Deferoxamine but Not Dimethyloxalylglycine, L-Mimosine, or Cobalt Dichloride Can Interfere with the MTT Assay

Hypoxia mimetic agents (HMAs) have been shown to have a positive influence on cellular functions in a multitude of tissue regenerative strategies. Novel experimental approaches use biomaterials as carriers for controlled delivery of these HMAs. Here, the cytotoxic aspects of biocompatibility are of key relevance. The MTT assay is widely used to evaluate cytotoxicity and proliferation. Based on the implications from the proceeding research we hypothesized that specific HMAs such as deferoxamine at high concentrations can interfere with the MTT assay. Thus, the aim of this study was to test the repercussions of the HMAs dimethyloxalylglycine, deferoxamine, L-mimosine, and CoCl2 on the validity of the MTT assay. Murine MC3T3-E1 cells were cultured in serum-free alphaMEM and in alphaMEM supplemented with 10 % fetal bovine serum with the HMAs dimethyloxalylglycine, deferoxamine, L-mimosine, and CoCl2, respectively, at 3 mM-0.3 mM for 24 h (experimental groups). Cells without HMAs served as control (control groups). The same experiments were performed with medium and phosphate buffered saline (PBS) without cells. In all settings MTT solution was added to PBS-washed or unwashed culture plates for the last two hours of the incubation period. Then MTT solution was removed and dimethyl sulfoxide was added to dissolve the formazan crystals and absorption was measured. Our data show that the presence of deferoxamine can interfere with the MTT assay if not removed before the addition of MTT. This is particularly important when evaluating cell viability in setups where deferoxamine-loaded biomaterials are used.

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Data-Driven-Based Approach to Identifying Differentially Methylated Regions Using Modified 1D Ising Model

Background. DNA methylation is essential for regulating gene expression, and the changes of DNA methylation status are commonly discovered in disease. Therefore, identification of differentially methylation patterns, especially differentially methylated regions (DMRs), in two different groups is important for understanding the mechanism of complex diseases. Few tools exist for DMR identification through considering features of methylation data, but there is no comprehensive integration of the characteristics of DNA methylation data in current methods. Results. Accounting for the characteristics of methylation data, such as the correlation characteristics of neighboring CpG sites and the high heterogeneity of DNA methylation data, we propose a data-driven approach for DMR identification through evaluating the energy of single site using modified 1D Ising model. Applied to both simulated and publicly available datasets, our approach is compared with other popular methods in terms of performance. Simulated results show that our method is more sensitive than competing methods. Applied to the real data, our method can identify more common DMRs than DMRcate, ProbeLasso, and Wang's methods with a high overlapping ratio. Also, the necessity of integrating the heterogeneity and correlation characteristics in identifying DMR is shown through comparing results with only considering mean or variance signals and without considering relationship of neighboring CpG sites, respectively. Through analyzing the number of DMRs identified in real data located in different genomic regions, we find that about 90% DMRs are located in CGI which always regulates the expression of genes. It may help us understand the functional effect of DNA methylation on disease.

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Lead Environmental Pollution and Childhood Lead Poisoning at Ban Thi Commune, Bac Kan Province, Vietnam

Lead poisoning is a public health problem in many areas of the world. Children are at particularly high risk for adverse effects of lead exposure; even at low concentrations, lead can affect physical, mental, and behavioral development. Children living near lead-zinc mines are at high risk for environmental lead poisoning, especially the contaminated soil. We conducted a cross-sectional descriptive study in Ban Thi Commune, northern Vietnam. 195 children (92,9% participation) aged 3-14 years old (average: 7.69 ± 2.90) were randomly selected from a list of all children prepared by the village health collaborators. 109 (55.90%) were boys and 86 (44.10%) were girls. The research measures were the lead concentration in native soil and the children's total blood lead concentration determined by the inductively coupled plasma-mass spectrometry (ICP-MS) method. The results showed that lead content in soil was many times higher than American Environmental Protection Agency and Vietnam standards (average 2980.23 ± 6092.84 mg/kg dry weight of soil (range 80.05 – 33820.62)). Average blood lead levels for children were 15.42 ± 6.45 μg/dL (95% CI: 14.50 -16.33 μg/dL). The percentage of children with lead levels >10 μg/dL (value considered to be lead poisoning for children according to the Ministry of Health of Vietnam) was 79.49% of the total number of children. None of the children in this study had blood lead level (BLL) that required chelation treatment according to Vietnam MOH guideline (BLL ≥45 μg/dL). There is weakly evidence that lead exposure relates to the physical development of children. Children with low lead concentrations (less than 10 μg/dL) had height and weight of 1.47-3.51 cm and 1.19-2.81 kg, greater than those with BLL >10 μg/dL (p>0.05).

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A Comparison between the i-gel® and air-Q® Supraglottic Airway Devices Used for the Patients Undergoing General Anesthesia with Muscle Relaxation

Objectives. The aim of the present study was to compare two supraglottic airway (SGA) devices (i.e., the i-gel® © Intersurgical Ltd and air-Q® (Reusable) Cookgas company) in terms of the insertion time, amount of leak during ventilation with maximum positive pressure, and postoperative complications in patients referring to Modarres Hospital in Tehran. Method. The present double-blind clinical trial was performed on 60 patients undergoing elective surgeries that required general anesthesia with muscle relaxation. Patients were randomly assigned to either i-gel® (n = 30) or Air-Q® (n = 30) groups. Results. The mean age, body mass index, duration of surgery, duration of anesthesia, and gender ratio were not significantly different between the two groups. Mean ± SD values of the SGA devices' insertion time (in seconds) in the air-Q® and i-gel® groups were 4.87 ± 1.6 and 6.80 ± 1.2, respectively (P

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Ewing’s Sarcoma of the Head and Neck: Margins are not just for surgeons

We present a prospective large series (n = 47) of head and neck Ewing's sarcomas (HNES) homogeneously treated by the Euro‐Ewing 99 trial (EE99) from 1999 to 2014 in France. All our findings plead for a multidisciplinary approach of HNES in specialized centers from the diagnosis to maximize for these young patients the chance of cure with a minimum of sequelae. We highlight that margin interpretation is crucial to discuss postoperative radiotherapy indication and should be questioned by a multidisciplinary team beyond the only surgeon and pathologist opinion.

Abstract

Background, Methods

To describe the characteristics, treatments (systemic/local), and outcome (oncological/functional) of French patients with head and neck Ewing's sarcomas (HNES) registered in the Euro‐Ewing 99 (EE99) database. Specific patient‐level data were reviewed retrospective.

Results

Forty‐seven HNES patients in the EE99 database had a median age of 11 years, 89% had bone tumors (skull 55%, mandible 21%, maxilla 11%), 89% had small tumors (<200 mL), and they were rarely metastatic (9%). Local treatment was surgery radiotherapy (55%), exclusively surgery (28%), or radiotherapy (17%). Metastatic relapses occurred in five patients with high relapse risk factors (metastasis at diagnosis, poor histological response, large tumors). Local progression/relapses (LR) after exclusive radiotherapy occurred in three patients with persistent extra‐osseous residue and in four patients considered R0 margins (postchemotherapy surgery, without postoperative radiotherapy [PORT]), reclassified by pathological review as R1a. Pathological review reclassified 72% of R0 margins: 11/18 to R1a and 2/18 to R2. Five patients had confirmed R0 margins after postchemotherapy surgery without PORT and had no LR Eight patients had R2 margins (initial surgery without previous chemotherapy, with PORT) and had no LR With a median follow‐up of 9.3 years, the 3‐year LR rate, EFS, and OS were 84.8%, 78.6%, and 89.3%, respectively. Among the 5‐year survivors, 88% had long‐term sequelae.

Conclusion

To optimize HNES management, patients should be treated from diagnosis in expert centers with multidisciplinary committees to discuss treatment strategy (type of surgery, need for PORT) and validate surgical margins.

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Updates on autoinflammatory diseases

Narcisa Martinez-Quiles | Raphaela Goldbach-Mansky

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Soft Tissue Disorders of the Mouth

Soft tissue disorders of the mouth encompass a wide expanse of pathophysiology. This article focuses on the identification, etiology, management, and complications of common infectious processes (candidiasis, dental caries, and herpes labialis), inflammatory lesions (sialolithiasis, oral lichen planus, and aphthous ulcer), and benign entities (bony tori and mucocele).

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