Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study.

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

Evaluation of Normal Morphology of Mandibular Condyle: A Radiographic Survey.

OBJECTIVES: The temporomandibular joint (TMJ) is a complex, highly specialized joint. Along with the teeth, these joints are considered to be a "tri-joint complex." Mandibular condyle morphology is characterized by a rounded bone projection with an upper biconvex and oval surface in axial plane. Anatomical knowledge of the TMJ is one of the basic foundations of clinical practice, allowing the understanding of TMJ pathologies and fabrication of condylar prostheses. The cross-sectional descriptive study was undertaken to evaluate normal variation in the condylar morphology on radiographs in persons without TMJ symptomatology and its relation to age, gender, dentition status, chewing habits, parafunctional habits, history of orthodontic treatment, and denture wearing was assessed. MATERIAL AND METHODS: A total of 350 subjects without TMJ symptomatology included in the study were further grouped by age, gender, dentition status, chewing habits, parafunctional habits, history of orthodontic treatment, and denture wearing history. Panoramic radiograph was taken for the assessment of condylar morphology. RESULTS: A significant association between dentition status and bilaterally similar condylar morphology was noticed. Bilaterally similar condyles were seen in 81.4% of subjects. Round-shaped condyles were seen in 176 (62%) persons. Loss of bilateral occlusion tends to alter the condylar morphology. Association between normal chewing habits and bilaterally similar condyle shapes was significant. CONCLUSION: The study describes the normal morphology of mandibular condyles in a population attending the tertiary dental care center, Kozhikode. The dentition status and chewing habits of individuals had a significant role in determining condylar morphology.

Plasma-Cell Gingivitis a Challenge to the Oral Physician.

Plasma-cell gingivitis (PCG) is an uncommon inflammatory condition of idiopathic etiology. PCG is a rare condition, appearing as erythema (redness) and edema (swelling) of the attached gingiva. The diagnosis of PCG is based on arrant history taking, clinical examination, and appropriate diagnostic tests. Here, we are presenting a case of PCG in a 12-year-old boy, its management and treatment outcome after 3 years of regular follow-up in tertiary health-care center in North Kerala.

Conversion of solid waste to activated carbon to improve landfill sustainability.

Heterogeneous composite wastes from landfills were evaluated as precursors for the generation of activated carbon (AC). A single-step chemical activation process was applied involving irradiation with microwave energy and impregnation with KOH. The average percentage yield of AC from active landfill precursor was higher than that from closed landfill for all depths sampled. Increase in impregnation ratio and irradiation power decreased the average percentage yield for both landfill precursors (active: 38.1 to 33.1%; closed: 42.1 to 33.3%). The optimum pH range for adsorption of methylene blue was pH 6-7, while adsorption increased with increase in temperature over the range 30 to 50°C. Carbonyl and hydroxyl groups were the major functional groups on the surface of AC. The properties of the AC are potentially suitable for the removal of cationic dyes and pollutants. AC generated from the landfill composite was comparable to that from other biomass being managed through AC generation. This is the first report to demonstrate the possible reuse of landfill composite as AC. The reuse option of landfill composite could provide a means of sustainable management of landfilled municipal waste.

Pre-discharge and early post-discharge troponin elevation among patients hospitalized for heart failure with reduced ejection fraction: findings from the ASTRONAUT trial.

AIMS: Troponin levels are commonly elevated among patients hospitalized for heart failure (HF), but the prevalence and prognostic significance of early post-discharge troponin elevation are unclear. This study sought to describe the frequency and prognostic value of pre-discharge and post-discharge troponin elevation, including persistent troponin elevation from the inpatient to outpatient settings. METHODS AND RESULTS: The ASTRONAUT trial (NCT00894387; http://www.clinicaltrials.gov) enrolled hospitalized HF patients with ejection fraction ≤40% and measured troponin I prior to discharge (i.e. study baseline) and at 1-month follow-up in a core laboratory (elevation defined as >0.04 ng/mL). This analysis included 1469 (91.0%) patients with pre-discharge troponin data. Overall, 41.5% and 29.9% of patients had elevated pre-discharge [median: 0.09 ng/mL; interquartile range (IQR): 0.06-0.19 ng/mL] and 1-month (median: 0.09 ng/mL; IQR: 0.06-0.15 ng/mL) troponin levels, respectively. Among patients with pre-discharge troponin elevation, 60.4% had persistent elevation at 1 month. After adjustment, pre-discharge troponin elevation was not associated with 12-month clinical outcomes. In contrast, 1-month troponin elevation was independently predictive of increased all-cause mortality [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.18-2.13] and cardiovascular mortality or HF hospitalization (HR 1.28, 95% CI 1.03-1.58) at 12 months. Associations between 1-month troponin elevation and outcomes were similar among patients with newly elevated (i.e. normal pre-discharge) and persistently elevated levels (interaction P ≥ 0.16). The prognostic value of 1-month troponin elevation for 12-month mortality was driven by a pronounced association among patients with coronary artery disease (interaction P = 0.009). CONCLUSIONS: In this hospitalized HF population, troponin I elevation was common during index hospitalization and at 1-month follow-up. Elevated troponin I level at 1 month, but not pre-discharge, was independently predictive of increased clinical events at 12 months. Early post-discharge troponin I measurement may offer a practical means of risk stratification and should be investigated as a therapeutic target.

Multivariate analysis of the effects of age, particle size and landfill depth on heavy metals pollution content of closed and active landfill precursors.

Multivariate analysis of a heavy metal pollution survey of closed and active landfill precursors was carried out in order to compare environmental risk levels in relation to age, particle size and depth of the precursors. Landfill precursors (77) were collected and analyzed for 15 USEPA toxic heavy metals using ICP-MS. Heavy metals concentrations in closed landfill precursors were significantly higher than those in the active landfill for 11 of 15 heavy metals investigated (closed landfill order: Fe > Al > Mn > Cu > Pb > Ba > Co > Cr > Ni > Cd > As > Se > Ti). Cluster analysis and correlation studies indicated the distribution of the metals was more influenced by landfill precursor size than by depth of the sample. Principal component analysis (PCA) showed that 10 of 15 of heavy metals of both landfill precursors were from similar anthropogenic sources. Heavy metals pollution indices (Igeo > 5, EF > 40 and CF > 7) of both active and closed landfill precursors exceeded limits in the order of Zn > Cd > Pb > Cu > Ag, indicating a major potential health risk influenced by age and particle size of precursor. Zn, Cd, Cu and Pb of both landfill precursors exceeded the USEPA set standard for assessment of human health risk for each of the metals (1 × 10-4 to 1 × 10-3). This study highlights the need for the integration of a clean-up process for precursors from both types of landfill to reduce possible environmental pollution during a reuse process.

Comparative Evaluation of Two Different Flap Designs and Postoperative Outcome in the Surgical Removal of Impacted Mandibular Third Molar.

AIM: The aim of this study is to compare triangular and envelope flap designs and the postoperative outcome in the surgical removal of impacted mandibular third molar. MATERIALS AND METHODS: A total of 50 participants were assessed clinically and were divided randomly into two groups. Group I (participants operated by triangular flap) and group II (participants operated by envelope flap), with 25 participants each between the age group of 20 and 30 years. Patient satisfaction was assessed subjectively using a graded scale from very satisfied to very unsatisfied. The degree of pain was recorded for 7 days with reference to predefined values on visual analog scale (VAS). Trismus was evaluated on the day 3, day 5, and day 7 of the postoperative period in millimeters. Quantitative data were analyzed by unpaired t-test and qualitative data were by Fischer's exact test. RESULTS: The mean overall age is 25.5 years. There was no statistically significant difference between the study groups with respect to age. There was no significant association between the patient satisfaction and flap type (p = 0.684). A significant difference between the study groups on 4th, 5th, and 6th days with respect to pain was observed, wherein fewer subjects operated with triangular flap reported pain. A highly significant difference in mouth opening was observed, with triangular flap group participants having a higher mouth opening than envelope flap subjects on day 7. CONCLUSION: The present study indicated that participants operated by triangular flap had a better mouth opening postoperatively compared with envelope flap participants, whereas there were no significant differences in patient satisfaction and pain scores at the end of the 7th day after third molar surgery. CLINICAL SIGNIFICANCE: Flap design is a significant factor in the surgical removal of impacted third molar, and it influences the severity of complications. Furthermore, it is important for allowing optimal visibility and access to the impacted tooth and also for subsequent healing of the surgically created defect.

Experimental Probing and Molecular Dynamics Simulation of the Molecular Recognition of DNA Duplexes by the Flavonoid Luteolin.

Luteolin (C15H10O6) is an important flavonoid found in many fruits, plants, medicinal herbs, and vegetables exhibiting many pharmacological properties. The anticancer, antitumor, antioxidant, and anti-inflammatory activities of luteolin have been reported. The pharmacological action of small molecules is dependent upon its interaction with biomacromolecules. The interactions of small molecules with DNA play a major role in the transcription and translation process. In this work, we explored the energetic profile of DNA-luteolin interaction by isothermal titration calorimetry (ITC). The effect of temperature and salt concentration on DNA binding was examined by UV-Vis method. The mode of interaction was further probed by UV melting temperature analysis and differential scanning calorimetry. An atomic level insight on the recognition of luteolin with DNA was achieved by employing molecular dynamics (MD) simulation on luteolin in complex with AT- and GC-rich DNA sequences. AMBER force field proves to be appropriate in providing an understanding on the binding mode and specificity of luteolin with duplex DNA. MD results suggest a minor groove binding of luteolin with DNA and the binding free energy obtained is in agreement with the experimental results.

Use of Cone-Beam Computed Tomography in the Diagnosis and Treatment of an Unusual Canine Abnormality.

Diagnosis and treatment planning are important for successful endodontic treatment. We report a 24-year old male who presented to the Government Dental College in Kozhikode, Kerala, India, in 2015 with pain in his right upper canine. A digital periapical radiograph indicated the presence of a supernumerary tooth superimposing the root of the canine. However, cone-beam computed tomography (CBCT) confirmed that the supernumerary tooth was an illusion and that the canine root had a sharp invagination involving the labial and pulpal dentin surfaces, with evidence of periapical bone destruction. A blunt resection was performed at the level of the invagination and the resected end was filled with a dentin substitute. At a one-year follow-up, the patient was asymptomatic and the periapical region appeared to be healing well. This report highlights the importance of CBCT in visualising abnormal canine morphology, thus allowing appropriate endodontic treatment.

Influence of atrial fibrillation on post-discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the ASTRONAUT trial.

AIMS: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear. METHODS AND RESULTS: This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non-AFF patients, AFF patients experienced greater reduction from baseline in log-transformed NT-proBNP (interaction P < 0.001), but this difference was not significant after adjustment (interaction P = 0.726). The ability of aliskiren to lower NT-proBNP during follow-up differed by AFF status (interaction P = 0.001), with aliskiren lowering NT-proBNP more than placebo among non-AFF patients only. After adjustment, baseline AFF was not associated with mortality or HF hospitalization at 12 months (all P ≥ 0.152). CONCLUSION: In this hospitalized HF cohort, AFF status did not influence post-discharge NT-proBNP trajectory or clinical outcomes after adjustment for patient characteristics. Aliskiren lowered follow-up NT-proBNP levels in patients without AFF, but had no influence among patients with AFF. This study generates the hypothesis that the ability of a HF trial to meet an NT-proBNP defined endpoint may be influenced by the prevalence of AFF in the population. Because aliskiren did not improve outcomes in patients without AFF, this analysis suggests changes in NT-proBNP induced by investigational therapies may be dissociated from clinical effects.

A comprehensive approach to ascertain the binding mode of curcumin with DNA.

Curcumin is a natural phytochemical from the rhizoma of Curcuma longa, the popular Indian spice that exhibits a wide range of pharmacological properties like antioxidant, anticancer, anti-inflammatory, antitumor, and antiviral activities. In the published literatures we can see different studies and arguments on the interaction of curcumin with DNA. The intercalative binding, groove binding and no binding of curcumin with DNA were reported. In this context, we conducted a detailed study to understand the mechanism of recognition of dimethylsulfoxide-solubilized curcumin by DNA. The interaction of curcumin with calf thymus DNA (ctDNA) was confirmed by agarose gel electrophoresis. The nature of binding and energetics of interaction were studied by Isothermal Titration Calorimetry (ITC), Differential Scanning Calorimetry (DSC), UV-visible, fluorescence and melting temperature (Tm) analysis. The experimental data were compared with molecular modeling studies. Our investigation confirmed that dimethylsulfoxide-solubilized curcumin binds in the minor groove of the ctDNA without causing significant structural alteration to the DNA.

Changes in Dyspnea Status During Hospitalization and Postdischarge Health-Related Quality of Life in Patients Hospitalized for Heart Failure: Findings From the EVEREST Trial.

BACKGROUND: Dyspnea is the most common symptom among hospitalized patients with heart failure and represents a therapeutic target. However, the association between short-term dyspnea relief and postdischarge clinical outcomes and health-related quality of life (HRQOL) remains uncertain. METHODS AND RESULTS: A post hoc analysis was performed of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which enrolled 4133 patients within 48 hours of admission for heart failure with an ejection fraction ≤40%. Physician-assessed dyspnea was recorded on a daily basis from baseline until discharge or day 7 as none, seldom, frequent, or continuous. Patient-reported dyspnea was measured using a 7-point Likert scale, and patients experiencing moderate or marked dyspnea improvement on day 1 were classified as early responders. The Kansas City Cardiomyopathy Questionnaire summary score, which ranges from 0 to 100, was collected postdischarge at week 1. The primary outcome was unfavorable HRQOL, defined a priori as a Kansas City Cardiomyopathy Questionnaire score <45. Secondary outcomes included 30-day all-cause mortality, and all-cause and cause-specific hospitalizations. The final analytic cohort included 1567 patients discharged alive with complete HRQOL data. Patients were 66.0±12.7 years old and had a mean ejection fraction of 25±8%. Physician-assessed dyspnea was rated as frequent or continuous in 1399 patients (90%) at baseline, which decreased to 250 patients (16%) by discharge, whereas patient-reported early dyspnea relief was reported by 610 patients (40%). The median Kansas City Cardiomyopathy Questionnaire score at week 1 was 50 (35, 65). All-cause mortality was 3.0%, and all-cause hospitalization was 20.5% within 30 days of discharge. Physician-assessed and patient-reported dyspnea was not independently associated with HRQOL, all-cause mortality, or all-cause or cause-specific hospitalization. CONCLUSIONS: In-hospital physician-assessed, and patient-reported dyspnea was not independently associated with postdischarge HRQOL, survival, or readmissions. Although dyspnea relief remains a goal of therapy for hospitalized patients with heart failure with reduced ejection fraction, this measure may not be a reliable surrogate for long-term patient-centered or hard clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00071331.

Serum Osmolality and Postdischarge Outcomes After Hospitalization for Heart Failure.

Serum osmolality may fluctuate with neurohormonal activation and in response to certain therapeutics in patients with heart failure (HF). The clinical relevance of osmolality in patients with HF has not been defined. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan trial, we analyzed serum osmolality measured at discharge in 3,744 patients hospitalized for HF and reduced ejection fraction (EF ≤40%). Median follow-up was 9.9 months. The association between discharge osmolality and all-cause mortality (ACM) and composite cardiovascular mortality or HF hospitalization was nonlinear; and thus, patients were divided into low (≤284), normal (285 to 300), and high (≥300 mOsm/kg) osmolality. Median serum osmolality at discharge was 297 (290 to 304) mOsm/kg. Patients in the low osmolality group (n = 454,12.1%) were more likely to be younger, men, have lower rates of hypertension, coronary artery disease, chronic kidney disease, diabetes, and have lower serum sodium, creatinine, systolic blood pressure, and EF (all p <0.001). Low discharge osmolality was associated with higher ACM (low 29.3%; normal 23.6%; high 25.2%; p = 0.04) and the composite endpoint (low 45.6%; normal 39.3%; high 41.8%; p = 0.04). After risk adjustment, a 15 mOsm/kg decrease in osmolality was predictive of higher ACM (hazard ratio 1.61, 95% CI 1.19 to 2.17) and the composite endpoint (hazard ratio 1.37, 95% CI 1.06 to 1.75) in the low osmolality group. These associations were not seen in patients with normal or high osmolality. Interaction analyses for tolvaptan treatment were nonsignificant (p >0.4). In conclusion, low discharge serum osmolality was independently predictive of worse postdischarge mortality and readmission. Further study is required to clarify the clinical utility of serum osmolality in hospitalized patients with HF.

Conformational features of benzo-homologated yDNA duplexes by molecular dynamics simulation.

yDNA is a base-modified nucleic acid duplex containing size-expanded nucleobases. Base-modified nucleic acids could expand the genetic alphabet and thereby enhance the functional potential of DNA. Unrestrained 100 ns MD simulations were performed in explicit solvent on the yDNA NMR sequence [5'(yA T yA yA T yA T T yA T)2 ] and two modeled yDNA duplexes, [5'(yC yC G yC yC G G yC G G)2 ] and [(yT5' G yT A yC yG C yA yG T3')•(yA5' C T C yG C G yT A yC A3')]. The force field parameters for the yDNA bases were derived in consistent with the well-established AMBER force field. Our results show that DNA backbone can withstand the stretched size of the bases retaining the Watson-Crick base pairing in the duplexes. The duplexes retained their double helical structure throughout the simulations accommodating the strain due to expanded bases in the backbone torsion angles, sugar pucker and helical parameters. The effect of the benzo-expansion is clearly reflected in the extended C1'-C1' distances and enlarged groove widths. The size expanded base modification leads to reduction in base pair twist resulting in larger overlapping area between the stacked bases, enhancing inter and intra strand stacking interactions in yDNA in comparison with BDNA. This geometry could favour enhanced interactions with the groove binders and DNA binding proteins., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 55-64, 2016.

Energetics, Thermodynamics, and Molecular Recognition of Piperine with DNA.

Piperine, the bioactive phytochemical from black pepper (Piper nigrum L.), is a nontoxic natural compound exhibiting many physiological and pharmacological properties. They include antioxidant, anti-inflammatory, antimutagenic, antitumor, antiapoptotic, antigenotoxic, antiarthritic, antifungal, antimicrobial, antidepressant, anti-HBV, and gastro-protective activities. It also enhances the bioavailability of phytochemicals and drugs. The molecular mechanism of action of piperine with DNA has not yet been addressed, while its pharmacological activities have been reported. In this work we report for the first time the interaction of piperine molecule with DNA duplex. We have carried out UV-vis absorption and fluorescence spectroscopy to confirm the binding of piperine with calf thymus DNA (ctDNA). The energetics of interaction of piperine with ctDNA was monitored by isothermal titration calorimetry (ITC). Differential scanning calorimetry (DSC) and melting temperature (Tm) analysis were also performed, confirming a minor groove mode of binding of piperine with ctDNA. The binding free energy ΔG values obtained from molecular dynamics simulation studies agree well with ITC values and reveal a sequence dependent minor groove binding exhibiting a specificity toward AT rich sequences.

Relation of serum uric acid levels and outcomes among patients hospitalized for worsening heart failure with reduced ejection fraction (from the efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan trial).

We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) ≤40%, with specific focus on gender, race, and renal function based interactions. In 3,955 of 4,133 patients (96%) with baseline sUA data, clinical characteristics and outcomes were compared across sUA quartiles. The primary end points were all-cause mortality and a composite of cardiovascular mortality or heart failure hospitalization. Interaction analyses were performed for gender, race, and baseline renal function. Median follow-up was 9.9 months. Mean sUA was 9.1 ± 2.8 mg/dl and was higher in men than in women (9.3 ± 2.7 vs 8.7 ± 3.0 mg/dl, p <0.001) and in blacks than in whites (10.0 ± 2.7 vs 9.0 ± 2.8 mg/dl, p <0.001). Higher sUA was associated with lower systolic blood pressure and EF, higher natriuretic peptides, and more impaired renal function. After accounting for 24 baseline covariates, in patients with enrollment estimated glomerular filtration rate ≥30 ml/min/1.73 m(2), sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p <0.001) and the composite end point (hazard ratio 1.44, 95% confidence interval 1.26 to 1.64, p <0.001). However, in patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2), sUA was not related with either end point (both p >0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction.

Urinary excretion of arsenic following rice consumption.

Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) ∼40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis.