anti-TPO levels. This association should be interpreted cautiously, given the exploratory design and limited sample size.

Background This study aimed to assess the effect of Low-Level Laser Therapy (LLLT) on sagittal, transverse and vertical Orthodontic miniscrew displacement. Materials and methods The study included CBCTs from the records of 12 adult patients who underwent upper first premolar extraction and canine retraction with orthodontic miniscrews for maximum anchorage. The miniscrews on one side received LLL, while the other side served as a control. The Low-Level Laser was applied to assess its effect on the displacement of the miniscrews. The used CBCTs have been taken at two-time points: immediately after miniscrew insertion (T0) and four months after the start of canine retraction (T1) with a total of 24 CBCTs. Miniscrew displacement was assessed by measuring head (HMS) and tail (TMS) displacement to the axial, coronal and mid-sagittal planes on the CBCT at the two time points. Miniscrews displacement (T1-T0) was compared between LLL side and control side. Comparisons were performed using paired samples t-test. The significance level was set at p -value < 0.05. The reproducibility of measurements was assessed by intraclass correlation coefficient (ICC). Results After four months of canine retraction, HMS and TMS from both laser and control sides showed significant three-dimensional displacement at p  < 0.05. No significant difference in mean displacement in the vertical, sagittal, nor transverse planes between both sides was elicited. Conclusion LLL application in the used protocol does not affect the amount of miniscrew displacement in any of the three planes of space. Miniscrew displacement was significant in both groups.

RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in DKC1, NOP10, or NHP2 cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. Females with heterozygous DKC1 p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin–NOP10 binding interface in a region distinct from those implicated in DC, impair the dyskerin–NOP10 interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafish dkc1 mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction.

Abstract Context Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome). Case description This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel for steroid-resistant nephrotic syndrome, compound heterozygous missense mutations were identified in LAMB2 (c.737G>A p.Arg246Gln, c.3982G>C p.Gly1328Arg). Immunohistochemical analysis revealed reduced glomerular laminin β2 expression compared to control kidney and a thin basement membrane on electron microscopy. Laminin β2 is expressed during pituitary development and Lamb2–/– mice exhibit stunted growth, abnormal neural retinae, and here we show, abnormal parenchyma of the anterior pituitary gland. Conclusion We propose that patients with genetically undefined optic nerve hypoplasia syndrome should be screened for albuminuria and, if present, screened for mutations in LAMB2.

Background Vitamin D deficiency (VDD) is an important public health problem worldwide, and polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, with prevalence up to 10%. It is characterized by ovulatory dysfunction, resulting in oligomenorrhea and/or anovulation, hyperandrogenism, and polycystic ovarian morphology by ultrasound. Metabolic disturbances are present in most women with PCOS, including impaired glucose tolerance and insulin resistance (IR) with compensatory hyperinsulinemia. It may also create health risks such as T2DM, endometrial cancer, and cardiovascular disease. Accumulating evidence from several studies suggests that VDD may be involved in the pathogenesis of PCOS as the possible missing link between IR and PCOS. The aim of this study was to evaluate the suggested role of vitamin D in PCOS. Participants and methods The study included 70 women in reproductive age (16-44 years old) divided into two groups: group I included 50 women in reproductive age with PCOS, and group II included 20 healthy women in reproductive age with regular menstrual cycles. All were subjected to history taking; clinical examination, including blood pressure measurement; anthropometric measurements, such as body weight, height, and calculation of BMI, and waist and hip circumference with calculation of the waist/hip ratio; skin examination for acanthosis nigricans (sign of IR) and signs of androgen excess, such as hirsutism, androgenic alopecia, and acne; laboratory investigations, such as fasting blood glucose, lipid profile (total cholesterol, serum triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol), serum levels of ionized calcium, serum levels of 25 (OH) vitamin D3, serum insulin level with calculation of Homeostatic Model Assessment of Insulin Resistance, serum luteinizing hormone, serum follicle-stimulating hormone with calculation of luteinizing hormone/follicle-stimulating hormone ratio, serum prolactin, serum total testosterone, and sex hormone-binding globulin with calculation of free androgen index; and imaging studies, such as pelvic ultrasonography with a 3.5 MHz convex electronic probe to examine the ovaries or transvaginal ultrasound. Results Serum 25 OH vitamin D level was statistically significantly lower in group I (women with PCOS) than group II (the control group) (mean: 6.05±2.56 vs 21.58±1.92 ng/ml) (P< 0.001). There was a statistically significant positive correlation between serum 25 (OH) vitamin D level and serum ionized calcium (r=0.465, P=0.001) and sex hormone-binding globulin (r=0.407, P=0.003). However, there was a statistically significant negative correlation between serum 25 (OH) vitamin D level and BMI (r=−0.363, P=0.010), waist/hip ratio (r=−0.255, P=0.049), serum fasting insulin level (r=-0.487, P<0.001), Homeostatic Model Assessment of Insulin Resistance (r=−0.521, P<0.001), serum total testosterone (r=−0.418, P=0.003), free androgen index (r=−0.597, P<0.001), right ovarian volume (r=−0.44, P=0.001), left ovarian volume(r=-0.407, P=0.003), total ovarian volume (r=−0.447, P=0.001), right ovarian follicular number (r=−0.445, P=0.001), left ovarian follicular number (r=−0.488, P< 0.001), and total ovarian follicular number (r=−0.474, P=0.001). Conclusion VDD is very common in women with PCOS and is associated with metabolic derangement, including IR, cardiovascular risk factors, as well as ovulatory dysfunction, infertility, and hirsutism.

Background Thyroid disorders are the second most common endocrine disorders after type 2 diabetes mellitus. Copeptin, the C-terminal part of pre-pro arginine vasopressin, and brain natriuretic peptide (BNP) are new markers of cardiac and endothelial diseases. The relationship between thyroid status and copeptin has not been studied yet. Serum BNP levels are also affected by thyroid function status; however, its value in the presence of thyroid dysfunction has been recently questioned. Aim of the work The aim of this work was to assess the alteration of serum copeptin and BNP in patients with thyroid dysfunction and the relationship between this alteration and cardiovascular performance in patients with thyroid dysfunction. Materials and methods This study included 60 patients who were divided into two groups: group 1 included 30 patients with hyperthyroidism and group 2 included 30 patients with primary hypothyroidism. A total of 20 healthy euthyroid individuals served as the control group (group 3). All patients and controls were subjected to estimation of serum and urine osmolarity and electrolyte study and evaluation of T3, T4, thyroid-stimulating hormone, serum copeptin, and serum BNP using enzyme-linked immunosorbent assay. Echocardiographic study was conducted to assess left ventricle (LV) systolic and diastolic functions. In addition, endothelial function was assessed by measuring flow-mediated dilatation of the brachial artery. Results In patients with hyperthyroidism, serum copeptin was significantly lower than that in controls (mean = 2.24 ± 1.68 vs. 3.34 ± 2.93 pmol/l, P = 0.03). However, it was significantly higher in hypothyroid patients in comparison with controls (mean = 18.78 ± 11.29 vs. 3.34 ± 2.93 pmol/l, P = 0.0001). Serum BNP in the hypothyroid group was significantly higher than that in the control group (mean = 15.02 ± 6.9 vs. 3.60 ± 1.38 ng/l, P = 0.028). E′/ A′ was significantly lower in hypothyroid patients in comparison with the control group (mean = 1.15 ± 0.72 vs. 1.48 ± 0.48, P = 0.03), and more than half of the patients (53%) had E′/ A′ less than 1, suggesting the presence of diastolic dysfunction in hypothyroid patients. There was a significant negative correlation between ejection fraction (P = 0.002), fractional shortening (P = 0.01), and copeptin in the hypothyroid group. There was a significant positive correlation between copeptin and flow-mediated dilatation (P = 0.01) in the hyperthyroid group. Conclusion Serum copeptin and BNP were significantly increased in hypothyroid patients, whereas serum copeptin was significantly decreased in hyperthyroid patients. In hyperthyroid patients, LV systolic function was increased. More than half of the hypothyroid patients with high serum copeptin levels had impaired LV filling.

Congestive heart failure (CHF), the most frequent reason for hospital admission of elderly patients, is an important and rapidly increasing cause of morbidity and mortality worldwide. Its development is accompanied by left-ventricle (LV) dilatation and pump dysfunction. The extracellular space in the heart is now recognized as an essential element of myocardial structure and function, and a dynamic participant in remodelling. The matrix metalloproteinases (MMPs) are an endogenous enzyme system responsible for extracellular collagen degradation and remodelling. To evaluate the potential role of several MMPs (MMP-1, MMP-3 and MMP-9) in CHF. We recruited 30 consecutive patients with moderate to severe CHF who presented for heart-failure management, along with 15 age- and sex-matched control participants. Two-dimensional and M-mode echocardiographic studies were used to assess LV size and function and hence assess LV remodelling. MMP-1, -3 and -9 concentrations in serum were measured by ELISA at the time of admission and diagnosis. Serum levels of all 3 metalloproteinases were higher in patients with CHF than in controls; those of MMP-3 were markedly increased in patients with severe CHF. The association found between LV performance and MMP levels suggests that MMPs are implicated in CHF, that serum concentrations of MMPs may serve as markers for CHF, and that MMPs are a potential novel therapeutic target.