Effect of different apical actions of new integrated endodontic motors on apical debris extrusion: An in vitro study.

The new generation endodontic motors can perform different kinematics when they reach a certain predetermined level thanks to the integrated apex locator system. These actions consist of apical reverse, apical slow down and apical stop. The aim of this study is to compare this action's effect on apical debris extrusion. Sixty extracted human lower premolars were selected. Teeth are divided into four random groups (n = 15). Groups are prepared accordance to their group names as continuous rotation, apical slow down, apical reverse and apical stop. Extruded debris is collected into preweighted Eppendorf tubes and then calculated. One-way ANOVA test showed no statistically significant result between experimental groups. Similar debris extrusion values of all motion modes of the integrated endodontic motor can be interpreted that there will be similar debris extrusion and consequently similar postoperative pain on clinical setting. More in vitro and in vivo research is needed to make a conclusion.

The Effect of Root Canal Preparation Size and Taper of Middle Mesial Canals on Fracture Resistance of the Mandibular Molar Teeth: An In Vitro Study.

INTRODUCTION: The aim of the present study was to investigate the influence of root canal preparation size and taper of middle mesial (MM) canals on fracture resistance of mandibular molars. METHODS: Fifty-five mandibular molar teeth having an MM canal were selected based on the cone-beam computed tomographic analysis. After the decoronation and distal root separation procedure, the lengths of the mesial roots were standardized to 13 mm. The specimens were randomly distributed into 5 groups (n = 11). Mesiobuccal and mesiolingual canals were prepared up to size 30.06 using VDW.ROTATE rotary files (VDW, Munich, Germany). The MM canal was prepared up to size 25.04, 25.06, 30.04, and 30.06, respectively. No preparation was done in the MM canal in the control group. After the irrigation protocol, the canals were obturated with the single-cone technique. A thin layer of silicone-coated specimens was embedded in acrylic resin and subjected to a fracture strength test by a universal testing machine. A vertical force was applied to the roots until they fracture. Statistical analysis was performed with 1-way analysis of variance and post hoc Duncan tests (P = .05). RESULTS: There was no significant difference between group 25.04 and the control group, but the fracture strengths of these groups were found to be significantly higher than that of groups 25.06, 30.04, and 30.06 (P < .05). CONCLUSIONS: Within the limitations of this study, we concluded that increasing the apical diameter and taper in the MM canal reduces the fracture strength of mandibular molar teeth. Among the tested instrumentation sizes, fracture strength decreased significantly when greater than 25.04 instrumentation sizes were chosen.

Does the 2017 revision improve the ability of GOLD to predict risk of future moderate and severe exacerbation?

INTRODUCTION: In 2017 update, GOLD separated spirometry from ABCD classification. OBJECTIVES: The aim was to investigate the predictive reliability of GOLD 2017 grading system in terms of future moderate and severe exacerbations. METHODS: COPD patients were classified into A to D groups according to GOLD 2011 and 2017. Patients who were assigned to C/D groups according to GOLD 2011 were divided into subgroups C 1/D1, C2/D2, C3/D3 according to FEV1 % of predicted and exacerbation history. C1/D1 patients defined as FEV1  < 50% predicted and without ≥2 exacerbations or hospitalization in the last year. RESULTS: A total of 225 patients were enrolled. Among them, 25.8% were in groups C1/D1 according to GOLD 2011. These patients shifted to A/B according to GOLD 2017. C1/D1 patients had a significantly higher risk of future moderate and severe exacerbation compared to A/B (P = 0.018). The risk of future moderate and severe exacerbation was significantly higher in patients with a FEV1  < 50% (P = 0.018).The risk of future moderate and severe exacerbation was higher in GOLD 2017 groups A and B compared to GOLD 2011 groups A and B. CONCLUSION: Low FEV1 was an important risk factor for future exacerbations. Downstaging of C1/D1 patients caused heterogeneity in A/B with including patients with low and high risk of future exacerbation. This resulted in a low discriminative power of GOLD 2017 regarding the risk of future exacerbation in groups A and B. This may cause underestimation of disease severity and inadequate treatment especially in A/B patients with low FEV1 .

The concept of crosstalk-directed embryological target mining and its application to essential hypertension treatment failures.

This review aims to introduce the novel concept of embryological target mining applied to interorgan crosstalk network genesis, and applies embryological target mining to multidrug-resistant essential hypertension (a prototype, complex, undertreated, multiorgan systemic syndrome) to uncover new treatment targets and critique why existing strategies fail. Briefly, interorgan crosstalk pathways represent the next frontier for target mining in molecular medicine. This is because stereotyped stepwise organogenesis presents a unique opportunity to infer interorgan crosstalk pathways that may be crucial to discovering novel treatment targets. Insights gained from this review will be applied to patient management in a clinician-directed fashion.

The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells.

STUDY QUESTION: Do different chemotherapy drugs exert the same magnitude of cytotoxicity on dormant primordial follicles and the growing follicle fraction in the ovary in vivo and on mitotic non-luteinized and non-mitotic luteinized granulosa cells in vitro? SUMMARY ANSWER: Cyclophosphamide (alkylating agent) and cisplatin (alkylating like) impacted both primordial and pre-antral/antral follicles and both mitotic and non-mitotic granulosa cells, whereas the anti-metabolite cancer drug gemcitabine was detrimental only to pre-antral/antral follicles and mitotic non-luteinized granulosa cells. WHAT IS KNOWN ALREADY: It is already known that anti-metabolite cancer drugs are less detrimental to the ovary than alkylating and alkylating like agents, such as cyclophosphamide and cisplatin. This assumption is largely based on the results of clinical reports showing lower rates of amenorrhea in women receiving anti-metabolite agent-based regimens compared with those treated with the protocols containing an alkylating drug or a platinum compound. But a quantitative comparison of gonadotoxicity with a histomorphometric proof of evidence has not been available for many chemotherapy drugs. Therefore, we combined in this study in vivo and in vitro models of human and rat origin that allows a comparative analysis of the impact of different chemotherapy agents on the ovary and granulosa cells using real-time quantitative cell indices, histomorphometry, steroidogenesis assays, and DNA damage and cell death/viability markers. We also aimed to investigate if there is a difference between mitotic and non-mitotic granulosa cells in terms of their sensitivity to the cytotoxic actions of chemotherapy drugs with different mechanisms of action. This issue has not been addressed previously. STUDY DESIGN, SIZE, DURATION: This translational research study involved in vivo analyses of ovaries in rats and in vitro analyses of granulosa cells of human and rat origin. PARTICIPANTS/MATERIALS, SETTING, METHODS: For the in vivo assays, 54 4- to 6-week old Sprague-Dawley young female rats were randomly allocated into four groups of 13 to receive a single IP injection of: saline (control), gemcitabine (200 mg/kg), cisplatin (50 mg/kg) or cyclophosphamide (200 mg/kg). The animals were euthanized 72 h later. Follicle counts and serum AMH levels were compared between the groups. In vitro cytotoxicity studies were performed using mitotic non-luteinized rat (SIGC) and human (COV434, HGrC1) granulosa cells, and non-mitotic luteinized human (HLGC) granulosa cells. The cells were plated at a density of 5000 cells/well using DMEM-F12 culture media supplemented with 10% FBS. Chemotherapy agents were used at their therapeutic blood concentrations. The growth of mitotic granulosa cells was monitored real-time using xCelligence system. Live/dead cell and apoptosis assays were also carried out using intravital Yo-Pro-1 staining and cleaved caspase-3 expression, respectively. Estradiol (E2), progesterone (P) and anti-Mullerian hormone (AMH) levels were assayed with ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Cyclophosphamide and cisplatin caused massive atresia of both primordials and growing follicles in the rat ovary whereas gemcitabine impacted pre-antral/antral follicles only. Cyclophosphamide and cisplatin induced apoptosis of both mitotic non-luteinized and non-mitotic luteinized granulosa cells in vitro. By contrast, cytotoxicity of gemcitabine was confined to mitotic non-luteinized granulosa cells. LIMITATIONS, REASONS FOR CAUTION: This study tested only three chemotherapeutic agents. The experimental methodology described here could be applied to other drugs for detailed analysis of their ovarian cytotoxicity. WIDER IMPLICATIONS OF THE FINDINGS: These findings indicate that in vivo and in vitro cytotoxic actions of chemotherapy drugs on the ovarian follicles and granulosa cells vary depending upon the their mechanism of action and the nature of the granulosa cells.