Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers.

Potent immunosuppressive mechanisms within the tumor microenvironment contribute to the resistance of aggressive human cancers to immune checkpoint blockade (ICB) therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs) to induce T cell tolerance is through secretion of reactive nitrogen species (RNS), which nitrates tyrosine residues in proteins involved in T cell function. However, so far very few nitrated proteins have been identified. Here, using a transgenic mouse model of prostate cancer and a syngeneic cell line model of lung cancer, we applied a nitroproteomic approach based on chemical derivation of 3-nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is nitrated at Tyr394 by MDSCs. LCK nitration inhibits T cell activation, leading to reduced interleukin 2 (IL2) production and proliferation. In human T cells with defective endogenous LCK, wild type, but not nitrated LCK, rescues IL2 production. In the mouse model of castration-resistant prostate cancer (CRPC) by prostate-specific deletion of Pten, p53, and Smad4, CRPC is resistant to an ICB therapy composed of antiprogrammed cell death 1 (PD1) and anticytotoxic-T lymphocyte-associated protein 4 (CTLA4) antibodies. However, we showed that ICB elicits strong anti-CRPC efficacy when combined with an RNS neutralizing agent. Together, these data identify a previously unknown mechanism of T cell inactivation by MDSC-induced protein nitration and illuminate a clinical path hypothesis for combining ICB with RNS-reducing agents in the treatment of CRPC.

Evaluation of Three Different Regression Equations Based Mixed Dentition Analysis in Children of Moradabad City, India

Objective: To assess the accuracy and applicability of three regression equations based mixed dentition analysis in children of Moradabad city, India. Material and Methods: Actual mesiodistal width of maxillary and madibular incisors, canines and premolars of 100 children (50 male and 50 female) aged 11-14 years were measured on dental cast with electronic digital vernier caliper. The analysis of Tanaka- Johnston, Ling-Wong and Jaroontham-Godfrey regression equations were tested on the dental casts. All analyses were performed on SPSS software. Data were summarized as Mean ± standard deviation (SD) paired observations were compared by paired t-test (two-tailed test) while independent groups were compared by independent Student's t-test. The level of significance was at P < 0.001. Results: The analysis of Tanaka-Johnston, Ling-Wong, Jaroontham-Godfrey regression equations tended to overestimate the mesiodistal width of the canines and premolars with the actual measured values. Conclusion: All the three regression equations based mixed dentition overestimated the mesiodistal width of canines and premolars in Moradabad population.

Opposing roles of TGFß and BMP signaling in prostate cancer development.

SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor ß (TGFß) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFß receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing its promoting role in BMP6-driven prostate cancer progression. These analyses reveal the complexity of TGFß-BMP signaling and illuminate potential therapeutic targets for prostate cancer.

Knowledge, attitude & practice on human papillomavirus vaccination: A cross-sectional study among healthcare providers.

BACKGROUND & OBJECTIVES: Cervical cancer is a major health problem and a leading cause of death among women in India. Of all the associated risk factors, high-risk human papillomavirus (HPV) infections being the principal aetiologic agent, two HPV vaccines are in use for the control of cervical cancer. The present study was undertaken to explore the knowledge, attitude and practice (KAP) on HPV vaccination among the healthcare providers in India. METHODS: A cross-sectional study was conducted among 590 healthcare professionals from 232 hospitals and 80 PHCs of nine districts of Delhi-NCR (National Capital Region). A total of 590 (526 female, 64 male) healthcare providers were surveyed. RESULTS: Only 47 per cent of respondents recommended young women to get vaccinated against HPV. Majority of respondents (81%) were found to be aware about the existence of vaccines for cervical cancer prevention. District-wise, highest (88.3%) awareness about the existence of vaccines against HPV was reported from Gautam Budh Nagar and lowest (64%) in Faridabad. Although 86 per cent of gynaecologists were aware about the names of HPV vaccines available in the market, only 27 per cent of paramedical staff had this knowledge. There was a significant difference between the respondents from government and private sectors regarding their awareness about HPV vaccines. Lack of awareness about the principal cause, risk factors and symptoms for cervical cancer and HPV vaccination was significantly (P< 0.05) reported in the respondents from paramedical staff category. INTERPRETATION & CONCLUSIONS: The findings reinforce continued medical education of healthcare providers, particularly those from the government sector on HPV vaccination for cervical cancer prevention. Public education is also pertinent for a successful HPV vaccination programme in the country.

Estimation of changes in nickel and chromium content in nickel-titanium and stainless steel orthodontic wires used during orthodontic treatment: An analytical and scanning electron microscopic study.

INTRODUCTION: The biocompatibility of orthodontic dental alloys has been investigated over the past 20 years, but the results have been inconclusive. The study compares standard 3 M Unitek nickel-titanium (NiTi) and stainless steel archwires with locally available JJ orthodontics wires. Scanning electron microscope (SEM) study of surface changes and complexometric titration to study compositional change was performed. MATERIALS AND METHODS: Ten archwires each of group 1-3 M 0.016" NiTi, group 2-JJ 0.016" NiTi, group 3-3 M 0.019" *0.025" SS and group 4-JJ SS contributed a 10 mm piece of wire for analysis prior to insertion in the patient and 6 weeks post insertion. SEM images were recorded at ×2000, ×4000 and ×6000 magnification. The same samples were subjected to complexiometric titration using ethylenediaminetetraacetic acid to gauge the actual change in the composition. OBSERVATIONS AND RESULTS: The SEM images of all the archwires showed marked changes with deep scratches and grooves and dark pitting corrosion areas post intraoral use. 3M wires showed an uniform criss-cross pattern in as received wires indicating a coating which was absent after intraoral use. There was a significant release of Nickel and Chromium from both group 3 and 4. Group 2 wires released ions significantly more than group 1 (P = 0.0). CONCLUSION: Extensive and stringent trials are required before certifying any product to be used in Orthodontics.

Situation analysis of existing facilities for screening, treatment and prevention of cervical cancer in hospitals/primary health centers of Delhi-NCR region, India.

Cervical cancer, the second most common malignancy all over the world, is associated with HPV infection. In a developing country like India, lack of early detection and treatment facilities is the main cause for its high burden. Therefore, through our study we e tried to present the current scenario of existing facilities for the detection and treatment of cervical cancer in hospitals and primary health centers (PHCs) of Delhi-NCR region. Data were collected from 312 healthcare facilities including public and private hospitals and PHCs of all nine districts from Delhi-NCR region. Healthcare providers including gynecologists, medical officers, women health care providers and paramedical staff were interviewed, using a questionnaire; the facilities for screening, diagnosing, and treating cervical cancer in each institution were recorded, using a previously designed checklist. Our study has shown that the basic facilities for the detection and treatment of cervical cancer are abhorrently lacking in Public hospitals and PHCs as compared to the Private hospitals in Delhi-NCR region. This study demonstrates that there is an urgent need for more investment in the diagnosis and treatment of cervical cancer facilities in public and rural healthcare facilities of Delhi-NCR region.

Oral melanotic neuroectodermal tumor of infancy.

Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare, benign neoplasm of neural crest origin composed of relatively primitive pigment-producing cells. It usually affects new born or infants of <1 year of age, generally involving the face or cranium. This case report describes a 4-month-old child with MNTI involving the anterior region of maxilla. A partial maxillectomy was performed on the left side of maxilla and the patient is now under follow-up.

Bilateral dens evaginatus (talon cusp) in permanent maxillary lateral incisors: a rare developmental dental anomaly with great clinical significance.

Talon cusp is an accessory cusp-like structure which projects from the cingulum area or cementoenamel junction. It is important for dentists to be aware of the potential complications that may occur with talon cusp. Early diagnosis and treatment is important, especially to prevent pulpal complications in permanent teeth which may be in developing stage in paediatric patients. The purpose of this paper is to report a case of bilateral talon cusp in permanent maxillary lateral incisors. Associated dental anomalies and clinical problems are discussed along with successful management of the case with conservative therapy.

Keratocystic odontogenic tumour (KCOT) misdiagnosed as a dentigerous cyst.

Keratocystic odontogenic tumours are known for their peculiar behaviour, varied origin, debated development, unique tendency to recur and disputed treatment modalities. Thus, it has been the subject of much research over the last 40 years. It was formerly known as odontogenic keratocyst (OKC). OKC received its new title as keratocystic odontogenic tumour (KCOT) by the WHO (2005) in order to suggest its aggressive and recurrent nature. KCOT is a benign intraosseous neoplasm of the jaw. Involvement of the maxillary sinus is an unusual presentation. We present the case of an 11-year-old child with extensive KCOT and an impacted canine in the right maxillary sinus. The cyst was initially misdiagnosed to be a dentigerous cyst based on the clinical and radiographic features though a differential diagnosis of KCOT and adenomatoid odontogenic tumour was made. The histological examination of the specimen finally confirmed it to be a KCOT. The clinical, radiological and histological features of this tumour along with its surgical management have been discussed.

Sequelae of dental trauma: the malformed tooth.

Here, we report a case of 10-year-old boy who came with a complaint of missing upper front teeth and was also concerned about his aesthetics. Significant history of trauma was present in his toddler period. Diagnosis of malformed upper right central incisor (11) by radiological investigations was carried out. Surgery was performed and there was removal of the impacted malformed upper right central incisor (11). Healing was uneventful. The patient is under follow-up for aesthetic rehabilitation to be carried out.