A challenging case of ectopic ACTH-dependent Cushing's syndrome due to medullary thyroid carcinoma.

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Eagle's syndrome mimicking thyroid-associated orbitopathy.

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The Shear Bond Strength of Resin-Based Luting Cement to Zirconia Ceramics after Different Surface Treatments.

Due to its unique properties, zirconia is increasingly being used in dentistry, but surface preparation for bonding is difficult because of its polycrystalline structure. This study aimed to determine the effect of a new etching technique (Zircos-E) on Ceramill Zi (Amann Girrbach). The effect of etching and the use of primers (Monobond Plus and MKZ Primer) on the bond strength of zirconia with resin cement (NX3) was assessed. Shear bond strength was evaluated after storage in water for 24 h and after thermal aging (5000 thermocycling at 5 °C/55 °C). A scanning electron microscope (Hitachi S-4700) was used to evaluate the surface structure before and after the Zircos-E system. The roughness parameters were assessed using an SJ-410 profilometer. The etched zirconia surface is more homogeneous over the entire surface, but some localized forms of erosion exist. The etching of zirconia ceramics caused changes in the surface structure of zirconia and a significant increase in the shear bond strength between zirconia and resin cement. The use of primers positively affects the adhesion between resin cement and zirconia. Aging with thermocycler significantly reduced the shear bond strength, with one exception-sandblasted samples with MKZ Primer. Standard ceramic surface preparation, involving only alumina sandblasting, does not provide a satisfactory bond. The use of etching with the Zircos-E system and primers had a positive effect on the strength of the zirconium-resin cement connection.

Liquid levothyroxine in the treatment of myxoedema coma.

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AIP gene germline variants in adult Polish patients with apparently sporadic pituitary macroadenomas.

Introduction: Up to 5% of all pituitary tumors are hereditary e.g. due to MEN1 or aryl hydrocarbon receptor-interacting protein (AIP) genes mutations. Objectives: The study was aimed at the assessment of the frequency and characteristics of AIP-mutation related tumors in patients with apparently sporadic pituitary macroadenomas in the Polish population. Materials and methods: The study included 131 patients (57 males, 74 females; median age 42 years) diagnosed with pituitary macroadenomas, and with a negative family history of familial isolated pituitary adenoma (FIPA) or multiple endocrine neoplasia type 1 (MEN1) syndromes. Sanger sequencing was used for the assessment of AIP gene variants. The study was approved by the Ethics Board of JUMC. Results: AIP variants were identified in five of the 131 included subjects (3.8%): one diagnosed with Cushing's disease, two with acromegaly, and two with non-secreting adenomas. Patients harboring hereditary AIP gene alterations did not differ from the rest of the study group in median age at diagnosis (41.0 vs. 42.5 years, P=0.8), median largest tumor diameter (25 vs. 24 mm, P=0.6), gender distribution (60.0% vs. 56.3% females, P=0.8), secreting tumor frequency (60.0% vs. 67.5%, P=0.7), or acromegaly diagnosis frequency (40.0% vs.37.3%, P=0.9). Conclusions: In our series of apparently sporadic pituitary macroadenomas, AIP gene variant carriers did not differ substantially from patients with negative genetic testing. A risk factor-centred approach to AIP genetic screening may result in missing germline variants. Considering the clinical impact of such genetic variants and their relatively low penetrance, it is, however, doubtful if general genetic screening benefits the whole cohort of pituitary macroadenoma patients and their families.

A patient with advanced breast cancer and hyperthyroidism associated with struma ovarii.

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Nystatin Effectiveness in Oral Candidiasis Treatment: A Systematic Review & Meta-Analysis of Clinical Trials.

Oral candidiasis is the most common opportunistic fungal infection caused by commensal Candida species. Since there are various local and systemic predisposing factors for the disease, the treatment also varies from topical to systemic antifungal agents. Nystatin is a common antifungal agent used topically. The aim of this systematic review was to evaluate and compare the efficacy of different antifungal agents and the safety of nystatin in the treatment of oral candidiasis. Three electronic databases were searched for randomized controlled trials comparing nystatin with other anti-fungal therapies or placebo. Clinical and/or mycological cure was the outcome evaluation. A meta-analysis and descriptive study on the efficacy, treatment protocols, and safety of nystatin was also conducted. The meta-analysis included five studies, which compared the efficacy of nystatin suspensions with photodynamic therapy. A significant difference in the colony-forming units per milliliters (CFU/mL) of Candida species was observed at 60 days intervals for both palatal mucosa and denture surfaces, with both groups favoring nystatin with low heterogeneity at a 95% confidence interval. Nystatin and photodynamic therapy were found to be equally effective for the clinical remission of denture stomatitis as well as a significant reduction of CFU/mL of Candida species from dentures and palatal surfaces of the patients.

Adrenal crisis prompted by SARS-CoV-2 infection in a patient with autoimmune polyglandular syndrome type 1 (APS type 1).

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Disseminated medullary thyroid cancer - an alternative therapeutic approach.

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Changes of IgG N-Glycosylation in Thyroid Autoimmunity: The Modulatory Effect of Methimazole in Graves' Disease and the Association With the Severity of Inflammation in Hashimoto's Thyroiditis.

The N-glycome of immunoglobulin G (IgG), the most abundant glycoprotein in human blood serum, reflects pathological conditions of autoimmunity and is sensitive to medicines applied in disease therapy. Due to the high sensitivity of N-glycosylation, the IgG N-glycan profile may serve as an indicator of an ongoing inflammatory process. The IgG structure and its effector functions are strongly dependent on the composition of N-glycans attached to the Fc fragment, and the binding of antigens is regulated by Fab sugar moieties. Because of the crucial role of N-glycans in IgG function, remodeling of its N-oligosaccharides can induce pathological changes that ultimately contribute to the development of autoimmunity; restoration of their physiological structure is critical to the reduction of disease symptoms. Our recently published data have shown that the pathology of autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), is accompanied by alterations of the composition of IgG N-glycans. The present study is a more in-depth investigation of IgG glycosylation in both AITDs, designed to determine the relationship between the severity of thyroid inflammation and IgG N-glycan structures in HT, and to assess the impact of immunosuppressive therapy on the N-glycan profile in GD patients. The study material consisted of human serum samples collected from donors with elevated anti-thyroglobulin (Tg) and/or anti-thyroperoxidase (TPO) IgGs without symptoms of hypothyroidism (n=68), HT patients characterized by high autoantibody titers and advanced destruction of the thyroid gland (n=113), GD patients with up-regulated IgG against thyroid-stimulating hormone receptor (TSHR) before (n=62) and after (n=47) stabilization of TSH level as a result of methimazole therapy (study groups), and healthy donors (control group, n=90). IgG was isolated from blood serum using protein G affinity chromatography. N-glycans were released from IgG by PNGase F digestion and analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) after 2-aminobenzamide (2-AB) labeling. UPLC-MS chromatograms were integrated into 25 peaks (GP) in the Waters UNIFI Scientific Information System, and N-glycans were assigned based on the glucose unit values and mass-to-charge ratios (m/z) of the detected ions. The Kruskal-Wallis non-parametric test was used to determine the statistical significance of the results (p<0.05). The obtained results suggest that modifications of IgG sialylation, galactosylation and core-fucosylation are associated with the severity of HT symptoms. Methimazole therapy implemented in GD patients affected the IgG N-glycan profile; as a result, the content of the sialylated and galactosylated oligosaccharides with core fucose differed after treatment. Our results suggest that N-glycosylation of IgG undergoes dynamic changes during the intensification of thyroiditis in HT, and that in GD autoimmunity it is affected significantly by immunosuppressive therapy.

Vitamin D status and its associations with clinical and laboratory parameters in patients with Addison's disease.

INTRODUCTION: There is increasing evidence that several autoimmune diseases, as well as their activity, are associated with vitamin D (VD) deficiency. Our study aimed to evaluate the prevalence of VD insufficiency in patients with Addison's disease (AD), as well as to evaluate associations between VD concentrations and various clinical and laboratory parameters of the disease. MATERIALS AND METHODS: We retrospectively analyzed medical records of 31 adult patients diagnosed with autoimmune Addison's disease, in whom serum VD was measured. We assessed correlations between serum VD and various clinical and laboratory parameters. R e s u l t s: 90.3% of AD patients had inadequate VD concentrations (<30 ng/mL), and 19.3% of them were found to be severely VD deficient (<10 ng/mL). Among assessed laboratory variables, only serum calcium concentrations significantly correlated with VD status (r = 0.53, p = 0.006). The mean serum VD concentration was significantly lower in patients with severe fatigue (15.17 ± 8.41 vs 26.83 ± 12.29 ng/mL, p = 0.011) and limited exercise capacity (12.38 ± 6.9 vs 21.63 ± 10.87 ng/mL, p = 0.016). C o n c l u s i o n s: This study demonstrates a high prevalence of VD deficiency in AD patients, as well as the association between low VD concentrations with symptoms such as severe fatigue or limited exercise capacity. Further studies are needed to clarify if impaired VD status is a risk factor in the pathogenesis of AD and to assess if VD supplementation improves the quality of life of AD patients.

Does Simulated Porcelain Firing Influence Corrosion Properties of Casted and Sintered CoCr Alloys?

The aim of the study was to evaluate how heat processing used for dental porcelain firing influences the surface properties of sintered and casted CoCr alloy. Two CoCr alloys, Soft Metal LHK (milling in soft material and sintering) and MoguCera C (casting), were used for the study. The samples were examined using SEM-EDS before and after heat treatment. Next, corrosion examinations (Ecorr, jcorr, polarization curve, Ebr) were performed. Finally, the samples were evaluated under SEM. Based on the results, the following conclusions might be drawn: 1. Thermal treatment (porcelain firing) did not cause chemical impurities formation on the surface of CoCr alloy; 2. The sintered metal exhibited significantly higher corrosion resistance than the casted one due to its homogeneity of structure and chemical composition; 3. Heat treatment (porcelain firing) decreased the resistance of casted and sintered CoCr alloy to electrochemical corrosion. The reduction in corrosion resistance was significantly higher for the casted alloy than for the sintered alloy; 4. The corrosion resistance decrease might be due to an increased thickness and heterogeneity of oxide layers on the surface (especially for the casted alloy). The development of corrosion process started in the low-density areas of the oxide layers; 5. The sintered metal seems to be a favourable framework material for porcelain fused to metal crowns.

Graves' disease and exophthalmos - a mask for meningioma.

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The Influence of Cement Layer Thickness on the Stress State of Metal Inlay Restorations-Photoelastic Analysis.

The successful restoration of teeth requires a good connection between the inlay and natural tissue. A strong bond may improve retention and reinforce tooth structure. The purpose of this study was to evaluate the influence of cement layer thickness on contraction stress generated during photopolymerization, and to determine the changes in stress state of the cement occurring during aging in water (over 84 days). Two cements were used: resin composite cement (NX3) and self-adhesive resin cement (Maxcem Elite Chroma). A cylindrical sample made of CuZn alloy was used to imitate the inlay. The stress state was measured by photoelastic analysis. The contraction stress of the inlay restoration was calculated for cement layer thicknesses of 25 µm, 100 µm, 200 µm, and 400 µm. For both tested materials, the lowest contraction stress was observed for the thinnest layer (25 µm), and this increased with thickness. Following water immersion, a significant reduction in contraction stress was observed due to hygroscopic expansion. Applying a thin layer (approximately 25 µm) of composite and self-adhesive resin cements resulted in high levels of expansion stresses (over -6 MPa) after water aging.

Proximity Ligation Assay Detection of Protein-DNA Interactions-Is There a Link between Heme Oxygenase-1 and G-quadruplexes?

G-quadruplexes (G4) are stacked nucleic acid structures that are stabilized by heme. In cells, they affect DNA replication and gene transcription. They are unwound by several helicases but the composition of the repair complex and its heme sensitivity are unclear. We found that the accumulation of G-quadruplexes is affected by heme oxygenase-1 (Hmox1) expression, but in a cell-type-specific manner: hematopoietic stem cells (HSCs) from Hmox1-/- mice have upregulated expressions of G4-unwinding helicases (e.g., Brip1, Pif1) and show weaker staining for G-quadruplexes, whereas Hmox1-deficient murine induced pluripotent stem cells (iPSCs), despite the upregulation of helicases, have more G-quadruplexes, especially after exposure to exogenous heme. Using iPSCs expressing only nuclear or only cytoplasmic forms of Hmox1, we found that nuclear localization promotes G4 removal. We demonstrated that the proximity ligation assay (PLA) can detect cellular co-localization of G-quadruplexes with helicases, as well as with HMOX1, suggesting the potential role of HMOX1 in G4 modifications. However, this colocalization does not mean a direct interaction was detectable using the immunoprecipitation assay. Therefore, we concluded that HMOX1 influences G4 accumulation, but rather as one of the proteins regulating the heme availability, not as a rate-limiting factor. It is noteworthy that cellular G4-protein colocalizations can be quantitatively analyzed using PLA, even in rare cells.

Current iodine nutrition status in Poland (2017): is the Polish model of obligatory iodine prophylaxis able to eliminate iodine deficiency in the population?

OBJECTIVE: The monitoring of the populations' iodine status is an essential part of successful programmes of iodine deficiency elimination. The current study aimed at the evaluation of current iodine nutrition in school children, pregnant and lactating women as a marker of the effectiveness and sustainability of mandatory iodine prophylaxis in Poland. DESIGN: The following iodine nutrition indicators were used: urinary iodine concentration (UIC) (all participants) and serum thyroglobulin (pregnant and lactating women). SETTING: The study was conducted in 2017 within the National Health Programme in five regions of Poland. PARTICIPANTS: The research included 300 pregnant women, 100 lactating women and 1000 school children (aged 6-12 years). RESULTS: In pregnant women, median UIC was 111·6 µg/l; there was no significant difference in median UIC according to the region of residence. In 8 % of pregnant women, thyroglobulin level was >40 ng/ml (median thyroglobulin 13·3 ng/ml). In lactating women, median UIC was 68·0 µg/l. A significant inter-regional difference was noted (P = 0·0143). In 18 % of breastfeeding women, thyroglobulin level was >40 ng/ml (median thyroglobulin 18·5 ng/ml). According to the WHO criteria, the investigated sample of pregnant and lactating women was iodine-deficient. Median UIC in school children was 119·8 µg/l (with significant inter-regional variation; P = 0·0000), which is consistent with iodine sufficiency. Ninety-four children (9·4 %) had UIC < 50 µg/l. CONCLUSIONS: Mandatory iodisation of household salt in Poland has led to a sustainable optimisation of iodine status in the general population. However, it has failed to assure adequate iodine nutrition during pregnancy and lactation.

The Contribution of IgG Glycosylation to Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC) in Hashimoto's Thyroiditis: An in Vitro Model of Thyroid Autoimmunity.

Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) are involved in destruction of thyroid tissue in Hashimoto's thyroiditis (HT). N-glycosylation of the Fc fragment affects the effector functions of IgG by enhancing or suppressing the cytotoxicity effect. The aim of the present study was to assess the impact of HT-specific IgG glycosylation in ADCC and CDC, using in vitro models. The normal thyroid Nthy-ori 3-1 cell line and thyroid carcinoma FTC-133 cells were used as the target cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors and the HL-60 human promyelotic leukemia cell line served as the effector cells. IgG was isolated from sera of HT and healthy donors and then treated with α2-3,6,8-neuraminidase to cut off sialic acids (SA) from N-glycans. We observed more intensive cytotoxicity in the presence of IgG from HT patients than in the presence of IgG from healthy donors. Removal of SA from IgG N-glycans increased ADCC intensity and reduced CDC. We conclude that the enhanced thyrocyte lysis resulted from the higher anti-TPO content in the whole IgG pool of HT donors and from altered IgG glycosylation in HT autoimmunity.

Short- and long-term results of laparoscopic adrenalectomy for Conn's syndrome.

INTRODUCTION: The primary treatment of Conn's syndrome (CS) is laparoscopic adrenalectomy and aims to normalize arterial blood pressure and biochemical parameters. AIM: To analyse short- and long-term results of laparoscopic adrenalectomy for Conn's syndrome (CS). MATERIAL AND METHODS: The analysis included 44 consecutive patients, who underwent laparoscopic adrenalectomy between 2004 and 2015 for CS. We analysed short- and long-terms results of operations. All patients were followed up 6 and 24 months after surgery to determine changes in the biochemical parameters, and clinical regression of arterial hypertension. We also evaluated the aldosteronoma resolution score (ARS) in predicting the resolution of hypertension. RESULTS: No conversions were needed. Complications occurred in 5 (11.4%) patients. Preoperative hypokalaemia and hypernatraemia were present in 83.4% and 15.8% of patients, respectively. After surgery, both hypokalaemia and hypernatraemia resolved in all patients. At the follow-up 6 months after the surgery, only 11.3% of patients had complete remission (CR) of hypertension. In 43.2% of cases we observed partial remission (PR). After 24 months CR was found in 13.6% of patients, 45.5% patients fulfilled criteria for PR, and 29.5% of patients changed the group of remission comparison to the first follow-up visit. Only 50% of patients with an ARS of 4 or 5 points achieved CR 6 months after surgery. CONCLUSIONS: Laparoscopic adrenalectomy is a safe method of treatment for CS. Although it effectively eliminates electrolyte imbalance, it does not allow for the CR of hypertension in the majority of patients, especially in the elderly group. We did not find ARS to be an effective tool in predicting postoperative resolution of hypertension.

Dental Resin Cements-The Influence of Water Sorption on Contraction Stress Changes and Hydroscopic Expansion.

Resin matrix dental materials undergo contraction and expansion changes due to polymerization and water absorption. Both phenomena deform resin-dentin bonding and influence the stress state in restored tooth structure in two opposite directions. The study tested three composite resin cements (Cement-It, NX3, Variolink Esthetic DC), three adhesive resin cements (Estecem, Multilink Automix, Panavia 2.0), and seven self-adhesive resin cements (Breeze, Calibra Universal, MaxCem Elite Chroma, Panavia SA Cement Plus, RelyX U200, SmartCem 2, and SpeedCEM Plus). The stress generated at the restoration-tooth interface during water immersion was evaluated. The shrinkage stress was measured immediately after curing and after 0.5 h, 24 h, 72 h, 96 h, 168 h, 240 h, 336 h, 504 h, 672 h, and 1344 h by means of photoelastic study. Water sorption and solubility were also studied. All tested materials during polymerization generated shrinkage stress ranging from 4.8 MPa up to 15.1 MPa. The decrease in shrinkage strain (not less than 57%) was observed after water storage (56 days). Self-adhesive cements, i.e., MaxCem Elite Chroma, SpeedCem Plus, Panavia SA Plus, and Breeze exhibited high values of water expansion stress (from 0 up to almost 7 MPa). Among other tested materials only composite resin cement Cement It and adhesive resin cement Panavia 2.0 showed water expansion stress (1.6 and 4.8, respectively). The changes in stress value (decrease in contraction stress or built up of hydroscopic expansion) in time were material-dependent.

Markers of proliferation and invasiveness in somatotropinomas.

Introduction In the search for markers of invasiveness of pituitary adenomas, we studied the expression of Ki-67 antigen, TOPO 2A (topoisomerase 2 alpha), AIP (Aryl Hydrocarbon Receptor-Interacting Protein) and VEGF (Vascular Endothelial Growth Factor) in somatotropinomas. Material and Methods We retrospectively studied a group of 31 patients who underwent pituitary tumour surgery. Expression of Ki-67, TOPO 2A, AIP and VEGF in surgical specimens was determined by immunohistochemistry. Relations between quantitatively determined markers and clinical symptoms, tumour features, and MR imaging, were analysed. Acromegaly was confirmed by hormonal tests in all patients studied. Local invasiveness (cavernous sinus penetration, optic chiasm compression or suprasellar extension) was observed in 18/31 patients (58,1%). Results Ki-67 was expressed in 77.4%, TOPO 2A in 87.1%, AIP in 83.8%, and VEGF in 87.1% of 31 cases of somatropinoma. Median values of Ki-67, TOPO 2A, AIP and cytoplasmic VEGF indices were 1.2% [IQR=2.2], 1.5% [IQR=1.6], 21.26% [IQR=20.1] and 20.4% [IQR=15.4], respectively. Ki-67, TOPO 2A, AIP and VEGF expression was not correlated with age nor with patient gender (p > 0.05). Only Ki-67 and TOPO 2A correlated with tumour size (for Ki-67: r=0.42, p=0.025; for TOPO 2A: r=0.53, p=0.003). Ki-67 and TOPO 2A levels were significantly higher in invasive compared to noninvasive somatropinomas (Ki67 mean values: 1.85±1.33% vs. 0.95±1.07%, p=0.024; TOPO 2A mean values: 2.19±1.63% vs. 1.45±1.23%, , p=0.011). Conclusions Ki-67, TOPO 2A, AIP and VEGF were expressed in over 70% of all somatotropinomas. Only Ki-67 and TOPO 2A expression correlated with tumour size and tumour invasiveness.