Explore the vast range of titles available.

The degeneration of dopaminergic and other neurons in the aging brain is considered a process starting well beyond the infantile and juvenile period. In contrast to other dopamine-associated neuropsychiatric disorders, such as schizophrenia and drug addiction, typically diagnosed during adolescence or young adulthood and, thus, thought to be rooted in the developing brain, Parkinson’s Disease (PD) is rarely viewed as such. However, evidences have accumulated suggesting that several factors might contribute to an increased vulnerability to death of the dopaminergic neurons at an already very early (developmental) phase in life. Despite the remarkable ability of the brain to compensate such dopamine deficits, the early loss or dysfunction of these neurons might predispose an individual to suffer from PD because the critical threshold of dopamine function will be reached much earlier in life, even if the time-course and strength of naturally occurring and age-dependent dopaminergic cell death is not markedly altered in this individual. Several signaling and transcriptional pathways required for the proper embryonic development of the midbrain dopaminergic neurons, which are the most affected in PD, either continue to be active in the adult mammalian midbrain or are reactivated at the transition to adulthood and under neurotoxic conditions. The persistent activity of these pathways often has neuroprotective functions in adult midbrain dopaminergic neurons, whereas the reactivation of silenced pathways under pathological conditions can promote the survival and even regeneration of these neurons in the lesioned or aging brain. This article summarizes our current knowledge about signaling and transcription factors involved in midbrain dopaminergic neuron development, whose reduced gene dosage or signaling activity are implicated in a lower survival rate of these neurons in the postnatal or aging brain. It also discusses the evidences supporting the neuroprotection of the midbrain dopaminergic system after the external supply or ectopic expression of some of these secreted and nuclear factors in the adult and aging brain. Altogether, the timely monitoring and/or correction of these signaling and transcriptional pathways might be a promising approach to a much earlier diagnosis and/or prevention of PD.

Direct reprogramming based on genetic factors resembles a promising strategy to replace lost cells in degenerative diseases such as Parkinson's disease. For this, we developed a knock‐in mouse line carrying a dual dCas9 transactivator system (dCAM) allowing the conditional in vivo activation of endogenous genes. To enable a translational application, we additionally established an AAV‐based strategy carrying intein‐split‐dCas9 in combination with activators (AAV‐dCAS). Both approaches were successful in reprogramming striatal astrocytes into induced GABAergic neurons confirmed by single‐cell transcriptome analysis of reprogrammed neurons in vivo . These GABAergic neurons functionally integrate into striatal circuits, alleviating voluntary motor behavior aspects in a 6‐OHDA Parkinson's disease model. Our results suggest a novel intervention strategy beyond the restoration of dopamine levels. Thus, the AAV‐dCAS approach might enable an alternative route for clinical therapies of Parkinson's disease. Synopsis GABAergic neurons generated by CRISPR‐mediated direct reprogramming of striatal astrocytes rescue voluntary motor behavior in a toxin‐induced murine model for Parkinson's disease, suggesting a novel intervention strategy beyond the restoration of dopamine levels. A novel CRISPRa mouse line dCAM is developed for the conditional induction of endogenous target genes. An AAV‐based split‐dCas9‐activator system is established for translational applications of CRISPRa. Direct reprogramming of murine striatal astrocytes using the factor combination Ascl1 , Lmx1a , and Nr4a2 results in induced GABAergic neurons in vivo . Induced GABAergic neurons are capable of ameliorating specific motor symptoms of Parkinson's disease. Graphical Abstract GABAergic neurons generated by CRISPR‐mediated direct reprogramming of striatal astrocytes rescue voluntary motor behavior in a toxin‐induced murine model for Parkinson's disease, suggesting a novel intervention strategy beyond the restoration of dopamine levels.

ABSTRACT Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of heterozygosity, and chromosomal number aberrations. Screening and early detection of such abnormalities facilitates proper care and also helps to prevent further progression of potentially malignant lesions to malignancy. In such way, the presence of DNA aneuploidy in oral potentially malignant disorders (OPMDs) may serve as an indicator for the malignant transforming potential. Various assessment methods have been proposed to find the DNA ploidy status of cells. This current systematic review is mainly designed to assess the importance of ploidy status in OPMD while measuring the feasibility of using this biomarker for evaluating the hazard of malignant transformation. As an upshot of this systematic review, we can conclude that use of DNA ploidy status can serve as an independent bio-marker for predicting the malignant transformation of lesions. Furthermore, as a future scope the use of DNA ploidy analysis in normal mucosa of smokers will help to assess the malignancy risk and this technique might also help to predict the genetic predisposition of patients with malignancy.

Introduction: Identifying an osseointegrated dental implant could become vitally important in case some other clinician tries to restore it and plays a vital role in forensic odontology. However, existing ways to identify them are very crude and nonspecific. In addition, they are not focusing on implants used frequently in India. Aims: The aim of this study was to design a guidance system to identify different implant systems and their subtypes used in India and to evaluate the efficiency of this guidance system to identify an unknown dental implant. Materials and Methods: Radiographs of the 15 most common dental implant systems used in India were analyzed and categorized based on their morphological appearance under the headings. Nontapered or tapered/threaded or not, neck design, thread length, shape, etc., were observed on intraoral periapical radiographs, and a guidance system in the form of a flow chart was made. Based on the flow chart, 15 randomized assessor-blinded radiographs were tested for the accuracy of the guidance system that was developed. The Chi-square test was used at a 95% confidence interval to determine the accuracy of the guidance system used for the identification of assessor-blinded radiographs. Results: The newly designed dental implant identification guidance system effectively identified 14 out of 15 unknown implant radiographs among implant systems and subtypes used in this study. Nonparametric Chi-square test was applied and the results were highly significant (P < 0.05). Conclusions: The guidance system developed has the potential to identify the implant system mentioned in this study based on its radiographic appearance.

Dopamine-synthesizing neurons located in the mammalian ventral midbrain are at the center stage of biomedical research due to their involvement in severe human neuropsychiatric and neurodegenerative disorders, most prominently Parkinson’s Disease (PD). The induction of midbrain dopaminergic (mDA) neurons depends on two important signaling centers of the mammalian embryo: the ventral midline or floor plate (FP) of the neural tube, and the isthmic organizer (IsO) at the mid-/hindbrain boundary (MHB). Cells located within and close to the FP secrete sonic hedgehog (SHH), and members of the wingless-type MMTV integration site family (WNT1/5A), as well as bone morphogenetic protein (BMP) family. The IsO cells secrete WNT1 and the fibroblast growth factor 8 (FGF8). Accordingly, the FGF8, SHH, WNT, and BMP signaling pathways play crucial roles during the development of the mDA neurons in the mammalian embryo. Moreover, these morphogens are essential for the generation of stem cell-derived mDA neurons, which are critical for the modeling, drug screening, and cell replacement therapy of PD. This review summarizes our current knowledge about the functions and crosstalk of these signaling pathways in mammalian mDA neuron development in vivo and their applications in stem cell-based paradigms for the efficient derivation of these neurons in vitro.

Abstract Introduction: Nonmetric dental traits have a crucial role in ethnic classification of populations that help in forensic racial identification. Many studies have demonstrated the differences in the expression and frequency of dental traits between various ethnic groups for ancestry determination in the context of forensic dental anthropology. The present study is an attempt to assess the frequency and variation in nonmetric traits for establishing ethnicity in the Vidarbha subpopulation. Aim: The aim of the study was to assess the frequency and variation of nonmetric traits in permanent teeth for establishing ethnicity in the Vidarbha subpopulation. Materials and Methods: Participants of the Vidarbha subpopulation were selected by random sampling method. Molars, premolars, and incisors were evaluated for frequency of nonmetric traits, and variations were graded according to Dentoanthropological System of State University of Arizona criteria. Descriptive statistics, Chi-square test, and Student's t-test were used for analysis of data. Results: The most common occlusal morphology in mandibular first and second molar was 5 cusp and 4 cusp, respectively, with the \"+\" groove pattern. Cusp 3 and cusp 4 were observed frequently in the maxillary molars. One lingual cusp was most commonly seen in mandibular premolars show while incisors showed faint shoveling. Conclusion: Our study concludes that nonmetric traits were present and showed variation in permanent maxillary and mandibular teeth among the Vidarbha subpopulation. Cusp 5 and Cusp 4 in first and second mandibular molars, respectively, groove pattern \"+\" and grade 1 protostylid were the most frequent grades observed in permanent mandibular molars. One lingual cusp was most commonly seen in mandibular premolars and faint shoveling was a notable feature in incisors of this population.

Advances in the regenerative stem cell field have propelled the generation of tissue-specific cells in the culture dish for subsequent transplantation, drug screening purposes, or the elucidation of disease mechanisms. One major obstacle is the heterogeneity of these cultures, in which the tissue-specific cells of interest usually represent only a fraction of all generated cells. Direct identification of the cells of interest and the ability to specifically isolate these cells in vitro is, thus, highly desirable for these applications. The type VI intermediate filament protein NESTIN is widely used as a marker for neural stem/progenitor cells (NSCs/NPCs) in the developing and adult central and peripheral nervous systems. Applying CRISPR-Cas9 technology, we have introduced a red fluorescent reporter (mScarlet) into the NESTIN (NES) locus of a human induced pluripotent stem cell (hiPSC) line. We describe the generation and characterization of NES-mScarlet reporter hiPSCs and demonstrate that this line is an accurate reporter of NSCs/NPCs during their directed differentiation into human midbrain dopaminergic (mDA) neurons. Furthermore, NES-mScarlet hiPSCs can be used for direct identification during live cell imaging and for flow cytometric analysis and sorting of red fluorescent NSCs/NPCs in this paradigm.

Context: Oral cancer is a significant cause of death across the world. A combined multimodal approach integrating surgery and radiation therapy (RT) with or without chemotherapy (CT) is commonly employed in advanced oral cancer to prevent recurrences and locoregional spread. Oral mucositis is a common acute toxicity reported in patients undergoing RT and CT. The delivery of optimal cancer therapy protocols is compromised due to morbidity caused by oral mucositis. Aims: To compare the severity of oral mucositis in oral cancer patients undergoing 3-Dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) with or without concomitant CT. Settings and Design: This was a prospective, unicentric and longitudinal study conducted in a cancer centre. Methods and Material: One hundred four patients with locally advanced oral cancer were enrolled in this study. Fifty-two patients were treated with IMRT and 52 patients with 3DCRT to a dose of >60 Gy, along with concurrent cisplatin weekly CT. Mucositis was recorded before the start, in the end, 1 month, and 3 months post-chemoradiotherapy treatment. Statistical Analysis Used: Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software (v. 21.0, Chicago. 2012). Descriptive and frequency statistics were performed for different parameters assessed in 3DCRT and IMRT group. Results: Grade 3 mucositis was the most predominant grade observed in both groups at the end of treatment. Thirty-six patients (69.3%) versus 24 patients (46.1%) developed grade 3 mucositis in 3DCRT and IMRT group, respectively (P = 0.013). Healing was better with IMRT group when compared to 3DCRT group 1 month and 3 months post-RT. Mucositis was severe in patients undergoing concomitant CT. Conclusions: IMRT reduced the incidence of severe mucositis and also improved the treatment-compliance compared to 3DCRT in locally advanced head neck cancer patients treated by chemoradiotherapy.

Context: Decalcification of bone is a challenging aspect since penetration of decalcifying agents through dense alveolar bone is a slow process. Striking the right balance between speed and quality of staining is essential for accurate and timely diagnosis of bone pathologies. Aims: This study aimed to compare the rate of decalcification of bone by employing conventional method and tissue floatation bath (TFB) using 10% nitric acid and 10% formic acid. It also compared the cellular and staining characteristics of decalcified specimens of bone by the abovementioned methods. Materials and Method: Forty bone slices of hemimandibulectomy specimens were decalcified by employing conventional method and TFB at elevated temperature using 10% nitric acid and 10% formic acid. Following evaluation by chemical endpoint test, they were then subjected to tissue processing and staining with hematoxylin and eosin stain and assessed for various parameters. Statistical Analysis Used: Statistical analysis was done using statistical software SPSS version 18.0. One-way ANOVA was applied to evaluate the significant differences among the mean values in different groups. Results: The heat-accelerated TFB method significantly reduced the time of decalcification of bone without compromising the cellular and nuclear details. The cellular and staining characteristics of TFB method were better than those decalcified by conventional method. Conclusions: TFB method using 10% formic acid at elevated temperature provided the best cellular and nuclear details with reduced decalcification time as compared to conventional methods.

Context: Oral squamous cell carcinoma (OSCC) of the head and neck are a heterogeneous group of neoplasms with an increasing rate of mortality and morbidity. OSCCs are characterized by a high degree of local invasiveness and metastasis to cervical lymph nodes but show a lower rate of distant metastasis. Galectin-1 (Gal-1), a β-galactoside-binding lectin, is known to regulate tumor cell growth, angiogenesis, mediate cell-cell or cell-extracellular matrix adhesion and promote cancer cell migration. Aims: This study aims to evaluate the Gal-1 expression in different clinical stages and histological grades of OSCC. Settings and Design: Forty histopathologically diagnosed cases of OSCC, including 16 cases of well-differentiated, 18 moderately differentiated and 6 poorly differentiated carcinomas, were included in the study group. Materials and Methods: The samples were subjected to staining using primary mouse monoclonal antibodies against Gal-1 and visualized using polymer-HRP detection system. Statistical Analysis: The nonparametric Mann-Whitney U-test and Kruskal-Wallis ANOVA test were used for the statistical analysis. Results: Gal-1 expression was higher in advanced stages of OSCC, and the results were statistically significant. Immunoexpression of Gal-1 increased with advancing histological grades of OSCC with statistically significant results. Conclusion: Gal-1 plays an important role in invasion, metastasis and as a prognostic marker.