Temporomandibular joint and cervical spine disability assessment in people with hypermobility joint syndrome.

BACKGROUND: Temporomandibular disorders (TMDs) and cervical spine problems are a growing public health issue, as they increase the risk of disability in people with hypermobility joint syndrome (HJS). OBJECTIVES: The present study aimed to assess the prevalence of TMD symptoms, and cervical spine and TMJ disability in HJS patients. MATERIAL AND METHODS: A survey was conducted among physical therapy students (mean age: 21 years). The study comprised 2 stages. The 1st one was HJS assessment (the Beighton scale and the Brighton criteria). Based on the assessment, 56 HJS subjects were enrolled for the study. The control group (CG) consisted of 60 HJS-free subjects, according to the aforementioned criteria. The 2nd stage of the study involved conducting a self-administered questionnaire on the prevalence of TMD symptoms. Both the TMD disability questionnaire (TMD-Q) and the neck disability index (NDI) scores were recorded. Pain intensity was assessed using the numeric rating scale (NRS). RESULTS: The HJS group showed higher NRS scores (p < 0.001). Headache, neck and shoulder girdle pain, and temporomandibular joint (TMJ) pain were found to be more severe in almost each patient from the HJS group as compared to CG. Those individuals had a greater degree of disability on the TMD-Q and the NDI scales (p < 0.001). The HJS group showed significant positive correlations between the TMD-Q and NDI scores (p = 0.0035), and between the TMD-Q and TMJ symptom questionnaire scores (p = 0.0047). A significant positive correlation between the NDI and TMJ symptom questionnaire scores was found both in the HJS group (p < 0.001) and CG (p < 0.001). CONCLUSIONS: The HJS bearers tended to obtain higher TMJ and cervical spine disability scores, at the same time reporting increased headache, neck and shoulder girdle pain, and TMJ pain intensity. Therefore TMJs should be carefully examined for possible signs of dysfunction in HJS subjects prior to dental or prosthetic treatment. According to our data, TMJ and cervical spine disability assessment should be included as a routine practice in the case of HJS patients, who should remain under the long-term care of a multidisciplinary team of doctors and therapists.

Effect of physiotherapeutic procedures on the bioelectric activity of the masseter muscle and the range of motion of the temporomandibular joints in the female population with chronic pain: a randomized controlled trial.

INTRODUCTION: Physical therapy (PT) methods applied in dentistry are increasingly discussed nowadays. Taking into account a rapidly growing number of temporomandibular disorders (TMDs) and orofacial pain patients, it is reasonable to determine which of the available physiotherapeutic (PT) methods are more effective than others, especially in terms of their possible analgesic and myorelaxant effects. OBJECTIVE: To assess manual and physical factors influencing pain reduction or elimination and increased muscle tension in patients with TMD; yet the influence of the applied forms of PT on the range of motion (ROM) of temporomandibular joints (TMJ). MATERIAL AND METHODS: A randomized, parallel-group, RCT, single-blind, equi-randomized (1:1) study was conducted in DC/TMD Group Ib patients (20-45 years of age). An experimental group (G1, n = 104) and a control group without TMD (G2, n = 104) were created according to CONSORT guidelines. Diagnostic measurements were performed in both groups (mass sEMG, temporomandibular joint range of motion-ROM, pain intensity - NRS). Group G1 was randomly divided (envelope method) into 4 therapeutic groups, in which therapy was carried out for 10 days: magnetostimulation (MS), magnetoledotherapy (MLE), magnetolaserotherapy (MLA), manual therapy (MT). Each time after the therapy, ROM and NRS measurements were performed, and after the 5th and 10th day sEMG. RESULTS: Statistically significant differences were found in the sEMG values of the masseter muscles, TMJ ROM and the pain intensity in G1 and G2 (p < 0.00). The largest decrease in sEMG (% MVC) of the masseter muscle occurred in the subgroup in which the manual therapy (MT) procedures were applied, p < 0.000. There was no clinically significant difference in and between other subgroups. There was a distinct mandible ROM increase noted in the MT group, with minimal changes in the MLA and MLE groups and no changes in the MS group. There was a clear increase in the lateral mobility of both right and left TMJ in the MT group. There were no differences in the course of the study in the MS group, and slight increases in the MLA and MLE groups. In the case of pain measurements, the greatest decrease in pain intensity was observed in the MT subgroup. CONCLUSIONS: According to our results manual therapy is an effective form of treatment in patients with pain, increased masticatory muscle tension and limitation in mandible ROM. Dental physiotherapy should become an integral part of multimodal TMD patients' treatment.

B7H3 Role in Reshaping Immunosuppressive Landscape in MSI and MSS Colorectal Cancer Tumours.

The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale and grading. Moreover, we analyzed the B7H3-related pathways using available online datasets and the immunological context of B7H3 expression, through the 48-cytokine screening panel of cancer tissues homogenates, immunogenic features and immune composition. The study included 158 patients diagnosed with CRC. To assess B7H3 levels, we performed an immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). To elucidate the immune composition of colorectal cancer, we performed the Bio-Plex Pro Human 48-cytokine panel. To study biological characteristics of B7H3, we used online databases. Expression of B7H3 was upregulated in CRC tumour tissues in comparison to adjacent noncancerous margin tissues. The concentrations of B7H3 in tumours were positively associated with T parameter of patients and negatively with tumour-infiltrating lymphocytes score. Additionally, Principal Component Analysis showed that B7H3 expression in tumours correlated positively with cytokines associated with M2-macrophages and protumour growth factors. The expression of B7H3 in tumours was independent of MSI/MSS status. These findings will improve our understanding of B7H3 role in colorectal cancer immunity. Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer.

Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer.

The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, and histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, and cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape and HHLA2-related pathways in colorectal cancer using available online datasets were analyzed. The study included 167 patients diagnosed with CRC. Expression of HHLA2 was detected by immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). The IHC was used to evaluate the MSI and CD8+ status. The budding and TILs were measured using a light microscope. The concentrations of cytokines, chemokines, and cell signaling molecules were measured to analyze the data by the Bio-Plex Pro Human cytokine screening panel, 48 cytokine assay, and principal component analysis (PCA). Geneset enrichment analysis (GSEA) was conducted to identify HHLA2-related pathways. The biological function of HHLA2 was predicted by Gene Ontology (GO). Analysis of the immune infiltration landscape of HHLA2 in colorectal cancer was made by the web-based tool Camoip. High HHLA2 expression was detected in CRC tumor tissues compared to the adjacent noncancerous tissues. The percentage of HHLA2-positive tumors was 97%. GSEA and GO showed that HHLA2 upregulation correlated with cancer-related pathways and several biological functions. Tumor-infiltrating lymphocytes score correlated positively with IHC HHLA2 expression level percentage. There was a negative correlation between HHLA2, anti-tumor cytokines and pro-tumor growth factors. This study provides a valuable insight into the role of HHLA2 in CRC. We reveal the role of HHLA2 expression as well as a stimulatory and inhibitory immune checkpoint in colorectal cancer. Further research may verify the therapeutic values of the HHLA2-KIR3DL3/TMIGD2 pathway in colorectal cancer.

B7H4 Expression Is More Frequent in MSS Status Colorectal Cancer and Is Negatively Associated with Tumour Infiltrating Lymphocytes.

The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called "cold tumours", and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.

Incidence of Concomitant Neoplastic Diseases, Tumor Characteristics, and the Survival of Patients with Lung Adenocarcinoma or Squamous Cell Lung Carcinoma in Tobacco Smokers and Non-Smokers-10-Year Retrospective Single-Centre Cohort Study.

Changes in smoking trends and changes in lifestyle, together with worldwide data regarding the incidence of lung cancer in the group of patients with no previous history of smoking, leads to consideration of the differences in the course of the disease, the time of cancer diagnosis, the survival rate, and the occurrence of comorbidities in this group of patients. This study aimed to determine the occurrence of non-smokers among patients undergoing anatomical resection of the lung tissue due to lung carcinoma and to investigate the differences between the course of lung cancer, survival, and the comorbidities in the groups of patients with lung cancer depending on the history of tobacco smoking. The study included a cohort of 923 patients who underwent radical anatomical resection of the lung tissue with lung primary adenocarcinoma or squamous cell carcinoma. The Chi2 Pearson's test, the t-test, the Mann-Whitney U test, the Kaplan-Meier method, the Log-rank test with Mantel correction, and the Cox proportional hazard model were used for data analysis. We observed a significantly higher mean age of smoking patients compared to the mean age of non-smoking patients. The coexistence of former neoplastic diseases was significantly more frequent in the group of non-smokers compared to the group of smoking patients. We did not observe differences depending on smoking status in the tumor stage, grade, vascular and pleural involvement status in the diagnostic reports. We did not observe differences in the survival between smokers vs. non-smokers, however, we revealed better survival in the non-smoker women group compared to the non-smoker men group. In conclusion, 22.11% of the patients undergoing radical anatomical resection of the lung tissue due to lung cancers were non-smokers. More research on survival depending on genetic differences and postoperative treatment between smokers and non-smokers is necessary.

Does the Immunohistochemical Expression of CD44, MMP-2, and MMP-9 in Association with the Histopathological Subtype of Renal Cell Carcinoma Affect the Survival of Patients with Renal Cancer?

CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of patients with renal cancer. The study population included 243 clear cell RCC (ccRCC) and 59 non-ccRCC cases. A total of 302 tumors were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The expression levels of the proteins were scored by semi-quantitative methods, and the correlation with overall patient survival was verified. We found no significant differences in CD44 expression levels between cc-RCC and non-ccRCC cases; however, significant differences existed in the degree of MMP-2 and MMP-9 expression between cc-RCC and non-ccRCC cases. There was significantly higher MMP expression in non-ccRCC than in ccRCC cases. Univariate Cox regression analysis showed that increased CD44 expression and histopathological subtype of ccRCC were predictors of shorter overall survival. Moreover, MMP-2 overexpression slightly reduced the risk of patient death, while MMP-9 expression did not show an association with patients' survival. However, on multivariate analysis, only the histopathological subtypes of ccRCC and CD44 expression were independent risk factors for patient death.

Immunohistochemical Expression of CD44, MMP-2, MMP-9, and Ki-67 as the Prognostic Markers in Non-Clear Cell Renal Cell Carcinomas-A Prospective Cohort Study.

CD44 is the most frequently reported marker of the cancer stem cells in renal cell carcinoma (RCC). Matrix metalloproteinases MMP-2 and MMP-9 are key regulators of tumor invasion and metastasis. The aim of this study was to investigate the clinicopathologic and prognostic values of the immunohistochemical expression of CD44, MMP2, MMP9, and Ki-67 in papillary and chromophobe RCCs. In the case of papillary RCC, MMP-2 expression was positively correlated with patient age (p < 0.05), while CD44 expression was positively correlated with tumor stage (τ = 0.26, p < 0.05). Moreover, CD44 expression positively correlated with MMP-9 (τ = 0.39, p < 0.05). In the case of chromophobe RCC, only Ki-67 expression was negatively correlated with tumor stage (τ = −0.44, p < 0.05). During follow-up, a death was documented in 6 patients with papillary RCC. In these patients, CD44 expression was not a significant factor affecting the overall survival of patients (p > 0.05), whereas there was a positive correlation between increased MMP-9 expression and shorter overall survival (p < 0.05). Taken together, carcinogenesis in papillary RCC is probably dependent on both cancer stem cells and metalloproteinases activity. Expression of CD44 and MMP-9 can significantly improve the prediction of papillary RCC prognosis in the future.

Salivary Concentrations of Chemerin, α-Defensin 1, and TNF-α as Potential Biomarkers in the Early Diagnosis of Colorectal Cancer.

Colorectal cancer is one of the most prevalent cancers worldwide. There is a great interest and need to find simple, inexpensive, and minimally invasive diagnostic tests. The aim of the study was to analyze the salivary concentrations of chemerin, α-defensin 1, and TNF-α in colorectal cancer (CRC) patients and in a healthy control group. The concentration of these proteins was simultaneously determined in the serum of subjects. We also aimed to assess the correlation of these results and selected clinicopathological features. This prospective study was comprised of 39 CRC patients and 40 control group patients. Salivary and serum concentrations were determined by enzyme immunoassays. The salivary and serum concentrations of chemerin, α-defensin 1, and TNF-α were significantly higher in cancer patients compared to the control group. No correlation was found between concentrations of the proteins and the clinical stage of cancer and tumor location. The ROC curve analysis showed that although salivary concentrations of all proteins showed 100% sensitivity and 100% specificity, serum concentrations of the analyzed proteins were characterized by 100% sensitivity and over 90% specificity. The assessment of chemerin, α-defensin 1, and TNF-α concentrations in saliva seem to have great potential as quick and useful biomarkers in the early diagnosis of CRC.

Assessment of the RANTES Level Correlation and Selected Inflammatory and Pro-Angiogenic Molecules Evaluation of Their Influence on CRC Clinical Features: A Preliminary Observational Study.

Background and Objectives: Assessment of RANTES level and concentrations of inflammatory cytokines: programmed death ligand 1 (PD-L1), interferon gamma IFN-γ, tumor necrosis factor alpha (TNF-α), transforming growht factor ß (TGF-ß) (and angiogenesis factors: vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor C (VEGF C) in tumor and margin tissues of colorectal cancer (CRC,) and evaluation of RANTES influence on histopathological parameters (microvessel density (MVD), budding, tumor-infiltrating lymphocytes (TILs)), in relation to patients' clinical features. Materials and Methods: The study used 49 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of RANTES, PD-L1, IFN-γ, TNF-α, TGF-ß, VEGF-A, and VEGF-C, we used the commercially available enzyme-linked immunosorbent assay kit. Additionally, RANTES and PD-L1 expression was assessed with the use of IHC staining in both tumor cells and TILS in randomly selected cases. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope. Results: We found significantly higher levels of RANTES, PD-L1, IFN-γ, TNF-α, TGF-ß, VEGF-A, and VEGF-C in the tumor in comparison with the margin. The RANTES tumor levels correlated significantly with those of PD-L1, TNF-α, TGF-ß, VEGF-A, and VEGF-C. The RANTES margin levels were significantly associated with the margin levels of all proteins investigated-PD-L1, IFN-γ, TNF-α, TGF-ß, VEGF-A, and VEGF-C. Additionally, we observed RANTES- and PD-L1-positive immunostaining in TILs. In a group of 24 specimens, 6 different CRC tumors were positive for RANTES and PD-L1 immunostaining. The IFN-gamma concentration in both tumor and margin and TGF-ß in tumor correlated with TILs. TILs were negatively associated with the patients' disease stage and N parameter. Conclusions: RANTES activity might be associated with angiogenesis, lymphogenesis, and immune escape in CRC. RANTES is an important chemokine that is a part of the chemokine-cytokine network involved in the modulation of TME composition in CRC. Further research may verify which processes are responsible for the associations observed in the study.

Periostin in Angiogenesis and Inflammation in CRC-A Preliminary Observational Study.

Background and Objectives: To assess the periostin level and the concentrations of pro-inflammatory cytokines: TNFα, IFN-γ, IL-1ß and IL-17 in tumor and marginal tissues of CRC and to investigate the influence of periostin on angiogenesis by MVD (microvessel density) and concentration of VEGF-A in relation to clinicopathological parameters of patients. Materials and Methods: The study used 47 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of periostin, VEGF-A, TNFα, IFNγ, IL-1ß and IL-17, we used the commercially available enzyme- linked immunosorbent assay kit. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope Results: We found significantly higher concentrations of periostin, VEGF-A, IFN-γ, IL-1 ß, IL-17 and TNFα in the tumor samples compared with surgical tissue margins. The tumor concentrations of periostin were correlated with tumor levels of VEGF-A, IFN-γ, IL-1ß and TNFα. We observed significant correlation between margin periostin and VEGF-A, IFN-γ, IL-17 and TNFα in tumor and margin specimens. Additionally, we found a significantly negative correlation between periostin tumor concentration and microvessel density at the invasive front. Tumor periostin levels were also correlated positively with tumor budding. Conclusions: Periostin activity may be associated with pro-inflammatory cytokine levels: TNFα, IFN-γ, IL-1ß and IL-17. Our results also suggest the role of periostin in angiogenesis in CRC and its upregulation in poorly vascularized tumors. Further research on the regulations between periostin and cytokines are necessary to understand the interactions between tumor and immune tumor microenvironment, which could be helpful in the development of new targeted therapy.

The Concentration of CMKLR1 Expression on Clinicopathological Parameters of Colorectal Cancer: A Preliminary Study.

Background and Objectives: Colorectal cancer (CRC) is the second-most common cause of cancer-related deaths worldwide. Angiogenesis is crucial for cancer growth, infiltration of surrounding tissues, and metastasis and plays a key role in the pathogenesis of CRC. Chemerin/chemokine-like receptor 1 (CMKLR1) is one of the biochemical pathways involved in the regulation of angiogenesis in solid tumors. The aim of the study was to assess the CMKLR1 level in tumor and margin tissues of CRC in relation to histopathological parameters: microvessel density (MVD), budding, tumor-infiltrating lymphocytes (TILs), TNM scale, and grading. Materials and Methods: The study involved 43 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of CMKLR1 a commercially available enzyme-linked immunosorbent assay kit was used. For 35 cases, we performed CD34 immunostaining. The MVD, budding, and TILs were assessed using a light microscope. Results: The levels of CMKLR1 in both tumor and margin were negatively correlated with MVD and budding. CMKLR1 concentration in margin was higher in tissues with lymphocytic infiltration. Conclusions: Low vascularity and low budding are associated with higher CMKLR1 expression. CMKLR1 might play a multifunctional role in CRC pathogenesis by influencing tumor budding and peritumoral lymphocytic infiltration.

COL5A1 RS12722 Is Associated with Temporomandibular Joint Anterior Disc Displacement without Reduction in Polish Caucasians.

Numerous reports describe the association between the single-nucleotide polymorphism (SNP) rs12722 and rs13946 in the COL5A1 gene and injuries, such as Achilles tendon pathology, anterior cruciate ligament (ACL) injuries, and tennis elbow. Hence, there were no studies investigating COL5A1 and temporomandibular joint (TMJ) pathology. The aim of this study is to evaluate the relationship between COL5A1 rs12722 and rs13946 SNPs and TMJ articular disc displacement without reduction (ADDwoR). In this case-control study, the study group consisted of 124 Caucasian patients of both sexes. Each patient had a history of ADDwoR no more than 3 months prior. The control group comprised 126 patients with no signs of TMD according to DC/TMD. Genotyping of the selected SNPs was performed by real-time PCR using TaqMan probes. The significance of the differences in the distribution of genotypes was analyzed using Pearson's chi-square test. Logistic regression modeling was performed to analyze the influence of the 164 investigated SNPs on ADDwoR. The COL5A1 marker rs12722 turned out to be statistically significant (p-value = 0.0119), implying that there is a difference in the frequencies of TMJ ADDwoR. The distribution of rs12722 SNPs in the study group TT(66), CC(27), CT(31) vs. control group TT(45), CC(26), CT(51) indicates that patients with CT had an almost 2.4 times higher likelihood of ADDwoR (OR = 2.41) than those with reference TT (OR = 1), while rs13946 genotypes were shown to be insignificant, with a p-value of 0.1713. The COL5A1 rs12722 polymorphism is a risk factor for ADDwoR in the Polish Caucasian population.

Growth Abnormalities as a Risk Factor of Adverse Neonatal Outcome in Hypertensive Pregnancies-A Single-Center Retrospective Cohort Study.

(1) Background: Hypertensive disorders of pregnancy (HDP) include gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and preeclampsia superimposed on chronic hypertension (CH with PE). HDP is associated with several short and long-term perinatal and neonatal complications, such as newborn growth restriction and death. This study aimed to establish the association between HDP, newborn growth abnormalities, and neonatal outcome. (2) Methods: This is a single-center retrospective cohort study of 63651 singleton deliveries. (3) Results: Univariate analysis showed a significantly increased risk of intrauterine and neonatal death associated with maternal hypertension and growth disorders. There were differences between growth charts used, with the highest risk of stillbirth for SGA defined by the Intergrowth chart (OR 17.2) and neonatal death for newborn growth restriction (NGR) based on Intergrowth (OR 19.1). Multivariate analysis showed that NGR is a stronger risk factor of neonatal death than SGA only. (4) Conclusions: HDP is significantly associated with growth abnormalities and is an independent risk factor of adverse outcomes. The presence of newborn growth restriction is strongly associated with the risk of neonatal death. The choice of growth chart has a substantial effect on the percentage of diagnosis of SGA and NGR.

Pressure Algometry Evaluation of Two Occlusal Splint Designs in Bruxism Management-Randomized, Controlled Clinical Trial.

The aim of this pilot study was to evaluate the short-term effectiveness of two different occlusal devices and their impact on the pressure pain threshold (PPT) values among patients who reported to the Dental Prosthetics Outpatient Clinic of Pomeranian Medical University (Szczecin, Poland) and who were diagnosed with probable bruxism. Two groups were formed (A and B) to which patients were assigned randomly. Each group used a different occlusal splint for bruxism management. The occlusal appliance by Okeson, or the bimaxillary splint, was used overnight by each patient for 30 days of the study. The PPT was measured twice, at the first visit and after 30 days of using each occlusal device, with Wagner Paintest FPX 25 algometer. Bruxism was diagnosed based on data from the patient's medical history and from the physical examination. Nocturnal Bruxism Criteria according to the International Classification of Sleep Disorders (Third Edition) was used for the patient's evaluation. Results: similar pain factor (PF) reduction was observed in both the examined groups, regardless of the device used; canine guidance and no guidance were similarly effective in terms of increasing pain resilience.

GDF-15 Level Correlates with CMKLR1 and VEGF-A in Tumor-free Margin in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, responsible for over 880 000 deaths each year. Growth/differentiation factor 15 (GDF-15) is reported to be a promising diagnostic and prognostic factor in CRC. It induces pleiotropic effects in tumor cells: proliferation, stemness, invasion and metastasis. Some studies indicate that GDF-15 may stimulate angiogenesis in malignant neoplasms. However, it has not been investigated in CRC yet. The aim of our study was to determine the level of GDF-15 and the concentrations of hypoxia-inducible factor-1α (HIF-1α), VEGF-A and chemokine-like receptor 1 (CMKLR1) in tumor and margin specimens of CRC in relation to histological grade and TNM staging. The study comprised 33 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of GDF-15, HIF-1α, VEGF-A and CMKLR1, commercially available enzyme-linked immunosorbent assay (ELISA) kits were used. We found significantly increased levels of GDF-15 and CMKLR1 in tumor tissue compared to margin tissue and higher concentrations of HIF-1α and VEGF-A in margin tissue than in tumor tissue. The levels of GDF-15 and HIF-1α were significantly correlated with VEGF-A and CMKLR1 in margin tissue. In CRC, the increased level of GDF-15 might stimulate angiogenesis through upregulation of HIF-1α, VEGF A and CMKLR1 expression. Our study is the first one to reveal the correlation between the levels of GDF-15 and CMKLR1 in CRC. The elevated levels of HIF-1α and VEGF-A in tumor-free margin tissues suggest that noncancer cells in the tumor microenvironment are an important source of proangiogenic factors.

Selected E2F2 Polymorphisms in Oral and Oropharyngeal Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are subgroups of head and neck squamous cell carcinoma. E2F Transcription Factor 2 (E2F2) could contribute to cancer development, because it plays a critical role in many cellular processes, including the cell cycle, proliferation, differentiation, DNA damage response, and cell death. In the current study, we assessed the associations of five E2F2 polymorphisms (rs6667575, rs3218121, rs3218211, rs3218148, and rs3218203) with OSCC and OPSCC and influence on the TNM staging and grading. This is the first such survey to concern the European population. The study included 94 primary tumour samples following surgical resection from patients, whereas the control group consisted of 99 healthy individuals. We tried a matching of cases and controls for age and sample size. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination. Our results suggested that the most significant difference between the control group and the cancer group was the A/G heterozygote for rs3218121. Samples containing this genotype were mostly found in the control group. In our samples, rs6667575, rs3218121, rs3218211, and rs3218148 polymorphisms may affect the course of OSCC and OPSCC, while rs3218203 was not associated with OSCC and OPSCC. However, further studies are warranted to confirm our findings.

miREIA - an immunoassay method in assessment of microRNA levels in tumor tissue-pilot study. The impact of miR-93-5p, miR-142-5p and IFNγ on PD-L1 level in colorectal cancer.

Colorectal cancer is the second and third most common cancer in females and males, respectively. The PD-L1/PD-1 immune checkpoint is an important source of immunosuppression in the tumor microenvironment and is associated with IFNγ. Recent studies have revealed that a significant number of tumor suppressive miRNAs can regulate the expression of PD-L1.                The objective quantification of selected microRNAs using the miREIA method in CRC tissue was performed. We investigated the roles of miR-93-5p and miR-142-5p expression and the levels of IFNγ in regulating the expression of PD-L1 in tumor and margin tissues of CRC in relation to the histological grade, TNM classification, and tumor localization. 37 samples of tumor and margin tissues from CRC patients were evaluated. MiR-93-5p and miR-142-5p levels were measured by a method for quantitative measurement of human microRNA (miREIA). The concentrations of PD-L1 and IFNγ were determined by the ELISA kit. We found higher concentrations of miR-93-5p, PD-L1 and IFNγ in tumor samples compared to tumor margin samples. A significant correlation was found between PD-L1 and IFNγ in tumor and margin specimens; between miR-142-5p and miR-93-5p levels  in tumor and margin specimens. A higher level of miR-93-5p was found in tumor margin tissues on the left side of the colon. Patients with distant metastases were characterized by higher miR-93-5p concentration compared to patients without metastases. CRC is an important source of PD-L1, IFNγ and miR-93-5p expression. Understanding the mechanisms underlying intratumoral PD-L1 expression may open new opportunities for targeted immunotherapy for colorectal cancer.

Salivary gland lesions: diagnostic reliability and challenges of fine needle aspiration cytology.

Fine needle aspiration cytology (FNAC) is a valuable, safe and widely used method for preoperative diagnosis of salivary gland lesions. The diagnostic accuracy of FNAC is dependent on the quality and yield of the aspirate, as well as the experience and knowledge of the cytopathologist. 247 cases of FNAC of salivary gland lesions were performed in our 4-year retrospective study. FNAC diagnoses were divided into non-neoplastic lesions, benign and malignant neoplasms. Histopathologic confirmation was done in 101 cases. The cases with discrepancies between the FNAC and histopathologic results were reviewed to establish possible reasons for discordance. The measures of diagnostic validity of FNAC in diagnosing non-neoplastic, benign and malignant lesions were evaluated. Of the 247 FNAC samples, 135 cases were diagnosed as benign neoplasms, 15 as malignant neoplasms, and 97 as non-neoplastic lesions. Out of the 101 cases with histopathologic confirmation, discordant results between cytologic and histopathologic diagnosis were observed in 15 cases. Our study showed no false positive and 4 false negative results for cancer. Cystic presentation of a lesion was a common reason for diagnostic pitfall. Sensitivity of FNAC in various types of salivary gland lesions ranged from 75%-100%, specificity 81-100%, diagnostic accuracy 85-96%, PPV 31-100% and NPV 60-96%. FNAC is a highly sensitive and specific method for diagnosis of most salivary gland lesions. Despite the fact that histopathology remains the gold standard, preoperative FNAC should be considered for preliminary investigation. Due to the diagnostic pitfalls, FNAC should be used in conjunction with clinical information, physical examination, and radiologic findings to reach the right diagnosis.

The Impact of SARS-CoV-2 Outbreak on the Polish Dental Community's Standards of Care-A Six-Month Retrospective Survey-Based Study.

Currently, SARS-CoV-2 is the primary pathogen worldwide, disrupting most of our everyday activities. The study aim was to evaluate its impact on the Polish dental community, standards of care, health, and welfare. METHODS: A Google Forms survey was conducted among 303 dental practitioners. RESULTS: Of respondents, 54.93% curbed the number of patients in the last six months, 34.21% declared no changes, and 10.86% reported an increase; whereas 70.7% of the respondents reported a treatment price increase within the same period (27.96% and 1.32% reported no changes and a decrease, respectively). Of the respondents, 15.5% did not close their businesses during the first wave of the pandemic. Most declared 1 or 2 month break, 30.7% and 34.7%, respectively. Some reported 3, 4, or 5 month breaks (15.84%, 1.32%, and 0.99%, respectively), and only two respondents (0.66%) did not admit patients at all. Headache episodes were more frequent among female dentists before the pandemic; after the pandemic, headache frequency increased among both sexes. Temporomandibular disorders (TMDs) were more frequent among women (p = 0.017). CONCLUSIONS: Most Polish dentists followed SARS-CoV-2 recommendations and restricted their practices to admitting only patients with pain or incomplete treatment. Decreased sleep parameters, head, back, and neck pain, were observed. This situation may affect dental health conditions in Polish society over time.