Explore the vast range of titles available.

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.

Hashimoto’s thyroiditis (HT) is one of the most common organ-specific autoimmune diseases, characterized by chronic thyroid gland inflammation. Helper T (Th) CD4 + cells, whose surface receptors are highly glycosylated, are involved in the pathomechanism of HT. Our study aimed to characterize N -glycosylation profiles in two pools of CD4 + T cells, defined by the expression of CD25 + late activation marker (CD4 + CD25 + ) and CD25-negative cells (CD4 + CD25 - ) in HT. Two study groups were recruited: HT1 with elevated thyroid autoantibodies and TSH level within the normal range without hypothyroidism, and HT2, hypothyroid HT patients, adequately metabolically controlled while on L-thyroxine replacement therapy, and healthy subjects to the control group (CTR). N -glycans from CD4 + cell proteins, released using N -glycosidase F, were analyzed by MALDI-Tof mass spectrometry. RT-qPCR was used to determine the expression of selected glycogenes. We found significant differences in the glycome of CD4 + CD25 - and CD4 + CD25 + cells. In homeostasis (CTR), a predominance of complex-type glycans was observed in CD4 + CD25 - cells, whereas the oligomannose-type structures prevail in CD4 + CD25 + lymphocytes. In autoimmunity and progressive thyroid dysfunction, the rearrangement of N -glycans in Th cells was observed, in opposite directions in the CD4 + pools. Complex-type structures are replaced by oligomannose forms in CD4 + CD25 - in the HT1 group, while in HT2, a restoration of glycosylation profile to the level of CTR was detected. CD4 + CD25 + cells accelerated complex-type synthesis in HT1, which was normalized in HT2 patients. Changes in the profile of N -linked glycans are partially reflected in the expression of mannosidases and glycosyltransferases. Our study demonstrates for the first time the diverse N -glycosylation profiles in CD4 + CD25 - and CD4 + CD25 + cells, and the rearrangement of N -glycan structures specific for each pool of Th cells in HT. Further studies are needed to determine the functional aspect of the identified N -glycosylation changes during thyroid autoimmunity.

Heme oxygenase-1 (HO1, Hmox1 ) degrades excess heme and is considered an anti-oxidative and anti-inflammatory enzyme. Our previous studies in Hmox1 knockout mice revealed the induction of interferon-stimulated genes (ISGs) in all cell types analyzed, despite unchanged interferon production. Here, we sought to determine whether this induction is driven by intrinsic cellular mechanisms or extrinsic cues at the organismal level, and to identify the pathway underlying HO1-dependent ISG regulation. To this end, we analyzed how ISG expression changes in cultured cells exposed to stressors typical of Hmox1 knockout mice. Using murine wild-type and Hmox1 -deficient (Hmox1 KO) fibroblasts, we found that under control conditions, the expression of most tested ISGs was independent of cellular HO1 status. We next examined the effects of extrinsic stressors, including hemolytic, oxidative, genotoxic, and replication stress, proinflammatory TNFα, and endogenous heme overload. TNFα, which is upregulated in Hmox1 knockout mice, was the sole and universal inducer of ISGs in both wild-type and Hmox1 KO fibroblasts. Unexpectedly, the response of Hmox1 KO cells to exogenous TNFα was weakened, likely due to impaired NF-κB activity and reduced nuclear retention of the p65 subunit. A similar decrease we observed for STAT1. Additionally, the presence of the TREX1 exonuclease in the nucleus pointed to compromised nuclear envelope integrity in HO-deficient cells. Notably, HO1 colocalizes with PARP1, a protein involved in envelope maintenance and regulation of cytoplasmic-nuclear transport. Inhibition of PARP1 with olaparib dampened TNFα-induced nuclear accumulation of p65 and STAT1 in wild-type cells, but not in Hmox1 KO counterparts. In summary, the inflammation observed in Hmox1 -deficient mice appears to be the main cell-extrinsic driver of ISG induction in vivo. Despite this, the inflammatory response to exogenous TNFα is intrinsically attenuated in Hmox1 KO cells, likely due to decreased nuclear retention of NF-κB and STAT1.

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.

The procedure of ceramics fusion to cobalt–chromium (Co–Cr) base dental crowns affects their corrosion behavior and biological tolerance. This study’s purpose was to comparatively evaluate the effect of heat treatment (HT) applicable for dental ceramics firing on the corrosion properties among Co–Cr base alloys fabricated via different methods: casting (CST), milling soft metal and post sintering (MSM), and selective laser melting (SLM). All specimens were subjected to a heat treatment corresponding to a full firing schedule. The microstructure and elemental composition of oxidized surfaces were investigated by scanning electron microscopy and energy dispersive spectroscopy. Corrosion properties were examined by electrochemical potentiodynamic polarization tests. The values of jcorr, Ecorr, Rp, and breakdown potential Ebr were estimated. The oxide layers formed during the HT process corresponded to the composition of the original alloys’ structure. Among the thermal treated alloys, SLM showed the highest corrosion resistance, followed by the MSM and CST. This may be attributed to uniform distribution of alloying elements in homogenous structure and to the reduced porosity, which enhances corrosion resistance and decreases the risk of crevice corrosion. The overall corrosion behavior was strongly influenced by the segregation of alloying elements in the microstructure, thus, is directly determined by the manufacturing method.

The COVID-19 pandemic was a major challenge for all health care employees, but it was also difficult for patients to gain access to health care services. Myxedema coma (MC) is an extremely rare but potentially fatal endocrine emergency. The aim of the study was to report an increased incidence of life-threatening myxedema coma that occurred in relation to the COVID-19 pandemic. In this paper, we report a cohort of 11 patients with MC who were treated at the University Hospital in Krakow, Poland, in the period from 2015 to 2023. Only 1 case of MC was recorded in the period from 2015 to 2019, and, in the same area, 10 cases of MC were recorded after the start of COVID-19 pandemic until present. Hypothyroidism was diagnosed de novo in 2 (18%) patients; the remaining patients were severely hypothyroid due to therapy non-compliance. Nine patients had primary hypothyroidism, and 2 had central hypothyroidism. Besides longstanding hypothyroidism, an additional precipitating factor for MC was identified in 4 (36%) of the patients. Due to the inaccessibility of parenteral levothyroxine, patients were treated with oral, mostly liquid, form of levothyroxine. The mortality rate in this cohort was 27.2%. In conclusion, the increase of the incidence of MC, which is a life-threatening complication of inadequately treated hypothyroidism, during the COVID-19 pandemic, when resources were limited, and in the post-pandemic era, underlines the importance of adequate communication with patients and of long-term availability of primary care for patients with thyroid disease.

Biocompatibility is a critical aspect of the use of materials in the human body. The use of base metal alloys in dentistry is primarily regulated by health and safety standards set by regulatory authorities in various countries. The porcelain-fused-to-metal (PFM) process applied to Ni-Cr dental alloys can alter their properties, particularly in terms of corrosion and surface characteristics. This study aimed to assess the effect of the heat processing used for dental porcelain firing on these properties. The two casted alloys: Ceramic N and Ivoclar Vivadent 4all, used in the study were characterized by analyzing the microstructure by scanning electron microscopy (SEM), composition with energy dispersive x-ray spectroscopy (EDS), hardness, surface profile and electrochemical corrosion resistance (E corr , j corr , polarization curve, E br and electrochemical impedance spectroscopy (EIS) results), as well as ions release before and after the simulated porcelain firing. Based on the conducted research the following conclusions can be drawn: Analyzes of the material characteristics before and after the simulation showed that the discussed process, although it does not cause the formation of chemical impurities on the surface of the alloys, results in changes in the chemical composition and structure of surface oxides, increases roughness and reduces hardness. The results of the corrosion examinations showed a deterioration in anti-corrosion properties after the simulation. The statistically significant decrease in corrosion resistance may result from the increased heterogeneity of the surface oxide layers and partial changes in their composition.

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.

BACKGROUND: Primary hyperparathyroidism (PHP) diagnosis is based on abnormalities in biochemical blood tests. Preoperative localization of the affected gland with imaging may increase the effectiveness of the surgical treatment. The aim of this study is to evaluate predictive strategies for the assessment of radiotracer uptake in pre-operative [99mTc]Tc-sestamibi scintigraphy ([99mTc] Tc-MIBI SPECT-CT) among PHP patients to identify individuals with a high probability of negative results, and to develop clinical decision-making tools. MATERIAL AND METHODS: Development and evaluation of logistic regression (LR), classification trees utilizing the classification and regression trees (CART) algorithm, random forest (RF), and boosted trees employing XGBoost (XGB) predictive models. All models were constructed using data obtained from 499 patients diagnosed with PHP who underwent [99mTc]Tc-MIBI SPECT-CT imaging between 2010 and 2022 at the University Hospital in Cracow, Poland. RESULTS: The LR model demonstrated the best out-of-sample performance, achieving a specificity of 81.3% and an accuracy of 69.3%, with a sensitivity of 55.7%. Along with CART and XGB, LR performed well when using only 5 predictors: concentrations of parathormone (PTH), serum calcium, serum phosphates, total serum vitamin D, and maximal lesion diameter measured in ultrasound. Random forest (RF) exhibited higher sensitivity (62.7%), but lower specificity (74.2%) and accuracy (68.6%). Other models demonstrated subpar performance. CONCLUSIONS: Logistic regression and RF models were the most effective in predicting radiotracer uptake in pre-operative hybrid imaging of the parathyroids, suggesting their suitability as the foundation for software to be used in clinical settings. However, opting for the CART model, despite its easier interpretation, would come at the expense of performance.

Not required for Clinical Vignette.