Nanoencapsulation of Docetaxel Induces Concurrent Apoptosis and Necroptosis in Human Oral Cancer Cells (SCC-9) via TNF-α/RIP1/RIP3 Pathway.

Human oral squamous cell carcinoma is the sixth most frequent malignant cancer, with an unacceptably high death rate that affects people's health. Albeit, there are several clinical approaches for diagnosing and treating oral cancer they are still far from ideal. We previously synthesised and characterised the docetaxel nanoformulation (PLGA-Dtx) and discovered that docetaxel nanoencapsulation may suppress oral cancer cells. The goal of this study was to figure out the mechanism involved in the suppression of oral cancer cell proliferation. We discovered that PLGA-Dtx inhibited SCC-9 cell growth considerably as compared to free docetaxel (Dtx), and that the viability of SCC-9 cells treated with PLGA-Dtx was decreased dose-dependently. MTT assay showed that PLGA-Dtx selectively inhibited the growth of PBMCs from oral cancer patients while sparing PBMCs from normal healthy controls. Further, flow cytometry analysis showed that PLGA-Dtx induced apoptosis and necroptosis in SCC-9 cells. G2/M cell cycle arrest has been confirmed on exposure of PLGA-Dtx for 24 h in SCC-9 cells. Interestingly, western blot investigation found that PLGA-Dtx increased the amounts of necroptic proteins and apoptosis-related proteins more efficiently than Dtx. Furthermore, PLGA-Dtx was more effective in terms of ROS generation, and mitochondrial membrane potential depletion. Pretreatment with necroptosis inhibitor Nec-1 efficiently reversed the ROS production and further recover MMP caused by PLGA-Dtx. Overall, this study revealed a mechanistic model of therapeutic response for PLGA-Dtx in SCC-9 cells and proposed its potency by inducing cell death via activation of concurrent apoptosis and necroptosis in SCC-9 cells via TNF-α/RIP1/RIP3 and caspase-dependent pathway.

Optical temperature sensing by tuning photoluminescence in a wide (visible to near infrared) wavelength range in a Eu3+-doped Bi-based relaxor ferroelectric.

The prevalent material design principles for optical thermometry primarily rely on thermally driven changes in the relative intensities of the thermally coupled levels (TCLs) of rare-earth-doped phosphor materials, where the maximum achievable sensitivity is limited by the energy gap between the TCLs. In this work, a new, to the best of our knowledge, approach to thermometric material design is proposed, which is based on temperature tuning of PL emission from the visible to the NIR region. We demonstrate a model ferroelectric phosphor, Eu3+-doped 0.94(Na1/2Bi1/2TiO3)-0.06(BaTiO3) (NBT-6BT), which, by virtue of the contrasting effects of temperature on PL signals from the host and Eu3+ intraband transitions, can achieve a relative thermal sensitivity as high as 3.05% K-1. This model system provides a promising alternative route for developing self-referencing optical thermometers with high thermal sensitivity and good signal discriminability.

Electron microscopy of juvenile nasopharyngeal angiofibroma: clinical and histopathological correlates.

BACKGROUND: The histological and electron-microscopic (EM) characteristics of juvenile nasopharyngeal angiofibroma (JNA) have been described but no study has compared them with one another or with clinical features. The objective is to compare ultrastructural characteristics of JNA with clinical parameters. METHODS: This prospective study included histology of 21 samples of which only 13 underwent transmission-EM. Four clinical parameters (age, duration, epistaxis, recurrence), three radiological-staging, 13 histological and 15 EM characteristics were considered. A descriptive analysis for association of these characteristics and also with clinical parameters was attempted. Furthermore statistical analysis of clinical and radiological categories with respect to frequencies of ultrastructural characteristics was also undertaken. RESULTS: Dense-intranuclear-inclusions (DNI) and peripheral-nuclear-irregularities were universally encountered while other very prominent features were nuclear-blebs-and-pockets, myoid-features, thin-vessel-wall (TnVW), irregular-vascular-contour (IVC) and fibrous-stroma (FS). Statistical significance was obtained between recurrence with histology (p = 0.04) and Fisch staging with EM (p = 0.001). While muscle-in-vessel-wall, thick-vessel-wall, mast-cells, stellate-stromal-cells and cellular-stroma predominated in recurrent cases, the upfront disease showed predominance of scar-like-stroma, fusiform-stromal-cells, IVC, TnVW, FS, organised-collagen-bundles and less-cellular-stroma. A very unique Rod-like-structures were appreciated in the cytoplasm of the fibroblast for the first time. CONCLUSIONS: While histological parameters of recurrence need further validation, a larger sample may better define histopathological surrogate for predicting intracellular dynamics that may further correlate with underlying cellular stresses. Hence an 'ultrastructural staging' may better customise treatment protocol and prognosis. Furthermore 'characteristic' unique rods need to be further investigated along with validation of viral aetiology for DNI.

Olfaction in Juvenile Nasopharyngeal Angiofibroma: The first study.

BACKGROUND: To study the pattern of olfactory dysfunction/recovery in juvenile nasopharyngeal angiofibroma (JNA). METHODS: Olfactory assessment was undertaken in 30 patients (category1) both pre- & post-operatively and in another 18 (category 2) only postoperative. All patients underwent transpalatal excision and variables of interest included age, radiological stage/parameters & tumor size. RESULTS: Objective olfactory dysfunction was seen in 60% while involvement of olfactory strip was suggested in 50%. Despite some marginal trends only noted between size/age with change of olfaction, Pearson's correlation test did not reveal any significance amongst multiple variables. However a better recovery of olfaction following surgery was evident in Category-2 where Chi-Square test (p < 0.05) significantly revealed this to be a function of postoperative duration. This regenerative course in JNA suggests an optimum period of 4 years for full recovery after surgery. CONCLUSION: In this first study of olfaction in JNA many new trends have been appreciated. In general, deteriorations of olfaction were seen due to 'vascular-concussion' effect in early postoperative phase where post-surgical clearance of airway showed minimal effect in terms of improvement. The hypervascularity of olfactory epithelium with possible hormonal effects may be responsible for the unique pattern of olfactory function and recovery in JNA.

Molecular interactions in juvenile nasopharyngeal angiofibroma: preliminary signature and relevant review.

BACKGROUND: The molecular profile of juvenile nasopharyngeal angiofibroma (JNA) is extremely variable. In absence of established molecular signature the molecular targeting seems difficult for this heterogeneous disease. To establish a basic molecular signature, this paper analyses the interaction of 7 markers according to their ranks as per the decreasing scale of molecular expression. MATERIALS AND METHODS: Fourteen samples of JNA were obtained following surgical excision and mRNA expressions were established through real-time polymerase chain reaction (RT-PCR) for vasculoendothelial growth factor (VEGF), fibroblastic growth factor (FGF), c-Kit, c-myc, Ras, platelet-derived growth factor (PDGF) and tumor suppressor gene p53. Nasal polyp was taken as control. The quantitative expressions for every marker were ranked on a decreasing scale and were compared by Spearman's rank correlation test to define the statistically significant interaction. An attempt was also made to overview the basic clinical parameters (age, duration of symptoms, radiological staging, intraoperative haemorrhage and tumor-volume/weight) associated with enhanced molecular expressions for every marker. RESULTS: Five significant molecular interactions were identified on the basis of rank-correlation: (1) FGF/VEGF (p < 0.01); (2) Ras/FGF (p < 0.01); (3) Ras/VEGF (p < 0.001), (4) FGF/c-Kit (p < 0.05); (5) c-Myc/p53 (p < 0.05). These basic 'molecular signatures' suggested a preliminary 'molecular classification'. The implication of the interactions between FGF, VEGF and Ras were the most outstanding observation that not only revealed a direct relationship but were also consistent with the clinical behaviour. In addition, a non-significant interaction was identified with c-Myc/PDGF and also an inverse relationship between FGF/c-Kit. CONCLUSIONS: FGF, VEGF, and Ras being significantly interrelated seemed to be the 'most soft' molecular targets for JNA. The other targets observed included FGF/c-Kit and c-Myc/p53 interactions that seemed equally important but only after VEGF/FGF/Ras complex per se. These preliminary signatures are likely to provide a background for further expansion of the molecular classification of JNA.

Clinical correlation of molecular (VEGF, FGF, PDGF, c-Myc, c-Kit, Ras, p53) expression in juvenile nasopharyngeal angiofibroma.

BACKGROUND: A molecular surrogate may exist for the clinical behaviour of juvenile nasopharyngeal angiofibroma (JNA). METHODS: In 9-14 cases, a 'correlation' of clinical behaviour with molecular expression (m-RNA expression through RT-PCR) of VEGF, FGF, PDGF, Ras, c-Myc, c-Kit and p53 was undertaken. RESULTS: A comparison of the two extremes of expressions characterized some specific clinical phenotypes for every marker except c-Myc. A higher FGF was associated with post-adolescent presentation, smaller tumour size, enhanced haemorrhage and recurrence. A higher c-Kit was associated with adolescents, rapid growth, skull base involvement and recurrence. Enhanced Ras was associated with post-adolescence, smaller tumour size, skull base involvement and recurrence. Enhanced p53 and PDGF were associated with adolescents, early presentation and rapid progression. Higher VEGF expression was associated with skull base involvement and enhanced haemorrhage. CONCLUSION: This study is currently the only evidence revealing a clinical molecular association in JNA and larger multicentric studies need to be performed to show a statistical significance.

Time trends in recurrence of juvenile nasopharyngeal angiofibroma: Experience of the past 4 decades.

BACKGROUND: An analysis of time distribution of juvenile nasopharyngeal angiofibroma (JNA) from the last 4 decades is presented. METHODS: Sixty recurrences were analyzed as per actuarial survival. SPSS software was used to generate Kaplan-Meier (KM) curves and time distributions were compared by Log-rank, Breslow and Tarone-Ware test. RESULTS: The overall recurrence rate was 17.59%. Majority underwent open transpalatal approach(es) without embolization. The probability of detecting a recurrence was 95% in first 24months and comparison of KM curves of 4 different time periods was not significant. CONCLUSION: This is the first and largest series to address the time-distribution. The required follow up period is 2years. Our recurrence is just half of the largest series (reported so far) suggesting the superiority of transpalatal techniques. The similarity of curves suggests less likelihood for recent technical advances to influence the recurrence that as per our hypothesis is more likely to reflect tumor biology per se.

Human Papilloma virus in Juvenile Nasopharyngeal Angiofibroma: possible recent trend.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) has witnessed a four-fold increase in the incidence at our facility in the current decade as compared to the 1980s. With high global incidence of human pappilloma virus (HPV) related oropharyngeal cancer in India, we hypothesize its implication in JNA as it has not yet been reported. METHODS: Clinico-Surgical variables of 6 patients of JNA were included for correlation and their tissue samples were subjected to western blotting (WB), polymerase chain reaction and immunoflorescence to demonstrate a definite association with HPV. In addition 6 control samples (adenoids) underwent WB analysis. OBSERVATIONS: A universal presence of HPV with JNA is novel 'discovery' and has suggested a possibility of a definite association. Only a single case suggested weak infection. None of the controls suggested infection, thus ruling out the presence of HPV in nasopharynx of normal population. INTERPRETATION: With the dawn of this definite association, no specific conclusions can yet be drawn but a whole plethora of questions have emerged with our novel 'discovery'.

True bilateral nasopharyngeal angiofibroma: report and review.

This report describes the third case of a true bilateral Juvenile nasopharyngeal angiofibroma (JNA), i.e. two separate JNA arising from both sides simultaneously. The associated multiple recurrences in such a case have not yet been reported. A 21-year-man underwent transpalatal excision and recurred twice. The last 'neo-occurrence' encountered after 2 years was at a different site and was subsequently managed by post-embolization endoscopic resection. A complete report of its clinico-radiological features and management outcome is discussed.

Nitrogen-Enriched Biguanidine-Functionalized Cobalt Ferrite Nanoparticles as a Heterogeneous Base Catalyst for Knoevenagel Condensation under Solvent-Free Conditions.

Designing efficient, economical heterogeneous catalysts for the Knoevenagel condensation reaction is highly significant owing to the importance of reaction products in industries as well as pharmaceutics. Herein, we have designed and synthesized biguanidine-functionalized basic magnetically retrievable cobalt ferrite nanoparticles (CFNPs) for the synthesis of Knoevenagel condensation products using benzaldehydes and active methylene compounds (malononitrile/ethyl cyanoacetate/cyanoacetamide). Several advanced techniques, such as Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and vibration sample magnetometry (VSM), were utilized to precisely characterize the catalyst. The robust features of the current approach involve outstanding catalytic performance, solvent-free reaction conditions, ease of catalyst retrievability, easy workup procedure, large substrate tolerance, high turnover frequency (TOF) values (up to 486.88 h-1), values of green chemistry metrics such as E-factor (0.15), reaction mass efficiency (RME) value (87.07%), carbon efficiency (93.4%), and atom economy (AE) value (88.10%) close to their ideal values, and recyclability up to eight runs without a considerable reduction in activity, boosting the appeal of this approach from a commercial and ecological point of view.

Modified universal new-born hearing screening: Practical approach for developing world (Georgean experience).

AIM: Analysis of newborn hearing screening (NBS) outcomes and proposing a modified strategy for better performance of NBS in developing world. DESIGN: Descriptive (retrospective and prospective) study. METHODS: A total of 8412 newborns/neonates were subjected to risk factor assessment followed by a set of subjective (behavioral audiometry: BoA) and objective (OAE: otoacoustic emissions, ABR: auditory brainstem-evoked responses) hearing-screening in different combinations. DPOAE (primary objective tool) was undertaken in 2565 cases. Predictive value of risk factors on deafness was statistically analysed along with affectivity of objective, subjective and questionnaire-based screening tools. RESULTS: Amongst 8412 babies, 45.5% were 'at risk' (major 36.41%, minor 9.17%). The OAE was abnormal in 299 cases (11.6% of 2565 & 3.5% in 8412). The abnormal OAE rate in prospective cases was 3.5% while in retrospective cases that underwent initial screening with BoA was 41%. A significant correlation was seen with consanguinity, high blood pressure, NICU stay>5 days, low birth weight, neonatal jaundice, delayed birth cry, pre-mature status, birth asphyxia and maternal excessive vomiting, while regression models of OAE outcome (sensitivity 99%, accuracy 89%) revealed highest predictive value for the initial 3 factors. BoA-screening revealed a sensitivity of 72.6%, and negative predictive value of 42.4%. Also a perfect correlation was evident between OAE-ABR, OAE-BoA and ABR-BoA. CONCLUSION: A subjective NBS screening through questionnaire-based-risk-assessment and modified-BoA followed by selective referral for objective assessment is more practical and focussed approach for poor resourced countries that is likely to screen a larger population.

Microvessel density (Cluster of Differentiation-34 & Vascular Endothelial growth factor) in Nasopharyngeal Angiofibroma: Clinical correlation.

BACKGROUND: The literature on microvessel density (MVD) signifying neoangiogenesis/tumour-activity in juvenile nasopharyngeal angiofibroma (JNA) is limited. Accordingly, this study evaluates and correlates MVD characteristics with clinical parameters/aggressiveness/recurrence. MATERIAL AND METHODS: Sixty-two paraffin blocks of JNA were studied histopathologically and MVD was assessed following immunohistochemistry using VEGF and CD34 as vascular markers. A clinical correlation of MVD was undertaken in 43 cases. RESULTS: MVD scores of VEGF and CD34 showed strong inter-correlation. The 'age', 'duration of disease' and 'haemoglobin%' were the only clinical parameters that revealed significance with MVD. Significantly higher MVD scores were appreciated in recurrent cases as well as some other clinical differences from upfront cases. CONCLUSION: This is the first study of MVD with CD34 and VEGF simultaneously depicting clinical correlation. The strong correlation, supports a prognostic role of MVD scores in JNA and this can be better established in a larger multicentre study involving comprehensive examination of tumour dimensions.

Augmenting Community Diagnosis of Safe Ear Disease Through Tele-Myringoscopy with Borescope Using AIML Tecniques.

This study utilized AIML (artificial intelligence & machine learning) techniques to analyze 115 images of central perforation of tympanic membrane obtained from Telemyringoscopy through Borescope in order to establish a facilitation-model for the community ear diagnosis. The Modified VGG19 with batch normalization revealed the highest training accuracy of 85 as compared to other CNN techniques. The training accuracy started to saturate around mid-70% and the Test accuracy was around 50%. Although AIML did not reveal a high predictive value, its potential based on our observations cannot be underestimated considering many limitations (sample size, image-quality, associated pathologies, illumination-factor) in this study. Such limitations if resolved may revolutionize community ear care through a better cost effective tele-myringoscopy with innovations in AIML/ telemedicine.

A Clinicopathological Study of OSMF to Evaluate the Response After Treatment with Intralesional Steroid Versus Intralesional Steroid Plus Hyaluronidase.

Oral submucous fibrosis (OSMF) is a chronic debilitating and a well-recognized potentially malignant condition of the oral cavity, sometimes involving oropharynx associated with trismus and burning sensation. Apart from medical management and counselling, local injection of hyaluronidase mixed with triamcinolone acetonide has been used at our centre for the last 20 years with satisfactory clinical results and without any significant side effects. The problem with the treatment was that the doses and duration of treatment has not been standardized. Therefore, in this study, authors aim to evaluate and compare the efficacy of Triamcinolone alone versus Triamcinolone acetonide plus Hyaluronidase at weekly interval and improvement in Clinical and Histopathological staging of disease after 6 weeks of treatment. This study was conducted in Department of Otorhinolaryngology & Head Neck Surgery, with a total sample of 80 participants divided into two Groups, group A received Inj. Triamcinolone acetonide and group B received Inj. Triamcinolone Acetonide and Hyaluronidase 1500 IU at weekly interval. Pre-treatment and post-treatment clinical and histopathological profile of the patients were recorded and analyzed using SPSS 16 software. According to pre-treatment status, the proportion of clinical grades I, II and III were found in proportion 12.5%, 18.8% and 15.0% respectively. No significant difference was found in proportion of various grades between the groups (p = 0.388). At post treatment, the grading was reduced with changed proportion of grades I, II and III cases as 33.8%, 41.3% and 7.5% respectively. There was no significant difference in proportion of various grades between the groups (p = 0.681). Further, the intragroup comparison showed significant improvement Pre to post in group A (p = 0.002), Group B (p < 0.001) and overall, as well (p < 0.001). The inj. Triamcinolone acetonide and Inj. Hyaluronidase showed a better improvement on post treatment histopathological grading although the difference between the two groups was not significant statistically.

Compositional induced structural phase transitions in (1 - x)(K0.5Na0.5)NbO3-x(Ba0.5Sr0.5)TiO3 ferroelectric solid solutions.

Ferroelectric materials exhibiting switchable and spontaneous polarization have strong potential to be utilized in various novel electronic devices. Solid solutions of different perovskite structures induce the coexistence of various phases and enhance the physical functionalities around the phase coexistence region. The construction of phase diagrams is important as they describe the material properties, which are linked to the underpinning physics determining the system. Here we present the phase diagram of (K0.5Na0.5NbO3)-(Ba0.5Sr0.5TiO3) (KNN-BST) system as a function of composition and their associated physical properties. Lead-free (1 - x)KNN-xBST (0 ≤ x ≤ 0.3) solid solution ceramics were synthesized by conventional solid-state reaction technique. The X-ray diffraction and Raman spectroscopic studies indicate composition-dependent structural phase transitions from an orthorhombic phase for x = 0 to orthorhombic + tetragonal dual-phase (for 0.025 ≤ x ≤ 0.15), then a tetragonal + cubic dual-phase (x = 0.2) and finally a cubic single phase for x ≥ 0.25 at room temperature (RT). Among these, the orthorhombic + tetragonal dual-phase system shows an enhanced value of the dielectric constant at room temperature. The phase transition temperatures, orthorhombic to tetragonal (TO-T) and tetragonal to cubic (TC), decrease with the increase in BST concentrations. The ferroelectric studies show a decrease of both 2Pr and EC values with a rise in BST concentration and x = 0.025 showed a maximum piezoelectric coefficient.

Interventions for atrophic rhinitis.

BACKGROUND: Atrophic rhinitis is a chronic nasal pathology characterised by the formation of thick dry crusts in a roomy nasal cavity, which has resulted from progressive atrophy of the nasal mucosa and underlying bone. The common symptoms may include foetor, ozaena, crusting/nasal obstruction, epistaxis, anosmia/cacosmia and secondary infection with maggot infestation. Its prevalence varies in different regions of the world and it is common in tropical countries. The condition is predominantly seen in young and middle-aged adults, especially females, with a racial preference amongst Asians, Hispanics and African-Americans. A wide variety of treatment modalities have been described in the literature, however the mainstay of treatment is conservative (for example, nasal irrigation and douches; nose drops (e.g. glucose-glycerine, liquid paraffin); antibiotics and antimicrobials; vasodilators and prostheses). Surgical treatment aims to decrease the size of the nasal cavities, promote regeneration of normal mucosa, increase lubrication of dry nasal mucosa and improve the vascularity of the nasal cavities. OBJECTIVES: To assess the effectiveness of interventions for atrophic rhinitis. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 28 March 2011. SELECTION CRITERIA: Randomised controlled trials (RCTs) studying any treatment or combination of treatments in patients with atrophic rhinitis. We excluded studies with follow-up of less than five months following treatment/intervention. DATA COLLECTION AND ANALYSIS: Three review authors abstracted and assessed studies. We tabulated and then compared the responses of the review authors separately for the individual studies. MAIN RESULTS: No studies met the inclusion criteria for the review. We identified one RCT comparing oral rifampicin plus nasal wash versus nasal submucosal placentrex injection plus nasal wash versus a control group (nasal wash) but had to exclude this study due to inadequate length of follow-up. A further RCT comparing Young's operation with nasal lubrication for primary atropic rhinitis is underway. AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials concerning the long-term benefits or risks of different treatment modalities for atrophic rhinitis. Further high-quality research into this chronic disease, with a longer follow-up period, is therefore required to establish this conclusively. 

Single Stage Conservative Surgery to Avoid Recurrence in Combined Laryngocele: Important Modifications.

Laryngocele is very uncommon and no consensus regarding its surgical management is yet established. While traditional external approach is still being recommended some suggest a better microlaryngoscopic management assisted by CO2 laser that has gained popularity. Recurrence is better known with conservative surgery but this paper presents a modified single stage endolaryngeal technique for combined laryngoceles to overcome the same. The salient features are (1) A comparatively larger operculum is created and all the visible mucosa is excised; (2) the base of residual postoperative cavity is moistened with cotton soaked with concentrated carbolic acid for 1 min and (3) the residual 'charred' base with intermittent oozing is packed with single layer of surgicel. The reader is further encouraged to see surgical video of entire procedure.

Functional Transnasal Endoscopic Conjunctivorhinostomy.

The various surgical options for lacrimal tract reconstruction include canaliculodacryocystorhinostomy; fundal transposition; Conjunctivodacrocystorhinostomy with Jones tube; and in extreme cases conjunctivo-rhinostomy (CR) for total lacrimal bypass. The first three require partial lacrimal tract presence/ integrity while CR is indicated when the canaliculi and/or sac are nonfunctional. This report describes a novel technique of minimally invasive CR through a predominantly endoscopic endonasal approach and further discusses its advantages over other established techniques.

Enhancing India's Health Care during COVID Era: Role of Artificial Intelligence and Algorithms.

Computerization of health care is the only model to sustain safe health care in this COVID era particularly in overpopulated nations with limited health care providers/systems like India. Accordingly incorporation of computer-based algorithms and artificial intelligence seems very robust and practical models to assist the physician. The advantages of Computerized algorithms to facilitate better screening, diagnosis or follow-up and use of Artificial Intelligence (AI) to aid in medical diagnosis are discussed.

Least Expensive Facial Mask Against Corona Virus for Short Airway Procedures Generating Aerosol.

With ongoing Corona-pandemic, the quality of personal protection equipment (PPE) across the globe is creating controversy. This article presents a novel design of a facial mask that seems suitable to deal with short airway procedures protecting the surgeon from aerosol infection. The concept, design advantages and limitations are discussed. In absence of good quality PPEs this is an excellent option to deal with airway emergencies.