Morphological Variation of Mandibular Molars in Rohilkhand Population: An Original Research.

Introduction: In-depth knowledge of common and aberrant pulp morphology is essential for appropriate diagnosis and treatment planning before commencing root canal treatment. The radicular morphology of mandibular molars has been extensively studied. Considerable variation in the number of canals and roots found in these teeth has been reported. Aim: The purpose of this study is to investigate the root canal morphology of the mandibular molars among the Rohilkhand population using Dentascan. Materials and Methods: Dentascan images of mandibular molar were taken from 99 extracted teeth that were collected from the Department of Oral Surgery and Maxillofacial Surgery, Institute of Dental Sciences, Bareilly, and private clinics. The examination of root canal systems of the teeth was based on Vertucci's classification. Results: The mandibular molar (n = 99) were taken. Out of the 99 teeth examined, three canals were seen in 60 (60.6%) teeth, four canals in 39 (39.4%) teeth, 3% had extra distal roots, and 6% with C-shaped canals. Conclusion: Among mandibular first molars, only 3% had three roots. Mesial roots of the first molar typically present with two canals and two apical foramina with type IV or II canal configuration. Most distal roots of the first molar presented with a type I canal configuration. The remainder were distributed mainly between types II, IV, III, and V. Among 99 mandibular molars, 6% had single C-shaped roots.

Comparative Evaluation of Sealing Ability of Different Type of MTA as Root-End Filling Materials Using Dye Penetration Technique - An In Vitro Study.

Introduction: The main goal of the root-end filling material is to create a hermetic seal to protect against microbes and their by-products. Excellent biocompatibility and sealing ability are characteristics of MTA developed by Torabinejad et al. This study aimed to compare the sealing ability of different type MTA as root-end filling material using dye penetration technique. Material and Method: One-twenty (N = 120) extracted human maxillary anterior teeth were decontaminated, cleaned, and decoronated. Endodontic treatment and root-end resection were done. Then root-end cavity was prepared and filled with tested materials (N = 30). A calibrated stereomicroscope was used to evaluate linear measurement. All data were tabulated and statistically analyzed with a level of significance set at P < .05. Result: This order of increasing microleaks was observed: MTA Angelus < MTA Plus < PRO-Root MTA < Control group. There was a statistically significant difference in mean microleakage in MTA Angelus and MTA Plus groups (P = 0.040). MTA Angelus shows the least microleakage among all the bioceramic material groups. Conclusion: Although the sealing ability of MTA Angelus is superior to MTA Plus, PRO-Root MTA. MTA Plus, PRO-Root MTA could be considered an acceptable alternative to MTA Angelus in peri-radicular surgeries.

Gaining Wings to FLY: Using Drosophila Oogenesis as an Entry Point for Citizen Scientists in Laboratory Research.

Citizen science is a productive approach to include non-scientists in research efforts that impact particular issues or communities. In most cases, scientists at advanced career stages design high-quality, exciting projects that enable citizen contribution, a crowdsourcing process that drives discovery forward and engages communities. The challenges of having citizens design their own research with no or limited training and providing access to laboratory tools, reagents, and supplies have limited citizen science efforts. This leaves the incredible life experiences and immersion of citizens in communities that experience health disparities out of the research equation, thus hampering efforts to address community health needs with a full picture of the challenges that must be addressed. Here, we present a robust and reproducible approach that engages participants from Grade 5 through adult in research focused on defining how diet impacts disease signaling. We leverage the powerful genetics, cell biology, and biochemistry of Drosophila oogenesis to define how nutrients impact phenotypes associated with genetic mutants that are implicated in cancer and diabetes. Participants lead the project design and execution, flipping the top-down hierarchy of the prevailing scientific culture to co-create research projects and infuse the research with cultural and community relevance.

The AMPK-related kinase NUAK2 suppresses glutathione peroxidase 4 expression and promotes ferroptotic cell death in breast cancer cells.

Ferroptosis is a caspase-independent form of regulated cell death strongly linked to the accumulation of reactive lipid hydroperoxides. Lipid hydroperoxides are neutralized in cells by glutathione peroxidase 4 (GPX4) and inhibitors of GPX4 are potent ferroptosis inducers with therapeutic potential in cancer. Here we report that siRNA-mediated silencing of the AMPK-related kinase NUAK2 suppresses cell death by small-molecule inducers of ferroptosis but not apoptosis. Mechanistically we find that NUAK2 suppresses the expression of GPX4 at the RNA level and enhances ferroptosis triggered by GPX4 inhibitors in a manner independent of its kinase activity. NUAK2 is amplified along with MDM4 in a subset of breast cancers, particularly the claudin-low subset, suggesting that this may predict vulnerability to GPX4 inhibitors. These findings identify a novel pathway regulating GPX4 expression as well as ferroptotic sensitivity with potential as a biomarker of breast cancer patients that might respond to GPX4 inhibition as a therapeutic strategy.

Role of intra-tumoral vasculature imaging features on susceptibility weighted imaging in differentiating primary central nervous system lymphoma from glioblastoma: a multiparametric comparison with pathological validation.

PURPOSE: Primary objective of this study was to retrospectively evaluate the potential of a range of qualitative and quantitative multiparametric features assessed on T2, post-contrast T1, DWI, DCE-MRI, and susceptibility-weighted-imaging (SWI) in differentiating evenly sampled cohort of primary-central-nervous-system-lymphoma (PCNSL) vs glioblastoma (GB) with pathological validation. METHODS: The study included MRI-data of histopathologically confirmed ninety-five GB and PCNSL patients scanned at 3.0 T MRI. A total of six qualitative features (three from T2 and post-contrast T1, three from SWI: thin-linear-uninterrupted-intra-tumoral-vasculature, broken-intra-tumoral-microvasculature, hemorrhage) were analyzed by three independent radiologists. Ten quantitative features from DWI and DCE-MRI were computed using in-house-developed algorithms. For qualitative features, Cohen's Kappa-interrater-variability-analysis was performed. Z-test and independent t-tests were performed to find significant qualitative and quantitative features respectively. Logistic-regression (LR) classifiers were implemented for evaluating performance of individual and various combinations of features in differentiating PCNSL vs GB. Performance evaluation was done via ROC-analysis. Pathological validation was performed to verify disintegration of vessel walls in GB and rim of viable neoplastic lymphoid cells with angiocentric-pattern in PCNSL. RESULTS: Three qualitative SWI features and four quantitative DCE-MRI features (rCBVcorr, Kep, Ve, and necrosis-volume-percentage) were significantly different (p < 0.05) between PCNSL and GB. Best diagnostic performance was observed with LR classifier using SWI features (AUC-0.99). The inclusion of quantitative features with SWI feature did not improve the differentiation accuracy. CONCLUSIONS: The combination of three qualitative SWI features using LR provided the highest accuracy in differentiating PCNSL and GB. Thin-linear-uninterrupted-intra-tumoral-vasculature in PCNSL and broken-intra-tumoral-microvasculature with hemorrhage in GB are the major contributors to the differentiation.

Protocol for evaluating autophagy using LysoTracker staining in the epithelial follicle stem cells of the Drosophila ovary.

We have outlined the approach of visualizing autophagy specifically in the epithelial follicle stem cells of the Drosophila ovary using the LysoTracker dye. The advantage of using this protocol is that it details several techniques, including ovary dissection, immunofluorescence, and western blotting, that positively identify autophagy changes in a very small population of cells. One of the limitations of this protocol is that it needs to be combined with other genetic manipulations and positive markers of the autophagy pathway. For complete details on the use and execution of this protocol, please refer to Singh et al., (2018).

Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1.

Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.

Conjunctival and Corneal Fibrous Histiocytoma: Brief review.

Background: Fibrous histiocytoma (FH), a mesenchymal tumour, usually have an orbital presentation. Rarely, FH in both benign and malignant forms have been reported at limbus and conjunctiva. Present narrative review was conducted to determine demographic profile, clinical presentation and management options for this rare tumour.Methods: PubMed database was searched to identify articles presenting with fibrous histiocytoma of conjunctiva, cornea and limbus. Data was tabulated for age of presentation, sex, eye involved, area of involvement, if tumor was benign or malignant, management and recurrences.Results: Total of 35 articles were selected, which included 42 cases, of which 27 were benign and 15 malignant. 25 cases showed presence of limbal FH, 12 conjunctival, 4 caruncular and 1 corneal FH. Mean age of presentation was 30.9 years with male preponderance (females-10, males-17) in benign FH while malignant FH presented with mean age of 44.5 years and sex distribution of 7 females and 8 males. 4 cases of benign FH showed recurrence, which required re-excision and immunotherapy, while recurrence in malignant FH was 60%, where 4 needed exenteration, 3 enucleation and 1 expired due to metastasis.Conclusion: FH is one of the rare ocular tumours of eye presenting usually at the limbus and conjunctiva and rarely cornea. Histopathological examination along with immunostaining has a definite role in the diagnosis. Surgical excision with tumour free margins is the corner stone of treatment. Recurrences in benign varieties need re-excision or immunotherapy, while malignant cases need aggressive surgical options like exenteration or enucleation.

A rare case of benign fibrous histiocytoma of the cornea.

Fibrous histiocytoma (FH) commonly occurs in the superficial layers of the skin. Orbit and limbus are documented ophthalmic sites of involvement but isolated corneal FH has never been reported in literature. We present the first case of FH exclusively involving the cornea where a 10-year-old male child presented with a 3-month history of a painless growth on the superior cornea of the right eye with deterioration of vision. Tumor excision with therapeutic penetrating keratoplasty was done and the histopathological examination confirmed the diagnosis. There was no recurrence and the corneal graft was clear at 1 year.

Metabolite Profiling Reveals the Glutathione Biosynthetic Pathway as a Therapeutic Target in Triple-Negative Breast Cancer.

Cancer cells can exhibit altered dependency on specific metabolic pathways and targeting these dependencies is a promising therapeutic strategy. Triple-negative breast cancer (TNBC) is an aggressive and genomically heterogeneous subset of breast cancer that is resistant to existing targeted therapies. To identify metabolic pathway dependencies in TNBC, we first conducted mass spectrometry-based metabolomics of TNBC and control cells. Relative levels of intracellular metabolites distinguished TNBC from nontransformed breast epithelia and revealed two metabolic subtypes within TNBC that correlate with markers of basal-like versus non-basal-like status. Among the distinguishing metabolites, levels of the cellular redox buffer glutathione were lower in TNBC cell lines compared to controls and markedly lower in non-basal-like TNBC. Significantly, these cell lines showed enhanced sensitivity to pharmacologic inhibition of glutathione biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival. Consistent with this, patients whose tumors express elevated levels of γ-glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, had significantly poorer survival. We find, further, that agents that limit the availability of glutathione precursors enhance both glutathione depletion and TNBC cell killing by γ-glutamylcysteine ligase inhibitors in vitro Importantly, we demonstrate the ability to this approach to suppress glutathione levels and TNBC xenograft growth in vivo Overall, these findings support the potential of targeting the glutathione biosynthetic pathway as a therapeutic strategy in TNBC and identify the non-basal-like subset as most likely to respond. Mol Cancer Ther; 17(1); 264-75. ©2017 AACR.