Head and Neck Cancer Patients' Survival According to HPV Status, miRNA Profiling, and Tumour Features-A Cohort Study.

Head and neck cancers (HNC) are a heterogeneous group of tumours mainly associated with tobacco and alcohol use and human papillomavirus (HPV). Over 90% of all HNC are squamous cell carcinomas (HNSCC). Sample material from patients diagnosed with primary HNSCC (n = 76) treated with surgery as primary treatment at a single centre were assessed for HPV genotype, miR-9-5p, miR-21-3p, miR-29a-3p and miR-100-5p expression levels. Clinical and pathological data were collected from medical records. Patients were enrolled between 2015 and 2019 and followed-up until November 2022. Overall survival, disease-specific survival and disease-free survival were assessed and correlated with clinical, pathological, and molecular data. Kaplan-Meier and Cox proportional hazard regression was used to assess different risk factors. In the study, male gender, HPV-negative HNSCC (76.3%) mostly located in the oral region (78.9%) predominated. Most patients had stage IV cancer (47.4%), and the overall survival rate was 50%. HPV was found not to affect survival, indicating that in this population, classic risk factors predominate. The presence of both perineural and angioinvasion was strongly associated with survival in all analyses. Of all miRNAs assessed, only upregulation of miR-21 was consistently shown to be an independent predictor of poor prognosis and may thus serve as a prognostic biomarker in HNSCC.

THE EFFECT OF LOCAL AND SYSTEMIC FACTORS ON DENTAL IMPLANT FAILURE - ANALYSIS OF 670 PATIENTS WITH 1260 IMPLANTS.

The etiopathogenesis of dental implant failure is multifactorial and may include numerous local and systemic factors, however, studies including both local and systemic factors are still lacking. Therefore, the aim of this study was to evaluate whether periodontal disease, oral hygiene index, i.e. bleeding on probing (BOP), full mouth plaque index (FMPI), smoking, systemic diseases, as well as implant characteristics (length and diameter) affect failure of implant-prosthodontic therapy. Data on 670 patients were retrieved in whom 1260 dental implants had been placed and followed-up for at least five to ten years. Categorical data were analyzed by the χ2-test, whereas Mann-Whitney test was used for continuous variables (age, BOP and FMPI). The values of p<0.05 were considered significant. The effect of local and systemic factors on the success of implant-prosthodontic therapy was assessed by multiple logistic regression analysis. Forty-five (6.7%) patients had systemic diseases, of which diabetes mellitus was most common, followed by atherosclerosis, diabetes and atherosclerosis, diabetes mellitus type 1, lymphoma, and hepatitis C. One-third (33.4%) of the patients were smokers. Periodontal disease was present in 170 patients, while 500 patients were without periodontal disease. Nine implants were lost during the period of five years. There were no differences regarding the type of implant or type of connection to the prosthetic suprastructure. However, most of these patients had a periodontal disease. There were no significant differences in dental implant failure rates between smokers and non-smokers or between patients with and without systemic diseases. Furthermore, the results of this study showed that implant type (straight vs. tapered) and type of connection with prosthodontic appliance (cemented or screw retained) did not affect BOP and FMPI. In smokers, significant improvement of BOP and FMPI was noticed. Initially, smokers had a significantly worse BOP (0.0037) when compared to non-smokers; however, there were no differences regarding FMPI (p=0.4218) between the two groups. In patients with periodontal disease, improvement of BOP and FMPI was seen at 5-year follow-up and no significant differences were found when compared to patients without periodontal disease. There were no significant differences in BOP and FMPI between patients with and without diabetes at 5-year follow-up. Atherosclerosis had a significant negative effect on BOP, but not on FMPI at 5-year follow-up. It is concluded that periodontal disease had a significant impact on the implant-prosthodontic therapy.

DNA Methylome Distinguishes Head and Neck Cancer from Potentially Malignant Oral Lesions and Healthy Oral Mucosa.

There is a strong need to find new, good biomarkers of head and neck squamous cell carcinoma (HNSCC) because of the bad prognoses and high mortality rates. The aim of this study was to identify the potential biomarkers in HNSCC that have differences in their DNA methylome and potentially premalignant oral lesions, in comparison to healthy oral mucosa. In this study, 32 oral samples were tested: nine healthy oral mucosae, 13 HNSCC, and 10 oral lesions for DNA methylation by the Infinium MethylationEPIC BeadChip. Our findings showed that a panel of genes significantly hypermethylated in their promoters or specific sites in HNSCC samples in comparison to healthy oral samples, which are mainly oncogenes, receptor, and transcription factor genes, or genes included in cell cycle, transformation, apoptosis, and autophagy. A group of hypomethylated genes in HNSCC, in comparison to healthy oral mucosa, are mainly involved in the host immune response and transcriptional regulation. The results also showed significant differences in gene methylation between HNSCC and potentially premalignant oral lesions, as well as differently methylated genes that discriminate between oral lesions and healthy mucosa. The given methylation panels point to novel potential biomarkers for early diagnostics of HNSCC, as well as potentially premalignant oral lesions.

Expression of small leucine-rich extracellular matrix proteoglycans biglycan and lumican reveals oral lichen planus malignant potential.

OBJECTIVES: The aim of this study was to examine molecular alterations on the protein level in lesions of oral lichen planus (OLP), oral squamous cell carcinoma (OSCC) and healthy mucosa. MATERIALS AND METHODS: Global protein profiling methods based on liquid chromatography coupled to mass spectrometry (LC-MS) were used, with a special emphasis on evaluation of deregulated extracellular matrix molecules expression, as well as on analyses of IG2F and IGFR2 expression in healthy mucosa, OLP and OSCC tissues by comparative semi-quantitative immunohistochemistry. RESULTS: Mass spectrometry-based proteomics profiling of healthy mucosa, OLP and OSCC tissues (and accompanied histologically unaltered tissues, respectively) identified 55 extracellular matrix proteins. Twenty among identified proteins were common to all groups of samples. Expression of small leucine-rich extracellular matrix proteoglycans lumican and biglycan was found both in OSCC and OLP and they were validated by Western blot analysis as putative biomarkers. A significant increase (p < 0.05) of biglycan expression in OLP-AT group was determined in comparison with OLP-T group, while lumican showed significant up-regulation (p < 0.05) in OLP-T and OSCC-T groups vs. adjacent and control tissue groups. Biglycan expression was only determined in OSCC-AT group. Immunohistochemical analysis of IGF2 and IG2FR expression revealed no significant difference among groups of samples. CONCLUSION/CLINICAL RELEVANCE: Biglycan and lumican were identified as important pathogenesis biomarkers of OLP that point to its malignant potential.

Analysis of the integration of human papillomaviruses in head and neck tumours in relation to patients' prognosis.

Integration, which leads to the disruption of the circular HPV genome, is considered as a critical, albeit not obligatory, step in carcinogenic progression. Although cervical carcinomas with extrachromosomal HPV plasmid genomes have been described, the virus is integrated in 70% of HPV16-positive cervical tumours. Limited information is available about HPV integration in head and neck tumours (HNC). In this study, we have characterised the physical status of HPV in a set of tonsillar tumour samples using different methods--the mapping of E2 integration breakpoint at the mRNA level, the 3' RACE based Amplification of Papillomavirus Oncogene Transcripts (APOT) assay and Southern blot. Furthermore, the impact of HPV integration on patients' prognosis has been evaluated in a larger set of 186 patients with head and neck cancer. Based on the analysis of E2 mRNA, HPV was integrated in the host genome in 43% of the HPV-positive samples. Extrachromosomal or mixed form was present in 57%. In fresh frozen samples, the APOT and E2 mapping results were in agreement. The results were confirmed using Southern blotting. Furthermore, the type and exact site of integration were determined. The survival analysis of 186 patients revealed HPV positivity, tumour size and lymph node positivity as factors that influence disease specific survival. However, no statistically significant difference was found in disease specific survival between patients with HPV-positive integrated vs. extrachromosomal/mixed forms of the virus.

Comparison of the miRNA profiles in HPV-positive and HPV-negative tonsillar tumors and a model system of human keratinocyte clones.

BACKGROUND: Better insights into the molecular changes involved in virus-associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV-dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology. METHODS: Fresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection. RESULTS: We defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV-negative keratinocytes. CONCLUSIONS: We identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of clinically relevant diagnostic and/or therapeutic biomarkers for tumors of viral and non-viral etiology.

Geographical distribution and risk association of human papillomavirus genotype 52-variant lineages.

Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical distribution, with lineage B predominating in Asia (89.0% vs 0%-5.5%; P(corrected) < .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name "Asian lineage" be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B.

Ureaplasma urealyticum and Ureaplasma parvum in women of reproductive age.

OBJECTIVES: To determine the incidence of Ureaplasma urealyticum and Ureaplasma parvum (UP) in symptomatic and asymptomatic women of reproductive age and to estimate antibiotic susceptibility of ureaplasma isolates. MATERIALS AND METHODS: This study included 424 ureaplasma positive women of 1,370 tested women who visited gynecological practices during 2010. Cervicovaginal or urethral swab specimens from each patient were obtained for cultivation and molecular typing by RT-PCR. RESULTS: Ureaplasma spp. was identified by cultivation in 424 (34.4 %) cases, of which 79.0 % were from women with symptoms and 21.0 % from women without symptoms. Among ureaplasma positive women, 121 (28.5 %) were pregnant. Genotyping was successful in 244 strains, and the majority of samples were identified as UP (92.6 %). Among genotyped isolates, there were 79.5 % from symptomatic and 20.5 % from asymptomatic women; 29.9 % from pregnant and 70.1 % from non-pregnant women. There was no difference in the incidence of ureaplasma type regarding symptoms. Antibiotic susceptibility of 424 ureaplasma isolates identified by cultivation showed that all strains were susceptible to doxycycline, josamycin, erythromycin, tetracycline, clarithromycin and pristinamycin, but there was lower susceptibility to quinolone antibiotics, i.e., 42.9 and 24.5 % isolates were susceptible to ofloxacin and ciprofloxacin, respectively. CONCLUSION: This study shows that UP was the most frequent isolated ureaplasma species (92.6 %). Regarding antibiotic susceptibility, quinolones are not the best choice for the treatment of ureaplasma infections, while macrolides and tetracyclines are still effective.

Clinicopathologic correlation of oral lichen planus and oral lichenoid lesions: a preliminary study.

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are clinically and histologically similar lesions but their treatment planning and prognosis are different. The review of the literature indicates numerous criteria to distinguish these two lesions; however there is a lot of inconsistency. Thus, the aim of this study was to determine the correlation of histopathology and clinical OLP and OLL diagnosis and to clarify which histopathologic criteria could best distinguish these two diagnoses. A retrospective study showed that clinically diagnosed 92 OLPs and 14 OLLs have been confirmed histopathologically in 52.2% and 42.9% of cases, respectively. In addition, histopathology showed statistically significant more eosinophils (P<0.0005), plasma cells (P<0.0005), and granulocytes (P<0.05) in OLL than OLP. To establish histopathological diagnosis of OLP and OLL it should be mandatory to define the type of cells in mononuclear infiltrate, which can be associated more accurately with clinical feature and patient history. Therefore, currently accepted diagnostic criteria for OLP and OLL should be modified and validated on a larger number of patients taking into account particular distinguishing histopathological features.

Impact of soft and rigid gas-permeable contact lenses on visual performance in mesopic conditions.

CONTEXT: Evaluation of visual quality in soft and rigid gas-permeable contact lens wearers, with an emphasis on twilight vision. PURPOSE: To assess the visual acuity and visual performance at dusk before and after soft and rigid gas-permeable contact lens (CL) correction in healthy subjects. SETTINGS AND DESIGN: This prospective study was conducted in a tertiary eye-care center. METHODS: Sixty eyes corrected with soft contact lenses (SCLs) and 30 eyes with rigid gas-permeable contact lenses (RGPCLs) were enrolled in this study. Patients underwent corrected distance visual acuity with spectacles (CDVAs), corrected distance visual acuity with contact lenses (CDVAcl), and twilight vision (TV) testing (Vista Vision Far-Pola, DMD MedTech charts). Parameters were evaluated before and after the CL fitting and repeated 3 months after the baseline visit. STATISTICAL ANALYSIS USED: MedCalc for Windows, version 11.4 (MedCalc Software, Ostend, Belgium). RESULTS: Rigid gas-permeable CL wear showed significant improvement in CDVAcl compared to wearing spectacles on both visits ( P = 0.0039 and P = 0.0003, respectively). TV with CLs was significantly better in both groups compared to the TV with spectacles at the baseline visit ( P = 0.0011 in SCL group; P = 0.0001 in RGPCL group), and at the follow-up visit, this significance was proven for the RGPCL group ( P = 0.001). Also, spectacle TV showed a significant improvement on the follow-up visit ( P = 0.0022 in SCL group; P = 0.0269 in RGPCL group). CONCLUSION: Contact lens wear improves visual performance compared to spectacles. TV results showed superiority of CLs compared to the spectacles, without a statistical difference regarding the CL type.

Moderate SCRIB Expression Levels Correlate with Worse Prognosis in OPSCC Patients Regardless of HPV Status.

Head and neck cancers rank as the sixth most prevalent cancers globally. In addition to traditional risk factors such as smoking and alcohol use, human papillomavirus (HPV) infections are becoming a significant causative agent of head and neck cancers, particularly among Western populations. Although HPV offers a significant survival benefit, the search for better biomarkers is still ongoing. In the current study, our objective was to investigate whether the expression levels of three PDZ-domain-containing proteins (SCRIB, NHERF2, and DLG1), known HPV E6 cellular substrates, influence the survival of HNSCC patients treated by primary surgery (n = 48). Samples were derived from oropharyngeal and oral cancers, and HPV presence was confirmed by PCR and p16 staining. Clinical and follow-up information was obtained from the hospital database and the Croatian Cancer registry up to November 2023. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression. The results were corroborated through the reanalysis of a comparable subset of TCGA cancer patients (n = 391). In conclusion, of the three targets studied, only SCRIB levels were found to be an independent predictor of survival in the Cox regression analysis, along with tumor stage. Further studies in a more typical Western population setting are needed since smoking and alcohol consumption are still prominent in the Croatian population, while the strongest association between survival and SCRIB levels was seen in HPV-negative cases.

Monitoring HPV Prevalence and Risk Cofactors for Abnormal Cytology in the Post-Vaccination Period among Croatian Women.

The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV genotypes and risk factors for the development of cervical precancer after almost 16 years from the onset of HPV vaccination in Croatia. In this study, a total of 321 women attending gynecological care were evaluated. Relevant medical and demographic information, including cytology, were collected. HPV genotyping was performed by PCR. Comparing the HPV types found in circulation in the pre-vaccination (1999-2015) and post-vaccination periods (2020-2023), a statistically significant reduction in HPV 31 was noted, while the overall prevalence increased in the post-vaccination period. Besides the expected HPV positivity as a risk factor, the history of smoking was associated with LSIL or worse cytology at enrollment. For the first time, this population study revealed a statistically significant shift in the HPV genotype in the post-vaccination period, as well as the confirmation of risk factors for the development of abnormal cytology among Croatian women.

Integrative analysis in head and neck cancer reveals distinct role of miRNome and methylome as tumour epigenetic drivers.

Head and neck cancer is the sixth most common malignancy worldwide, with the relatively low 5-year survival rate, mainly because it is diagnosed at a late stage. Infection with HPV is a well known aetiology, which affects the nature of these cancers and patients' survival. Besides, it is considered that the main driving force for this type of cancer could be epigenetics. In this study we aimed to find potential epigenetic biomarkers, by integrating miRNome, methylome, and transcriptome analyses. From the fresh head and neck cancer tissue samples, we chose a group for miRNome, methylome and transcriptome profiling, in comparison to adequate control samples. Bioinformatics analyses are performed in R v4.2.2. Count normalisation and group differential expression for mRNA and the previously obtained miRNA count data was performed with DESeq2 v1.36. Gene set enrichment analysis was performed and visualised using gProfiler2 v0.2.1 Identification of miRNA targets was performed by querying in miRTarBase using multiMiR v1.18.0. Annotation of CpG sites merging into islands was obtained from RnBeads.hg19 v1.28.0. package. For the integrative analysis we performed kmeans clustering using stats v4.2.2 package, using 8-12 clusters and nstart 100. We found that transcriptome analysis divides samples into cancers and controls clusters, with no relation to HPV status or cancer anatomical location. Differentially expressed genes (n = 2781) were predominantly associated with signalling pathways of tumour progression. We identified a cluster of genes under the control of the transcription factor E2F that are significantly underexpressed in cancer tissue, as well as T cell immunity genes and genes related to regulation of transcription. Among overexpressed genes in tumours we found those that belong to cell cycle regulation and vasculature. A small number of genes were found significantly differentially expressed in HPV-positive versus HPV-negative tumours (for example NEFH, ZFR2, TAF7L, ZNF541, and TYMS). In this comprehensive study on an overlapping set of samples where the integration of miRNome, methylome and transcriptome analysis were performed for head and neck cancer, we demonstrated that the majority of genes were associated exclusively with miRNome or methylome and, to a lesser extent, under the control of both epigenetic mechanisms.

One Incremental Stride for Doxycycline, One Substantial Advancement for Thyroid Eye Disease.

The aim of this study is to assess the effectiveness of a 12-week doxycycline treatment for thyroid eye disease (TED), an autoimmune condition associated with thyroid dysfunction. In this randomized controlled clinical trial, 82 patients were randomly assigned at a 1:1 ratio to receive doxycycline (50 mg) or to undergo no treatment. Various metrics, including margin reflex distance (MRD1 and MRD2), eyelid aperture, levator muscle function, lagophthalmos, proptosis, ocular motility, diplopia, and Graves' ophthalmopathy-specific quality-of-life (GO-QOL) scale scoring were assessed. Exclusion criteria were uncontrolled systemic diseases, tetracycline allergies, pregnancy, lactation, or age below 18. The mean age was 51.6 years (SD), 87.8% of participants were female, and all were Caucasians. By week 12, the doxycycline group exhibited a significant improvement rate based on MRD2 (from 4 to 15 participants with physiological findings), clinical activity score (from 7 to 35 participants with non-active disease), and GO-QOL (from 51.22% to 70.73% of participants with a good life quality). Doxycycline showcased anti-inflammatory and immunomodulatory effects in treating TED, suggesting its potential efficacy for TED and other orbit inflammatory conditions. However, these results warrant further validation through future research involving extended follow-up periods and larger cohorts.

Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease-an analysis from transplant centers across Europe.

Introduction: Chronic graft-versus-host disease (cGvHD) is a serious late complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: This multicenter analysis determined the cumulative incidence (CI) of cGvHD and late acute GvHD (laGvHD) and its impact on transplantation-related mortality (TRM), relapse (R), and overall survival (OS) in 317 patients [296 adults, 21 pediatrics (<12 years of age)] who underwent their first allo-HSCT in 2017. Results: The CI of laGvHD was 10.5% in adults and 4.8% in pediatrics, and the CI of cGvHD was 43.0% in all adult transplant patients and 50.2% in the adult at-risk cohort at the study end. The onset of cGvHD was de novo in 42.0% of patients, quiescent in 52.1%, and progressive in 5.9%. In adults, prophylactic use of antithymocyte globulin or posttransplant cyclophosphamide was associated with a significantly lower incidence of cGvHD (28.7%) vs. standard prophylaxis with calcineurin inhibitors (30.6%) and methotrexate/mycophenolate mofetil (58.4%) (all p < 0.01). TRM was significantly higher in patients with aGvHD (31.8%) vs. cGvHD (12.6%) and no GvHD (6.3%) (all p = 0.0001). OS in the adult at-risk cohort was significantly higher in patients with cGvHD (78.9%) vs. without (66.2%; p = 0.0022; HR 0.48) due to a significantly lower relapse rate (cGvHD: 14.5%; without cGvHD: 27.2%; p = 0.00016, HR 0.41). OS was also significantly higher in patients with mild (80.0%) and moderate (79.2%) cGvHD vs. without cGvHD (66.2%), excluding severe cGvHD (72.7%) (all p = 0.0214). Discussion: The negative impact of severe cGvHD on OS suggests a focus on prevention of severe forms is warranted to improve survival and quality of life.

The ABCD grading system in assessment of corneal cross-linking effect in keratoconus with different cone locations.

PURPOSE: The aim of this study was to analyse the postoperative corneal cross-linking results of corneal parameters and the ABCD grading system, depending on the cone location. METHODS: Thirty eyes of 25 patients with keratoconus (KC), who received the corneal cross-linking (CXL) treatment, were included in this study. The exclusion criteria were: patients under 18 years of age, corneal pachymetry less than 400 µm, corneal scarring, history of ocular trauma, history of ocular surgery, and corneal pathology other than KC. Patients were examined at the baseline visit, and followed-up at three, six, and twelve months after the CXL. All patients underwent visual acuity and Scheimpflug tomography at all visits. Progression parameters, keratometries, and ABCD grading were compared between the visits. Patients were classified into two groups: central and paracentral cones group (within the central 5 mm corneal zone) and peripheral cones group (outside the central 5 mm corneal zone), based on X-Y coordinates of maximal keratometry (Kmax). RESULTS: Parameter A remained relatively stable throughout the follow-up period in both groups. Parameter B and parameter C showed a significant increase in both groups postoperatively. Parameter D showed stability at the 6-month post-CXL visit in the peripheral KC group, while the central and paracentral KC group showed improvement at the 12-month post-CXL visit. CONCLUSION: There was no significant difference in the postoperative response between different cone locations in the ABCD grading system, when classifying according to the Kmax, except an earlier recovery of the parameter D in peripherally located cones.

Detection of Leachable Components from Conventional and Dental Bulk-Fill Resin Composites (High and Low Viscosity) Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method.

The aim of this study was to investigate leachable components (monomers) in high and low viscosity dental bulk-fill resin composites and conventional resin composite materials after polymerization. Six bulk-fill and six conventional dental resin composite materials were used in this study. The samples of each material (three sets of triplicates) were cured for 20 s with irradiance of 1200 mW/cm2 with a LED curing unit and immersed in a 75% ethanol solution at 37 °C. The eluates from each triplicate set were analyzed after 24 h, 7 days or 28 days using liquid chromatography coupled with triple quadrupole tandem mass spectrometry (LC-MS/MS). Detectable amounts of 2-Hydroxyethyl methacrylate (HEMA) were found in both Gradia materials and the amount observed across different time points was statistically different (p ˂ 0.05), with the amount in solution increasing for Gradia and decreasing for Gradia Direct flo. Bisphenol A diglycidildimethacrylate (BIS GMA) was found in Filtek and Tetric materials. Triethylene glycol dimethacrylate (TEGDMA) was detected in all materials. On the other hand, there were no statistically significant differences in the amounts of TEGDMA detected across different time points in either of the tested materials. Monomers HEMA, TEGDMA, 4-dimethylaminobenzoic acid ethyl ester (DMA BEE) and BIS GMA in bulk-fill and conventional composites (high and low viscosity) can be eluted after polymerization. The good selection of composite material and proper handling, the following of the manufacturer's instructions for polymerization and the use of finishing and polishing procedures may reduce the elution of the unpolymerized monomers> responsible for the possible allergic and genotoxic potential of dental resin composites.

Tranexamic Acid vs Adrenaline for Controlling Iatrogenic Bleeding During Flexible Bronchoscopy: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The most commonly used topical hemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on use of other agents such as tranexamic acid (TXA) for this purpose are limited. RESEARCH QUESTION: Is TXA effective and safe in controlling iatrogenic bleeding during FB compared with adrenaline? STUDY DESIGN AND METHODS: We conducted a cluster-randomized, double-blind, single-center trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to three applications of TXA (100 mg, 2 mL) or adrenaline (0.2 mg, 2 mL, 1:10000) after hemostasis failure after three applications of cold saline (4 ° C, 5 mL). Crossover was allowed (for up to three further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analog scale (VAS; 1 = very mild, 10 = severe). RESULTS: A total of 2,033 FBs were performed and 130 patients were randomized successfully to adrenaline (n = 65) or TXA (n = 65), whereas 12 patients had to be excluded for protocol violations (two patients from the adrenaline arm and 10 patients from TXA arm). Bleeding was stopped in 83.1% of patients (54/65) in both groups (P = 1). The severity of bleeding and number of applications needed for bleeding control were similar in both groups (adrenaline: mean VAS score, 4.9 ± 1.3 [n = 1.8 ± 0.8]; TXA: mean VAS score, 5.3 ± 1.4 [n = 1.8 ± 0.8]). Both adrenaline and TXA were more successful in controlling moderate bleeding (86.7% and 88.7%, respectively) than severe bleeding (40% and 58.3%, respectively; P = .008 and P = .012, respectively) and required more applications for severe bleeding (3.0 ± 0 and 2.4 ± 0.5, respectively) than moderate bleeding (1.7 ± 0.8 and 1.7 ± 0.8, respectively) control (P = .006 and P = .002, respectively). We observed no drug-related adverse events in either group. INTERPRETATION: We found no significant difference between adrenaline and TXA for controlling noncatastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04771923; URL: www. CLINICALTRIALS: gov.

The Role of Thermal Camera in the Assessment of Thyroid Eye Disease Activity.

Background: Thyroid eye disease (TED; also known as thyroid - associated orbitopathy, Graves ophthalmopathy) is an autoimmune inflammatory disease which presents in typical signs and symptoms such as deep orbital pain, chemosis with or without caruncular edema, unilateral or bilateral proptosis, eyelid retraction, eyelid edema or erythema, restrictive strabismus and compressive optic neuropathy. Objective: The aim of this study was to investigate the role of thermal camera in the assessment of thyroid eye disease (TED) activity compared to the Clinical Activity Score (CAS) scale, exophthalmometry values, and thyroid hormone and antibody levels. Methods: A total of 50 patients participated in this cross-sectional study of whom 29 were in the active phase of TED according to the sum on CAS scale and 21 patients in the inactive phase. The Flir E8® thermal camera was used to measure the temperature of the orbital area and the values were compared with the CAS scale, exophthalmometry values and thyroid hormone and antibody levels. Results: Higher values of temperature (p>0.0001), CAS score (p>0.0001), exophthalmometry (p=0.022), FT4 (p=0.0176) and TRAb (p=0.0091) were found in patients in the active phase of TED. Temperature of orbital area showed statistically significant positive correlation with CAS scale (p=0.0001), exophthalmometry values (p=0.0022) and anti-TPO levels (p=0.019). Conclusion: Thermal camera showed higher values of the temperature of the orbital area in patients in the active phase of the disease and positively correlated with the CAS scale, exophthalmometry findings and anti-TPO levels.

Do or Die: HPV E5, E6 and E7 in Cell Death Evasion.

Human papillomaviruses (HPVs) infect the dividing cells of human epithelia and hijack the cellular replication machinery to ensure their own propagation. In the effort to adapt the cell to suit their own reproductive needs, the virus changes a number of processes, amongst which is the ability of the cell to undergo programmed cell death. Viral infections, forced cell divisions and mutations, which accumulate as a result of uncontrolled proliferation, all trigger one of several cell death pathways. Here, we examine the mechanisms employed by HPVs to ensure the survival of infected cells manipulated into cell cycle progression and proliferation.