Damsel in distress calling on her knights: Illuminating the pioneering role of E3 ubiquitin ligases in guarding the genome integrity.

The maintenance of genomic integrity is of utmost importance for the organisms to survive and to accurately inherit traits to their progenies. Any kind of DNA damage either due to defect in DNA duplication and/ or uncontrolled cell division or intracellular insults or environment radiation can result in gene mutation, chromosomal aberration and ultimately genomic instability, which may cause several diseases including cancers. Therefore, cells have evolved machineries for the surveillance of genomic integrity. Enormous exciting studies in the past indicate that ubiquitination (a posttranslational modification of proteins) plays a crucial role in maintaining the genomic integrity by diverse ways. In fact, various E3 ubiquitin ligases catalyse ubiquitination of key proteins to control their central role during cell cycle, DNA damage response (DDR) and DNA repair. Some E3 ligases promote genomic instability while others prevent it, deregulation of both of which leads to several malignancies. In this review, we consolidate the recent findings wherein the role of ubiquitination in conferring genome integrity is highlighted. We also discuss the latest discoveries on the mechanisms utilized by various E3 ligases to preserve genomic stability, with a focus on their actions during cell cycle progression and different types of DNA damage response as well as repair pathways.

In spite of successful curative surgery for buccal mucosa carcinoma the health-related quality-of-life continues to remain poor.

BACKGROUND: In early stage buccal mucosa carcinoma, in spite of successful curative surgery, the health-related quality-of-life (HRQoL) may not improve. We aimed to study HRQoL in these patients who had undergone successful curative surgery and determined factors that influence the HRQoL. METHODS: Subjects, aged 18-70 years, who had undergone successful curative surgery for stage I and II buccal mucosa cancer, were assessed for HRQoL using the University of Washington Quality of Life Questionnaire and factors affecting HRQoL were determined. Their scores were compared with normative reference scores. RESULTS: 54 patients (stages I 54%, II 46%) aged 44 ± 11 years (87% males) were studied. They had undergone curative surgery a median of 8.5 (IQR 4-13.5) months ago. Their mean global HRQoL score was 77 ± 30, with significantly poorer scores compared to reference in domains of appearance, activity, swallowing, chewing, speech, shoulder, saliva, mood and anxiety. Anxiety, activity, and chewing were considered the most important domains by the patients. Among the factors influencing HRQoL, duration since surgery was the most important factor, and patients with recent surgery had worse performance in chewing, saliva and mood. Patients with stage II had worse performance in shoulder and anxiety compared to stage I. Post-operative radiotherapy worsened swallowing and shoulder function. CONCLUSION: In spite of successful curative surgery for buccal mucosa carcinoma, the HRQoL continues to remain sub-optimal with poor scores in most of the domains. These domains must be focused on with appropriate measures in order to improve overall HRQoL in patients after successful curative surgery.

Influence of cholesterol on cancer progression and therapy.

Cholesterol is a fundamental molecule necessary for the maintenance of cell structure and is vital to various normal biological functions. It is a key factor in lifestyle-related diseases including obesity, diabetes, cardiovascular disease, and cancer. Owing to its altered serum chemistry status under pathological states, it is now being investigated to unravel the mechanism by which it triggers various health complications. Numerous clinical studies in cancer patients indicate an alteration in blood cholesterol level (either decreased or increased) in comparison to normal healthy individuals. This article elaborates on our understanding as to how cholesterol is being hijacked in the malignancy for the development, survival, stemness, progression, and metastasis of cancerous cells. Also, it provides a glimpse of how cholesterol derived entities, alters the signaling pathway towards their advantage. Moreover, deregulation of the cholesterol metabolism pathway has been often reported to hamper various treatment strategies in different cancer. In this context, attempts have been made to bring forth its relevance in being targeted, in pre-clinical and clinical studies for various treatment modalities. Thus, understanding the role of cholesterol and deciphering associated molecular mechanisms in cancer progression and therapy are of relevance towards improvement in the management of various cancers.

piNET: a versatile web platform for downstream analysis and visualization of proteomics data.

Rapid progress in proteomics and large-scale profiling of biological systems at the protein level necessitates the continued development of efficient computational tools for the analysis and interpretation of proteomics data. Here, we present the piNET server that facilitates integrated annotation, analysis and visualization of quantitative proteomics data, with emphasis on PTM networks and integration with the LINCS library of chemical and genetic perturbation signatures in order to provide further mechanistic and functional insights. The primary input for the server consists of a set of peptides or proteins, optionally with PTM sites, and their corresponding abundance values. Several interconnected workflows can be used to generate: (i) interactive graphs and tables providing comprehensive annotation and mapping between peptides and proteins with PTM sites; (ii) high resolution and interactive visualization for enzyme-substrate networks, including kinases and their phospho-peptide targets; (iii) mapping and visualization of LINCS signature connectivity for chemical inhibitors or genetic knockdown of enzymes upstream of their target PTM sites. piNET has been built using a modular Spring-Boot JAVA platform as a fast, versatile and easy to use tool. The Apache Lucene indexing is used for fast mapping of peptides into UniProt entries for the human, mouse and other commonly used model organism proteomes. PTM-centric network analyses combine PhosphoSitePlus, iPTMnet and SIGNOR databases of validated enzyme-substrate relationships, for kinase networks augmented by DeepPhos predictions and sequence-based mapping of PhosphoSitePlus consensus motifs. Concordant LINCS signatures are mapped using iLINCS. For each workflow, a RESTful API counterpart can be used to generate the results programmatically in the json format. The server is available at http://pinet-server.org, and it is free and open to all users without login requirement.

Use of Intravenous Cangrelor as Antiplatelet Bridge Therapy in a Patient Undergoing Esophageal Dilation Procedure.

Peri-procedural management of dual antiplatelet therapy following percutaneous coronary intervention for esophagogastroduodenoscopy and intervention is not clearly defined. We describe a case of a patient with a drug-eluting stent implanted in the setting of an acute myocardial infarction six weeks earlier who was bridged with cangrelor after interruption of ticagrelor for esophageal balloon dilatation because of dysphagia. The patient tolerated the procedure well and was transitioned back to ticagrelor without any complications.

Eosinophilic Granulomatosis With Polyangiitis Presenting as an Acute Coronary Syndrome.

Eosinophilic granulomatosis with polyangiitis, formerly Churg-Strauss Syndrome, is an uncommon disorder that carries a high mortality when coronary artery disease develops. Early recognition and treatment is crucial. We highlight an unusual presentation of acute coronary syndrome not associated with atherosclerotic coronary disease. (Level of Difficulty: Intermediate.).

Reduction of radiation and contrast agent exposure in a cryoballoon ablation procedure with integration of electromagnetic mapping and intracardiac echocardiography: a single center experience.

BACKGROUND: Pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) is routinely guided by fluoroscopy and utilizes contrast injection to ensure catheter positioning and pulmonary vein occlusion. Non-fluoroscopic imaging techniques including electromagnetic mapping (EM) and intracardiac echocardiography (ICE) have demonstrated reduced fluoroscopy times and contrast exposure. Utilization of color flow Doppler to evaluate vein occlusion with the balloon has not been evaluated as an alternative to contrast injection. In this study we evaluate the effectiveness of cryoablation guided by EM and ICE along with color Doppler to achieve PVI. METHODS: We designed a retrospective cohort study comparing patients who were treated before and after implementation of EM (Carto 3, Biosense Webster) and ICE during CBA (AF Solutions, Medtronic). We analyzed patients receiving CBA with fluoroscopy plus EM and ICE (group 2; N = 24) versus fluoroscopy alone (group 1; N = 25). Procedural success was defined as freedom from atrial fibrillation or other atrial arrhythmias at 1 year post ablation. Primary outcomes were radiation time and contrast exposure. RESULTS: Procedural success was achieved in all cases. Total fluoroscopy time was reduced from 22.4 ± 9.8 min to 8.9 ± 5.1 min (P < 0.001) in patients receiving CBA guided by EM and ICE. Furthermore, exposure to contrast media was significantly lower at 75.4 ± 24.1 ml and 16.5 ± 21.1 ml (P ≤ 0.001) in group 1 and group 2, respectively. Neither the number of required cryotherapy treatments nor procedure duration was negatively impacted by the implementation of non-fluoroscopic techniques. The 1-year success rate was identical between both groups at 72% and 79%. There was no difference in complication rates. CONCLUSION: This single-center cohort study demonstrates that CBA guided by EM and ICE can markedly reduce radiation and contrast exposure with excellent rates of acute PVI. This technique may be particularly effective in patients sensitive to intravenous contrast exposure.

Use of 3-D printing technologies in craniomaxillofacial surgery: a review.

Three-dimensional (3-D) printing is a method of manufacturing in which materials like plastic or metal are deposited onto one another in layers to produce a 3-D object. Because of the complex anatomy of craniomaxillofacial structures, full recovery of craniomaxillofacial tissues from trauma, surgeries, or congenital malformations is extremely challenging. 3-D printing of scaffolds, tissue analogs, and organs has been proposed as an exciting alternative to address some of these key challenges in craniomaxillofacial surgery. There are four broad types of 3-D printing surgical applications that can be used in craniomaxillofacial surgery: contour models (positive-space models to allow preapplication of hardware before surgery), guides (negative-space models of actual patient data to guide cutting and drilling), splints (negative-space models of virtual postoperative positions to guide final alignment), and implants (negative-space 3-D printed implantable materials or 3-D printed molds into which nonprintable materials are poured). 3-D printing technology is being successfully used for surgeries for head and neck malignancies, mandibular reconstruction, orthognathic surgeries, for mandibulectomies after osteoradionecrosis, orbital floor fracture surgeries, nasal reconstruction, and cranioplasties. The excitement behind 3-D printing continues to increase and hopefully will drive improvements in the technology and its surgical applications, especially in craniomaxillofacial region. This present review sets out to explore use of 3-D printing technologies in craniomaxillofacial surgery.

Prevalence and pattern of lobular capillary hemangioma in Eastern Madhya Pradesh, India: A clinicopathological analysis.

BACKGROUND: Lobular capillary hemangioma is a common benign vascular tumor seen in the oral cavity. It occurs in response to various stimuli such as low-grade local irritation, traumatic insult, and hormonal factors or as a response to a wide variety of drugs. MATERIALS AND METHODS: All patients presenting to the Department of Dentistry, Shyam Shah Medical College, Rewa, Madhya Pradesh during July 2014 to June 2016, who were diagnosed by histopathologic confirmation as oral lobular capillary hemangioma (OLCH), were evaluated for the area involved, clinicopathologic presentation, demographic features, and treatment. RESULTS: A total of 94 cases were identified as OLCH by histopathologic confirmation during this period. The lesion occurred most commonly in the age group of 21-30 years. A characteristic female predominance (female: male ratio of 2.24:1) was seen. Anterior maxillary labial gingiva was most frequently involved (34.04%) followed by posterior maxillary buccal gingiva (14.89%). CONCLUSION: The clinicopathologic picture of OLCH found in this study was similar to other studies conducted on same as well different ethnic and geographical populations. Poor oral-dental-hygiene was observed in majority of patients (87.23%) dental health education should be an integral component of imparting oral health care by health providers. Surgical excision as a treatment modality renders good results with low recurrence rate.

Utility of the HAS-BLED Score in Risk Stratifying Patients on Dual Antiplatelet Therapy Post 12 Months After Drug-Eluting Stent Placement.

INTRODUCTION: Current guidelines recommend continuation of dual anti-platelet therapy (DAPT) for 12 months after percutaneous coronary intervention (PCI). Recent studies have shown benefit in continuing DAPT beyond 12 months but at the risk of increase bleeding. To date, there has been little data on risk stratifying patients to determine who can continue DAPT beyond 12 months at minimal bleeding risk. METHODS: All patients who underwent drug-eluting stent (DES) placement from January 1, 2013 to September 30, 2014 were reviewed. Patients who had follow-up for at least 12 months, placement of 2nd generation everolimus-coated DES, and were on DAPT for at least 12 months were included. Patients with a history of atrial fibrillation, follow-up time less than 12 months, or were on concurrent oral anticoagulation therapy were excluded. RESULTS: Five hundred thirty-one patients were analyzed as described above. Two hundred two patients included in our study with 7 patients in the bleeding cohort and 195 patients in no-bleed cohort. The HAS-BLED score in patients who had a bleeding episode vs. those who did not was 3.29 vs. 2.24 (P value of 0.0009). Although not statistically significant, patients who had a bleeding episode were more likely to have renal dysfunction, alcohol use, be on prasugrel, and be on 325mg of aspirin. CONCLUSION: The study shows that the HAS-BLED score can be of utility in risk stratifying patients in determining who can continue DAPT beyond 12 months. Furthermore, a HAS-BLED score of less than 2 may help guide extended DAPT beyond 12 months at minimal bleeding risk. © 2016 Wiley Periodicals, Inc.

Maxillofacial Fractures in Bhopal, India: Analytic Study of 1268 Cases.

PURPOSE: To ascertain the pattern, incidence, causes, age and sex distribution, types, condition and treatment of maxillofacial fractures and their interwoven relationship being practiced in Bhopal. MATERIALS AND METHODS: Retrospectively 3 year records of patients with maxillofacial fractures from 12 selected centres in Bhopal were reviewed. The following data were extracted from the medical records: age; gender; site of the fracture(s); other associated injury(ies); cause of the trauma and method of treatment(s). RESULT: In 1268 patients, a total of 2613 fractures were found of which 44.58 % patients had mandibular fractures. Parasymphysis was the most common site of fracture overall. Most patients were in the 21-30 year old age group, and the male: female ratio was 3.3:1. Road traffic accident accounted for 858 cases (67.67 %). Head injury was the highest occurring associated injury. Open surgical modalities was the most employed treatment modality in 52.60 % of cases. CONCLUSION: Preference for open surgical treatment along with increasing trend of supplemental intermaxillary fixation was found, which prompts us to check for the underlying reason behind this, which could be the increasing number of displaced and comminuted fracture cases or the decreasing efficiency of open reduction treatment rendered. Latter reason prompts to re-evaluate the existing surgical techniques and expertise of the practicing surgeons.

Influence of tooth sectioning technique and various risk factors in reducing the IAN injury following surgical removal of an impacted mandibular third molar.

A prospective study on 100 patients presented with a mesioangular impacted mandibular third molar in close proximity to the inferior alveolar nerve canal (IANC) was done to evaluate the efficacy of tooth sectioning in reducing the incidence of inferior alveolar nerve (IAN) injury during their surgical removal. The patients were divided into two groups: group A, where tooth sectioning was not performed, and group B, where tooth sectioning was performed. Patients were recalled 7 days, 15 days, 30 days, 3 months, and 6 months postoperatively for evaluation of nerve injury and its recovery. A total of 13 patients suffered from nerve damage out of which 10 patients (10/50 or 20 %) belonged to group A and 3 patients (3/50 or 6 %) belonged to group B. All patients showed complete recovery from nerve damage within 6 months except 1 patient. The result of the study showed that tooth sectioning significantly reduces the incidence of nerve damage by 14 %. Deviation of the IANC, increased depth of the impacted tooth, intraoperative hemorrhage within socket/nerve exposure, and increased duration of procedure were found to be the significant risk factors associated with nerve injury.

Intraoperative neurophysiology in deep brain surgery for psychogenic dystonia.

Psychogenic dystonia is a challenging entity to diagnose and treat because little is known about its pathophysiology. We describe two cases of psychogenic dystonia who underwent deep brain stimulation when thought to have organic dystonia. The intraoperative microelectrode recordings in globus pallidus internus were retrospectively compared with those of five patients with known DYT1 dystonia using spontaneous discharge parameters of rate and bursting, as well as movement-related discharges. Our data suggest that simple intraoperative neurophysiology measures in single subjects do not differentiate psychogenic dystonia from DYT1 dystonia.

Unicystic ameloblastoma with mural proliferation: conservative or surgical approach?

Ameloblastoma occurs in a wide variety of forms. Various forms of ameloblastomas have various treatment modalities ranging from a conservative approach to surgical resection with reconstruction. We report a case of unicystic ameloblastoma with mural proliferation in a 17-year-old girl, who presented with a swelling in the lower left jaw associated with dull aching pain and was managed initially by a conservative approach followed by surgical enucleation on recurrence.

Metadata Standard and Data Exchange Specifications to Describe, Model, and Integrate Complex and Diverse High-Throughput Screening Data from the Library of Integrated Network-based Cellular Signatures (LINCS).

The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource. Integration and analysis of diverse LINCS data sets depend on the availability of sufficient metadata to describe the assays and screening results and on their syntactic, structural, and semantic consistency. Here we report metadata specifications for the most important molecular and cellular components and recommend them for adoption beyond the LINCS project. We focus on the minimum required information to model LINCS assays and results based on a number of use cases, and we recommend controlled terminologies and ontologies to annotate assays with syntactic consistency and semantic integrity. We also report specifications for a simple annotation format (SAF) to describe assays and screening results based on our metadata specifications with explicit controlled vocabularies. SAF specifically serves to programmatically access and exchange LINCS data as a prerequisite for a distributed information management infrastructure. We applied the metadata specifications to annotate large numbers of LINCS cell lines, proteins, and small molecules. The resources generated and presented here are freely available.

A complex odontoma of the anterior maxilla associated with an erupting canine.

Many developmental anomalies of the jaw are accidentally diagnosed during radiographic investigations for other symptoms. Complex odontomas are odontogenic tumours, relatively rare in the anterior maxilla and generally asymptomatic. Frequently the odontoma may interfere with the eruption of teeth. This paper describes a case of complex odontoma in an 8-year-old girl, which resulted in the palatal displacement of the lateral incisor and an erupting permanent canine. A calcified mass was seen on the radiograph and was provisionally diagnosed as an odontoma which was surgically enucleated. Routine follow-up was carried out for more than 1 year and no recurrence was seen.

Large ameloblastic fibro-odontoma in an 18-year-old girl and review of literature.

The ameloblastic fibro-odontoma is a rare, benign, mixed neoplasm composed of proliferating odontogenic epithelium, ectomesenchymal tissue and varying degrees of dental hard tissue formation. It occurs exclusively as an intraosseous lesion. It usually exhibits slow growth and is commonly seen in children and young adults. Radiologically, ameloblastic fibro-odontoma appears as a circumscribed radiolucency which may contain radiopaque foci. Most cases of ameloblastic fibro-odontoma exhibit benign behaviour, but cases of malignant transformation have been reported. The treatment modality in most cases involves conservative surgery, but in cases with malignant transformation more radical treatment will be required. A massive ameloblastic fibro-odontoma involving the mandible is being described here with its clinical, radiological and histopathological features.

Idiopathic facial swelling secondary to sickle cell anaemia.

Sickle cell disease is a common inherited autosomal disease that is characterised by abnormally shaped (sickle-shaped) red blood cells (RBCs). It can involve virtually any organ system. The clinical manifestations of sickle cell disease vary and are classified as vaso-occlusion, chronic anaemia and infection. The imaging appearances of central nervous system and musculoskeletal involvement by sickle cell disease have been well documented; however, involvement of the head and neck region is often unreported, although it is not uncommon. In the head and neck, sickle cell disease can involve the inner ears, orbits, paranasal sinuses, bones, lymph nodes and vessels. This paper describes a case of idiopathic facial swelling associated with sickle cell disease in a young patient.