The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence

Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAF^V600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.Subject terms: CNS cancer, Metastasis, Melanoma, Tumour biomarkers, Cancer     

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

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Ultra-low-dose unenhanced chest CT: Prospective comparison of high kV/low mA versus low kV/high mA protocols

Purpose

To qualitatively and quantitatively compare unenhanced ultra-low-dose chest computed tomography (ULD-CT) acquired at 80 kVp and 135 kVp.

Dexamethasone mediated downregulation of PGC-1α and visfatin regulates testosterone synthesis and antioxidant system in mouse testis

Dexamethasone, a synthetic glucocorticoid has been used as an immunosuppressive and anti-inflammatory and affects reproduction. It has been suggested that testicular steroidogenesis involves PGC-1α and visfatin as key regulators. Previous studies have shown that dexamethasone down-regulates PGC-1α and visfatin expression in muscle and mammary epithelial cells respectively. However, the effect of dexamethasone on testicular visfatin and PGC-1α expressions has not been investigated. The aims of the present study were to investigate the effect of dexamethasone, on the expression of PGC-1α, visfatin and antioxidant enzymes activities in mouse testis. The results of the present study showed that dexamethasone treatment significantly decreased the expression of visfatin and PGC-1α in mice testis, along with significant decreased in testicular antioxidant enzymes activates. Further, dexamethasone treatment also significantly increased the testicular lipid peroxidation and decreased testosterone synthesis. The dexamethasone induced changes in PGC-1α and visfatin in the testis were significantly correlated with changes in serum testosterone concentrations and antioxidant enzymes activities. Thus, dexamethasone induced testicular toxicity may involve the PGC-1α and visfatin as important molecules to exhibit its effects.     

The effect on the composition of subgingival plaque of a simplified oral hygiene system including pulsating jet subgingival irrigation

The aim of this study was to investigate the effect on subgingival plaque of a simplified oral hygiene regime consisting of instruction in Bass brushing without stress on interdental cleaning, scaling and root planing, in combination with subgingival pulsated jet irrigation with dilute solutions of chlorhexidine, metronidazole or placebos. Twenty-five patients, 14 women and 11 men, each with periodontal pockets ≥ 4 mm, participated in a randomized, double-blind, placebo-controlled study. The patients were assigned to 4 groups: 2 test groups (0.02% chlorhexidine and 0.05% metronidazole) and 2 placebo groups (0.01% quinine sulphate and 0.09% sodium chloride). Subgingival plaque samples were obtained from at least 4 sites in each subject on days 0 (prior to scaling and root planing), 7, 28, 56 and 84. Subgingival irrigation was terminated on d 28. Darkfield microscopy was used to assess the effects of treatment on the subgingival microflora by observing 4 morphologic groups: cocci, motile organisms, spirochetes and others (i.e. non-motile rods and filaments). All the groups showed marked beneficial changes at the end of the 28-d irrigation period, with increases in cocci and decreases in motile forms and spirochetes to less than baseline values. These beneficial effects were maintained for at least 8 weeks after irrigation was stopped. Metronidazole was more effective in reducing motile forms, but the reduction was not significant at d 84. It was concluded that pulsating monojet subgingival irrigation as part of a simplified oral hygiene program, with or without an active antimicrobial agent at low concentration, is effective in reducing the motile and spirochete portions of the subgingival microflora. These effects might be enhanced and prolonged if suitable antimicrobial solutions of higher concentration were used.     

Technical quality of root fillings performed by dental students at the dental teaching centre in Reims, France

Aim  To evaluate the technical quality of root fillings performed by undergraduate students at a dental teaching centre in France.
Methodology  A random sample of 419 records of patients who received dental treatment at the dental service of the teaching Hospital, in Reims, France between 2005 and 2006 was investigated. Evaluation of root filled was based on radiographical criteria defined by the French National Health Service. The length of root fillings, the radiodensity and the presence of voids in the root filling or between root filling and root canal walls were recorded and scored. Chi-square analysis was used to determine statistically significant differences between the technical quality of root fillings and tooth type.
Results  Of the 304 teeth included in the study, 69% had an adequate length of root filling and 42.7% had a dense root filling without voids; only 30.3% of teeth fulfilled these criteria at the same time. The relationship between the technical quality of root fillings and tooth type was statistically significant ( P  < 0.001), the highest percentage of adequate root fillings occurred in single-rooted teeth (36.1%). The highest percentage of inadequate root fillings according to the criteria of root filling length and lateral adaptation was found in molar teeth (71.9%).
Conclusion  Overall, the technical quality of root fillings performed by undergraduate students was poor.     

Electron microscope quantitation of inflammatory infiltrates in childhood gingivitis

Quantitation of inflammatory cell infiltrates in gingival connective tissues was carried out on 12 gingival biopsies from the deciduous dentition of 11 children aged 4–8 years. The tissue was prepared for electron microscopy and from ultrathin sections mounted on 200 mesh grids, cells in one third of the grid squares enclosing infiltrated connective tissue were counted.
The infiltrate displayed large numbers of small and medium lymphocytes and was moderately vascular. A distinct population of peripherally distributed plasma cells was present and pathologically altered fibroblasts together with marked collagen loss were notable features. Small numbers of macrophages, mast cells and polymorphonuclear neutrophils were recorded but T-blasts (immunoblasts) were very rarely encountered.
The childhood lesions have much in common with the early lesion of adult gingivitis which is considered to be a cell-mediated immune phenomenon. However, the lack of T-blasts and rather larger proportion of plasma cells suggest that the lesion of childhood gingivitis represents a position between the early and established phases of gingival disease described in older individuals. A more exact interpretation of these, the earliest stages of human gingival disease should be achieved when the lymphocytes contributing to the childhood infiltrates can be assigned to the T- and B- cell lines.     

Four-rooted maxillary first molar having C-shaped palatal root canal morphology evaluated using cone-beam computerized tomography: a case report

The aim of this article was to present an endodontically managed maxillary first molar with unusual C-shaped palatal root morphology confirmed by cone-beam computerized tomography (CBCT) images. CBCT axial images showed the presence of C-shaped palatal root canal anatomy with a palatal root bifurcation at the apical third. The evaluation of CBCT images can result in better understanding of root canal anatomy, which enables the clinician to investigate the root canal system and to clean, shape, and obturate it more effectively.