The immediate impact of mandatory helmet law on maxillo-facial trauma: A comparative study in a major trauma center, Uttar Pradesh.

Aim: To analyze the effect of the mandatory helmet rule in helmet usage among motorcycle riders and on facial trauma and to determine the significance of difference in the possibility of facial trauma between the helmeted and non-helmeted motorcycle riders. Setting and Design: A retrospective comparative study conducted in a major trauma center at Uttar Pradesh. Material and Method: Data for the present study was obtained from records of the Emergency Department of Trauma Center, for a period of two months before and after the implementation of The Motor Vehicles Act in UP. The study included patients with a history of non-fatal motorcycle accidents who sustained facial injuries regardless of the presence of injuries to other areas of the body during the study period. Information regarding helmet usage during the accident was also recorded. The results were compared between the pre-law period and post-law period. Statistical Analysis Used: Sample t-test was applied to find the level of significance. Results: Out of 219 injured patients, 152 (69.40%) subjects were not wearing helmets, whereas only 67 (30.59%) subjects were wearing helmets. It was observed that around 68.18% of people stated wearing helmets after law implementation with a statistical significance (P value < 0.05). Conclusion: Our study shows that the mandatory helmet rule with elevated penalty rates has significantly increased the usage of helmet among the motorcycle riders, and it also proves that the possibility of facial trauma is significantly higher in non-helmeted riders when compared to helmeted riders.

Effects of curcumin on oral cancer at molecular level: A systematic review.

This systematic review mainly focuses on the effects of curcumin on oral cancer cells at the molecular level and summarizes the results of the studies. We searched and analyzed various databases such as Pub Med, ProQuest, Google Scholar, Science Direct, and Scopus. Searches were conducted from 2006 to 2021. This systematic review evaluated various effects of curcumin on oral cancer at the molecular level. All the studies related to the effects of curcumin on oral cancer, both in-vivo and in-vitro, were included. After abstract and text screening a total of 13 articles were finally selected for the study based on the inclusion and exclusion criteria. All most all the included studies reported that after treating the cell lines with curcumin there is a reduction in cell proliferation and cell growth, analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Curcumin also induces S phase cell cycle arrest and also prevents Tregs migration. The curcumin reverses the process of epithelial mesenchymal transition (EMT) back to mesenchymal epithelial transition (MET). From this review, it is concluded that curcumin inhibited proliferation, migration, invasion, and metastasis, and induced apoptosis via modulating multiple signaling pathways in oral cancer cell lines. But further clinical trials are needed for a detailed evaluation of the effects of curcumin on patients with oral cancer.

How far we have come with the Management of Condylar Fractures? A Meta-Analysis of Closed Versus Open Versus Endoscopic Management.

Background: The treatment approaches for condylar fractures of the mandible include functional, closed reduction and open reduction-internal fixation. Recently endoscopic management of condylar fractures has been emphasized in the literature. We systematically review the studies comparing closed versus open versus endoscopic-assisted condyle fracture management with regard to the indications, effectiveness and complications of each modality. Methods: A total of 11 articles were selected based on the inclusion and exclusion criteria from PubMed, Cochrane and clinical trials.gov. Differences in means and risk ratios were used as principal summary measures with p value < 0.05 as significant. For detection of any possible biases in sample sizes, the OR and its 95% CI for each study were plotted against the number of participants. Chi-square test, I2 test and the Cochrane bias tool were used to assess the bias in and across studies. Results: Except for deviation on opening there was no significant difference between open versus closed treatment of condylar fractures. Endoscopic approach and open surgical approaches differed only in terms of operating time and TMJ pain. There was no significant difference in facial nerve injury among the two groups. Discussion: Closed reduction is particularly indicated for minimally displaced fractures; for moderate to severe displacement, open reduction is preferred. Open reduction can also be preferred over endoscopic approaches as there is no significant advantage of using latter. Limitations of the study included specific treatment according to the site of fracture not addressed, limited data regarding pediatric condylar fracture, lack of homogenous classification schemes, etc.

Mango-shaped Bi-paddled pectoralis major myocutaneous flap reconstruction for large full-thickness defects post resection of squamous cell carcinoma of oral cavity: An analysis of 232 cases.

Objectives: The objective of the study was to examine the feasibility of bi-paddled pectoralis major myocutaneous (PMMC) flap reconstruction in patient undergoing full thickness composite resection. Materials and Methods: Inclusion criteria: The subjects chosen were patients with clinically T4A squamous cell carcinoma of buccal mucosa, lower alveolus, and maxilla in with skin involvement. Patients required a full-thickness composite resection of intraoral lesion, bone (mandibular segment and/or maxilla), and overlying involved skin and had modified radical neck dissection. Exclusion criteria: Patients not requiring full thickness composite resection including skin. Patients were observed postoperatively for early and late postoperative complications, starting of oral feeding, post-operative trismus, and dysphagia during subsequent follow-up and cosmetic outcome. Results: Overall, the complication rate was 33.8% out of which only 7.8% required major re-surgery with second flap reconstruction. This is comparable with other large series of PMMC flap. Clavien-Dindo Grade I complications were seen in 9.5%, Grade II in 69.7%, Grade IIIA in 13.4%, and Grade IIIB in 7.45% of patients. Full-thickness partial flap necrosis included necrosis of either the external or the internal skin paddle. There were 15 cases - 6.5% of full thickness external paddle necrosis. These were mostly in patients with bite composite resections and having a larger random fasciocutaneous distal component of the flap without underlying muscle. Furthermore, 40% of these patients were females. In females, the flap necrosis comprised 4 of the 12 patients (33.33%). Conclusion: Pectoralis major mycocutaneous flap has been a boon to reconstruction of the oral cavity post its inception. In case of locally advanced squamous cell carcinomas of the oral cavity, in many instances, there is a clinically significant cervical lymph nodal spread vessels post mandating a comprehensive lymph node dissection. PMMC flap provides a robust well vascularized muscular cover to the cervical vessels poststernocleidomastoid excision.

Autoreconstruction of the tongue in case of extensive verrucous carcinoma.

Tongue reconstruction can be simple to complex depending on the size of the defect. Reconstruction of medium-to-large size defect is technically demanding to achieve better esthetic and functional outcome. There are various options in the reconstruction of tongue defect when it comes to the type of flap. Any type of flap has its own advantages and disadvantages. Local flaps seem to be the best option, as it avoids secondary donor site morbidity and has similar tissue characteristics as native tissue, therefore provides better esthetic and functional results. This case report illustrates a case of tongue reconstruction that was performed with the help of tongue base island flap after wide local excision of verrucous carcinoma, which provided us with excellent results.

En Block Versus Separate Management of Cervical Nodes in Tongue and Floor of the Mouth Cancers- Is There a Difference? An Analysis of 85 Cases in a Tertiary Care Institute.

To evaluate difference in local recurrence, regional (neck) recurrence as well as distant metastases between cases operated with en-block excision of primary cancer and neck nodes versus their separate removal, in squamous cell carcinomas of anterior 2/3 of tongue and floor of the mouth. A total 85 patients of cT1-T4a N0-N2b of carcinoma anterior 2/3 of tongue and floor of mouth were evaluated. Amongst these patients 39 cases of in-continuity en-block neck dissection and 46 cases of discontinuous neck dissection were evaluated for post-operative complications as well as oncological outcome for a follow up period of 3 years. Patient population was similar in both groups with tongue cancers being the commonest site and tobacco being the most common addiction. Primary site hematoma was seen more in the in-continuity en-block neck dissection group with a p-value of 0.0276, which was statistically significant. Post-operative oro-cutaneous fistula occurred more in in-continuity enblock neck dissection as compared to discontinuous neck dissection, but the difference was not statistically significant. Local recurrence rate was significantly more in cases of discontinuous neck dissection (19.565) as compared to in-continuity en-block neck dissection (5.12%) with a p-Value 0.0481. A statistically non-significant but higher loco-regional recurrence was observed in cases of discontinuous neck dissection as compared to cases of in-continuity en-block neck dissection (10.56% vs 2.56). In the present study recurrence-free survival RFS 3 year in cases of en-block in-continuity neck dissection (84.06%) cases as compared to discontinuous neck dissection cases (63.04%) with p Value 0.025698. In-continuity en-block in continuity neck dissection has lower loco-regional recurrence and may impact overall distant metastases. Though early postoperative complications are more in in-continuity en-block in continuity neck dissection as compared to discontinuous neck dissection, most are managed conservatively. Further studies with a larger sample size are needed to evaluate its outcome in a comprehensive manner.

Systematic Review of Intra Parotid Facial Nerve Schwannoma and a Case Report.

To evaluate the clinico-epidemiological aspects, pathological features, diagnostic methods, management protocol and functional outcome of the intra-parotid facial nerve schwannoma (IFNS) and to present a case report on intra parotid facial nerve schwannoma. PubMed, ProQuest, Google scholar, Science direct and Scopus were screened for studies. Article selection and data extraction was done by one investigator and other investigator confirmed its accuracy. After abstract and text screening a total of 69 articles were finally selected for the study with the inclusion and exclusion criteria of the systematic review as per PRISMA guidelines. With addition of one case reported to our department. The mean age of diagnosis was 43 ± 16 years with a slight female predominance. The mean duration of the tumour was 29.5 months and the mean size of the tumour on initial diagnosis was 3.6 ± 1.67 cm. Pleomorphic adenoma was the primary diagnosis in 44 cases. Superficial parotidectomy was done in 64 cases followed by resection in 47 cases. Reconstructive treatment was carried out by an end-to-end anastomosis in 3 patients and by facial-hypoglossal anastomosis in 16 patients, GAN cable grafting in 5 patients, a greater auricular nerve graft was done in18 patients and end-to-side interposed sural nerve graft in 8 patients. The type D tumours are treated by extended resection of the facial nerve, which is difficult to reconstruct and also employs a nerve graft that does not often give acceptable recovery of facial function. Facial nerve schwannomas being a rare entity poses a dilemma in diagnosis and management. Managing the lesions is also difficult as intraoperative adherence to the nerve makes a tumour free margin difficult without sacrificing the nerve. At present there is no consensus regarding the management of various types of intra-parotid facial nerve shwannoma.

Preferential CEBP binding to T:G mismatches and increased C-to-T human somatic mutations.

DNA cytosine methylation in mammals modulates gene expression and chromatin accessibility. It also impacts mutation rates, via spontaneous oxidative deamination of 5-methylcytosine (5mC) to thymine. In most cases the resulting T:G mismatches are repaired, following T excision by one of the thymine DNA glycosylases, TDG or MBD4. We found that C-to-T mutations are enriched in the binding sites of CCAAT/enhancer binding proteins (CEBP). Within a CEBP site, the presence of a T:G mismatch increased CEBPß binding affinity by a factor of >60 relative to the normal C:G base pair. This enhanced binding to a mismatch inhibits its repair by both TDG and MBD4 in vitro. Furthermore, repair of the deamination product of unmethylated cytosine, which yields a U:G DNA mismatch that is normally repaired via uracil DNA glycosylase, is also inhibited by CEBPß binding. Passage of a replication fork over either a T:G or U:G mismatch, before repair can occur, results in a C-to-T mutation in one of the daughter duplexes. Our study thus provides a plausible mechanism for accumulation of C-to-T human somatic mutations.

KRAB domain of ZFP568 disrupts TRIM28-mediated abnormal interactions in cancer cells.

Interactions of KRAB (Krüppel-associated box)-associated protein KAP1 [also known as TRIM28 (tripartite motif containing protein 28)] with DNA-binding KRAB zinc finger (KRAB-ZF) proteins silence many transposable elements during embryogenesis. However, in some cancers, TRIM28 is upregulated and interacts with different partners, many of which are transcription regulators such as EZH2 in MCF7 cells, to form abnormal repressive or activating complexes that lead to misregulation of genes. We ask whether a KRAB domain-the TRIM28 interaction domain present in native binding partners of TRIM28 that mediate repression of transposable elements-could be used as a tool molecule to disrupt aberrant TRIM28 complexes. Expression of KRAB domain containing fragments from a KRAB-ZF protein (ZFP568) in MCF7 cells, without the DNA-binding zinc fingers, inhibited TRIM28-EZH2 interactions and caused degradation of both TRIM28 and EZH2 proteins as well as other components of the EZH2-associated polycomb repressor 2 complex. In consequence, the product of EZH2 enzymatic activity, trimethylation of histone H3 lysine 27 level, was significantly reduced. The expression of a synthetic KRAB domain significantly inhibits the growth of breast cancer cells (MCF7) but has no effect on normal (immortalized) human mammary epithelial cells (MCF10a). Further, we found that TRIM28 is a positive regulator of TRIM24 protein levels, as observed previously in prostate cancer cells, and expression of the KRAB domain also lowered TRIM24 protein. Importantly, reduction of TRIM24 levels, by treatment with either the KRAB domain or a small-molecule degrader targeted to TRIM24, is accompanied by an elevated level of tumor suppressor p53. Taken together, this study reveals a novel mechanism for a TRIM28-associated protein stability network and establishes TRIM28 as a potential therapeutic target in cancers where TRIM28 is elevated. Finally, we discuss a potential mechanism of KRAB-ZF gene expression controlled by a regulatory feedback loop of TRIM28-KRAB.

PARP-1/2 Inhibitor Olaparib Prevents or Partially Reverts EMT Induced by TGF-ß in NMuMG Cells.

Poly- adenosine diphosphate (ADP)-ribose (PAR) is a polymer synthesized as a posttranslational modification by some poly (ADP-ribose) polymerases (PARPs), namely PARP-1, PARP-2, tankyrase-1, and tankyrase-2 (TNKS-1/2). PARP-1 is nuclear and has also been detected in extracellular vesicles. PARP-2 and TNKS-1/2 are distributed in nuclei and cytoplasm. PARP or PAR alterations have been described in tumors, and in particular by influencing the Epithelial- Mesenchymal Transition (EMT), which influences cell migration and drug resistance in cancer cells. Pro-EMT and anti-EMT effects of PARP-1 have been reported while whether PAR changes occur specifically during EMT is currently unknown. The PARP-1/2 inhibitor Olaparib (OLA) is approved by FDA to treat certain patients harboring cancers with impaired homologous recombination. Here, we studied PAR changes and OLA effects on EMT. Total and nuclear PAR increased in EMT while PAR belts were disassembled. OLA prevented EMT, according to: (i) molecular markers evaluated by immuno-cytofluorescence/image quantification, Western blots, and RNA quantitation, (ii) morphological changes expressed as anisotropy, and (iii) migration capacity in the scratch assay. OLA also partially reversed EMT. OLA might work through unconventional mechanisms of action (different from synthetic lethality), even in non-BRCA (breast cancer 1 gene) mutated cancers.

The calcium channel proteins ORAI3 and STIM1 mediate TGF-ß induced Snai1 expression.

Calcium influx into cells via plasma membrane protein channels is tightly regulated to maintain cellular homeostasis. Calcium channel proteins in the plasma membrane and endoplasmic reticulum have been linked to cancer, specifically during the epithelial-mesenchymal transition (EMT), a cell state transition process implicated in both cancer cell migration and drug resistance. The transcription factor SNAI1 (SNAIL) is upregulated during EMT and is responsible for gene expression changes associated with EMT, but the calcium channels required for Snai1 expression remain unknown. In this study, we show that blocking store-operated calcium entry (SOCE) with 2-aminoethoxydiphenylborane (2APB) reduces cell migration but, paradoxically, increases the level of TGF-ß dependent Snai1 gene activation. We determined that this increased Snai1 transcription involves signaling through the AKT pathway and subsequent binding of NF-κB (p65) at the Snai1 promoter in response to TGF-ß. We also demonstrated that the calcium channel protein ORAI3 and the stromal interaction molecule 1 (STIM1) are required for TGF-ß dependent Snai1 transcription. These results suggest that calcium channels differentially regulate cell migration and Snai1 transcription, indicating that each of these steps could be targeted to ensure complete blockade of cancer progression.

Leptin receptor signaling via Janus kinase 2/Signal transducer and activator of transcription 3 impacts on ovarian cancer cell phenotypes.

Ovarian cancer is a leading cause of cancer mortality in women world-wide. Considerable progress has been made to characterize the different subtypes of ovarian cancer, but specific therapies remain limited and prognosis poor. Cytokine signaling via the interleukin-6 receptor (IL-6R) family and related receptors has been implicated in a number of cancers, including those with an ovarian origin. The leptin receptor (LEPR) is structurally related to these receptors and utilizes similar downstream pathways. LEPR has diverse roles in metabolism, appetite and bone formation with obesity linked to both elevated levels of leptin and increased cancer incidence. This study investigated a potential role for LEPR signaling in ovarian cancer. Leptin stimulation led to increased proliferation, survival and migration of LEPR-expressing ovarian cancer cell lines, with the effects shown to be mediated by the downstream Janus kinase 2/Signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. A significant correlation was identified between high co-expression of leptin and LEPR and decreased patient survival. This study collectively suggests that leptin/LEPR signaling via JAK2/STAT3 has the potential to significantly impact on pathogenesis in a subset of ovarian cancer patients who may benefit from strategies that dampen this pathway.

Role of the interleukin 6 receptor family in epithelial ovarian cancer and its clinical implications.

Ovarian cancer is the most lethal gynecological malignancy, with few effective treatment options in most cases. Therefore, understanding the biology of ovarian cancer remains an important area of research in order to improve clinical outcomes. Cytokine receptor signaling through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is an essential component of normal development and homeostasis. However, numerous studies have implicated perturbation of this pathway in a range of cancers. In particular, members of the IL-6R family acting via the downstream STAT3 transcription factor play an important role in a number of solid tumors - including ovarian cancer - by altering the expression of target genes that impact on key phenotypes. This has led to the development of specific inhibitors of this pathway which are being used in combination with standard chemotherapeutic agents. This review focuses on the role of IL-6R family members in the etiology of epithelial ovarian cancer, and the application of therapies specifically targeting IL-6R signaling in this disease setting.

Alternative TEL-JAK2 fusions associated with T-cell acute lymphoblastic leukemia and atypical chronic myelogenous leukemia dissected in zebrafish.

BACKGROUND: Chromosomal translocations resulting in alternative fusions of the human TEL (ETV6) and JAK2 genes have been observed in cases of acute lymphoblastic leukemia and chronic myelogenous leukemia, but a full understanding of their role in disease etiology has remained elusive. In this study potential differences between these alternative TEL-JAK2 fusions, including their lineage specificity, were investigated. DESIGN AND METHODS: TEL-JAK2 fusion types derived from both T-cell acute lymphoblastic leukemia and atypical chronic myelogenous leukemia were generated using the corresponding zebrafish tel and jak2a genes and placed under the control of either the white blood cell-specific spi1 promoter or the ubiquitously-expressed cytomegalovirus promoter. These constructs were injected into zebrafish embryos and their effects on hematopoiesis examined using a range of molecular approaches. In addition, the functional properties of the alternative fusions were investigated in vitro. RESULTS: Injection of the T-cell acute lymphoblastic leukemia-derived tel-jak2a significantly perturbed lymphopoiesis with a lesser effect on myelopoiesis in zebrafish embryos. In contrast, injection of the atypical chronic myelogenous leukemia-derived tel-jak2a resulted in significant perturbation of the myeloid compartment. These phenotypes were observed regardless of whether expressed in a white blood cell-specific or ubiquitous manner, with no overt cellular proliferation outside of the hematopoietic cells. Functional studies revealed subtle differences between the alternative forms, with the acute lymphoblastic leukemia variant showing higher activity, but reduced downstream signal transducer and activator of transcription activation and decreased sensitivity to JAK2 inhibition. JAK2 activity was required to mediate the effects of both variants on zebrafish hematopoiesis. CONCLUSIONS: This study indicates that the molecular structure of alternative TEL-JAK2 fusions likely contributes to the etiology of disease. The data further suggest that this class of oncogene exerts its effects in a cell lineage-specific manner, which may be due to differences in downstream signaling.

Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile.

Epithelial mesenchymal transition (EMT) and cancer stem cells (CSC) have been associated with resistance to chemotherapy. Eighty percent of ovarian cancer patients initially respond to platinum-based combination therapy but most return with recurrence and ultimate demise. To better understand such chemoresistance we have assessed the potential role of EMT in tumor cells collected from advanced-stage ovarian cancer patients and the ovarian cancer cell line OVCA 433 in response to cisplatin in vitro. We demonstrate that cisplatin-induced transition from epithelial to mesenchymal morphology in residual cancer cells correlated with reduced E-cadherin, and increased N-cadherin and vimentin expression. The mRNA expression of Snail, Slug, Twist, and MMP-2 were significantly enhanced in response to cisplatin and correlated with increased migration. This coincided with increased cell surface expression of CSC-like markers such as CD44, α2 integrin subunit, CD117, CD133, EpCAM, and the expression of stem cell factors Nanog and Oct-4. EMT and CSC-like changes in response to cisplatin correlated with enhanced activation of extracellular signal-regulated kinase (ERK)1/2. The selective MEK inhibitor U0126 inhibited ERK2 activation and partially suppressed cisplatin-induced EMT and CSC markers. In vivo xenotransplantation of cisplatin-treated OVCA 433 cells in zebrafish embryos demonstrated significantly enhanced migration of cells compared to control untreated cells. U0126 inhibited cisplatin-induced migration of cells in vivo, suggesting that ERK2 signaling is critical to cisplatin-induced EMT and CSC phenotypes, and that targeting ERK2 in the presence of cisplatin may reduce the burden of residual tumor, the ultimate cause of recurrence in ovarian cancer patients.