Evaluating breast ultrasonography as a complementary diagnostic method in girls with central precocious puberty.

BACKGROUND: Assessment of breast development by physical examination can be difficult in the early stages and in overweight girls. OBJECTIVE: To investigate ultrasonography (US) for evaluation of early breast development. MATERIALS AND METHODS: In a prospective study, 125 girls (age 7.1 ± 1.5 years) with breast development before 8 years underwent US breast staging, breast volume, and elastography, in addition to clinical/hormonal evaluation for precocious puberty. Accuracy of US for determining breast development and predicting progression to central precocious puberty was investigated. RESULTS: Physical examination revealed glandular breast enlargement in 100 and predominantly lipomastia in 25. Breast US in the former confirmed glandular breast development in 92 (group 1, physical examination and US positive), but not in 8 (group 2, physical examination positive, US negative). Comparison of the two groups demonstrated lower Tanner and US staging, bone age/chronological age, basal luteinizing hormone (LH), breast volume, and uterine volume in group 2. In the 25 lipomastia patients, US demonstrated no breast tissue in 19 (group 3, physical examination and US negative), but US stage ≥ II in 6 (group 4, physical examination negative, US positive) without differences in clinical parameters. After follow-up of 19.8 ± 4.2 months, 46/125 subjects were diagnosed with precocious puberty. US stage, total breast volume, and shear-wave speeds were significantly higher in these 46 patients. Multivariate analyses demonstrated breast volume > 3.4 cc had odds ratio of 11.0, sensitivity of 62%, and specificity of 89, in predicting progression to precocious puberty, being second only to stimulated LH for all variables. CONCLUSION: Breast US is a useful predictive tool for diagnosis of precocious puberty in girls. Higher US stages and higher breast volume on US increased the likelihood of eventual diagnosis of precocious puberty.

Effect of different surface roughening treatment on polyether ether ketone and acrylic resin bonding: A pilot study.

BACKGROUND: As polyether ether ketone (PEEK) is a relatively new material in dentistry, its bonding properties with regard to dental acrylic base materials are not fully known. To ensure the long-term success of removable dentures with a PEEK framework, the base materials must be well bonded to each other. OBJECTIVES: The study aimed to investigate the effects of different kinds of surface roughening treatment on PEEK and acrylic resin bonding. MATERIAL AND METHODS: Eighty PEEK specimens (N = 80) were randomly divided into 5 groups (n = 16 per group) and subjected to various surface roughening treatment (control, grinding, sandblasting, tribochemical silica coating (CoJet), and sulfuric acid etching). Heat-polymerized acrylic resin was applied to the treated surfaces of the PEEK specimens. The shear bond strength (SBS) test, environmental scanning electron microscopy (ESEM) analysis and three-dimensional (3D) surface topography analysis were performed. The statistical analysis of the data was conducted using the analysis of variance (ANOVA) and Tukey's multiple comparison test. RESULTS: The one-way ANOVA showed significant differences in the SBS values between the groups (p = 0.001). Sandblasting, tribochemical silica coating and sulfuric acid etching resulted in high SBS values (p = 0.001). The highest SBS values were observed in the sulfuric acid etching group (8.83 ±3.63 MPa), while the lowest SBS values were observed in the control group (3.33 ±2.50 MPa). CONCLUSIONS: The additional roughening treatment applied to the PEEK surface increases the bond strength with heat-polymerized acrylic resin.

Investigation of color and physicomechanical properties of peek and pekk after storage in a different medium.

The aim of this study is to assess color stability, solubility, and water sorption on polyether ether ketone (PEEK) and polyether ketone ketone (PEKK) after immersion in different storage conditions. Material and Methods Ninety disc-shaped specimens (8 × 2) were obtained from CAD/CAM blocks [PEEK (n = 45) and PEKK (n = 45)]. Before immersion, baseline color value data were recorded with a spectrophotometer. The specimens were soaked in three solutions red wine, coffee, and distilled water at 37 °C for 28 days. Following immersion, color values were remeasured, and color-change values (ΔE) were calculated. Water sorption and solubility were assessed by mass gain or loss after storage in water for 28 days. The Kruskal-Wallis and the Mann-Whitney U test were used for analysis (P = 0.05). Results ΔE00 between PEEK and PEKK was significantly different statistically (P < 0.001). PEEK presented higher water sorption than PEKK (P = 0.005). The difference in solubility between PEEK and PEKK was not statistically significant (P = 0.163). The materials and storage medium types had a statistically significant impact (P = 0.100). In terms of staining potential, the solutions tested in this experiment were ranked as: coffee > red wine > distilled water. The results of this study demonstrated that PEKK was more successful in polymer-containing CAD/CAM materials as it exhibited less color change and water absorption.

Development of external genitalia during mini-puberty: is it related to somatic growth or reproductive hormones?

Although hypothalamo-pituitary-gonadal axis is active during mini-puberty, its relationship with somatic growth and the role on the development of external genitalia has not been fully elucidated. We aimed to evaluate the effects of somatic growth and reproductive hormones on the development of external genitalia during mini-puberty. Anthropometric data, pubertal assesment, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), sex-hormone binding globulin (SHBG), estradiol (E2) and inhibin-B, testosterone (T), and anti-Mullerian Hormone (AMH) of healthy infants aged 1-4 months were evaluated. Free sex hormone index was calculated as T/SHBG for boys and E2/SHBG for girls. The mean age of 148 (74 female) infants included in the study was 2.31 ± 0.76 months. Tanner stage 2-3 sex steroid and gonadotropin levels were observed. A statistically significant difference was found between the weight, height, BMI, weight gain and serum FSH, LH, and A4 measurements of girls and boys (p < 0.05). Penile length was associated with weight (r = 0.24, p = 0.03), height (r = 0.25, p = 0.02), and AMH (r = 0.3, p = 0.01), but not with testosterone (p = 0.56 respectively). A negative correlation was found between weight and serum LH (r = - 0.26, p = 0.2) and T/SHBG levels in males (r = - 0.38, p = 0.015 respectively). Weight-SDS was negatively correlated with testosterone in males (r = - 0.25, p = 0.02). Testicular size and breast stage did not correlate with any of the hormonal and anthropometric parameters.  Conclusions: External genitalia in males during mini-puberty is related more to somatic growth rather than reproductive hormones. Similar to pubertal developmental stages, both total and free testosterone are negatively associated with higher weight during mini-puberty. What is Known: • Mini-puberty allows early assessment of HPG axis function in infancy. • There is an inverse relationship between the amount of adipose tissue and circulating testosterone levels in males during puberty and adulthood. • The potential effect of somatic growth and reproductive hormones on external genital development during mini-puberty remains unclear. What is New: • During mini-puberty, males' external genitalia is more related to somatic growth than to reproductive hormones, but this relationship is not observed in girls. • Both total and free testosterone are negatively associated with higher weight during mini-puberty, similar to the pubertal developmental stages.

Rare forms of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to pathogenic variants in genes encoding enzymes and cofactors involved in adrenal steroidogenesis. Although 21-hydroxylase, 11ß-hydroxylase, 3ß-hydroxysteroid dehydrogenase type 2, 17α-hydroxylase/17,20-lyase, P450 oxidoreductase, steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme deficiencies are considered within the definition of CAH, the term 'CAH' is often used to refer to '21-hydroxylase deficiency (21OHD)' since 21OHD accounts for approximately 95% of CAH in most populations. The prevalence of the rare forms of CAH varies according to ethnicity and geographical location. In most cases, the biochemical fingerprint of impaired steroidogenesis points to the specific subtypes of CAH, and genetic testing is usually required to confirm the diagnosis. Despite there are significant variations in clinical characteristics and management, most data about the rare CAH forms are extrapolated from 21OHD. This review article aims to collate the currently available data about the diagnosis and the management of rare forms of CAH.

Venous thrombosis in a pseudohypoparathyroidism patient with a novel GNAS frameshift mutation and complete resolution of vascular calcifications with acetazolamide treatment.

Introduction Pseudohypoparathyroidism type IA (PHP1A) is characterized by end-organ resistance to multiple hormones and Albright's hereditary osteodystrophy (AHO). PHP1A is caused by inactivating mutations of the GNAS gene encoding the α-subunit of the stimulatory G protein (Gsα). In line with the underlying genetic defect, impaired inhibition of platelet aggregation has been demonstrated in some patients. However, no PHP1A case with thrombotic events has been described. Also, PHP1A cases typically have subcutaneous ossifications, but soft tissue calcifications are another common finding. Treatment options for those and other non-hormonal features of PHP1A are limited. Case Presentation A female patient presented with short stature, fatigue, and exercise-induced carpopedal spasms at age 117/12 years. Diagnosis of PHP1A was made based on hypocalcemia, hyperphosphatemia, elevated serum PTH, and AHO features, including short stature and brachydactyly. A novel frameshift variant was detected in the last exon of GNAS (c.1065_1068delGCGT, p.R356Tfs*47), showing complete loss of baseline and receptor-stimulated activity in transfected cells. The patient developed venous thrombosis and vascular and subcutaneous calcifications on both forearms after venous puncture on the right and extravasation of calcium gluconate during treatment on the left. The thrombosis and calcifications completely resolved following treatment with low molecular weight heparin and acetazolamide for 5 and 8 months, respectively. Conclusions This case represents the first PHP1A patient displaying thrombosis and the first successful use of acetazolamide for PHP1A-associated soft tissue calcifications, thus providing new insights into the treatment of non-endocrinological features in this disease.

Effects of repetitive firings on mechanical, optical, and phase formation changes of ceramic materials.

STATEMENT OF PROBLEM: Studies are sparse on how rapid heating and cooling negatively affect optical properties, including color and transparency, and mechanical properties, including hardness and durability, that affect esthetics and shorten the clinical usage period of the ceramics. PURPOSE: The purpose of this in vitro study was to determine the effects of repeated firing on the color difference, mechanical properties, and phase formation of different ceramic materials. MATERIAL AND METHODS: A total of 160 disks (12×1.35 mm) were produced from 4 different ceramic materials: lithium disilicate glass-ceramic, zirconia-reinforced lithium silicate ceramic, zirconia core, and monolithic zirconia. Specimens from all groups were divided into 4 groups (n=10) with a different number of veneer porcelain firings (1 to 4) by simple randomization. After the firings, color measurement, X-ray diffraction analysis, environmental scanning electron micrograph analysis, surface roughness evaluation, Vickers hardness evaluation, and biaxial flexural strength tests were performed. Data were analyzed with analysis of variance (2-way ANOVA) (α=.05). RESULTS: Repeated firing did not affect the flexural strength of the specimens in any of the groups (P>.05), while the color, surface roughness, and surface hardness were significantly affected (P<.05). The specimens fired 4 times showed the highest mean Vickers hardness and ΔE00 values but the lowest mean surface roughness values. Zirconia core specimens showed the highest mean ΔE00 and flexural strength values, and lithium disilicate glass-ceramic specimens had the highest mean Vickers hardness values. CONCLUSIONS: The increase in the number of firings affected the color, mechanical properties, and phase formation of the specimens; this change differed according to the ceramic tested.

Molecular analysis of MKRN3 gene in Turkish girls with sporadic and familial idiopathic central precocious puberty.

OBJECTIVES: Central precocious puberty (CPP) develops as a result of early stimulation of the hypothalamic-pituitary-gonadal (HPG) axis. The loss-of-function mutations in the Makorin-ring-finger3 (MKRN3) gene appear to be the most common molecular cause of familial CPP. We aimed to identify MKRN3 gene mutations in our CPP cohort and to investigate the frequency of MKRN3 mutations. METHODS: 102 patients with CPP included. 53 of them had family history of CPP in the first and/or second-degree relatives. MKRN3 gene was analyzed by next-generation sequencing. RESULTS: Possible pathogenic variants were found in 2/53 patients with family history of CPP (3.8%) and 1/49 patient without family history (2%). A novel heterozygous c.1A>G (p.Met1Val) mutation, a novel heterozygous c.683_684delCA (p.Ser228*) and a previously reported c.482dupC (Ala162Glyfs*) frameshift variations were detected. The two novel variants are predicted to be pathogenic in silico analyses. CONCLUSIONS: In our cohort, possible pathogenic variants in MKRN3 gene were detected in 2.9% of the total cohort, 3.8% of the familial and 2% of the nonfamilial cases, slightly lower than that reported in the literature. Two novel variants detected contribute to the molecular repertoire of MKRN3 defects in CPP. Classical pattern of paternal inheritance has been demonstrated in all three cases. However, the father of the patient 3 did not have history of CPP suggesting that the father inherited this variant from his mother and had phenotype skipping. Therefore, we emphasize that the absence of history of CPP in the father does not exclude the possibility of a MKRN3 mutation.

Challenges in the Management of a 7-Year-Old Child with Thyrotropin-Secreting Pituitary Adenoma and the Review of the Literature.

INTRODUCTION: Thyrotropin-producing pituitary adenoma (TSHoma) is a very rare disease, representing less than 1% of the pituitary tumours and presenting with elevated thyroid hormones and normal/high TSH concentrations. CASE PRESENTATION: A 7-year-old boy with nervousness was referred by his psychiatrist for elevated free T4, T3, and TSH levels. Initial evaluation revealed an elevated α-subunit. Pituitary magnetic resonance imaging (MRI) demonstrated a macroadenoma. The patient underwent a trans-sphenoidal tumour resection (TSS) which showed positive immunohistochemical staining for TSH, growth hormone, and prolactin in tumoral tissue. Euthyroidism was achieved for 1 year after TSS, then recurrence of tumour with elevated TSH and thyroid hormone levels necessitated a re-operation with TSS followed by gamma-knife radiosurgery. The euthyroid state was achieved and lasted for 2.5 years this time, but due to the recurrence, medical treatment had been commenced with cabergoline and octreotide. Euthyroidism was maintained for the last 4 years on monthly octreotide treatment. A repeat MRI demonstrated no pituitary mass, but a mass in the sphenoidal sinus had been detected. Removal of this mass by surgery did not achieve euthyroidism. 68Ga-DOTA-TATE positron emission tomography/computed tomography showed residual tissue extending from the pituitary region to the sphenoid sinus. The patient's bone age was advanced by 2 years at diagnosis which became 4 years in 1 year after the diagnosis and remained so throughout follow-up, leading to a final height of -3.3 SDS below his target height at the age of 16 years. CONCLUSION: The diagnosis, treatment, and follow-up of TSHomas are challenging, and short stature due to accelerated bone maturation is a complication of paediatric TSHomas.

Decline in the Age of Menarche in Istanbul Schoolgirls Over the Last 12 Years

Objective: Menarche is the endpoint of a sequence of maturational events of female puberty. The timing of menarche is a strongly heritable trait. However, secular trends suggest that lifestyle and environmental factors are important. To assess the trend in age at menarche (AAM), and its associated factors in Istanbul over the last 12 years. Methods: A cross-sectional study was carried out between March and April 2022 on schoolgirls aged 9-18 years. A predesigned and self-administered questionnaire was filled out anonymously by the students. The data of AAM was included in the statistical analysis if the time of AAM is remembered in both months and years. A probit model was used to calculate the median AAM. The findings were compared with those from a study performed 12 years ago in the same region of Istanbul. Results: Among 9000 girls to whom the questionnaire was distributed, 1749 (19.5%) responded. The median AAM of 1374 girls whose AAM information was considered valid was 12.04 years (95% confidence interval: 12.01-12.13), 0.7 years lower than was reported 12 years ago (p<0.0001). AAM was correlated positively with maternal AAM, and negatively with body mass index (BMI) standard deviation score and maternal educational status (p<0.0001, p<0.0001 and p=0.002), respectively. There was no correlation between the AAM and birth weight. Girls with BMI percentile ≥85% (n=251) had earlier menarche than the ones with BMI percentile <85% (n=1072) (11.5 vs. 12.1 years, p<0.0001). Among the mother-daughter pairs (n=1162), AAM of girls was 0.91 years (median 0.94 years) earlier than their mothers. Conclusion: The present study demonstrates a significant downward trend in the menarcheal age in Istanbul over the last twelve years. These findings support a strong contribution from genetic factors and BMI on AAM.

Non-hormonal Clitoromegaly due to Clitoral Priapism Caused by Appendicitis/Appendectomy

Clitoromegaly usually develops due to hyperandrogenism. There are a few cases of clitoromegaly described without clinical and biochemical hyperandrogenism. Clitoromegaly due to clitoral priapism and clitoral priapism after appendectomy have not been reported previously. A 7-year-old girl was referred for enlargement of the clitoris. She reported having a mild, pulsating clitoral pain starting three days after an appendectomy operation. Subsequently, painful swelling and an increase in the size of the clitoris was observed. Her growth and physical examination were otherwise normal. Causes of the clitoromegaly due to androgen excess were excluded after a comprehensive work-up. Color Doppler ultrasound revealed a high peak systolic velocity and resistance in the cavernosal artery, consistent with clitoral priapism. The clitoromegaly and associated symptoms improved significantly with oral pseudoephedrine and intracavernosal aspiration. This unique case illustrates that clitoral priapism is a rare, non-hormonal cause of clitoromegaly and may occur after appendectomy. Pseudoephedrine treatment is helpful in alleviating the symptoms.

Dysosteosclerosis: Clinical and Radiological Evolution Reflecting Genetic Heterogeneity.

Dysosteosclerosis (DSS), the term coined in 1968 for ultrarare dysplasia of the skeleton featuring platyspondyly with focal appendicular osteosclerosis, has become generic by encompassing the genetic heterogeneity recently reported for this phenotype. We studied four unrelated Turkish patients with DSS to advance understanding of the new nosology. Patient 1 suffered femur fractures beginning at age 1 year. DSS was suspected from marked metaphyseal osteosclerosis in early childhood and subsequently platyspondyly accompanying patchy osteosclerosis of her appendicular skeleton. She harbored in SLC29A3, in 2012 the first gene associated with DSS, a unique homozygous duplication (c.303_320dup, p.102_107dupYFESYL). Patient 2 presented similarly with fractures and metaphyseal osteosclerosis but with no platyspondyly at age 2 months. She was homozygous for a novel nonsense mutation in SLC29A3 (c.1284C>G, p.Tyr428*). Patient 3 had ocular disease at age 2 years, presented for short stature at age 11 years, and did not begin to fracture until age 16 years. Radiographs showed mild platyspondyly and focal metaphyseal and femoral osteosclerosis. She was homozygous for a unique splice site mutation in TNFRSF11A (c.616+3A>G). Patient 4 at age 2 years manifested developmental delay and frequent infections but did not fracture. He had unique metadiaphyseal splaying and osteosclerosis, vertebral end-plate osteosclerosis, and cortical thinning of long bones but no mutation was detected of SLC29A3, TNFRSF11A, TCIRG1, LRRK1, or CSF1R associated with DSS. We find that DSS from defective SLC29A3 presents earliest and with fractures. DSS from compromised TNFRSF11A can lead to optic atrophy as an early finding. Negative mutation analysis in patient 4 suggests further genetic heterogeneity underlying the skeletal phenotype of DSS. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Homozygosity for a novel INHA mutation in two male siblings with hypospadias, primary hypogonadism, and high-normal testicular volume.

Background: The human INHA gene encodes the inhibin subunit alpha protein, which is common to both inhibin A and B. The functional importance of inhibins in male sex development, sexual function, and reproduction remain largely unknown. Objective: We report for the first time two male siblings with homozygous INHAmutations. Methods: The medical files were examined for clinical, biochemical, and imaging data. Genetic analysis was performed using next-generation and Sanger sequencing methods. Results: Two brothers complained of gynecomastia, testicular pain, and had a history of hypospadias. Biochemistry revealed low serum testosterone, high gonadotropin and anti-Mullerian hormone, and very low/undetectable inhibin concentrations, where available. Both patients had azoospermia in the spermiogram. We have identified a homozygous 2 bp deletion (c.208_209delAG, R70Gfs*3) variant, which leads to a truncated INHA protein in both patients, and confirmed heterozygosity in the parents. The external genital development, pubertal onset and progression, reproductive functions, serum gonadotropins, and sex hormones of mother and father, who were heterozygous carriers of the identified mutation, were normal. Conclusion: Homozygosity for INHA mutations causes decreased prenatal and postnatal testosterone production and infertility in males, while the heterozygous female and male carriers of INHA mutations do not have any abnormality in sex development and reproduction.

Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency.

CONTEXT: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. OBJECTIVE: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. METHODS: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. RESULTS: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. CONCLUSION: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

Evaluation of the effects of different surface modification methods on the bond strength of high-performance polymers and resin matrix ceramics.

OBJECTIVES: The purpose of this in vitro study was to investigate the effects of various surface treatment methods on the shear bond strength of self-adhesive resin cement to polymer-infiltrated materials. MATERIALS AND METHODS: One hundred twenty-eight polymer-infiltrated specimens (n = 32) for four different computer aided design-computer-aided manufacturing (CAD-CAM) materials, polyether ether ketone (PEEK) (PE), polyether ketone ketone (PEKK) (PK), composite resin nanoceramic (Cerasmart) (CS), and polymer-infiltrated ceramic network (PICN) (VITA ENAMIC) (VE) were milled from CAD-CAM blocks. They were divided into two groups (n = 16) in terms of surface treatments: airborne-particle abraded (AA) or silica-coated (SC) and two subgroups (n = 8) according to adhesive application or no adhesive. The surface roughness, contact angle, and shear bond strength (SBS) values of specimens were measured. Data were analyzed with Shapiro-Wilk test, the generalized linear models' method, and Bonferroni corrected t test (α ˂ 0.05). RESULTS: No statistically significant differences were found between the groups in terms of surface roughness and SBS values (P > 0.05). A statistically significant effect of the main adhesive interaction on the bond strength was found independent of the material and surface treatments (P < 0.001). While the average bond strength of the non-adhesive was 4.9 MPa, the average of the adhesive applied was 9.1 MPa. On the other hand, there is a statistically significant difference between the means of the contact angle values (P ˂ 0.001). While the highest mean contact angle value was 117.1 ± 14.8° obtained from the non-adhesive PK in the AA group, the lowest mean contact angle value 22.6 ± 4.3° was obtained from the VE without adhesive in the SC group. CONCLUSIONS: Roughness and SBS values were similar between groups after surface treatments. Adhesive application increased the SBS values. Surface treatments were found to have an effect on the contact angle. CLINICAL RELEVANCE: Since the AA and SC surface treatments used in the study show similar bond strength values, the Cojet system, which is more practical and easier to use, can be preferred as an alternative to AA after restoration production with CAD-CAM as a chairside.

Efficacy of the Novel Degludec/Aspart Insulin Co-formulation in Children and Adolescents with Type 1 Diabetes: A Real-life Experience with One Year of IDegAsp Therapy in Poorly Controlled and Non-compliant Patients

Objective: To evaluate the efficacy of degludec/aspart (IDegAsp) insulin co-formulation in children and adolescents with poorly controlled type 1 diabetes (T1DM). Methods: Patients with poorly controlled T1DM on basal-bolus insulin regimes and having compliance problems related to insulin injections were switched to IDegAsp and were included. Data on hemoglobin A1c (HbA1c) levels, hypoglycemic episodes, frequency of diabetic ketoacidosis (DKA) and insulin doses were recorded at baseline and after one year of IDegAsp treatment. Results: Fifty patients (22 girls; 44%) were started on IDegAsp. The mean±standard deviation (range) age and duration of diabetes were 12.9±3.4 (4-18) and 5.2±3.1 (1.0-13.7) years, respectively. At the end of one year, 38 patients were still on IDegAsp, whereas 12 patients had opted to resume their original treatments. In those who continued on IDegAsp, HbA1c levels did not change, but the number of self-reported mild-moderate hypoglycemic episodes decreased significantly (p<0.05). In the year before switching to IDegAsp, 11 DKA attacks in 9 patients were observed, whereas this decreased to 4 DKA attacks in 4 patients after one year of IDegAsp therapy (p=0.06). Conclusion: IDegAsp regimen may improve clinical management in poorly controlled basal-bolus insulin regimen T1DM patients who have frequent hypoglycemia and DKA attacks, as well as in those with poor compliance with multiple injections. Although a simplified basal-bolus IDegAsp regimen is an attractive option for patients with T1DM, some may not adapt to this treatment due to the fixed IAsp dose of IDegAsp.

Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency.

BACKGROUND: Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up. OBJECTIVE: Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment. DESIGN AND METHOD: Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses. RESULTS: Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I. CONCLUSIONS: Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.

Effects of different polishing procedures on the surface roughness and hardness of polyether ether ketone (PEEK) / Efecto de diferentes procedimientos de pulido en la rugosidad y dureza de superficie de un material a base de poliéter éter acetona (PEEK)

ABSTRACT: There is insufficient information about the chairside polishing methods of polyether ether ketone material. Therefore, it is aimed in this study to investigate the effects of different polishing processes on polyether ether ketone surface roughness and hardness. A total of 66 disc-shaped specimens made of polyether ether ketone were used in this study. The specimens were polished conventionally and randomly divided into three groups (n=22). One group was designated as the control group, and no further treatment was applied. In the other two groups, the specimens' surfaces were abraded with diamond burs and polished using two different polishing kits. Their surface roughness and Vickers hardness were measured, and environmental scanning electron microscopy and atomic force microscopy examinations were performed. The data were statistically analysed using analysis of variance and Tukey's honest significant difference test (α=0.05). There were no statistically significant differences between the control and polishing kit groups in terms of either surface roughness or Vickers hardness (p>0.05). The polishing kits can be used reliably and effectively for polishing polyether ether ketone materials.

RESUMEN: No existe información suficiente sobre los métodos de pulido del material poliéter éter cetona. Por tanto, este estudio tiene como objetivo evaluar el efecto de diferentes procedimientos de pulido sobre la rugosidad y dureza de superficie de un material a base de poliéter éter acetona. Un total de 66 muestras en forma de disco fueron realizadas. Los especímenes fueron divididos en tres grupos (n=22). Un grupo fue designado como grupo de control, siendo que no se aplicó ningún tratamiento. En los otros dos grupos, las superficies de las muestras se lijaron con fresas de diamante y se pulieron con dos kits de pulido diferentes. Se investigó la rugosidad de superficie y la dureza Vickers en los diferentes grupos. También fueron evaluadas muestras representativas en microscopía electrónica de barrido y microscopía de fuerza atómica. Los datos se analizaron estadísticamente mediante el análisis de varianza (ANOVA) y el método de Tukey (α=0.05). No hubo diferencias estadísticamente significativas entre los grupos en términos de rugosidad de superficie o Dureza Vickers (p>0,05). Los kits de pulido se pueden utilizar de forma eficaz para el pulido de materiales a base de poliéter éter acetona.

Broad-spectrum XX and XY gonadal dysgenesis in patients with a homozygous L193S variant in PPP2R3C.

CONTEXT: Homozygous and heterozygous variants in PPP2R3C are associated with syndromic 46,XY complete gonadal dysgenesis (Myo-Ectodermo-Gonadal Dysgenesis (MEGD) syndrome), and impaired spermatogenesis, respectively. This study expands the role of PPP2R3C in the aetiology of gonadal dysgenesis (GD). METHOD: We sequenced the PPP2R3C gene in four new patients from three unrelated families. The clinical, laboratory, and molecular characteristics were investigated. We have also determined the requirement for Ppp2r3c in mice (C57BL6/N) using CRISPR/Cas9 genome editing. RESULTS: A homozygous c.578T>C (p.L193S) PPP2R3C variant was identified in one 46,XX girl with primary gonadal insufficiency, two girls with 46,XY complete GD, and one undervirilised boy with 46,XY partial GD. The patients with complete GD had low gonadal and adrenal androgens, low anti-Müllerian hormone, and high follicle-stimulating hormone and luteinizing hormone concentrations. All patients manifested characteristic features of MEGD syndrome. Heterozygous Ppp2r3c knockout mice appeared overtly normal and fertile. Inspection of homozygous embryos at 14.5, 9.5, and 8.5 days post coitum(dpc) revealed evidence of dead embryos. We conclude that loss of function of Ppp2r3c is not compatible with viability in mice and results in embryonic death from 7.5 dpc or earlier. CONCLUSION: Our data indicate the essential roles for PPP2R3C in mouse and human development. Germline homozygous variants in human PPP2R3C are associated with distinctive syndromic GD of varying severity in both 46,XY and 46,XX individuals.