OBJECTIVE: This study investigated the influence of photoinitiator types on degree of conversion (DC), rate of polymerization (RP), flexural strength (FS), flexural modulus (FM), and light transmittance (LT) of filled and unfilled light-curable resin cements through different thicknesses and shades of lithium disilicate ceramics.
METHODS: Lithium disilicate ceramic discs (IPS Emax Press, background [0.0], 0.5, 1.0, 2.0, 3.0, and 4.0 mm, shades A1 and BL3) were prepared. Experimental resin-based cements [TEGDMA/BisGMA (50/50 mass%)] were prepared using either camphorquinone (CQ)/amine (0.44/1.85 mol%) or TPO (0.44 mol%)], and a micro and nanofiller loads of nil (unfilled); 40/10 mass%; and 50/10 mass%). Resin cements (0.2 mm thick) were placed on the lower surface of the ceramic specimens and light-activated for 30 s from the upper surface using a Bluephase Style curing light (exitance at tip: 1236 mW/cm2 ± 1.20). LT and distribution of irradiance through the ceramics were measured using a UV-vis spectrometer and a beam profile camera, respectively (n = 3). The DC and RP were measured in real-time using mid infrared spectroscopy in attenuated total reflectance (ATR) mode (n = 3). FS and FM were measured using a universal testing machine (n = 5). Statistical analyses were performed on LT, DC, RP, FS, and FM data using a general linear model, and supplementary ANOVA and post hoc Tukey multiple comparison test were also performed (α = .05).
RESULTS: Thicknesses, shades, photoinitiator type, and fillers load significantly influenced the optical and mechanical characteristics of the resin-based materials (p < 0.05). The BL3 shade ceramic provided higher values of DC, RP, FS, FM, and LT compared with the A1 shade (p < 0.05). Increasing ceramic thickness decreased the properties of the resin-based materials (p < 0.05). Generally, TPO improved mechanical properties of the resin cement compared with CQ (p < 0.05).
CONCLUSIONS: The luting process of indirect restorations may be improved by using high molar absorptivity, more reactive, and more efficient photoinitiators such as TPO, as opposed to conventional CQ. The use of such initiator may allow the placement of thicker and more opaque indirect restorations.

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

The intricate network of glands and organs that makes up the endocrine system. Hormones are used to regulate and synchronize the nervous and physiological systems. The agents which perturbate an endocrine system are called endocrine disruptors and they can eventually affect cellular proliferation and differentiation in target tissues. A subclass of endocrine disruptors known as thyroid disruptors (TDs) or thyroid disrupting chemicals (TDCs) influence the hypothalamo-pituitary-thyroid axis or directly interfere with thyroid function by binding to thyroid hormone receptors. Thyroid hormone levels in circulation are now included in more test guidelines (OECD TG 441, 407, 408, 414, 421/422, 443/416). Although these might be adequate to recognize thyroid adversity, they are unable to explain the underlying mechanism of action. Thyroid peroxidase (TPO) and sodium iodide symporter (NIS), two proteins essential in the biosynthesis of thyroid hormones, are well-accepted molecular targets for inhibition. The screening of a large number of molecules using high throughput screening (HTS) requires a minimum quantity of sample, cost, and time consuming. Whereas 3-dimensional quantitative structure-activity relationship (3D-QSAR) analysis can screen the TDCs before synthesizing a compound. In the present study, the human TPO (hTPO) and NIS (hNIS) structures were modelled using homology modeling and the quality of the structures was validated satisfactorily using MD simulation for 100ns. Further, 190 human TPO inhibitors with IC50 were curated from Comptox and docked with the modelled structure of TPO using D238, H239 and D240 centric grid. The binding conformation of a molecule with low binding energy was used as a reference and the rest other molecules were aligned after generating the possible conformers. The activity-stratified partition was performed for aligned molecules and training set (139), test set (51) were defined. The machine learning models such as k Nearest Neighbor (kNN) and Random Forest (RF) models were built and validated using external experimental dataset containing 10 molecules. Among the 10 molecules, all 10 molecules were identified as TPO inhibitors and demonstrated 100 % accuracy qualitatively. To confirm the selective TPO inhibition all 10 molecules were docked with the modelled structure of hNIS and the results have demonstrated the selective TPO inhibition.

OBJECTIVE: Magnetic resonance imaging-guided laser interstitial thermal therapy (MRIgLITT) has been proven safe and effective for the treatment of focal epilepsy of different etiologies. It has also been used to disconnect brain tissue in more extensive or diffuse epilepsy, such as corpus callosotomy and hemispherotomy.
METHODS: In this study, we report a case of temporo-parieto-occipital disconnection surgery performed using MRIgLITT assisted by a robotic arm for refractory epilepsy of the posterior quadrant. A highly realistic cadaver simulation was performed before the actual surgery.
RESULTS: The patient was a 14-year-old boy whose seizures began at the age of 8. The epilepsy was a result of a left perinatal ischemic event that caused a porencephalic cyst, and despite receiving multiple antiepileptic drugs, the patient continued to experience daily seizures which led to the recommendation of surgery.
CONCLUSIONS: A Wada test lateralized language in the right hemisphere. Motor and sensory function was confirmed in the left hemisphere through magnetic resonance imaging functional studies and NexStim. The left MRIgLITT temporo-parieto-occipital disconnection disconnection was achieved using 5 laser fibers. The patient followed an excellent postoperative course and was seizure-free, with no additional neurological deficits 24 months after the surgery.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder determined by immune-mediated platelet demolition and reduction of platelet production. Romiplostim is a new thrombopoiesis motivating peptibody that binds and stimulates the human thrombopoietin receptor the patent of which was registered in 2008. It is used to treat thrombocytopenia in patients with chronic immune thrombocytopenic purpura. Romiplostim is a 60 kDa peptibody designed to inhibit cross-reacting immune responses. It consists of four high-affinity TPO-receptor binding domains for the Mpl receptor and one human IgG1 Fc domain. Escherichia coli is a good host for the fabrication of recombinant proteins such as romiplostim. The expression of a gene intended in E. coli is dependent on many factors such as a protein\'s inherent ability to fold, mRNA\'s secondary structure, its solubility, its toxicity preferential codon use, and its need for post-translational modification (PTM). This review focuses on the structure, function, mechanism of action, and expressive approach to romiplostim in E. coli.

Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3-1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg, Tpo, Interleukin-6 (Il6), and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG, TPO, IL6, and IL10 were elevated in Nthy ori3-1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid.

The introduction of thrombopoietin receptor agonists (TPO-RAs) led to a paradigm shift in the management of immune thrombocytopenia (ITP). However, TPO-RAs are not approved for use during pregnancy due to the absence of evidence and concerns for possible effects on the fetus due to their expected transplacental transfer. This comprehensive review examines the safety and efficacy of TPO-RA in 45 pregnancies of women with ITP (romiplostim n = 22; eltrombopag n = 21; both in the same pregnancy n = 2). Mothers experienced failure of the median of three treatment lines during pregnancy prior to TPO-RA administration. A platelet response (>30 × 109 /L) was seen in 86.7% of cases (including a complete response >100 × 109 /L in 66.7%) and was similar between eltrombopag and romiplostim (87.0% and 83.3%, p = 0.99). The maternal safety profile was favourable, with no thromboembolic events encountered. Neonatal thrombocytopenia was noted in one third of cases, with one case of ICH grade 3, and neonatal thrombocytosis was observed in three cases. No other neonatal adverse events attributable to TPO-RAs were seen. This review suggests that the use of TPO-RA during pregnancy is associated with a high response rate and appears safe. Nevertheless, TPO-RA should not be routinely used in pregnancy and should be avoided in the first trimester until further evidence is accumulated.

We report the case of a paediatric female patient affected by Bannayan-Riley-Ruvalcaba syndrome (BRRS) and congenital hypothyroidism (CH) with homozygous mutation of the TPO gene. She underwent total thyroidectomy at the age of seven years because of the development of a multinodular goiter. BRRS patients present an increased risk of benign and malignant thyroid disease since childhood because of inactivating mutation of PTEN, an onco-suppressor gene. Instead, homozygous mutations in the TPO gene can be associated with severe forms of hypothyroidism with goiter; previous studies have described cases of follicular and papillary thyroid cancer in CH patients with TPO mutation despite a perfectly controlled thyroid function with Levothyroxine therapy. To our knowledge, this is the first case that describes the possible synergic role of coexisting mutation of both TPO and PTEN in the development of multinodular goiter underlining the importance of a tailored surveillance program in these patients, especially during childhood.

Successful radioiodine treatment of differentiated thyroid cancer requires iodine avidity: that is, the concentration and retention of iodine in cancer tissue. Several parameters have previously been linked with lower iodine avidity. However, a comprehensive analysis of which factors best predict iodine avidity status, and the magnitude of their impact, is lacking.
Quantitative measurements of iodine avidity in surgical specimens (primary tumour and lymph node metastases) of 28 patients were compared to immunohistochemical expression of the thyroid-stimulating hormone receptor, thyroid peroxidase (TPO), pendrin, sodium-iodide symporter (NIS) and mutational status of BRAF and the TERT promoter. Regression analysis was used to identify independent predictors of poor iodine avidity.
Mutations in BRAF and the TERT promoter were significantly associated with lower iodine avidity for lymph node metastases (18-fold and 10-fold, respectively). Membranous NIS localisation was found only in two cases but was significantly associated with high iodine avidity. TPO expression was significantly correlated with iodine avidity (r = 0.44). The multivariable modelling showed that tumour tissue localisation (primary tumour or lymph node metastasis), histological subtype, TPO and NIS expression and TERT promoter mutation were each independent predictors of iodine avidity that could explain 68% of the observed variation of iodine avidity.
A model based on histological subtype, TPO and NIS expression and TERT promoter mutation, all evaluated on initial surgical material, can predict iodine avidity in thyroid cancer tissue ahead of treatment. This could inform early adaptation with respect to expected treatment effect.

Thyroid carcinoma (THCA) is a malignant endocrine tumor all around the world, which is influenced by genetic and environmental factors.
To explore the association between TPO rs2048722, PTCSC2 rs925489, SEMA4G rs4919510 polymorphisms and THCA susceptibility in Chinese population.
We recruited 365 THCA patients and 498 normal controls for the study. Logistic regression analysis was used to evaluate the association between TPO rs2048722, PTCSC2 rs925489, SEMA4G rs4919510 polymorphisms and THCA susceptibility. MDR was used to assess the genetic interactions among the three SNPs.
Overall analysis demonstrated that rs925489 of PTCSC2 was evidently associated with increased risk of THCA in multiple genetic models (OR = 1.59, 95%CI = 1.12-2.24, p = 0.009). The results of stratified analysis illustrated that rs2048722 of TPO can significantly increase the THCA susceptibility of participants less than or equal to 44 years old and smokers. Similarly, rs925489 of PTCSC2 obviously improved the risk of THCA among participants older than 44 years, males, smokers and drinkers. However, rs4919510 of SEMA4G has a protective effect on the development of THCA among participants with less than or equal to 44 years old and non-drinkers. Interestingly, there was a strong genetic interaction among the three SNPs in the occurrence of THCA risk.
TPO rs2048722, PTCSC2 rs925489 and SEMA4G rs4919510 polymorphisms were evidently associated with the risk of THCA in the Chinese population, which was affected by age, gender, smoking and drinking consumption.