Germline mutational variants of Turkish ovarian cancer patients suspected of Hereditary Breast and Ovarian Cancer (HBOC) by next-generation sequencing.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is characterized by an increased risk of developing breast cancer (BC) and ovarian cancer (OC) due to inherited genetic mutations. Understanding the genetic variants associated with HBOC is crucial for identifying individuals at high risk and implementing appropriate preventive measures. The study included 630 Turkish OC patients with confirmed diagnostic criteria of The National Comprehensive Cancer Network (NCCN) concerning HBOC. Genomic DNA was extracted from peripheral blood samples, and targeted Next-generation sequencing (NGS) was performed. Bioinformatics analysis and variant interpretation were conducted to identify pathogenic variants (PVs). Our analysis revealed a spectrum of germline pathogenic variants associated with HBOC in Turkish OC patients. Notably, several pathogenic variants in BRCA1, BRCA2, and other DNA repair genes were identified. Specifically, we observed germline PVs in 130 individuals, accounting for 20.63% of the total cohort. 76 distinct PVs in genes, BRCA1 (40 PVs), BRCA2 (29 PVs), ATM (1 PV), CHEK2 (2 PVs), ERCC2 (1 PV), MUTYH (1 PV), RAD51C (1 PV), and TP53 (1PV) and also, two different PVs (i.e., c.135-2 A>G p.? in BRCA1 and c.6466_6469delTCTC in BRCA2) were detected in a 34-year-old OC patient. In conclusion, our study contributes to a better understanding of the genetic variants underlying HBOC in Turkish OC patients. These findings provide valuable insights into the genetic architecture of HBOC in the Turkish population and shed light on the potential contribution of specific germline PVs to the increased risk of OC.

Aberrant miR-3135b and miR-1273g-3p expression in the peripheral blood samples of BRCA1/2 (±) ovarian cancer patients.

Ovarian cancer (OC) ranks as the eighth most prevalent malignancy among women globally. The short non-coding RNA molecules, microRNAs (miRNAs) target multiple mRNAs and regulate the gene expression. Here in this study, we aimed to validate miR-3135b and miR-1273g-3p as novel biomarkers for prognostic and diagnostic factor OC. After RNA isolation, we analyzed the miR-3135b and miR-1273g-3p expression in peripheral blood samples derived from 150 OC patients. Subsequently, we compared their expression levels with 100 healthy controls. The differences of miR-3135b and miR-1273g-3p expression were detected using the Quantitative Real Time-PCR (qRT-PCR) technique following miRNA-specific cDNA synthesis pursing miRNA separation. The miR-3135b and miR-1273g-3p were higher in OC patients who tested positive for BRCA1/2 compared to BRCA-negative patients, and healthy cases. The level of miR-3135b demonstrated a roughly 4.82-fold increase in OC patients in comparison to the healthy cases, while miR-1273g-3p expression exhibited a roughly 6.77-fold increase. The receiver operating characteristic (ROC) analysis has demonstrated the potential of miR-3135b and miR-1273g-3p as markers for distinguishing between OC patients and healthy controls. The higher expressions of miR-3135b and miR-1273g-3p could be associated with OC development. Moreover, miR-3135b may have a diagnostic potential and miR-1273g-3p may have both diagnostic and prognostic potential in OC cell differentiation. The string analysis has revealed an association between miR-1273g-3p and the MDM2 gene, suggesting a potential link to tumor formation through the proteasomal degradation of the TP53 tumor suppressor gene. Additionally, the analysis indicates an association of miR-1273g-3p with CHEK1, a gene involved in checkpoint-mediated cell cycle arrest. String analysis also indicates that miR-3135b is associated with the MAPK1 gene, causing activation of the oncogenesis cascade. In conclusion, miR-1273g-3p, and miR-3135b exhibit significant potential as diagnostic markers. However, further research is needed to comprehensively investigate these miRNAs diagnostic and predictive characteristics in a larger cohort.

Neuronal-immune axis alters pain and sensory afferent damage during dental pulp injury.

ABSTRACT: Dental pulp tissue is densely innervated by afferent fibers of the trigeminal ganglion. When bacteria cause dental decay near the pulpal tissue, a strong neuronal and immune response occurs, creating pulpitis, which is associated with severe pain and pulp tissue damage. Neuroimmune interactions have the potential to modulate both the pain and pathological outcome of pulpitis. We first investigated the role of the neuropeptide calcitonin gene-related peptide (CGRP), released from peptidergic sensory afferents, in dental pain and immune responses by using Calca knockout (Calca -/- ) and wild-type (Calca +/+ ) mice, in a model of pulpitis by creating a mechanical exposure of the dental pulp horn. We found that the neuropeptide CGRP, facilitated the recruitment of myeloid cells into the pulp while also increasing spontaneous pain-like behavior 20% to 25% at an early time point. Moreover, when we depleted neutrophils and monocytes, we found that there was 20% to 30% more sensory afferent loss and increased presence of bacteria in deeper parts of the tissue, whereas there was a significant reduction in mechanical pain response scores compared with the control group at a later time point. Overall, we showed that there is a crosstalk between peptidergic neurons and neutrophils in the pulp, modulating the pain and inflammatory outcomes of the disease.

Investigation of the methylation changes in the promoter region of RB1 gene in retinoblastoma: Unraveling the epigenetic puzzle in retinoblastoma.

Retinoblastoma is an infrequent neoplasm that arises during childhood from retinal nerve cells and is attributed to the biallelic inactivation of the RB1 gene. In conjunction with anatomical anomalies, it is widely acknowledged that epigenetic modifications play a significant role in the pathogenesis of cancer. The association between methylation of the RB1 gene promoter and tumor formation has been established; however, there is currently no scholarly evidence to substantiate the claim that it is responsible for the inheritance of retinoblastoma. The initial hypothesis posited for this work was that familial retinoblastoma disease would be similarly observed in cases with RB1 promotor gene methylation, akin to RB1 mutations. The RB1 gene promoter region was subjected to methylation screening using real-time PCR in individuals diagnosed with familial retinoblastoma but lacking RB1 mutations. The study involved a comparison of the germline methylation status of the RB1 gene in the peripheral blood samples of 50 retinoblastoma patients and 52 healthy individuals. The healthy individuals were carefully selected to match the retinoblastoma patients in terms of age, sex, and ethnicity. The data obtained from both groups were subjected to statistical analysis. The study revealed that the methylation level in a cohort of 50 individuals diagnosed with retinoblastoma and 52 healthy control participants was determined to be 36.1% and 33.9%, respectively. As a result, there was no statistically significant disparity observed in RB1 promoter methylation between the patient and control groups (p = 0.126). The methylation of the promoter region of the RB1 gene in familial retinoblastoma does not exert any influence on the hereditary transmission of the disease.

DNA methylation of KIFC1 gene in determination of histological diagnosis, prognosis and metastasis of lung cancer.

BACKGROUND: One of the main features of cancer, especially lung cancer (LC), is abnormal cell division. Abnormal expression of kinesin family member C1 (KIFC1/HSET), which is involved in mitotic cell division and ensures equatorial alignment of chromosomes during division, is observed in both premalignant and malignant lesions. There are no studies in the literature addressing the role of KIFC1 in the diagnosis and follow-up of LC. In this study, we investigated the epigenetic role of KIFC1 in the diagnosis, stage, and prognosis of various histological subtypes diagnosed with LC. MATERIAL AND METHODS: The expression and methylation status of the KIFC1 gene were examined after DNA/RNA isolation in tumor, conjugate normal tissue, and blood samples from 39 patients diagnosed with LC and in blood samples from 39 healthy controls. Changes in KIFC1 gene expression were examined by the Quantitative Real Time-PCR (qRT-PCR) method after cDNA synthesis following RNA isolation. The Methylation-Specific PCR (MSP) method was used to determine the methylation status of the KIFC1 gene. In this study, the expression/methylation profiles of the KIFC1 gene and the clinical and pathological characteristics of the patients were analyzed by statistical methods. RESULT: Hypomethylation was detected in 95.8% of the 62.1% of patients' tissues with increased KIFC1 gene expression. The expression level of the KIFC1 gene was found to be increased 3.2-fold in the tumor tissues of the patients compared with the conjugated normal tissues and 2.4-fold in the serum of the patients compared with the healthy serum. Statistical comparison of patients' clinical parameters and methylation and expression results revealed statistical significance between KIFC1 expression and metastasis, tumor stage and tumor grade. CONCLUSION: In conclusion, the increase in the expression level of the KIFC1 gene is higher in patients diagnosed with LC than in the healthy population, and therefore, the increase in the expression level of the KIFC1 gene due to hypomethylation can be used as a screening biomarker in LC. It can also be considered that the methylation profile of the KIFC1 gene may be a potential biomarker for determining the subtype of squamous cell carcinoma in LC. The results of the study need to be analyzed and continued with a larger number of patients.

Dynamics of Innate Immune Response in Bacteria-Induced Mouse Model of Pulpitis.

INTRODUCTION: During pulpitis, as bacteria penetrate deeper into the dentin and pulp tissue, a pulpal innate immune response is initiated. However, the kinetics of the immune response, how this relates to bacterial infiltration during pulpitis and an understanding of the types of immune cells in the pulp is limited. METHODS: Dental pulp exposure in the molars of mice was used as an animal model of pulpitis. To investigate the kinetics of immune response, pulp tissue was collected from permanent molars at different time points after injury (baseline, day 1, and day 7). Flow cytometry analysis of CD45+ leukocytes, including macrophages, neutrophils monocytes, and T cells, was performed. 16S in situ hybridization captured bacterial invasion of the pulp, and immunohistochemistry for F4/80 investigated spatial and morphological changes of macrophages during pulpitis. Data were analyzed using two-way ANOVA with Tukey's multiple comparisons. RESULTS: Bacteria mostly remained close to the injury site, with some expansion towards noninjured pulp horns. We found that F4/80+ macrophages were the primary immune cell population in the healthy pulp. Upon injury, CD11b + Ly6Ghigh neutrophils and CD11b + Ly6GintLy6Cint monocytes constituted 70-90% of all immune populations up to 7 days after injury. Even though there was a slight increase in T cells at day 7, myeloid cells remained the main drivers of the immune response during the seven-day time period. CONCLUSIONS: As bacteria proliferate within the pulp chamber, innate immune cells, including macrophages, neutrophils, and monocytes, predominate as the major immune populations, with some signs of transitioning to an adaptive immune response.

RB1 gene mutations and genetic spectrum in retinoblastoma cases.

The aim of the study was to investigate the frequency and types of mutations on the retinoblastoma gene (RB1 gene) in Turkish population. RB1 gene mutation analysis was performed in a total of 219 individuals (122 probands with retinoblastoma, 14 family members with retinoblastoma and 83 clinically healthy family members). All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and the large deletions and duplications were investigated using the MLPA analysis and CNV algorithm. The bilateral/trilateral retinoblastoma rate was 66% in the study population. The general frequency of RB1 gene mutation in the germline of the patients with retinoblastoma was 41.9%. Approximately 51.5% of the patients were diagnosed earlier than 12 months old, and de novo mutation was found in 32.4% of the patients. Germline small genetic rearrangement mutations were detected in 78.9% of patients and LGRs were detected in 21.1% of patients. An association was detected between the eye color of the RB patients and RB1 mutations. 8 of the mutations detected in the RB1 gene were novel in the study.

Lipopolysaccharide-Induced TRPA1 Upregulation in Trigeminal Neurons is Dependent on TLR4 and Vesicular Exocytosis.

Pain from bacterial infection was believed to be the consequence of inflammation induced by bacterial products. However recent studies have shown that bacterial products can directly activate sensory neurons and induce pain. The mechanisms by which bacteria induce pain are poorly understood, but toll-like receptor (TLR)4 and transient receptor potential A1 (TRPA1) receptors are likely important integrators of pain signaling induced by bacteria. Using male and female mice we show that sensory neuron activation by bacterial lipopolysaccharides (LPS) is mediated by both TRPA1 and TLR4 and involves the mobilization of extracellular and intracellular calcium. We also show that LPS induces neuronal sensitization in a process dependent on TLR4 receptors. Moreover, we show that TLR4 and TRPA1 are both involved in sensory neurons response to LPS stimulation. Activation of TLR4 in a subset of sensory neurons induces TRPA1 upregulation at the cell membrane through vesicular exocytosis, contributing to the initiation of neuronal sensitization and pain. Collectively these data highlight the importance of sensory neurons to pathogen detection, and their activation by bacterial products like LPS as potentially important to early immune and nociceptive responses.SIGNIFICANCE STATEMENT Bacterial infections are often painful and the recent discovery that bacteria can directly stimulate sensory neurons leading to pain sensation and modulation of immune system have highlighted the importance of nervous system in the response to bacterial infection. Here, we showed that lipopolysaccharide, a major bacterial by-product, requires both toll-like receptor (TLR)4 and transient receptor potential A1 (TRPA1) receptors for neuronal activation and acute spontaneous pain, but only TLR4 mediates sensory neurons sensitization. Moreover, we showed for the first time that TLR4 sensitize sensory neurons through a rapid upregulation of TRPA1 via vesicular exocytosis. Our data highlight the importance of sensory neurons to pathogen detection and suggests that TLR4 would be a potential therapeutic target to modulate early stage of bacteria-induced pain and immune response.

Elevated Cytokine Levels in Gingival Crevicular Fluid of Teeth with Apical Periodontitis.

INTRODUCTION: Biomarkers assayed from gingival crevicular fluid (GCF) are a potential tool for endodontic diagnosis and for monitoring treatment response. This cross-sectional study measured cytokines in GCF from teeth with apical periodontitis and evaluated their relationship with preoperative pain and other clinical findings. METHODS: Participants presenting for root-end resection surgery due to apical periodontitis diagnosis (n = 56) underwent standardized clinical testing and completed preoperative questionnaires. GCF from diseased and control teeth were collected, processed, and analyzed. Mann-Whitney U and Wilcoxon tests were used to examine the cytokine levels in diseased compared to healthy control teeth. We also assessed the relationship of cytokine levels with clinical findings. RESULTS: Interleukins (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, and tumor necrosis factor-⍺ (TNF-⍺) were detected in GCF. TNF-⍺ levels were significantly higher in GCF collected from diseased versus control teeth (P = .02) and increased IL-1ß levels in diseased teeth were detected (P = .06). Lower IL-10 levels were observed in teeth with a sinus tract and/or swelling compared to teeth without a sinus tract and/or swelling (P = .08). Cytokine levels did not clearly relate to the presence of pain. CONCLUSIONS: Elevated levels of proinflammatory cytokines, including TNF-⍺ and IL1- ß, were detected in GCF from diseased teeth compared to the healthy controls. Additional studies are needed to further investigate the utility of these biomarkers for objectively evaluating periradicular pathology.

Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion.

The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache1,2. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system, affecting more than 2.5 million people a year3-5. How pain and neuroimmune interactions impact meningeal antibacterial host defences are unclear. Here we show that Nav1.8+ nociceptors signal to immune cells in the meninges through the neuropeptide calcitonin gene-related peptide (CGRP) during infection. This neuroimmune axis inhibits host defences and exacerbates bacterial meningitis. Nociceptor neuron ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors through its pore-forming toxin pneumolysin to release CGRP from nerve terminals. CGRP acted through receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, suppressing macrophage chemokine expression, neutrophil recruitment and dural antimicrobial defences. Macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses and bacterial clearance in the meninges and brain. Therefore, bacteria hijack CGRP-RAMP1 signalling in meningeal macrophages to facilitate brain invasion. Targeting this neuroimmune axis in the meninges can enhance host defences and potentially produce treatments for bacterial meningitis.

Contribution of Endodontic Pathology to Persistent Orofacial Pain: A Case Report.

Identifying the etiology and correct diagnoses for long-standing orofacial pain can be very challenging, especially in patients who have both odontogenic and nonodontogenic pain. This case report describes the successful management of a complex case of chronic orofacial pain in a patient with nonodontogenic chronic pain conditions and a maxillary molar tooth with persistent periapical pathology after endodontic treatment. The debilitating orofacial pain began after initial nonsurgical root canal treatment of the maxillary molar 3 years before presenting to our clinic. The initial clinical and radiographic assessment by our multidisciplinary team found that there were potentially both peripheral endodontic pathology and central pain mechanisms contributing to the long-standing pain. The diagnosis was shared with the patient's neurologist, who prescribed gabapentin, a centrally acting analgesic, and partial pain reduction was achieved. The odontogenic component of the orofacial pain was then addressed, by treating the persistent periapical infection and buccal bone fenestration of the roots of the maxillary molar. Treatments included both nonsurgical retreatment and surgical endodontic therapy (including root resection, root-end preparation, and retrofilling), and each significantly improved the patient's ongoing orofacial pain. After the successful endodontic treatments, the patient reported minimal pain and normal oral function. The case report highlights the importance of systematically treating endodontic pathology in a patient with long-standing orofacial pain, with both odontogenic and nonodontogenic components.

Identification of candidate genes in a family with cancer overload by whole-exome sequencing.

BACKGROUND: Approximately 120 out of every 1 million children in the world develop cancer each year. In Turkey, 2500-3000 children are diagnosed with new cancer each year. The causes of childhood cancer have been studied for many years. It is known that many cancers in children, as in adults, cause uncontrolled cell growth, and develop as a result of mutations in genes that cause cancer. METHODS: The investigation of family history within this context in the study, a total of 13 individuals consisting of all children and adults in the family were examined using the whole-exome sequencing (WES) with the individuals who were diagnosed with cancer in the family, who were detected to have different cancer profiles, and defined as high risk and to determine the gene or genes through which the disease has developed. RESULTS: At the end of the study, a total of 30 variants with a pathogenic record in the family were identified. A total of 10 pathogenic variants belonging to 8 different genes from these variants have been associated with various cancer risks. CONCLUSIONS: A significant scientific contribution has been made to the mechanism of disease formation by studying a family with a high cancer burden and by finding the genes associated with the disease. In addition, by the results obtained, family members with cancer predisposition were selected after a risk analysis conducted in this family, and the necessary examinations and scans were recommended to provide an early diagnostic advantage.

Bupivacaine for Root Canal Treatment - Practitioner Behaviors and Patient Perspectives: Survey Studies.

INTRODUCTION AND OBJECTIVES: Local anesthesia is essential in dentistry in providing intraoperative analgesia and anesthesia. However, knowledge related to its use for management of post-operative pain is limited. Perioperative pain management is especially important for root canal treatment (ie, endodontic therapy), performed by endodontists. In this study, we sought to better understand endodontists' attitudes regarding the use of long-lasting anesthetic, namely 0.5% bupivacaine HCl with 1:200,000 epinephrine, for the management of post-endodontic pain. Additionally, we aimed to understand the perspectives of dental patients about receiving longer lasting anesthesia for endodontic therapy and to determine factors that affect their anesthetic preferences within the orofacial region. METHODS: An email invitation to participate in an anonymous online survey was sent to members of the American Association of Endodontists. Also, 82 patients attending an in-person visit to an endodontic clinic were recruited to the study. RESULTS: Data from 474 endodontic practitioners and 82 patients included in analysis. Among practitioners, the majority reported to either never (33.31%) or rarely (34.84%) using bupivacaine. Most chose "I don't think I need it" (47%) and "patient discomfort because of longer duration of soft tissue anesthesia" (30.81%) as reasons for not preferring the use of bupivacaine. Of the practitioners who reported at least rare use, most chose bupivacaine for post-operative pain management (78.02%). Conversely, 52% of patients reported that they were likely/most likely to request long-lasting anesthetics for post-operative pain control. CONCLUSION: Bupivacaine is rarely used as a post-operative pain management strategy for endodontic therapy. Specifically, bupivacaine is not preferred not because of adverse events, toxicity, or slow onset concerns, but rather, because of longer duration of soft tissue anesthesia. However, our data suggest that patients may be willing to receive long-lasting anesthesia. Further patient-centered research should investigate the use of long-lasting anesthetic agents for management of post-endodontic pain.

miRNA Sequence Analysis in Patients With Kaposi's Sarcoma-Associated Herpesvirus.

MicroRNAs (miRNAs) are the non-coding RNAs that can both attach to the untranslated and coding sections of target mRNAs, triggering destruction or post-transcriptional alteration. miRNAs regulate various cellular processes such as immune function, apoptosis, and tumorigenesis. About 35,000 miRNAs have been discovered in the human genome. The increasing evidence suggests that the dysregulation of human miRNAs may have a role in the etiology of some disorders including cancer. Only a small sub-set of human miRNAs has functionally been validated in the pathogenesis of oncogenic viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the cause of various human malignancies including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS), which are mainly seen in AIDS patients or other immunocompromised people. We aimed to identify the miRNAs in Kaposi's sarcoma cases, with the comparison of KSHV seropositive and seronegative tumors with the controls and in each other in Turkish Kaposi's sarcoma patients. We performed the miRNA-sequencing at genome level in the peripheral blood mononuclear cells of 16 Kaposi's sarcoma patients, and in 8 healthy controls matched for age, gender, and ethnicity. A total of 642 miRNA molecules with different expression profiles were identified between the patients and the healthy controls. Currently, out of 642 miRNAs, 7 miRNAs (miR-92b-3p, miR-490-3p, miR-615-3p, miR-629-5p, miR-1908, miR-3180, miR-4433b-3p) which have not been described in the literature in the context of Kaposi's sarcoma were addressed in the study for the first time and 9 novel miRNAs, not found previously in the database, have been detected in Kaposi's sarcoma using the miRNA-sequencing technique. This study demonstrates the identification of differently expressed miRNAs which might be the new therapeutic targets for Kaposi's sarcoma, that has limited treatment options and can be used in the etiology, diagnosis, and prognosis of this cancer.

New biomarkers in peripheral blood of patients with ovarian cancer: high expression levels of miR-16-5p, miR-17-5p, and miR-638.

OBJECTIVES: Ovarian cancer is one of the most fatal gynecologic malignities. miR-16-5p, miR-17-5p, and miR-638 genes were found to have been associated with ovarian cancer in accordance with the data obtained from the previous microarray research performed by Tuncer et al. (J Ovarian Res 13(1):99, 2020). The expression levels of these miRNAs in the peripheral blood samples of 142 ovarian cancer patients, and 97 healthy controls were investigated for performing the validation, and to identify whether these genes were the possible biomarkers to be used in the early diagnosis of high-risk ovarian cancer patients, and in the prognosis of patients. METHODS: The miRNA expression analysis was performed using the miRNA-specific cDNA synthesis, and real-time PCR methods following the RNA isolation from the peripheral blood lymphocytes. RESULTS: miR-16-5p, miR-17-5p, and miR-638 miRNA gene expression levels were found to have twofold higher expression levels in patient groups compared with the gene expression levels in healthy controls, and were statistically significant (p < 0.05). In addition, the comparison of the miRNA expression levels with the clinical data of patients showed that there was a significant difference with smoking history and the increased expression level of miR-17-5 (p: 0.007). There was a significant difference between the increased expression level of miR-638 with the locally advanced stage, and abdominal/pelvic metastatic patients (p: 0.03). CONCLUSIONS: The obtained data suggest that miR-16-5p, miR-17-5p, and miR-638 molecules might be the noninvasive biomarkers in identifying the ovarian cancer. However, the investigation and monitoring of the changeability of these biomarkers in benign ovarian diseases, and during the treatment must be performed in future studies for identifying the accurate diagnostic, and prognostic features of miRNAs.

Outcomes of referrals from endodontic to orofacial pain specialists: A retrospective cohort study.

OBJECTIVES: Diagnosis and treatment of non-odontogenic pain is challenging for endodontists. The purpose of the study was to investigate the outcomes of referrals to orofacial pain specialists made for patients with suspected non-odontogenic pain, after evaluation and/or treatment by an endodontist. MATERIALS AND METHODS: A retrospective review of dental records was conducted for 60 patients referred from a postgraduate endodontic clinic to an orofacial pain clinic. Patient demographics, pain history, endodontic, and orofacial pain diagnoses were collected. Number of visits, length of treatment, and treatments prescribed were recorded. For analysis of outcomes, data pertinent to resolution/persistence of symptoms and patient compliance were analyzed. RESULTS: Thirty-five patients were included in the study. The most frequent pulpal and periapical diagnoses were previously treated (62%) and symptomatic apical periodontitis (72%), respectively. The most common orofacial pain diagnosis was temporomandibular disorder. The average time spent to diagnose and treat the pain was 17 months. Pain reduction varied and was documented for 51% of patients. Indications of non-compliance with orofacial pain appointments and treatments were documented for 66% of patients. CONCLUSIONS: Non-odontogenic pain diagnosis and treatment are challenging. Patients may have an increased predilection for developing persistent pain after endodontic treatment and/or have an undiagnosed, chronic orofacial pain condition as a true source of their chief complaint. It may be helpful for endodontists to set expectations of typical treatment times/plans when referring patients for evaluation and treatment of non-odontogenic pain.

High expression level of miR-1260 family in the peripheral blood of patients with ovarian carcinoma.

The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America (USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous) monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.

Comparison of Marginal Bone Levels Around Tissue-Level Implants with Platform-Matched and Bone-Level Implants with Platform-Switching Connections: 1-Year Results of a Prospective Cohort Study with a Split-Mouth Design.

PURPOSE: This clinical study was conducted to compare the influence of a platform-switched bone-level implant and a platform-matched tissue-level implant on marginal bone loss during the first year after loading. MATERIALS AND METHODS: Edentulous subjects who applied for two-implant-retained mandibular overdentures and showing sufficient bone volume for implants with 4.3-mm diameter and 12-mm length were enrolled. For standardization reasons, all subjects received a platform-matched tissue-level implant and a platform-switched bone-level implant in the anterior mandible. Since implants from the same manufacturer were used, both implants had identical implant thread designs and surface properties. All subjects received two-implant-retained mandibular overdentures with opposing maxillary complete dentures, and the implants were loaded after 6 weeks. Marginal bone loss was monitored via panoramic radiographs obtained immediately after loading and at the 6- and 12-month recalls after implant loading, and periodontal parameters, such as pocket probing depths, Plaque Index scores, and bleeding on probing, were also measured and recorded. RESULTS: Twenty-six patients received 26 bone-level and 26 tissue-level implants. No statistically significant differences were detected between the bone loss of the two groups for all the measurements (P > .05). Additionally, no significant difference was detected between the measured periodontal parameters of the two groups (P > .05). CONCLUSION: Within the limitations of this prospective clinical study with a follow-up time of 12 months, it can be concluded that the platform-switching bone-level design and the platform-matching tissue-level design show similar bone loss in the anterior edentulous mandible.

Reliability and validity of the Turkish version of oral health impact profile for edentulous subjects.

PURPOSE: The validated translations of the OHIP-EDENT exist in different languages; however, there is no reliable and validated Turkish translation. The present study was conducted to evaluate the reliability and to validate the Oral Health Impact Profile in edentulous subjects translated to Turkish (OHIP-EDENT-T). MATERIALS AND METHODS: The study sample included 104 conventional complete denture wearers (58 women and 46 men, mean age: 61.13 ± 9.43 years). The original English version of OHIPEDENT was translated into Turkish using a forward-backward method and applied to the subjects. The reliability of the OHIP-EDENT-T was evaluated using internal consistency and the test-retest method. Validity was determined as construct and convergent validity. The construct validity of OHIP-EDENT-T was assessed using exploratory and confirmatory factor analysis. RESULTS: The Cronbach's alpha value for OHIP-EDENT-T was 0.890. The intraclass correlation coefficient (ICC) was 0.749 for the OHIP-EDENT-T total score, and ICCs for the subscales ranged from 0.630 (95% CI = 0.501-0.823) to 0.859 (95% CI = 0.531-0.897), indicating good to excellent agreement. The Kaiser-Meyer-Olkin value for sampling adequacy was 0.820 and results of Bartlett's sphericity test indicated statistical significance (χ2=1139.767; df=171, p=0.001). This showed that factorial analysis could be applied to the data set. The three-factor structure of the scale explained 81.1% of the observed variance. The agreement of the three-factor solution was further tested with confirmatory factor analysis, and the fit index was found to be acceptable (chi-square fit test=1.449, RMSEA=0.040, GFI=0.94, CFI=0.93). CONCLUSION: Within the limitations of this study, it can be concluded that OHIP-EDENT-T is a valid and reliable instrument for evaluating the quality of life of edentulous patients.

Associations between Pain Severity, Clinical Findings, and Endodontic Disease: A Cross-Sectional Study.

INTRODUCTION: Thorough pain assessment and thermal and mechanical testing are the primary diagnostic tools used to assess the status of pulp and periapical tissues in teeth with potential endodontic pathology. This study evaluated predictors of acute odontogenic pain to better understand the relationship between endodontic pain, clinical testing, endodontic disease, and diagnoses. METHODS: Participants (N = 228) presenting with acute odontogenic pain underwent standardized clinical testing and reported their pain intensity. Univariate and multiple regression analyses were performed to evaluate the predictors of acute endodontic pain. Chi-square tests with Bonferroni adjustments were conducted to measure the frequency of endodontic diagnostic test findings and clinical observations in patients with different pulpal diagnoses. RESULTS: A negative response to cold stimulation on the causative tooth and percussion hypersensitivity on the healthy adjacent tooth were the strongest predictors of higher levels of acute endodontic pain. Percussion hypersensitivity on the healthy adjacent tooth was present in a quarter of the cohort and was reported with equal frequency in teeth diagnosed with irreversible pulpitis, necrotic pulp, and previously initiated/treated teeth. Although painful percussion on the causative tooth was more frequently reported in teeth diagnosed with necrotic pulp, painful palpation was more frequently reported on teeth diagnosed with previously initiated/treated teeth. CONCLUSIONS: Percussion hypersensitivity on the healthy adjacent tooth may reveal a lowered pain threshold and heightened pain sensitization. It is also possible that the 2 commonly performed mechanical sensory tests, percussion and palpation hypersensitivity, may detect different aspects of endodontic pathophysiology and pain processing.