Dual oxidase (DUOX) system genes defects in Children with Congenital Hypothyroidism

Endocrinology ◽  
2021 ◽  
Author(s):  
Fengqi Wang ◽  
Li Xiaole ◽  
Ruixin Ma ◽  
Dehua Zhao ◽  
Shiguo Liu
Keyword(s):  
Congenital Hypothyroidism ◽  
Functional Domain ◽  
Target Region ◽  
Pathogenic Variants ◽  
Significant Difference ◽  
Ef Hand ◽  
Dual Oxidase ◽  
Variation Rate ◽  
Relationship Of

Abstract Purpose The objectives of this study were to analyze the distribution of Dual oxidase (DUOX) system genes (containing DUOX2, DUOX1, DUOXA2 and DUOXA1) variants in children with congenital hypothyroidism and their phenotypes. Methods Target region sequencing technology was performed on DUOX system genes among 606 congenital hypothyroidism (CH) subjects covering all the exon and intron regions. Detailed clinical data were collected for statistical analysis. Results A total of 95 suspected pathogenic variants were detected in the DUOX system genes, showing a 39.11% rate in variant carrying (237/606). DUOX2 was with the highest rate in this study. There were statistical difference in maximum adjusted dose and current dose of L-T4 between the DUOX system genes non-mutated group with the mutated group (p<0.001; p<0.001). The cases in DUOX system genes mutated group were more likely to develop into transient CH (χ 2 = 23.155, p<0.001) and more likely to manifested as goiter or gland-in-situ (χ 2 = 66.139, p<0.001). In addition, there was no significant difference in clinical characteristics between DUOX system genes mono-allelic and non mono-allelic. Although 20% of the variants affected the functional domain regions (EF hand, and FAD and NADPH binding sites), there was no significant effect on the phenotype severity whether the variation is located in the functional domain regions. Conclusions Our results showed the high variation rate of DUOX2 in the DUOX system genes among the Chinese CH patients. And the complex genotype-phenotype relationship of DUOX system genes broadened the understanding of CH phenotype spectrum.

Pancreas cancer: Influence of gender and other demographic and clinical parameters on survival.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Patricia Renee Blank ◽  
Thomas D. Szucs
Keyword(s):  
Pancreas Cancer ◽  
Total Sample ◽  
The United States ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Cox Proportional Hazard Models ◽  
Male Patients ◽  
Disease Stages ◽  
Relationship Of

200 Background: Research suggests that lower excess mortality risk for females compared to men do exist for several cancer types. The primary aim of this study was to investigate whether gender affects pancreas cancer (PC) prognosis. In addition, the relationship of gender and survival adjusted for clinical and demographic factors was assessed. Methods: The SEER database (version 1973-2009) was used to identify patients with primary histological confirmed PC (≥18 years, 80,689 males and 82,356 females) in the United States. The analysis was stratified by five different stages according to the categories of the American Joint Committee on Cancer (in situ, locally invasive, regional, distant, unstaged). The crude effect of gender was assessed in the total sample and in age-stratified Kaplan-Meier Curves (<55 years) in all five stages, respectively. Univariate and multivariate Cox proportional hazard models were run within the local stage at diagnosis. The predictors included in the models were demographic and clinical factors based on a prior clinical and scientific knowledge. Two-sided p-values of 0.05 were assumed as statistical significant. Results: In total, 128,645 PC-related deaths were reported with a median follow-up time of 13 months (censored patients). Kaplan-Meier curves showed a significant difference in survival among men and female in the locally invasive group (median survival in male and female: 7 months; 1-year survival: 35.5% and 35.1% among female and men, respectively; Log-Rank: p=0.0072). The remaining strata had non-significant differences (p= <.0001), except the unstaged group. The local recurrence group had a 5.6% (95%CI: 1.4%, 9.9%, p=0.0081) higher rate of dying among men compared to female. Among the population <55 years, the gender difference was significant across all disease stages, except the in situ group. Histology grade, age, race, and marital status was associated with survival from PC in the multivariate analysis. Conclusions: The present study indicates that male patients with PC have a worse prognosis than female patients. However, these results need validation and further studies are needed in the research on the prognostic value of gender in PC survival.

Increse of newly - detected in situ cancers in non-palpable breast lesions

2006 ◽  
Vol 53 (1) ◽  
pp. 73-75
Author(s):  
N. Miletic ◽  
D. Stojiljkovic ◽  
M. Inic ◽  
M. Prekajski ◽  
A. Celebic ◽  
...  
Keyword(s):  
Breast Tissue ◽  
Malignant Disease ◽  
Clinical Stage ◽  
Diagnostic Procedures ◽  
Basal Membrane ◽  
Needle Aspiration ◽  
Screening Mammography ◽  
Significant Difference ◽  
Malignant Lesions

Great importance in detecting cancer in the phase of in situ lays in the fact that the epithelial layer is deprived of blood and lymph vessels, so metastases may develop only when basal membrane has been broken. This paper includes 46 operated women in whom it preoperatively had been verified suspect non-palpable lesion. The preoperative diagnostics included use of high- resolution mammography, aimed mammography, palpatory examination, as well as fine-needle aspiration (FNA), biopsy and cytologic analysis of the sample. The methodology of this work implies the use of stereotaxic marking, specimen mammography and ex-tempore pathohistology analysis. Out of 46 investigated patients in clinical stage T0N0M0, in whom there were no signs of malignant disease, and according to suspect lesion of initial screening mammography, malignant lesions of breast tissue were diagnosed in 19 patients (41%) intraoperatively. Three of these lesions (15,8%) were histopathologically verified as in situ. Comparing our results with data of the Institute of oncology and radiology of Serbia hospital registry (IORS) for the year 2001, from 1173 patients registered with malignant lesions, only 16 ones (1,4%) had in situ cancer, operated on the basis of the suspect mammography of clinical stage T0N0M0. Statistically significant difference was found related to the number of detected cancers in this early phase of the breast malignant disease. This limits surgical intervention to tumorectomy, with preservation of the remaining breast tissue, what brings to healing, justifying in that way, screening examinations and routine application of the most contemporary diagnostic procedures.

scholarly journals Testing telediagnostic thyroid ultrasound in Peru: a new horizon in expanding access to imaging in rural and underserved areas

2021 ◽  
Author(s):  
T. J. Marini ◽  
S. L. Weiss ◽  
A. Gupta ◽  
Y. T. Zhao ◽  
T. M. Baran ◽  
...  
Keyword(s):  
Thyroid Nodule ◽  
Standard Of Care ◽  
The United States ◽  
Epidemiological Studies ◽  
Thyroid Ultrasound ◽  
Target Region ◽  
Experienced Radiologist ◽  
Significant Difference ◽  
Size Evaluation

Abstract Purpose Thyroid ultrasound is a key tool in the evaluation of the thyroid, but billions of people around the world lack access to ultrasound imaging. In this study, we tested an asynchronous telediagnostic ultrasound system operated by individuals without prior ultrasound training which may be used to effectively evaluate the thyroid and improve access to imaging worldwide. Methods The telediagnostic system in this study utilizes volume sweep imaging (VSI), an imaging technique in which the operator scans the target region with simple sweeps of the ultrasound probe based on external body landmarks. Sweeps are recorded and saved as video clips for later interpretation by an expert. Two operators without prior ultrasound experience underwent 8 h of training on the thyroid VSI protocol and the operation of the telemedicine platform. After training, the operators scanned patients at a health center in Lima. Telediagnostic examinations were sent to the United States for remote interpretation. Standard of care thyroid ultrasound was performed by an experienced radiologist at the time of VSI examination to serve as a reference standard. Results Novice operators scanned 121 subjects with the thyroid VSI protocol. Of these exams, 88% were rated of excellent image quality showing complete or near complete thyroid visualization. There was 98.3% agreement on thyroid nodule presence between VSI teleultrasound and standard of care ultrasound (Cohen’s kappa 0.91, P < 0.0001). VSI measured the thyroid size, on average, within 5 mm compared to standard of care. Readers of VSI were also able to effectively characterize thyroid nodules, and there was no significant difference in measurement of thyroid nodule size (P = 0.74) between VSI and standard of care. Conclusion Thyroid VSI telediagnostic ultrasound demonstrated both excellent visualization of the thyroid gland and agreement with standard of care thyroid ultrasound for nodules and thyroid size evaluation. This system could be deployed for evaluation of palpable thyroid abnormalities, nodule follow-up, and epidemiological studies to promote global health and improve the availability of diagnostic imaging in underserved communities.

scholarly journals SMILE and Wavefront-Guided LASIK Out-Compete Other Refractive Surgeries in Ameliorating the Induction of High-Order Aberrations in Anterior Corneal Surface

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Min-jie Ye ◽  
Cai-yuan Liu ◽  
Rong-feng Liao ◽  
Zheng-yu Gu ◽  
Bing-ying Zhao ◽  
...  
Keyword(s):  
Spherical Aberration ◽  
Laser In Situ Keratomileusis ◽  
Small Incision Lenticule Extraction ◽  
Corneal Surface ◽  
Small Incision ◽  
Significant Difference ◽  
Lenticule Extraction ◽  
A Prospective Study ◽  
High Order Aberrations

Purpose. To compare the change of anterior corneal higher-order aberrations (HOAs) after laser in situ keratomileusis (LASIK), wavefront-guided LASIK with iris registration (WF-LASIK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE).Methods. In a prospective study, 82 eyes underwent LASIK, 119 eyes underwent WF-LASIK, 88 eyes underwent FS-LASIK, and 170 eyes underwent SMILE surgery. HOAs were measured with Pentacam device preoperatively and 6 months after surgery. The aberrations were described as Zernike polynomials, and analysis focused on total HOAs, spherical aberration (SA), horizontal coma, and vertical coma over 6 mm diameter central corneal zone.Results. Six months postoperatively, all procedures result in increase of anterior corneal total HOAs and SA. There were no significant differences in the induced HOAs between LASIK and FS-LASIK, while SMILE induced fewer total HOAs and SA compared with LASIK and FS-LASIK. Similarly, WF-LASIK also induced less total HOAs than LASIK and FS-LASIK, but only fewer SA than FS-LASIK (P<0.05). No significant difference could be detected in the induced total HOAs and SA between SMILE and WF-LASIK, whereas SMILE induced more horizontal coma and vertical coma compared with WF-LASIK (P<0.05).Conclusion. FS-LASIK and LASIK induced comparable anterior corneal HOAs. Compared to LASIK and FS-LASIK, both SMILE and WF-LASIK showed advantages in inducing less total HOAs. In addition, SMILE also possesses better ability to reduce the induction of SA in comparison with LASIK and FS-LASIK. However, SMILE induced more horizontal coma and vertical coma compared with WF-LASIK, indicating that the centration of SMILE procedure is probably less precise than WF-LASIK.

scholarly journals High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

2021 ◽  
pp. jmedgenet-2020-107347
Author(s):  
D Gareth Evans ◽  
Elke Maria van Veen ◽  
Helen J Byers ◽  
Sarah J Evans ◽  
George J Burghel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Ductal Carcinoma ◽  
Cancer Genes ◽  
Early Onset Breast Cancer ◽  
Younger Women ◽  
Pathogenic Variants ◽  
Younger Age ◽  
Predisposition Genes

BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

Infants Diagnosed with Athyreosis on Scintigraphy May Have a Gland Present on Ultrasound and Have Transient Congenital Hypothyroidism

2021 ◽  
pp. 1-8
Author(s):  
Niamh McGrath ◽  
Colin Patrick Hawkes ◽  
Stephanie Ryan ◽  
Philip Mayne ◽  
Nuala Murphy
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Thyroid Tissue ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Ultrasound ◽  
Free T4 ◽  
Median Serum ◽  
Thyroid Glands ◽  
Rule Out

Scintigraphy using technetium-99m (<sup>99m</sup>Tc) is the gold standard for imaging the thyroid gland in infants with congenital hypothyroidism (CHT) and is the most reliable method of diagnosing an ectopic thyroid gland. One of the limitations of scintigraphy is the possibility that no uptake is detected despite the presence of thyroid tissue, leading to the spurious diagnosis of athyreosis. Thyroid ultrasound is a useful adjunct to detect thyroid tissue in the absence of <sup>99m</sup>Tc uptake. <b><i>Aims:</i></b> We aimed to describe the incidence of sonographically detectable in situ thyroid glands in infants scintigraphically diagnosed with athyreosis using <sup>99m</sup>Tc and to describe the clinical characteristics and natural history in these infants. <b><i>Methods:</i></b> The newborn screening records of all infants diagnosed with CHT between 2007 and 2016 were reviewed. Those diagnosed with CHT and athyreosis confirmed on scintigraphy were invited to attend a thyroid ultrasound. <b><i>Results:</i></b> Of the 488 infants diagnosed with CHT during the study period, 18/73 (24.6%) infants with absent uptake on scintigraphy had thyroid tissue visualised on ultrasound (3 hypoplastic thyroid glands and 15 eutopic glands). The median serum thyroid-stimulating hormone (TSH) concentration at diagnosis was significantly lower than that in infants with confirmed athyreosis (no gland on ultrasound and no uptake on scintigraphy) (74 vs. 270 mU/L), and median free T4 concentration at diagnosis was higher (11.9 vs. 3.9 pmol/L). Six of 10 (60%) infants with no uptake on scintigraphy but a eutopic gland on ultrasound had transient CHT. <b><i>Conclusion:</i></b> Absent uptake on scintigraphy in infants with CHT does not rule out a eutopic gland, especially in infants with less elevated TSH concentrations. Clinically, adding thyroid ultrasound to the diagnostic evaluation of infants who have athyreosis on scintigraphy may avoid committing some infants with presumed athyreosis to lifelong levothyroxine treatment.

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

Verification of In Situ Thresholds and Integrated Real-Ear Measurements

2010 ◽  
Vol 21 (10) ◽  
pp. 663-670 ◽  
Author(s):  
Jeffrey J. DiGiovanni ◽  
Ryan M. Pratt
Keyword(s):  
Measurement System ◽  
Hearing Aids ◽  
Hearing Aid ◽  
Normal Hearing ◽  
Analysis Tool ◽  
Ohio University ◽  
Positive Direction ◽  
Significant Difference ◽  
Threshold Measurement

Background: Accurate prescriptive gain results in a more accurate fit, lower return rate in hearing aids, and increased patient satisfaction. In situ threshold measurements can be used to determine required gain. The Widex Corporation uses an in situ threshold measurement strategy, called the Sensogram. Real-ear measurements determine if prescriptive gain targets have been achieved. Starkey Laboratories introduced an integrated real-ear measurement system in their hearing aids. Purpose: To determine whether the responses obtained using the Widex Sensogram were equivalent to those obtained using current clinical threshold measurement methods. To determine the accuracy of the Starkey IREMS™ (Integrated Real Ear Measurement System) in measuring RECD (real-ear to coupler difference) values compared to a dedicated real-ear measurement system. Research Design: A verification design was employed by comparing participant data measured from standard, benchmark equipment and procedures against new techniques offered by hearing-aid manufacturers. Study Sample: A total of 20 participants participated in this study. Ten participants with sensorineural hearing loss were recruited from the Ohio University Hearing, Speech, and Language Clinic participated in the first experiment. Ten participants with normal hearing were recruited from the student population at Ohio University participated in both experiments. The normal-hearing group had thresholds of 15 dB HL or better at the octave frequencies of 250–8000 Hz. The hearing-impaired group had thresholds of varying degrees and configurations with thresholds equal to or poorer than 25 dB HL three-frequency pure-tone average. Data Collection and Analysis: The order of measurement method for both experiments was counterbalanced. In Experiment 1, thresholds obtained via the Widex Sensogram were compared to thresholds obtained for each participant using a clinical audiometer and ER-3A insert ear phones. In Experiment 2, RECD values obtained via the Starkey IREMS were compared to RECD values obtained via the Audioscan Verifit™. A repeated-measures analysis of variance (ANOVA) was used for statistical analysis, and a Fisher's LSD (least significant difference) was used as a post hoc analysis tool. Results: A significant difference between Sensogram thresholds and conventional audiometric thresholds was found with the Sensogram method resulting in better threshold values at 0.5, 1.0, and 2.0 kHz for both groups. In Experiment 2, a significant difference between RECD values obtained by the Starkey IREMS and the Audioscan Verifit system was found with significant differences in RECD values found at 0.25, 0.5, 0.75, 1.5, 2.0, and 6.0 kHz. Conclusions: The Sensogram data differ significantly from traditional audiometry at several frequencies important for speech intelligibility. Real-ear measures are still required for verification of prescribed gain, however, calling into question any claims of shortened fitting time. The Starkey IREMS does perform real-ear measurements that vary significantly from benchmark equipment. These technologies represent a positive direction in prescribing accurate gain during hearing-aid fittings, but a stand-alone system is still the preferred method for real-ear measurements in hearing-aid fittings.

scholarly journals MUC1 and MUC5AC Acting on Helicobacter pylori-Related Deficiency and Solid Syndrome of Spleen and Stomach

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Ling Hu ◽  
Wanqun Chen ◽  
Ming Cheng ◽  
Ting Zhang ◽  
Shaoyang Lan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Dynamic Equilibrium ◽  
Deficiency Syndrome ◽  
Blue Staining ◽  
Significant Difference ◽  
Tai Ji ◽  
Hematoxylin And Eosin ◽  
Relationship Of ◽  
Heat Syndrome ◽  
The Relationship

To investigate the relationship of MUC1, MUC5AC, and the syndrome of spleen and stomach, 109 subjects (34 peptic ulcer (PU), 62 chronic gastritis (CG), and 13 healthy volunteers (CON)) were included. All the subjects included were surveyed with questionnaire to classify them into damp-heat syndrome of spleen and stomach (DHSS), spleen-qi deficiency syndrome (SQD), and CON, examined by gastric endoscope, and biopsied. Rapid urease and methylene blue staining (MBS) were performed on every subject to diagnose for Helicobacter pylori (Hp) infection, and both were defined as Hp-positive. Hematoxylin and eosin (HE) staining was performed on every specimen to explore the histomorphology, inflammatory degree, and inflammatory activity of different groups; then Elivision™ plus kit was used to test the expression of MUC1 and MUC5AC. All the results of digital images were reviewed by two experts blindly. The inflammatory degree with Hp infection was higher than those uninfected or CON, but no significant difference was found between DHSS and SQD. And the expressions of MUC5AC with positive Hp was higher than those with negative Hp or CON regardless of the deficiency and solid syndrome of spleen-stomach but not for MUC1. We speculate that the deficiency and solid syndrome of spleen-stomach is a condition like Tai Ji symbol of dynamic equilibrium, showing the higher expression of MUC5AC but no change of MUC1 in the circumstance of Hp infection.

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