Cissus Extracts in Dentistry: A Comprehensive Review on its Untapped Potential.

Natural products have received a lot of attention in a variety of medical sectors, including dentistry. Cissus, a flowering plant genus, has long been used for its therapeutic benefits. The purpose of this review is to thoroughly investigate the possibilities of Cissus extracts in dentistry. To that end, we used specific selection criteria for the selection of pertinent scientific articles published in the scientific information databases of PubMed, Web of Science, Google Scholar, Scopus, and ProQuest. We found that the diverse array of bioactive compounds found in varied species of Cissus holds promise for applications ranging from oral wound healing to periodontal health. This review summarizes known studies on antibacterial, anti-inflammatory, and tissue-regenerative characteristics of Cissus extracts, shedding light on their potential significance in modernizing modern dental practices. It exerts that Cissus extracts have the potential to supplement established dentistry therapies by providing all-natural remedies for a variety of oral health conditions.

Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.

PURPOSE: Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. Genetic testing is currently recommended for adults diagnosed with heritable, idiopathic, anorexigen-, hereditary hemorrhagic telangiectasia-, and congenital heart disease-associated PAH, PAH with overt features of venous/capillary involvement, and all children diagnosed with PAH. Variants in at least 27 genes have putative evidence for PAH causality. Rigorous assessment of the evidence is needed to inform genetic testing. METHODS: An international panel of experts in PAH applied a semi-quantitative scoring system developed by the NIH Clinical Genome Resource to classify the relative strength of evidence supporting PAH gene-disease relationships based on genetic and experimental evidence. RESULTS: Twelve genes (BMPR2, ACVRL1, ATP13A3, CAV1, EIF2AK4, ENG, GDF2, KCNK3, KDR, SMAD9, SOX17, and TBX4) were classified as having definitive evidence and 3 genes (ABCC8, GGCX, and TET2) with moderate evidence. Six genes (AQP1, BMP10, FBLN2, KLF2, KLK1, and PDGFD) were classified as having limited evidence for causal effects of variants. TOPBP1 was classified as having no known PAH relationship. Five genes (BMPR1A, BMPR1B, NOTCH3, SMAD1, and SMAD4) were disputed because of a paucity of genetic evidence over time. CONCLUSION: We recommend that genetic testing includes all genes with definitive evidence and that caution be taken in the interpretation of variants identified in genes with moderate or limited evidence. Genes with no known evidence for PAH or disputed genes should not be included in genetic testing.

Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks.

SORCS2 is one of five proteins that constitute the Vps10p-domain receptor family. Members of this family play important roles in cellular processes linked to neuronal survival, differentiation and function. Genetic and functional studies implicate SORCS2 in cognitive function, as well as in neurodegenerative and psychiatric disorders. DNA damage and DNA repair deficits are linked to ageing and neurodegeneration, and transient neuronal DNA double-strand breaks (DSBs) also occur as a result of neuronal activity. Here, we report a novel role for SORCS2 in DSB formation. We show that SorCS2 loss is associated with elevated DSB levels in the mouse dentate gyrus and that knocking out SORCS2 in a human neuronal cell line increased Topoisomerase IIß-dependent DSB formation and reduced neuronal viability. Neuronal stimulation had no impact on levels of DNA breaks in vitro, suggesting that the observed differences may not be the result of aberrant neuronal activity in these cells. Our findings are consistent with studies linking the VPS10 receptors and DNA damage to neurodegenerative conditions.

A pilot study to examine association of BMI with functional class and 6 min walk distance in idiopathic and heritable PAH: Possible association with estrogen metabolism.

The hypothesis that a relationship exists between body mass index (BMI), functional class, and 6 min walk distance (6MWD) in Group 1-pulmonary arterial hypertension (PAH) was examined. Analysis of data from the UK National Cohort Study for heritable pulmonary arterial/idiopathic PAH suggests increased BMI is a predictor of worse functional class and shorter 6MWD; increased body-weight in mice and man may be associated with increased estrogen metabolism.

CBCT Analysis of Maxillary First Molar in Indian Population.

Aim: This study aimed to assess the variations in root canal morphology of permanent maxillary first molar with the use of cone-beam computed tomography (CBCT). Materials and methods: One hundred extracted teeth were cleaned and arranged in U shape template mimicking natural arch in set of five teeth. These arches were scanned in CBCT and were analyzed by expert radiologist for number of roots, number of canals per root, and Vertucci classification. Result: A maximum number of permanent maxillary first molars had three roots, and only 2% had two roots. All the palatal roots and 99% of distobuccal roots had one canal, but one of the distobuccal roots had two canals. Incidence of two canals in MB root is more frequent (60%) than incidence of one canal. The most common type of Vertucci's classification for MB root is a type I, followed by type IV, type II, type VI, type V, type VII. How to cite this article: Sharma M, Gupta S, Bhayya DP, et al. CBCT Analysis of Maxillary First Molar in Indian Population. Int J Clin Pediatr Dent 2022;15(3):258-262.

Mucormycosis - The deadly fungus - A case report with dental perspective.

Mucormycosis is a fungal infection caused by members of Mucorales and zygomycotic species. These are saprophytes known as Mucormycotina that grow from rotten matter or soils during the decomposition of soil. It has been seen affecting many COVID-19-affected patients recently in India. Mucormycosis can be diagnosed in six different sites depending on the immunological status and the site of the body affected. The six manifestations are rhinocerebral, pulmonary, cutaneous, gastrointestinal, and central nervous system or disseminated forms. Here, we present a dental case of mucormycosis or black fungus disease that has affected an immune-compromised patient who had suffered from COVID-19 2 months ago. Surgical debridement was done and the histopathologic study revealed fungal hyphae. Systemic antifungal therapy was administered that helped the patient to recover in 7-week time.

Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.

Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. METHODS: To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource - Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. RESULTS: Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e-5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. CONCLUSIONS: Rare variant analysis of a large international consortium identified two new candidate genes-FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants.

Bayesian Inference Associates Rare KDR Variants with Specific Phenotypes in Pulmonary Arterial Hypertension.

Background - Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods - We analyzed 13,037 participants enrolled in the NIHR BioResource - Rare Diseases (NBR) study, of which 1,148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension (PH), we used the Bayesian rare-variant association method BeviMed. Results - Heterozygous, high impact, likely loss-of-function variants in the Kinase Insert Domain Receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (KCO, posterior probability (PP)=0.989) and older age at diagnosis (PP=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the five patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions - The Bayesian inference approach allowed us to independently validate KDR, which encodes for the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.

'There and Back Again'-Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension.

Although the invention of right heart catheterisation in the 1950s enabled accurate clinical diagnosis of pulmonary arterial hypertension (PAH), it was not until 2000 when the landmark discovery of the causative role of bone morphogenetic protein receptor type II (BMPR2) mutations shed new light on the pathogenesis of PAH. Since then several genes have been discovered, which now account for around 25% of cases with the clinical diagnosis of idiopathic PAH. Despite the ongoing efforts, in the majority of patients the cause of the disease remains elusive, a phenomenon often referred to as "missing heritability". In this review, we discuss research approaches to uncover the genetic architecture of PAH starting with forward phenotyping, which in a research setting should focus on stable intermediate phenotypes, forward and reverse genetics, and finally reverse phenotyping. We then discuss potential sources of "missing heritability" and how functional genomics and multi-omics methods are employed to tackle this problem.

Kaposi's sarcoma associated with advanced HIV infection: A case report.

Acquired immunodeficiency syndrome was recognized in the early 1980s. It was more common in men who had sex with previously healthy men and young people and were affected by atypical pneumopathy caused by an opportunistic microorganism, identified as Pneumocystis carinii, and presently known as Pneumocystis jiroveci. Histopathology of the purplish or brown nodular lesions revealed Kaposi's sarcoma (KS). KS is the most frequent neoplasm in patients with human immunodeficiency virus infection. Its pathophysiology has been associated with the presence of a herpes virus, whose etiologic agent is a member of herpes virus type 8 family, which gets transmitted through sexual contact. Here, we present a case report to present the diagnosis and bring the light of knowledge to the Dentist the need of therapeutic measures in the treatment of the pathology.

"Two third tumor": A case report and its differential diagnosis.

Adenamatoid odontogenic tumor (AOT) is an odontogenic tumor with a prevalence of 2.2-7.1%. AOT is a benign, noninvasive, and progressive lesion which is also known as "a two third tumor." As the name suggests the tumor occurs in the maxilla in two third of cases. It occurs in young patients in two third of cases and associated with missing or unerupted teeth in two third of cases. Two third cases are associated with the maxillary canine. Characterized by slow growing, gradually enlarging, painless swelling associated with missing teeth. We report a case of a male patient of age 22 years, with characteristic findings. AOT resembles different odontogenic cysts and tumors which may include dentigerous cyst, globulomaxillary cyst, ameloblastoma, and other entities, hence must be well differentiated. Conservative surgical enucleation is the treatment of choice. Recurrence rate for AOT is 0.2%. Prognosis is excellent when completely removed in toto.

Role of Chemiluminescence examination as non-invasive diagnostic tool in early detection of Leukoplakia.

OBJECTIVES: To assess the efficacy of Chemiluminescent light (Vizilite plus) in enhancing visualization and its ability to highlight Leukoplakia lesion. MATERIAL AND METHODS: This was a cross-sectional study done on 40 study subjects. Subjects were inducted into the study irrespective of age and sex based on the specific inclusion and exclusion criteria. The lesion parameters like the location of the lesion, the shape of lesion, the size, the extent, borders and the presence or absence of any adjacent satellite lesions were assessed under Incandescent light followed by Toluidine blue and Vizilite plus examinations. Histopathological examination results were considered as the gold standard and TBLU and CHEM outcomes were compared to them. RESULTS: Vizilite plus examination method was most effective in assessing the size, borders and shape of the lesions followed by Toluidine blue and Incandescent light examinations. Toluidine blue and Vizilite plus examination methods demonstrated the sensitivity of 100% and specificity of 97.3%. They also demonstrated PPV of 100% and NPV of 75% with reliable accuracy of 97.5%. CONCLUSION: Chemiluminescent light is a stepping stone and has the potential to revolutionize the diagnostic protocol for patients with potentially premalignant lesions. The device can be used as a general oral mucosal examination system and may in particular improve the visualization of potentially premalignant lesions.

Assessment and Correlation of Urea and Creatinine Levels in Saliva and Serum of Patients with Chronic Kidney Disease, Diabetes and Hypertension- A Research Study.

INTRODUCTION: Serum urea and creatinine are most widely accepted parameters to assess Chronic Kidney Disease (CKD)status as well as to assess renal status in susceptible diabetic and hypertensive subjects. AIM: To assess and correlate the serum and salivary urea and creatinine levels of CKD, diabetes mellitus and hypertensive subjects. MATERIALS AND METHODS: This cross-sectional study was done on 120 subjects involving 30 CKD, 30 diabetic, 30 hypertensive subjects and 30 healthy controls. After collection of saliva and blood samples, urea was analyzed by enzymatic calorimetric method and creatinine by Jaffe's method. Kruskal Wallis test and Mann Whitney U test were used for comparison between different groups and correlations between serum and salivary parameters were evaluated by applying Spearman's correlation test. The p-value <0.05 was considered statistically significant. RESULTS: The median serum and salivary urea and creatinine levels were highest in CKD group followed by diabetic, hypertensive groups and controls. The correlation coefficient for serum urea and salivary urea was 0.977 and for serum creatinine and salivary creatinine was 0.976, with p-value <0.001. CONCLUSION: This study showed that there is a significant positive relationship between salivary and serum urea and creatinine. Thus, salivary urea and creatinine levels can be used non-invasively to detect serum urea and creatinine levels respectively in renal disease and diabetic and hypertensive nephropathic cases.