Protein-Protein Interaction Studies Using Molecular Dynamics Simulation.

Protein-protein interaction (PPI) is a crucial event for many biological functions. Studying the molecular details of PPI requires structure determination using X-ray crystallography, nuclear magnetic resistance (NMR), and single particle Cryo-EM. However, sometimes it is not easy to solve the complex structure for various reasons. For example, complex may be unstable, not enough protein expression for structural studies, etc. Further, PPI are intricate processes, and its molecular details cannot be fully explained by experimental observations. Here, we describe a quick and simple method to study the PPI using the combinatorial approach of molecular dynamics simulation and biophysical methods.

Midface fracture pattern in a tertiary care hospital - A prospective study.

Introduction: The midface with multiple bones and cavities is vulnerable to fractures more commonly. Midface is one of the most frequently injured areas of the body, accounting for 23%-97% of all facial fractures. The classic LeFort type of fractures are uncommon nowadays and a more common picture is more severe forms primarily due to the high-speed vehicles that are a major cause of these fractures. It, therefore, has become imperative to determine the commonly occurring patterns of fractures in this area in the present time for a better insight into diagnosis and treatment plans. The aim of this article was to determine fracture patterns in midface trauma to ease the treatment planning in such a scenario. Materials and Methods: This prospective study included 114 patients who reported to a tertiary hospital during a 4-year period and were diagnosed with suspected midface fractures. The etiology and pattern of fractures of midface were assessed based on history, clinical examination, and imaging data. The diagnosis of a fracture was based on the clinical history, signs and symptoms, manual examination, and correct interpretation of radiographs and computed tomography. Midface fractures were recorded as LeFort I, II, III, dentoalveolar, palatal, zygomatic complex fracture, nasal bones, naso-orbital-ethmoidal complex, and orbital and zygomatic arch fractures. Etiological factors were classified as road traffic accidents (RTAs), fall, assault, and sports injuries. Results: During the 4-year period, a total of 114 patients were included. Patients' ages ranged from 17 to 68 years, with 102 males and 12 females. The most common fracture in this study was found to be zygomatic complex fractures (52%), and RTA was identified as the main cause of fracture in this study (79.2%). Conclusion: The midface fractures are more common in males due to the propensity of males to use two-wheelers more than females. The prominence of the zygoma makes it more vulnerable to fractures than rest of the bones in the midface. Increased speed of vehicles and lack of discipline in following traffic rules have resulted in RTA, being the biggest etiological factor in midface injuries.

Taxifolin and Lucidin as Potential E6 Protein Inhibitors: p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells.

Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all HPV types, and have poor accessibility in developing countries, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. Considering HPV E6's oncogenic role, this protein has been proposed as a relevant target for cancer treatment. In the present work, we employed in silico tools to discover potential E6 inhibitors, as well as biochemical and cellular assays to understand the action of selected compounds in HPV-positive cells (Caski and HeLa) vs. HPV-negative (C33A) and non-carcinogenic (NHEK) cell lines. In fact, by molecular docking and molecular dynamics simulations, we found three phenolic compounds able to dock in the E6AP binding pocket of the E6 protein. In particular, lucidin and taxifolin were able to inhibit E6-mediated p53 degradation, selectively reduce the viability, and induce apoptosis in HPV-positive cells. Altogether, our data can be relevant for discovering promising leads for the development of specific anti-HPV drugs.

Ophthalmic Complications Associated with Zygomatic Complex Fractures: A Randomised Descriptive Clinical Study.

Background and Objectives: Trauma to the maxillofacial region is usually associated with varying degrees of disruption of the soft and hard tissues in the region and injuries to the neighbouring structures such as eyes, brain, nasal apparatus and paranasal sinuses. Injuries to the middle third of the face commonly destroys the integrity of the orbital skeleton, and are frequently complicated by injury to the eye, ranging between 2.7 and 67% as reported in the literature. These injuries may result in loss of vision or compromised ocular function. When these injuries are severe, they may be detected with ease by any medical or maxillofacial surgeon but many injuries appear minimal and may be missed by the non-ophthalmologist. Methods: A total of thirty patients were selected who were diagnosed with a zygomatic complex fracture, irrespective of sex predilection and in the age group of 18-70 years. All patients underwent a thorough ophthalmic examination by an Oral and Maxillofacial Surgeon and an Ophthalmologist preoperatively and on postoperative day 2, and 7 and all findings were documented separately by the surgeon and the ophthalmologist and the findings were later compared. Results: The statistical analysis was performed using SPSS VERSION 21.0, Shapiro-Wilk test which was used to assess the normality. Descriptive analysis was done for age and gender distribution of study subjects, which are expressed as number and frequency. Cochran's q test was used to determine if there are differences in various study factors among OMFS and ophthalmologists at three time intervals which are expressed as number and frequency. Kappa agreement was used to assess the measurement of agreement between OMFS and ophthalmologists for each factor at each time interval and these are expressed as number and frequency, and p ≤ 0.05 is considered as statistically significant. Upon examination by an OMFS periorbital oedema (p = 0.000), periorbital ecchymosis (p = 0.002), chemosis (p = 0.02) and exophthalmos (p = 0.03) were considered clinically significant. Upon examination by an ophthalmologist subconjunctival haemorrhage (p = 0.05), periorbital oedema (p = 0.05), periorbital ecchymosis (p = 0.00), ptosis (p = 0.006), enopthalmos (p = 0.05) and diplopia (p = 0.05) were considered to be clinically significant. Upon correlation of the findings of the surgeon and the ophthalmologist it was seen that certain parameters like corneal injury, Phthisis bulbing, examination of posterior segment can be better done by the ophthalmologist. Interpretation and Conclusion: In conclusion, it was determined that there is a significant correlation between ophthalmic injuries caused by zygomatic complex fractures. There are a wide array of injuries affecting the eye due to trauma to the middle third of the face, and the superficial injury can be well evaluated and documented by a surgeon; however due to the extensive nature of the injuries in trauma and the importance of the eye, an ophthalmic examination cannot be ruled out. The need for evaluation of such injures deem it pertinent for observation by an ophthalmologist.

Role of the Maxillofacial Surgeon in Identifying the Correlation Between Facial Bone Fractures and Traumatic Brain Injury - A Prospective Study.

Introduction: Maxillofacial trauma accounts for a high percentage of patients reporting to the emergency medicine department and being admitted in the hospital. The purpose of this study was to form a direct association between maxillofacial fractures and traumatic brain injury (TBI). Methods: Ninety patients with maxillofacial fractures that reported to/were referred to the Department of Oral and Maxillofacial Surgery were observed for features indicative of TBI based on clinical presentation and radiological interpretations. Parameters such as loss of consciousness, vomiting, dizziness, headache, seizures and the requirement for intubation, cerebrospinal fluid rhinorrhoea and otorrhoea were also assessed. Appropriate radiographs for the diagnosis of the fracture were taken followed by a computed tomography (CT) scan when indicated in accordance to the Canadian CT Head Rule. These scans were then assessed for contusion, extradural haemorrhage, subdural haemorrhage, subarachnoid haemorrhage, pneumocephalus and cranial bone fracture. Results: A total of 90 patients were evaluated, of which 91.1% were males and 8.9% were females. Association between the occurrence of head injury and different maxillofacial bone fractures using the Chi-square test showed a statistical significance of <0.001 in patients with naso-orbito-ethmoid as well as frontal bone fractures. There was a clear association between fractures present in the upper as well as the middle third of the face and traumatic head injury (P ≤ 0.001). Discussion: Patients with the frontal bone and zygomatic bone fractures have a high prevalence of TBI. Patients with the upper and middle third of the face injury are more prone to traumatic head injury and importance should be given to patients with the same and prevent poor prognosis.

Infiltrating lipomatosis, an etiology for TMJ ankylosis?

Infiltrating lipomatosis is a rare benign condition causing diffuse fatty infiltration into the surrounding soft tissue and in rare cases causes hyperplasia of the adjacent bone. We report a case with clinical and radiological evidence of a 34-year-old female patient who reported a swelling in the left middle third of the face with exophytic temporomandibular joint (TMJ) ankylosis of the left side resulting in restricted mouth opening and facial asymmetry since 21 years. The number of cases reported in the literature is rare. Surgery is the treatment of choice.

A potential peptide inhibitor of SARS-CoV-2 S and human ACE2 complex.

The disease COVID-19 has caused heavy socio-economic burden and there is immediate need to control it. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The viral entry into human cell depends on the attachment of spike (S) protein via its receptor binding domain (RBD) to human cell receptor angiotensin-converting enzyme 2 (hACE2). Thus, blocking the virus attachment to hACE2 could serve as potential therapeutics for viral infection. We have designed a peptide inhibitor (ΔABP-α2) targeting the RBD of S protein using in-silico approach. Docking studies and computed affinities suggested that peptide inhibitor binds at the RBD with ∼95-fold higher affinity than hACE2. Molecular dynamics (MD) simulation confirms the stable binding of inhibitor to hACE2. Immunoinformatics studies suggest non-immunogenic and non-toxic nature of peptide. Thus, the proposed peptide could serve as potential blocker for viral attachment.Communicated by Ramaswamy H. Sarma.

Correlation of Panoramic Radiological and Intra-Operative Findings of Impacted Mandibular 3rd Molar in Relation to Inferior Alveolar Canal: A Prospective Study.

AIM: The objective of this study was to correlate the preoperative radiological findings and intraoperative surgical findings during removal of impacted mandibular 3rd molar with respect to the inferior alveolar canal. MATERIALS AND METHOD: The prospective study design included 100 patients between the age group of 20 years and 50 years who visited the Department of Oral and Maxillofacial Surgery at Vydehi Institute of Dental Sciences and Research Centre, Whitefield, Bengaluru. A preoperative panoramic radiograph was taken and the parameters were assessed and a normal surgical protocol was followed to extract the impacted mandibular 3rd molar with intra-operative assessment as well. RESULTS: Out of the 100 patients with definitive radiological signs showing close relation of the third molar to the mandibular canal who underwent surgical removal, only 12 patients presented with definitive clinical findings of the association. CONCLUSION: A true close relationship between the third molars and mandibular canal increases the risk of inferior alveolar nerve injury, and accurate evaluation of the relationship is essential to avoid the risk of surgery. The accuracy of the plain radiographs to diagnose an intimate relationship between the neurovascular bundle and the third molar root has its limitations, since only 12 of the 100 patients with positive radiological signs showed clinical evidence of involvement. Surgeons should be aware of the limitations of the radiographic markers of panoramic radiography and should consider more detailed imaging in more specific cases in which one or more radiographic marker is present.

The mechanism of complex formation between calmodulin and voltage gated calcium channels revealed by molecular dynamics.

Calmodulin, a ubiquitous eukaryotic calcium sensor responsible for the regulation of many fundamental cellular processes, is a highly flexible protein and exhibits an unusually wide range of conformations. Furthermore, CaM is known to interact with more than 300 cellular targets. Molecular dynamics (MD) simulation trajectories suggest that EF-hand loops show different magnitudes of flexibility. Therefore, the four EF-hand motifs have different affinities for Ca2+ ions, which enables CaM to function on wide range of Ca2+ ion concentrations. EF-hand loops are 2-3 times more flexible in apo CaM whereas least flexible in Ca2+/CaM-IQ motif complexes. We report a unique intermediate conformation of Ca2+/CaM while transitioning from extended to compact form. We also report the complex formation process between Ca2+/CaM and IQ CaM-binding motifs. Our results showed how IQ motif recognise its binding site on the CaM and how CaM transforms from extended to compact form upon binding to IQ motif.

Assessment of Postoperative Bleeding after Dental Extractions in Patients Who Are On Antiplatelet Therapy: A Prospective Study.

INTRODUCTION: Patients with ischemic heart disease are placed on antiplatelet therapy (APT). This study allows a definite protocol to be set which will allow us the make the right judgment when it comes to extractions in patients on APT. MATERIALS AND METHODS: For this study, 100 patients were taken up for dental extraction after obtaining a thorough case history. Bleeding time was assessed preoperatively for all the patients and patients with normal bleeding time were taken up for surgery under local anesthesia. Local haemostatic measures were employed after the extraction. Patients were monitored for first 30 minutes at the clinic and a telephonic review of all the patients was done at 24 h-48 h interval after the procedure. If there was an active ooze from the surgical site at any point, haemostatic measures with local haemostatic agents were carried out. RESULTS: In patients with mono antiplatelet therapy, bleeding was noted in 16 patients after the 1 h time interval and was absent after 24h-48 h time intervals. The q = 32 and the P < 0.001, making it statistically significant. Regarding patients on dual APT, bleeding was noted in ten patients after 1 h, and in one patient after 24 h with no patients presenting with bleeding at the 48 h time interval. The q = 16.545 and P < 0.001, making it statistically significant. DISCUSSION: The benefits of continuing APT for patients who require dental extraction outweighs the risks of postoperative bleeding. CONCLUSION: Antiplatelets are used for the prevention of myocardial infarction, ischemic stroke, and vascular death among patients who are at high risk of these events. Antiplatelets have minimal impact on the amount and duration of bleeding following routine dental extractions.

TMJ Ankylosis Management: Our Experience.

AIM: Temporomandibular joint (TMJ) ankylosis is an extremely disabling affliction that causes problems in mastication, digestion, speech, appearance and hygiene. Surgery of TMJ ankylosis needs careful evaluation and planning to yield predictable results. Temporomandibular joint ankylosis is very common among young children. The aim of treatment is not only to treat the movement of the joint but also to prevent relapse. MATERIALS AND METHOD: In this series, 18 cases of temporomandibular joint ankylosis were treated at our institute from January 2012 to January 2017 with osteoarthrectomy and interpositional arthroplasty. Patients were in the age range of 5-57 years, with 11 males and 7 females and including 8 unilateral and 10 bilateral cases. Duration of ankylosis ranged from less than 2 years to more than 6 years. Seven of the patients were secondarily taken up for correction of their deformities with either orthognathic surgery or distraction osteogenesis. RESULTS: Good mouth opening was achieved in all the patients with a mean follow-up period of 12 months. The early post-operative mouth opening ranged from 24 to 37 mm. The late post-operative mouth opening ranged from 20 to 33 mm. There was a stress on aggressive physiotherapy for a minimum of 6 months in all our patients. CONCLUSION: Interpositional arthroplasty using vascularized temporalis fascia flap is a very reliable method to prevent recurrence of ankylosis, and it also avoids the disadvantages of alloplastic materials as well as nonvascularized autogenous tissues.

In-silico design of a potential inhibitor of SARS-CoV-2 S protein.

The SARS-CoV-2 virus has caused a pandemic and is public health emergency of international concern. As of now, no registered therapies are available for treatment of coronavirus infection. The viral infection depends on the attachment of spike (S) glycoprotein to human cell receptor angiotensin-converting enzyme 2 (ACE2). We have designed a protein inhibitor (ΔABP-D25Y) targeting S protein using computational approach. The inhibitor consists of two α helical peptides homologues to protease domain (PD) of ACE2. Docking studies and molecular dynamic simulation revealed that the inhibitor binds exclusively at the ACE2 binding site of S protein. The computed binding affinity of the inhibitor is higher than the ACE2 and thus will likely out compete ACE2 for binding to S protein. Hence, the proposed inhibitor ΔABP-D25Y could be a potential blocker of S protein and receptor binding domain (RBD) attachment.

Conservative Management of Odontogenic Keratocyst in a Tertiary Hospital.

INTRODUCTION: Odontogenic keratocysts (OKCs) are benign intraosseous odontogenic lesions that have a locally aggressive behavior and exhibit a high recurrence rate after the treatment. The most appropriate surgical approaches for the successful treatment of OKCs remain controversial. AIM: The aim of this study was to evaluate the conservative management of OKCs by enucleation along with peripheral ostectomy and chemical cauterization in terms of recurrence rates after the surgical procedure. MATERIALS AND METHODS: A retrospective study on 36 cases of OKCs treated at the Oral and Maxillofacial Surgery Department of a tertiary hospital from 2010 to 2017 was done. The demographic, clinical, radiographic, and histologic data were collected for each patient. All cases were surgically treated by enucleation followed by peripheral ostectomy and chemical cauterization using Carnoy's solution. The teeth that were involved in the lesion were extracted. The diagnosis was confirmed with excisional biopsy and histopathology reports. RESULTS: Most of the OKCs were found in the mandible, except three which were present in the maxilla. A significantly higher incidence was seen in males in the age group of 21-30 years. Most of the cases (30 out of 36 cases) were accessed intraorally. Patients were followed up for up to 5 years. Recurrence of the operated OKCs was observed in five cases which were managed by enucleation with peripheral ostectomy and chemical cauterization again with good results. CONCLUSION: The results suggest that proper enucleation followed by peripheral ostectomy and chemical cauterization using Carnoy's solution may be the best and optimal approach for the management of OKC.

Anterior Tonsillar Fossa Approach to Elongated Styloid Process.

AIM: To demonstrate the efficacy of a new novel anterior tonsillar fossa approach in management of elongated styloid process syndrome. MATERIAL AND METHOD: We operated upon 20 patients with confirmed, symptomatic elongated styloid process. None of these patients gave a previous positive history of trauma or any other procedure relating to tonsillar area. All these patients had undergone treatment or were under treatment for neuralgia/TMJ dysfunction syndrome. Diagnosis was confirmed by clinical examination followed by radiological findings. RESULTS: 12 patients underwent bilateral styloidectomy (60%) and 8 patients, underwent unilateral styloidectomy (40%). The length of stolid process ranged from 34mm to 62mm (mean 44 mm). Post operative follow up period ranges from 6 months to 12 months.17 patients (85%) were asymptomatic & had complete remission of symptoms over a follow up period of 12 months. 2 patients had partial remission of symptoms & 1 patient was lost to follow-up. CONCLUSION: Our anterior tonsillar fossa approach to elongated styloid is safe & adequate in effective surgical management & more so with an additional advantage of not requiring tonsillectomy which is often performed in trans-pharyngeal technique.

A Retrospective Study of Condylar Fracture Management in a Tertiary Care Hospital-A 10-Year Experience.

INTRODUCTION: Since the advent of rigid fixation, there has been a paradigm shift in the management of condylar fractures from closed treatment options to open reduction and rigid internal fixation. MATERIALS AND METHOD: Sixty-eight cases of condylar fractures reporting to Vydehi Institute of Dental Sciences, Bangalore, between 2009 and 2018 were reviewed in terms of age, sex, type of fracture, position of the mandibular third molar and the treatment rendered. RESULTS: The majority of the patients were males (60). There was an involvement of the right side in 34, left in 21 and bilateral involvement in 13 cases. Forty-three of the fractures were subcondylar, and 25 were intracapsular. Significantly in most cases, the mandibular third molar was either fully erupted (42) or missing (12). Sixty-one cases were subjected to surgical management including 49 cases of rigid internal fixation, and 12 of the intracapsular fractures had the condylar stump/segment removed. Only seven cases were not treated surgically. Most of the cases (44) were in the age group of 21-40, 12 were in the age group of 41-60, 9 were in the age group of 1-20, and 3 patients were above 60. CONCLUSION: Condylar fractures more often do not require surgical intervention, and their incidence is more likely to occur when the third molar is either fully erupted or missing.

The unusual di-domain structure of Dunaliella salina glycerol-3-phosphate dehydrogenase enables direct conversion of dihydroxyacetone phosphate to glycerol.

Dunaliella has been extensively studied due to its intriguing adaptation to high salinity. Its di-domain glycerol-3-phosphate dehydrogenase (GPDH) isoform is likely to underlie the rapid production of the osmoprotectant glycerol. Here, we report the structure of the chimeric Dunaliella salina GPDH (DsGPDH) protein featuring a phosphoserine phosphatase-like domain fused to the canonical glycerol-3-phosphate (G3P) dehydrogenase domain. Biochemical assays confirm that DsGPDH can convert dihydroxyacetone phosphate (DHAP) directly to glycerol, whereas a separate phosphatase protein is required for this conversion process in most organisms. The structure of DsGPDH in complex with its substrate DHAP and co-factor nicotinamide adenine dinucleotide (NAD) allows the identification of the residues that form the active sites. Furthermore, the structure reveals an intriguing homotetramer form that likely contributes to the rapid biosynthesis of glycerol.

Ameloblastoma Management: "Horses for Courses" Protocol.

PURPOSE: The purpose of the article is to review 45 cases of ameloblastoma treated in a tertiary care centre depending on the extent of the pathology, in terms of recurrence and morbidity of the patients. MATERIALS AND METHOD: This was a retrospective study of patients who underwent treatment for ameloblastoma between 2009 and 2018 at Vydehi Institute of Dental Sciences, Bangalore. During the first phase of 4 years, the focus of the treatment was on avoiding any recurrence, and therefore, resection followed by reconstruction with reconstruction plates was the only modality used in ten patients. However, from 2014, it was decided to treat each patient based on the extent of the lesion and decide on either conservative management in the form of enucleation followed by peripheral ostectomy and chemical cauterisation or resection with safe margins and reconstruction with reconstruction plates. RESULTS: The study sample consisted of 45 patients, and the ages ranged from 12 to 65 years with an average of 36. There were 30 males and 15 females. In the first phase of treatment protocol adopted, ten patients underwent resection. In the later period, 18 patients were treated by conservative methods and 16 patients were treated by radical management. There were only three recurrences over a period of 3-year follow-up in the group treated conservatively. CONCLUSION: Considering the benign nature of the tumour and the morbidity after resection, patients, most of whom are in the younger age group, can still be subjected to conservative treatment provided they are followed up for a long period thus assuring them of a better quality of life.

Ribosome protection by ABC-F proteins-Molecular mechanism and potential drug design.

Members of the ATP-binding cassette F (ABC-F) proteins confer resistance to several classes of clinically important antibiotics through ribosome protection. Recent structures of two ABC-F proteins, Pseudomonas aeruginosa MsrE and Bacillus subtilis VmlR bound to ribosome have shed light onto the ribosome protection mechanism whereby drug resistance is mediated by the antibiotic resistance domain (ARD) connecting the two ATP binding domains. ARD of the E site bound MsrE and VmlR extends toward the drug binding region within the peptidyl transferase center (PTC) and leads to conformational changes in the P site tRNA acceptor stem, the PTC, and the drug binding site causing the release of corresponding drugs. The structural similarities and differences of the MsrE and VmlR structures likely highlight an universal ribosome protection mechanism employed by antibiotic resistance (ARE) ABC-F proteins. The variable ARD domains enable this family of proteins to adapt the protection mechanism for several classes of ribosome-targeting drugs. ARE ABC-F genes have been found in numerous pathogen genomes and multi-drug resistance conferring plasmids. Collectively they mediate resistance to a broader range of antimicrobial agents than any other group of resistance proteins and play a major role in clinically significant drug resistance in pathogenic bacteria. Here, we review the recent structural and biochemical findings on these emerging resistance proteins, offering an update of the molecular basis and implications for overcoming ABC-F conferred drug resistance.

Maxillofacial Fracture Patterns in Road Traffic Accidents.

OBJECTIVE: The objective of this study is to analyze the maxillofacial fracture pattern from road traffic accidents (RTAs) in cases treated surgically in a tertiary hospital during July 2008-June 2018. MATERIALS AND METHOD: Data available in the department of oral and maxillofacial surgery of the institution of patients with maxillofacial fractures sustained due to RTAs that were treated in the department between the period July 2008 and June 2018 were collected and analyzed. The variables analyzed for the study were etiology, gender, age, and type of fracture. All cases were treated by open reduction and rigid internal fixation. RESULTS: A total of 348 patients with maxillofacial fractures were diagnosed, of which 335 were male and 13 were female. The ages ranged from 7 to 70 years. The maximum cases were in the age group of 16-30 years with 181 fractures followed by 31-45 group with 133 fractures, 45-60 years with 21 fractures, 0-15 years with 8 fractures, and >60 years with five fractures. The maximum incidence of fractures was in the mandible with 168 cases followed by 92 in zygomatic complex, combination of fractures in 53 cases, 13 LeFort I fractures, nine frontal bone fractures, three fractures in other areas, five nasal fractures, and five LeFort II fractures. Males predominated the cases of mandibular fractures involving multiple sites and cases involving multiple bones. CONCLUSION: A maximum number of maxillofacial fractures cases were in the second and third decades of life, and the high-speed vehicles and lack of protective safety accessories such as helmets and seatbelts were responsible for the wide variety of pattern fractures of facial bones.