Bone Fracture-healing Properties and UPLC-MS Analysis of an Enriched Flavonoid Fraction from Oxystelma esculentum.

Oxystelma esculentum has been used as a folk medicine to treat jaundice, throat infections, and skin problems. In the current study, the bone fracture-healing properties of a flavonoid-enriched fraction (Oxy50-60F) of O. esculentum were investigated in Swiss mice using a drill-hole injury model. Oxy50-60F (1 mg/kg/day, 5 mg/kg/day, and 10 mg/kg/day) was administered orally (from the next day) after a 0.6 mm drill-hole injury in mice femur mid-diaphysis for 7 days and 14 days. Parathyroid hormone (40 µg/kg; 5 times/week) was given subcutaneously as the positive control. Confocal imaging for bone regeneration, micro-architecture of femur bones, ex vivo mineralization, hematoxyline and eosin staining, measurement of reactive oxygen species, and gene expression of osteogenic and anti-inflammatory genes were studied. Quercetin, kaempferol, and isorhamnetin glycosides were identified in the active fraction using mass spectrometry techniques. Our results confirm that Oxy50-60F treatment promotes fracture healing and callus formation at drill-hole sites and stimulates osteogenic and anti-inflammatory genes. Oxy50-60F administration to fractured mice exhibited significantly better micro-CT parameters in a dose-dependent manner and promoted nodule mineralization at days 7 and 14 post-injury. Oxy50-60F also prevents ROS generation by increasing expression of the SOD2 enzyme. Overall, this study reveals that Oxy50-60F has bone regeneration potential in a cortical bone defect model, which supports its use in delayed-union and non-union fracture cases.

Causes of stillbirth in ethnically diverse women in a Perth metropolitan hospital: A retrospective study.

BACKGROUND: Most published reports analysing the differences in causation of stillbirth between different ethnic groups focus on stillbirth risk factors, with a paucity of data comparing actual causes of stillbirth. AIMS: To determine whether causes of stillbirth differ between Caucasian and non-Caucasian ethnic groups in an Australian context. MATERIALS AND METHODS: Data from all stillbirths occurring at 20 or more completed weeks of gestation between 1 January 2010 and 31 December 2020 at a secondary level, outer metropolitan hospital, were analysed in this retrospective case series. Causes of stillbirth as determined by perinatal autopsy and placental histopathology were categorised using the Perinatal Society of Australia and New Zealand Perinatal Death Classification and compared between Caucasian and non-Caucasian groups. RESULTS: Ninety-two stillbirths (0.7% of all births) were identified during the study period. A greater proportion of non-Caucasian women had small for gestation age placentas compared to Caucasian women (n = 22/43 (51%) vs n = 12/49 (24%); P = 0.025). A greater proportion of stillbirths were caused by hypoxic peripartum death in non-Caucasian than in Caucasian women (n = 4/43 (9%) vs n = 0/49 (0%); P = 0.044), and a greater prevalence of placental dysfunction was seen in the non-Caucasian cohort compared to Caucasian women (n = 14/43 (33%) vs n = 8/49 (16%); P = 0.057). CONCLUSIONS: The differences observed in causes of stillbirth between Caucasian and non-Caucasian women are hypothesis generating and warrant further larger-scale, multi-centred studies using standardised definitions and classification systems to determine whether these differences persist in a more representative sample.

Impact of National Institutes of Health and Food and Drug Administration Tobacco Research Funding: A Bibliometrics Analyses.

INTRODUCTION: Conduct bibliometric analyses documenting the output of National Institutes of Health (NIH) tobacco-related and Food and Drug Administration (FDA) tobacco regulatory science (FDA-TRS) research portfolios. AIMS AND METHODS: PubMed identifiers for publications between 2015 and 2020 citing tobacco funding by NIH and/or FDA were imported into NIH iCite generating measures of productivity and influence, including number of citations, journal, relative citation ratios (RCR), and comparison of research influence across Web of Science (WoS) disciplines. Coauthorship and measures of centrality among and between NIH and FDA-supported investigators gauged collaboration. RESULTS: Between FY 2015 and 2020, 8160 publications cited funding from NIH tobacco-related grants, 1776 cited FDA-TRS grants and 496 cited Common funding (ie, both NIH and FDA-TRS funding). The proportion of publications citing NIH grants declined while those citing FDA-TRS or Common funding rose significantly. Publications citing Common funding showed the highest influence (mean RCR = 2.52). Publications citing FDA-TRS funding displayed higher median RCRs than publications citing NIH funding in most WoS categories. Higher translational progress was estimated over time for FDA-TRS and Common publications compared to NIH publications. Authors citing Common funding scored highest across all collaboration measures. CONCLUSIONS: This study demonstrates the high bibliometric output of tobacco research overall. The rise in publications citing FDA-TRS and Common likely reflects increased funding for TRS research. Higher RCRs across WoS subject categories and trends towards human translation among FDA-TRS and Common publications indicate focus on research to inform regulation. This analysis suggests that FDA support for TRS has expanded the field of tobacco control resulting in sustained productivity, influence, and collaboration. IMPLICATIONS: This paper is the first effort to better describe the impact of tobacco research resulting from the addition of FDA funding for TRS in the past decade. The analysis provides impetus for further investigation into the publication topics and their focus which would offer insight into the specific evidence generated on tobacco control and regulation.

Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.

Maintenance of increased bone mass after PTH withdrawal by sequential medicarpin treatment via augmentation of cAMP-PKA pathway.

Osteoporosis is a metabolic bone disorder associated with impaired bone microarchitecture leading to fragility fractures. Long-term usage of parathyroid hormone (PTH) enhances bone resorption and leads to osteosarcoma in rats which limits its exposure to maximum 2 years in human. Notably, the anabolic effects of PTH do not endure in the absence of sustained administration. Studies in our lab identified osteogenic and antiresorptive activity in medicarpin, a phytoestrogen belonging to the pterocarpan class. Considering dual-acting property of medicarpin and limitations of PTH therapy, we envisaged that medicarpin sequential treatment after PTH withdrawal could serve as promising therapeutic approach for osteoporosis treatment. As PTH exerts its bone anabolic effect by increasing osteoblast survival, our study aims to determine whether medicarpin amplifies this effect of PTH. Our results show that PTH withdrawal led to reduced bone mineral density and bone parameters, while sequential treatment of medicarpin after PTH withdrawal significantly enhanced these parameters. Remarkably, these effects were more pronounced than 8-week PTH treatment. Sequential therapy also significantly increased P1NP levels and decreased CTX levels and TRAP positive cells compared to PTH 8W group where CTX levels were quite high due to bone resorptive action of PTH. Protein expression studies revealed that medicarpin along with PTH betters the antiapoptotic potential compared to PTH alone, through augmentation of cyclic adenosine monophosphate-PKA-CREB pathway. These results proclaim that medicarpin sequential treatment prevented the reduction in bone accrual and strength accompanying PTH withdrawal and also aided in antiapoptotic role of PTH. The study points toward the potential use of medicarpin as a replacement therapeutic option postdiscontinuation of PTH.

Pyrazoline analogues: Design, synthesis, and evaluation of anti-osteoporosis activity.

A series of pyrazoline compounds were synthesised and their osteogenic potential was explored. Out of fifteen, six compounds (3a, 4ac, 5aaa, 7, 8ab and 4aa) showed significant osteoblast differentiation in the range of 1 pM -1 µM concentrations. Amongst all, compound 4aa was identified as most active molecule which showed effective mineralisation of osteoblast cells and up regulates the osteogenic marker gene such as Bmp-2, Runx-2 and Type-1col at both transcriptional and translational level. Besides exhibiting potential osteogenic activity, 4aa also possess significant anti-apoptotic activity at 1 pM &100 pM concentration and increases the osteoblast survival in serum deprived conditions.

NIH Tobacco Research and the Emergence of Tobacco Regulatory Science.

INTRODUCTION: This study explores how the emergence of FDA-funded Tobacco Regulatory Science (TRS) research complements and perhaps influenced the direction of tobacco research supported by NIH. AIMS AND METHODS: New NIH- and FDA-funded tobacco projects awarded in fiscal years (FY) 2011-2020 were identified using internal NIH databases of awarded grants. Project abstracts and research aims were coded by the authors to characterize research domains and tobacco products studied. RESULTS: Between FY 2011 and 2020, NIH funded 1032 and FDA funded 322 new tobacco projects. For the years and grant activity codes studied, the number of new NIH tobacco projects declined while FDA's increased; combined the number of new projects held steady. Much of NIH research included smoking combustibles (43.7%). The most common products in FDA research were cigarettes (74.8%) and e-cigarettes/ENDS (48.1%). Most NIH (58.6%) and FDA (67.7%) projects included research on the determinants of tobacco use. Another area of apparent overlap was health effects (29.5% NIH and 30.1% FDA). Projects unique to NIH included treatment interventions (33.3%), disease pathology/progression (17.8%) and neurobiology (18.9%). A minority of both NIH and FDA projects included populations particularly vulnerable to tobacco product use. CONCLUSIONS: In total, support for new tobacco research supported by NIH and FDA combined remained steady for the time period covered, though there was a concomitant decline in NIH tobacco projects with the increase in FDA-funded TRS projects for the activity codes studied. Despite the apparent overlap in some areas, both NIH and FDA support research that is unique to their respective missions. IMPLICATIONS: NIH continues to support tobacco research that falls within and outside of FDA's regulatory authorities. This research still is needed not only to bolster the evidence base for regulatory decisions at the national and state levels, but also to advance a comprehensive scientific agenda that can inform multiple levels of influence on tobacco control, use and addiction. It will be important to continue monitoring FDA-funded TRS and NIH-funded tobacco research portfolios to ensure that the level of support for and focus of the research is sufficient to address the burden of tobacco-related morbidity and mortality.

Rapid single cell evaluation of human disease and disorder targets using REVEAL: SingleCell™.

BACKGROUND: Single-cell (sc) sequencing performs unbiased profiling of individual cells and enables evaluation of less prevalent cellular populations, often missed using bulk sequencing. However, the scale and the complexity of the sc datasets poses a great challenge in its utility and this problem is further exacerbated when working with larger datasets typically generated by consortium efforts. As the scale of single cell datasets continues to increase exponentially, there is an unmet technological need to develop database platforms that can evaluate key biological hypotheses by querying extensive single-cell datasets. Large single-cell datasets like Human Cell Atlas and COVID-19 cell atlas (collection of annotated sc datasets from various human organs) are excellent resources for profiling target genes involved in human diseases and disorders ranging from oncology, auto-immunity, as well as infectious diseases like COVID-19 caused by SARS-CoV-2 virus. SARS-CoV-2 infections have led to a worldwide pandemic with massive loss of lives, infections exceeding 7 million cases. The virus uses ACE2 and TMPRSS2 as key viral entry associated proteins expressed in human cells for infections. Evaluating the expression profile of key genes in large single-cell datasets can facilitate testing for diagnostics, therapeutics, and vaccine targets, as the world struggles to cope with the on-going spread of COVID-19 infections. MAIN BODY: In this manuscript we describe REVEAL: SingleCell, which enables storage, retrieval, and rapid query of single-cell datasets inclusive of millions of cells. The array native database described here enables selecting and analyzing cells across multiple studies. Cells can be selected using individual metadata tags, more complex hierarchical ontology filtering, and gene expression threshold ranges, including co-expression of multiple genes. The tags on selected cells can be further evaluated for testing biological hypotheses. One such example includes identifying the most prevalent cell type annotation tag on returned cells. We used REVEAL: SingleCell to evaluate the expression of key SARS-CoV-2 entry associated genes, and queried the current database (2.2 Million cells, 32 projects) to obtain the results in < 60 s. We highlighted cells expressing COVID-19 associated genes are expressed on multiple tissue types, thus in part explains the multi-organ involvement in infected patients observed worldwide during the on-going COVID-19 pandemic. CONCLUSION: In this paper, we introduce the REVEAL: SingleCell database that addresses immediate needs for SARS-CoV-2 research and has the potential to be used more broadly for many precision medicine applications. We used the REVEAL: SingleCell database as a reference to ask questions relevant to drug development and precision medicine regarding cell type and co-expression for genes that encode proteins necessary for SARS-CoV-2 to enter and reproduce in cells.

Phenanthrenoid Coelogin Isolated from Coelogyne cristata Exerts Osteoprotective Effect Through MAPK-Mitogen-Activated Protein Kinase Signaling Pathway.

Osteoporosis is a major health problem in postmenopausal women globally. This study determined the mechanism through which coelogin stimulates osteoblastogenesis and its osteoprotective and bone regenerating potential. Coelogin effect on primary calvarial osteoblast cells was determined by measuring alkaline phosphatase activity, mineralization, osteoblast survival, and apoptosis and protein expression studies. The osteoprotective effect of coelogin was also evaluated on osteopenic adult female Swiss mice. At autopsy, bones were collected for dynamic and histomorphometry studies. Serum samples were also collected for assessment of serum parameters. Coelogin treatment led to increased osteoblast proliferation, survival, differentiation, and mineralization in osteoblast cells. Coelogin supplementation to Ovx mice promoted new bone formation, prevented Ovx-induced deterioration of bone microarchitecture, and enhanced bone regeneration. In addition, signaling studies revealed that coelogin treatment activates the ER-Erk and Akt-dependent signaling pathways which stimulate the osteoblastogenesis in osteoblast cells.

Synthesis and biological evaluation of substituted amide derivatives of C4-ageratochromene dimer analog.

Substituted amide derivatives of C4-ageratochromene dimer analog (19) were synthesized through structural modification of precocene-I (4a), isolated from the essential oil of Ageratum conyzoides L. The target compounds (18-20, 23I-VI, 24I-VI, and 25I-VI) were evaluated for their bone-forming effect using osteoblast differentiation assay. Seven compounds (23I, 23II, 23IV, 23VI, 24III, 24VI, and 25VI) presented good activity within 1 pM-1 nM concentration. At 1 pM concentration, the most active compound i.e. 23II showed effective mineralization of osteoblast cells along with expression of osteogenic marker genes viz RUNX 2, BMP-2, and type 1 collagen (Type-1 col) without any toxicity towards osteoblast cells. Single crystal X-ray analysis of 18 and 20 revealed that the core nucleus of these molecules bear phenyl rings in a Trans-stilbenoid system and had a good structural correlation with 17ß-estradiol (1) and diethylstilbestrol (DES, 3). In-silico study about 23II showed its structural complementarities with the LBD of estrogen receptor (ER) which indicated possible ER-mediated activity of compounds.

A drone-based networked system and methods for combating coronavirus disease (COVID-19) pandemic.

Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. It is similar to influenza viruses and raises concerns through alarming levels of spread and severity resulting in an ongoing pandemic worldwide. Within eight months (by August 2020), it infected 24.0 million persons worldwide and over 824 thousand have died. Drones or Unmanned Aerial Vehicles (UAVs) are very helpful in handling the COVID-19 pandemic. This work investigates the drone-based systems, COVID-19 pandemic situations, and proposes an architecture for handling pandemic situations in different scenarios using real-time and simulation-based scenarios. The proposed architecture uses wearable sensors to record the observations in Body Area Networks (BANs) in a push-pull data fetching mechanism. The proposed architecture is found to be useful in remote and highly congested pandemic areas where either the wireless or Internet connectivity is a major issue or chances of COVID-19 spreading are high. It collects and stores the substantial amount of data in a stipulated period and helps to take appropriate action as and when required. In real-time drone-based healthcare system implementation for COVID-19 operations, it is observed that a large area can be covered for sanitization, thermal image collection, and patient identification within a short period (2 KMs within 10 min approx.) through aerial route. In the simulation, the same statistics are observed with an addition of collision-resistant strategies working successfully for indoor and outdoor healthcare operations. Further, open challenges are identified and promising research directions are highlighted.

Beneficiary, Caregiver, and Case Manager Perspectives on the Medication Therapy Management Program Standardized Format.

Plan sponsors of Medicare Part D must provide beneficiaries who receive a comprehensive medication review (CMR) with a written summary using the Medicare Part D Medication Therapy Management Standardized Format (SF). The SF is a means to advance consistency in the CMR program by providing a template of expected content. However, barriers remain with beneficiary use and integration into existing electronic health records. The current study assessed Medicare beneficiary, caregiver, and case manager perceptions of the SF through five focus group interviews with a total of 23 participants. Qualitative analysis found that beneficiaries and case managers preferred a consolidated SF document to share and update their entire health care team. Beneficiaries suggested adding information to the SF on dosage, timing, drug interactions, cost, and less expensive alternatives. Identifying elements of the SF that are perceived as useful to beneficiaries will allow for a more streamlined SF that may enhance interoperability among the health care team. [Journal of Gerontological Nursing, 45(4), 7-13.].

Prosthetic treatment need and associated life course determinants in partially edentulous adults of age 18-35 years in Udupi taluk: A cross-sectional study.

AIM: The aims of this study were to assess the prevalence of use and need for dental prostheses and to associate need with the life course determinants in young adults of age 18-35 years in Udupi taluk, Karnataka, India. MATERIALS AND METHODS: It was a cross-sectional survey conducted on a total of 580 individuals those attended dental screening camps organized at random locations. A self-administered questionnaire was administered to participants to assess their life course determinants such as socioeconomic, behavioral, and psychological circumstances followed by an oral examination to assess their prosthetic status (WHO, 1997). Bivariate analysis followed by multivariate logistic regression analysis was carried out to determine the adjusted odds ratios (ORs) with 95% confidence interval (CI) for independent variables and the outcome. RESULTS: The need and use of dental prostheses was observed in 38% and 2.2% of young adults, respectively. Adjusted multivariable analysis revealed that life course determinants such as parental rearing style (OR = 7.66 [95% CI: 3.88-15.14]) and interaction between expenditure at 10 years of age and economic hardships at 10 years of age (OR = 9.63 [95% CI: 3.12-29.72] and OR = 6.43 [95% CI: 1.89-21.88]) were significantly associated with the need for prostheses. CONCLUSION: The need for dental prostheses in the young adults can be related to socioeconomic and psychosocial circumstances during childhood, and thus the concept of life course approach has been highlighted.

Females' Peer Influence and Support for Adolescent Males Receiving Voluntary Medical Male Circumcision Services.

Background: While female involvement in voluntary medical male circumcision (VMMC) has been studied among adults, little is known about the influence of adolescent females on their male counterparts. This study explored adolescent females' involvement in VMMC decision making and the postoperative wound healing process in South Africa, Tanzania, and Zimbabwe. Methods: Across 3 countries, 12 focus group discussions were conducted with a total of 90 adolescent females (aged 16-19 years). Individual in-depth interviews were conducted 6-10 weeks post-VMMC with 92 adolescent males (aged 10-19 years). Transcribed and translated qualitative data were coded into categories and subcategories by 2 independent coders. Results: Adolescent female participants reported being supportive of male peers' decisions to seek VMMC, with the caveat that some thought VMMC gives males a chance to be promiscuous. Regardless, females from all countries expressed preference for circumcised over uncircumcised sexual partners. Adolescent females believed VMMC to be beneficial for the sexual health of both partners, viewed males with a circumcised penis as more attractive than uncircumcised males, used their romantic relationships with males or the potential for sex as leveraging points to convince males to become circumcised, and demonstrated supportive attitudes in the wound-healing period. Interviews with males confirmed that encouragement from females was a motivating factor in seeking VMMC. Conclusions: Adolescent female participants played a role in convincing young males to seek VMMC and remained supportive of the decision postprocedure. Programs aiming to increase uptake of VMMC and other health-related initiatives for adolescent males should consider the perspective and influence of adolescent females.

A regulatory hierarchy controls the dynamic transcriptional response to extreme oxidative stress in archaea.

Networks of interacting transcription factors are central to the regulation of cellular responses to abiotic stress. Although the architecture of many such networks has been mapped, their dynamic function remains unclear. Here we address this challenge in archaea, microorganisms possessing transcription factors that resemble those of both eukaryotes and bacteria. Using genome-wide DNA binding location analysis integrated with gene expression and cell physiological data, we demonstrate that a bacterial-type transcription factor (TF), called RosR, and five TFIIB proteins, homologs of eukaryotic TFs, combinatorially regulate over 100 target genes important for the response to extremely high levels of peroxide. These genes include 20 other transcription factors and oxidative damage repair genes. RosR promoter occupancy is surprisingly dynamic, with the pattern of target gene expression during the transition from rapid growth to stress correlating strongly with the pattern of dynamic binding. We conclude that a hierarchical regulatory network orchestrated by TFs of hybrid lineage enables dynamic response and survival under extreme stress in archaea. This raises questions regarding the evolutionary trajectory of gene networks in response to stress.

Geometry and energy constrained projection extension.

BACKGROUND: In clinical computed tomography (CT) applications, when a patient is obese or improperly positioned, the final tomographic scan is often partially truncated. Images directly reconstructed by the conventional reconstruction algorithms suffer from severe cupping and direct current bias artifacts. Moreover, the current methods for projection extension have limitations that preclude incorporation from clinical workflows, such as prohibitive computational time for iterative reconstruction, extra radiation dose, hardware modification, etc.METHOD:In this study, we first established a geometrical constraint and estimated the patient habitus using a modified scout configuration. Then, we established an energy constraint using the integral invariance of fan-beam projections. Two constraints were extracted from the existing CT scan process with minimal modification to the clinical workflows. Finally, we developed a novel dual-constraint based optimization model that can be rapidly solved for projection extrapolation and accurate local reconstruction. RESULTS: Both numerical phantom and realistic patient image simulations were performed, and the results confirmed the effectiveness of our proposed approach. CONCLUSION: We establish a dual-constraint-based optimization model and correspondingly develop an accurate extrapolation method for partially truncated projections. The proposed method can be readily integrated into the clinical workflow and efficiently solved by using a one-dimensional optimization algorithm. Moreover, it is robust for noisy cases with various truncations and can be further accelerated by GPU based parallel computing.

Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.

Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators.

The multidisciplinary approach to mood disorders.

This article outlines the use of the multidisciplinary approach to mood disorders in the Short Stay Psychiatric Unit (SSPU) in Mater Dei Hospital, Msida, Malta. An audit was carried out on all patients whose first admission to SSPU was in 2008 and who were diagnosed with having a mood disorder. The aim was to see whether the use of a multidisciplinary approach is in actual fact affecting patient outcome or not. The latter was measured by recording whether the patients needed any further admission and if this was the case, the length in days leading to their 2nd admission.

The multifactorial etiology of eating disorders outlined in a case of anorexia nervosa and complicated by psychiatric co-morbidities.

This article outlines a case of anorexia nervosa within the context of its multifactorial etiology and complex neurobiology. Additionally, it also highlights that in this case there were several co-morbid personality traits and other psychiatric co-morbidites such as OCD and bipolar disorder.

Gene Polymorphism Influencing Persistent Bone Resorption in Brown Tumor: A Case Series with Possible Pathogenesis and Potential Therapeutic Approach.

Brown tumor represents a terminal stage of bone remodeling process due to an imbalance between osteoclastic and osteoblastic activity. It represents a reparative cellular process, rather than a neoplastic process mostly associated with primary or secondary hyperparathyroidism. Although parathyroidectomy is the first treatment of choice for brown tumors, several cases don't resolve even after normalization of parathyroid hormone levels which leads to surgical intervention. Therefore, to avoid multiple bone surgeries in the same patient, it is crucial to have a conservative approach like targeted therapy which could block certain molecules involved in bone resorption. In this string, we have recognized and quantified three molecules namely sclerostin, MCP-1 and CD73 in brown tumors and correlated their expression with bone resorption pathogenesis and potential therapeutic approach.