PFAS and their association with the increased risk of cardiovascular disease in postmenopausal women.

Cardiovascular diseases (CVD) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence cardiovascular disease risk. Per- and polyfluoroalkyl substances (PFAS) are a class of highly fluorinated chemicals used in household consumer and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonate (PFOS), Perfluorobutanesulfonic acid (PFBS) in postmenopausal women from our previously established CVD study. We used liquid chromatography with tandem mass spectrometry (LC-MS-MS), supported by machine learning approaches, and the detection and quantification of serum metabolites and proteins. Here, we show that PFOS can be a good predictor of coronary artery disease, while PFOA can be an intermediate predictor of coronary microvascular disease. We also found that the PFAS levels in our study are significantly associated with inflammation-related proteins. Our findings may provide new insight into the potential mechanisms underlying the PFAS-induced risk of cardiovascular diseases in this population.

Identification of Circulating Diagnostic Biomarkers for Coronary Microvascular Disease in Postmenopausal Women Using Machine-Learning Techniques.

Coronary microvascular disease (CMD) is a common form of heart disease in postmenopausal women. It is not due to plaque formation but dysfunction of microvessels that feed the heart muscle. The majority of the patients do not receive a proper diagnosis, are discharged prematurely and must go back to the hospital with persistent symptoms. Because of the lack of diagnostic biomarkers, in the current study, we focused on identifying novel circulating biomarkers of CMV that could potentially be used for developing a diagnostic test. We hypothesized that plasma metabolite composition is different for postmenopausal women with no heart disease, CAD, or CMD. A total of 70 postmenopausal women, 26 healthy individuals, 23 individuals with CMD and 21 individuals with CAD were recruited. Their full health screening and tests were completed. Basic cardiac examination, including detailed clinical history, additional disease and prescribed drugs, were noted. Electrocardiograph, transthoracic echocardiography and laboratory analysis were also obtained. Additionally, we performed full metabolite profiling of plasma samples from these individuals using gas chromatography-mass spectrometry (GC-MS) analysis, identified and classified circulating biomarkers using machine learning approaches. Stearic acid and ornithine levels were significantly higher in postmenopausal women with CMD. In contrast, valine levels were higher for women with CAD. Our research identified potential circulating plasma biomarkers of this debilitating heart disease in postmenopausal women, which will have a clinical impact on diagnostic test design in the future.

Combined Targeting of Estrogen Receptor Alpha and Exportin 1 in Metastatic Breast Cancers.

The majority of breast cancer specific deaths in women with estrogen receptor positive (ER+) tumors occur due to metastases that are resistant to therapy. There is a critical need for novel therapeutic approaches to achieve tumor regression and/or maintain therapy responsiveness in metastatic ER+ tumors. The objective of this study was to elucidate the role of metabolic pathways that undermine therapy efficacy in ER+ breast cancers. Our previous studies identified Exportin 1 (XPO1), a nuclear export protein, as an important player in endocrine resistance progression and showed that combining selinexor (SEL), an FDA-approved XPO1 antagonist, synergized with endocrine agents and provided sustained tumor regression. In the current study, using a combination of transcriptomics, metabolomics and metabolic flux experiments, we identified certain mitochondrial pathways to be upregulated during endocrine resistance. When endocrine resistant cells were treated with single agents in media conditions that mimic a nutrient deprived tumor microenvironment, their glutamine dependence for continuation of mitochondrial respiration increased. The effect of glutamine was dependent on conversion of the glutamine to glutamate, and generation of NAD+. PGC1α, a key regulator of metabolism, was the main driver of the rewired metabolic phenotype. Remodeling metabolic pathways to regenerate new vulnerabilities in endocrine resistant breast tumors is novel, and our findings reveal a critical role that ERα-XPO1 crosstalk plays in reducing cancer recurrences. Combining SEL with current therapies used in clinical management of ER+ metastatic breast cancer shows promise for treating and keeping these cancers responsive to therapies in already metastasized patients.

Coronary Microvascular Dysfunction and Estrogen Receptor Signaling.

Chest pain with non-obstructive coronary artery disease (NOCAD) occurs more frequently in women than in men and is mainly related to coronary microvascular disease (CMD). The majority of CMD patients are postmenopausal women, suggesting a role for lack of estrogens in the development and progression of CMD. Patients are often discharged without a clear treatment plan due to the limited understanding of etiology and diagnostic parameters of CMD and have significantly higher rates of future cardiovascular events. Thus, there is a need for a better understanding of the underlying biology, and CMD-specific diagnostic tests and therapies. In this article, we reviewed recent studies on CMD, estrogen action in coronary microvasculature, and diagnosis and treatment options for CMD in postmenopausal women.

Cancer and Cancer Stem Cells: New Molecular Perspectives.

Cancer, which causes the deaths of millions of people, is an important public health problem worldwide. Despite significant advances in the diagnosis and treatment of cancer, survival rates are still insufficient in progressive cancers. Today, one of the most important reasons for not being able to reach the desired level in the fight against progressive cancer types is cancer stem cells (CSCs). The ineffectiveness of conventional therapies on CSCs has made it necessary to investigate the molecular mechanisms and signaling pathways used in the survival, drug resistance, and metastasis of CSCs. In this context, studies investigating the biology of CSCs suggest that lipid metabolism and extracellular vesicles are critical for understanding the stemness and metastasis of these cells. These studies have demonstrated that a number of molecules play a vital role in resistant to apoptosis in CSCs, including the cellular FLICE-inhibitor protein (c-FLIP), which inhibits TRAIL-induced extrinsic apoptosis. Another important output of these studies is the demonstration of the relationship of the cancer microenvironment in terms of epithelial-mesenchymal transition, which CSCs frequently use in the metastasis process. In addition, studies investigating the differences in glycosylation observed in CSCs and investigating cancer vaccines are promisng. These findings will strengthen our aresnal in the fight against cancer. In this article, we summarize current molecular studies on CSCs, an important target in novel cancer therapies.

Secondary prevention of coronary heart disease in elderly population of Turkey: A subgroup analysis of ELDERTURK study.

BACKGROUND: Secondary prevention plays an important role after acute coronary event due to high risk of adverse events in elderly. In present study we aimed to evaluate the lifestyle, management of risk factors and medical treatment for secondary protection in elderly patients with known coronary heart disease (CHD). METHODS: ELDERTURK is a non-interventional, multi-centered, observational study, which included total of 5694 elderly patients ( > 65 years) from 50 centers in Turkey. In this study elderly patients from the ELDERTURK population with known CHD were evaluated for cardiovascular risk factors, comor- bidities and medication usage. RESULTS: A total of 2976 (52.3% of study) out of 5694 patients included in the ELDERTURK study were evaluated. All had known CHD with a mean age of 73.4 ± 6.2 years and 60.3% were male. 13.0% of patients were smokers, 42.4% were overweight and 21.1% were obese. Only 23.6% of patients reported to do regular exercise, 73.4% had history of hypertension, 47.4% had dyslipidemia and 33.9% had diabetes mellitus. The rate of patients with systolic blood pressure > 140 mmHg were 31.1% and only 13.9% of patients had a recommended ≤ 70 mg/dL level of low-density lipoprotein cholesterol. Anti- platelet, statin, beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker usage was limited to 27.3%. CONCLUSIONS: The ELDERTURK study shows that many patients with CHD have a high prevalence of modifiable risk factors and unhealthy lifestyle. Apart from this, many patients are not receiving thera- peutic intervention and as a consequence most were not achieving the recommended goals.

Shear bond strength of luting cements to fixed superstructure metal surfaces under various seating forces.

PURPOSE: In this study, the shear bond strengths (SBS) of luting cements to fixed superstructure metal surfaces under various seating forces were investigated. MATERIALS AND METHODS: Seven different cements [Polycarboxylate (PCC), Glass-Ionomer (GIC), Zinc phospahate (ZPC), Self-adhesive resin (RXU), Resin (C&B), and Temporary cements ((RXT) and (TCS))] were bonded to a total number of 224 square blocks (5×5×3 mm) made of one pure metal [Titanium (CP Ti) and two metal alloys [Gold-Platinum (Au-Pt) and Cobalt-Chrome (Co-Cr)] under 10 N and 50 N seating forces. SBS values were determined and data were analyzed with 3-way ANOVA. Pairwise comparisons and interactions among groups were analyzed with Tukey's simultaneous confidence intervals. RESULTS: Overall mean scores indicated that Co-Cr showed the highest SBS values (1.96±0.4) (P<.00), while Au-Pt showed the lowest among all metals tested (1.57±0.4) (P<.00). Except for PCC/CP Ti, RXU/CP Ti, and GIC/Au-Pt factor level combinations (P<.00), the cements tested under 10 N seating force showed no significantly higher SBS values when compared to the values of those tested under 50 N seating force (P>.05). The PCC cement showed the highest mean SBS score (3.59±0.07) among all cements tested (P<.00), while the resin-based temporary luting cement RXT showed the lowest (0.39±0.07) (P<.00). CONCLUSION: Polycarboxylate cement provides reliable bonding performance to metal surfaces. Resin-based temporary luting cements can be used when retrievability is needed. GIC is not suitable for permanent cementation of fixed dental prostheses consisting of CP Ti or Au-Pt substructures.

Retinal structural changes in systemic arterial hypertension: an OCT study.

PURPOSE: To assess retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and macular thickness changes in young adults with systemic arterial hypertension. METHODS: This study included 80 young patients (age 23.8 ± 2.8 years) with systemic hypertension (sHT) without any known systemic or ocular disease and 80 age-matched (23.5 ± 2.1 years) healthy controls. Retinal nerve fiber layer thickness, macular thickness, and GCC thickness were measured with spectral-domain optical coherence tomography. RESULTS: Mean disease duration was 3.45 ± 1.48 years (range 2-10). Differences in intraocular pressure, body mass index, axial length, and spherical equivalent between the groups were insignificant (p>0.05). The differences in RNFL thickness did not differ between the groups. Patients with sHT had significantly lower central macular thickness (p = 0.037), inner superior macular thickness (p = 0.045), and outer temporal superior and outer temporal inferior GCC (p<0.001 for both). The RNFL thickness did not differ significantly in all quadrants between the groups (p>0.05). Systolic and diastolic blood pressure were significantly correlated with inner temporal superior and inner temporal inferior GCC thickness in a negative manner (p<0.05 for all). CONCLUSIONS: Ganglion cell complex thickness decrease is possibly a better retinal marker for hypertensive changes with respect to RNFL and macular thickness.

Polymerization efficiency of two dual-cure cements through dental ceramics.

PURPOSE: The aim of this study was to evaluate the effect of thickness of zirconia on curing efficiency of resin cements. MATERIALS AND METHODS: Four discs with 4.0 mm in diameter were prepared from non-HIP translucent zirconia blocks using a CAD/CAM system and feldspathic ceramic was layered onto discs. Thus, 4 ceramic disc samples were fabricated: (G) 0.5 mm zirconia- as a control group, (G1) 0.5 mm zirconia and 0.5 mm feldspathic, (G2) 1.0 mm zirconia and 0.5 mm feldspathic and (G3) 2.0 mm zirconia and 0.5 mm feldspathic ceramic layer. 2 different dual cure cements were polymerized using a LED curing unit. Degree of conversion was evaluated using Vickers Hardness Test and depths of cure of samples were measured. Data were analyzed statistically using One-way ANOVA and Tukey's HSD test (p<0.05). RESULTS: Microhardness and depth of cure values were different under same thickness of ceramic discs for two resin cements. As the thickness of the zirconia discs increased, the microhardness values and depth of cure decreased. CONCLUSION: Photocuring time cannot be the same for all clinical conditions, under thicker zirconia restorations (>2.0 mm), an extended period of light curing or a light unit with a high irradiance should be used.

Curing efficiency of dual-cure resin cement under zirconia with two different light curing units.

PURPOSE: Adequate polymerization is a crucial factor in obtaining optimal physical properties and a satisfying clinical performance from composite resin materials. The aim of this study was to evaluate the polymerization efficiency of dual-cure resin cement cured with two different light curing units under zirconia structures having differing thicknesses. MATERIALS AND METHODS: 4 zirconia discs framework in 4 mm diameter and in 0.5 mm, 1 mm and 1.5 mm thickness were prepared using computer-aided design system. One of the 0.5 mm-thick substructures was left as mono-layered whereas others were layered with feldspathic porcelain of same thickness and ceramic samples with 4 different thicknesses (0.5, 1, 1.5 and 2.0 mm) were prepared. For each group (n=12) resin cement was light cured in polytetrafluoroethylene molds using Light Emitting Diode (LED) or Quartz-Tungsten Halogen (QHT) light curing units under each of 4 zirconia based discs (n=96). The values of depth of cure (in mm) and the Vickers Hardness Number values (VHN) were evaluated for each specimen. RESULTS: The use of LED curing unit produced a greater depth of cure compared to QTH under ceramic discs with 0.5 and 1 mm thickness (p<0.05).At 100µm and 300 µm depth, the LED unit produced significantly greater VHN values compared to the QTH unit (p<0.05). At 500 µm depth, the difference between the VHN values of LED and QTH groups were not statistically significant. CONCLUSION: Light curing may not result in adequate resin cement polymerization under thick zirconia structures. LED light sources should be preferred over QTH for curing dual-cure resin cements, especially for those under thicker zirconia restorations.

Finite element analysis of heat generation from different light-polymerization sources during cementation of all-ceramic crowns.

STATEMENT OF PROBLEM: Exothermic composite resin chemical reactions and visible light generators can produce heat during a restorative polymerization process. These thermal changes in restored teeth may cause pain and irreversible pulpitis. PURPOSE: The purpose of this study was to analyze the temperature distribution and heat flow patterns of a crowned mandibular second premolar tooth model using 3 different light-polymerization technologies and a finite element technique. MATERIAL AND METHODS: A 2-dimensional finite element model was used to simulate a clinical condition. Heat flow and thermal stress distribution in a tooth during cementation of an all-ceramic crown using 4 commercially available light-polymerization units (LPUs), each with different wavelengths (Elipar TriLight, Elipar Freelight, Apollo 95 E, and ADT 1000 PAC), were investigated. The temperature values were measured at 3, 10, 12, and 40 seconds for each light-polymerizing unit (LPU) at 6 different finite element nodes. Two-dimensional temporal and spatial distribution of the thermal stress within the tooth, including the thermal coefficients and boundary conditions of the dental materials, were obtained and evaluated. RESULTS: The temperature at the nodal points did not exceed 42 degrees C, which is a threshold value for tissue vitality within the recommended operating periods at the dentin and pulp surface for all LPUs, except for Elipar TriLight. In the case of Elipar TriLlight, the temperatures at the dentin and pulp surfaces were 47 degrees C and 42 degrees C, respectively. CONCLUSIONS: When the light-polymerization units were used according to the manufacturers' operating procedures and without prolonged operating periods, with the exception of Elipar TriLight, the investigated LPUs did not produce significant heat. However, when the operating periods were prolonged, unacceptable temperature increases were observed, especially with the high-intensity LPUs.

Dental anxiety among adults in Turkey.

AIM: This aim of this study was to investigate the prevalence of dental anxiety and related factors in a Turkish population. METHODS AND MATERIALS: The Turkish translation of the Dental Fear Scale (DFS) and the Modified Dental Anxiety Scale (MDAS) were administered to 115 dental patients consisting of 21 subjects who had dental phobia and of 94 patients who did not. The scales were also administered to a non-clinical general population (N=183). RESULTS: The Turkish version of the DFS was internally consistent and reproducible. The scale had strong correlations (r=0.80, p<0.001 ) with the MDAS. Female participants scored higher (45.2+/-18.1) on the scale than men (38.2+/-15.7). The DFS had a negative correlation (r=-0.25, p<0.001) with education level. There was a statistically significant difference between dental phobics and the remaining groups on the DFS total score. At a cut-off point 55, the sensitivity of the scale was 0.80, specificity 0.80, positive predictive value 0.48, and negative predictive value 0.95. Thirty-nine subjects (21.3%) in the general population had total scores above this cut-off point. CONCLUSION: Dental fear is common in clinical and non-clinical settings in Turkey. The good psychometric characteristics of the DFS among Turkish participants supports its cross-cultural validity.

Reliability and validity of the Modified Dental Anxiety Scale (MDAS) in a Turkish population.

OBJECTIVES: Fear of dentistry is a common obstacle to obtaining dental care in Turkey. The aim of this study was to assess the reliability, validity and psychometric characteristics of the Turkish translation of the Modified Dental Anxiety Scale (MDAS) and compare it to the Dental Fear Survey (DFS) scores obtained in the same population. METHODS: The Turkish translated version of the MDAS was administered to 115 dental patients; 21 subjects who suffered from dental phobia, requiring general anesthesia for dental procedures, and 94 who did not have dental anxiety, in addition to 442 subjects from the general population. RESULTS: The Turkish translated version of the MDAS was internally consistent and reproducible. The patients with dentist phobia had the highest score. The Turkish MDAS correlated with the DFS (r = 0.80, P < 0.001). The MDAS scale correlated inversely (r = -0.14, P < 0.005) with level of education; however, it did not correlate with economic status. Women scored higher than men on the scale (mean = 12.3, SD = 5.2 vs. mean = 10.9, SD = 4.5, P < 0.005). At a cut-off point > or = 15, sensitivity was 0.80, specificity 0.74, positive predictive value 0.41 and negative predictive value 0.94. CONCLUSION: Although the specificity values were low, the Turkish MDAS demonstrated acceptable sensitivity, positive and negative predictive values. Thus, high reliability and validity of the MDAS supports its cross-cultural validity and indicated that it may be a valuable tool in quantifying fear of dentistry among Turks.

ITI implants and Dolder bars in the treatment of large traumatic defect of mandible: a clinical report.

The development of more sophisticated implant techniques to produce satisfying results improves the precise planning of both the surgical phase of the implantation and the following prosthetic rehabilitation. Ball and bar attachments are the main retainer systems for implant-bearing overdentures to achieve a successful treatment in the partial or full edentulism. In this clinical report, a 23-year-old male patient, presented with a large traumatic defect in the anterior mandible, was treated with ITI implant and ITI Dolder bar combinations. The reason to prefer this kind of treatment depends on the highest retention capacity and cleaning facilities of the system.