Involvement of autophagy in melatonin‐induced cytotoxicity in glioma‐initiating cells

Glioblastoma‐initiating cells (GICs) represent a stem cell‐like subpopulation within malignant glioblastomas responsible for tumor development, progression, therapeutic resistance, and tumor relapse. Thus, eradication of this subpopulation is essential to achieve stable, long‐lasting remission. We have previously reported that melatonin decreases cell proliferation of glioblastoma cells both in vitro and in vivo and synergistically increases effectiveness of drugs in glioblastoma cells and also in GICs. In this study, we evaluated the effect of the indolamine alone in GICs and found that melatonin treatment reduces GICs proliferation and induces a decrease in self‐renewal and clonogenic ability accompanied by a reduction in the expression of stem cell markers. Moreover, our results also indicate that melatonin treatment, by modulating stem cell properties, induces cell death with ultrastructural features of autophagy. Thus, data reported here reinforce the therapeutic potential of melatonin as a treatment of malignant glioblastoma both by inhibiting tumor bulk proliferation or killing GICs, and simultaneously enhancing the effect of chemotherapy.     

Hypovitaminosis D as a risk factor of hip fracture severity

Summary  

In a cross-sectional study including 324 patients older than 65 years admitted to our hospital for osteoporotic hip fracture, we found that those patients with a more severe vitamin D deficiency had more severe osteoporotic hip fractures (Garden grades III–IV and Kyle III–IV).     

Prevalence of overweight and obesity in non‐institutionalized people aged 65 or over from Spain: the elderly EXERNET multi‐centre study

Coupled with the growth of the older population, an increase in the prevalence of overweight and obesity in this age group has occurred in the last decades. The main aims of the present study were (i) to provide an updated prevalence of overweight and obesity in a representative sample of the Spanish elderly population; (ii) to calculate the prevalence of sarcopenic obesity (SO) and (iii) to analyse the relationships between adiposity measurements and lifestyle. A cross‐sectional study was carried out in a sample of 3136 persons representative of the non‐institutionalized population ≥65 years of age. Anthropometric measurements were obtained using standardized techniques and equipment. Overall, 84% of the population can be categorized as overweight and/or obese. The present study indicates that 67% of the Spanish elderly population has an increased percentage of fat mass and more than 56% suffer from central obesity. Moreover, SO is present in 15% of the Spanish elderly population. Finally, a strong relationship between both physically active and sedentary lifestyles and the level of adiposity was found. Prevalence of overweight and obesity among elderly people in Spain is very high and is still increasing. Lifestyle seems to be a determinant factor in the development of obesity among elderly people.     

Nuclear localization of epidermal growth factor receptor (EGFR) in ameloblastomas

Background: Ameloblastoma is a locally invasive neoplasm often associated with morbidity and facial deformities, showing increased Epidermal Growth Factor Receptor (EGFR) expression. Inhibition of EGFR was suggested as a treatment option for a subset of ameloblastomas. However, there are resistance mechanisms that impair anti-EGFR therapies. One important resistance mechanism for EGFR-inhibition is the EGFR nuclear localization, which activates genes responsible for its mitogenic effects, such as Cyclin D1.Methods: We assessed EGFR nuclear localization in encapsulated (unicystic, n = 3) and infiltrative (multicystic, n = 11) ameloblastomas and its colocalization with Cyclin D1 by using anti-EGFR and anti-lamin B1 double labeling immunofluorescence analyzed by confocal microscopy. Oral inflammatory fibrous hyperplasia and oral squamous cell carcinoma samples were used for comparison.Results: Twelve cases of ameloblastoma exhibited nuclear EGFR colocalization with lamin B1. This positive staining was mainly observed in the ameloblast-like cells. The EGFR nuclear localization was also observed in control samples. In addition, nuclear EGFR colocalized with Cyclin D1 in ameloblastomas.Conclusions: Nuclear EGFR occurs in ameloblastomas in association with Cyclin D1 expression, which is important in terms of tumor biology clarification and raises a concern about anti-EGFR treatment resistance in ameloblastomas.     

Silencing the Hired Guns

Reasonable Doubt: An Investigation Into The Assassination of John F. Kennedy, by Hurt, H. (Holt, Rinehart, and Winston, New York, 1985), 555 pages, $19.95.

Forensic Medicine, by Simpson, K., and Knight, B. (Edward Arnold, London, England, Ninth Edition, 1985), 348 pages, $39.50.     

Model for End-Stage Liver Disease and liver cirrhosis-related complications

The Model for End-Stage Liver Disease (MELD) score has gained wide acceptance for predicting survival in patients undergoing liver transplantation. The strength of this score remains in the mathematical formula derived from a multivariate Cox regression analysis; it is a continuous scale and lacks a ceiling or a floor effect with a wide range of discrimination. It is based on objective, reproducible, and readily available laboratory data and the wide range of samples which have been validated. Liver cirrhosis complications such as ascites, encephalopathy, spontaneous bacterial peritonitis and variceal bleeding were not considered in the MELD score underestimating their direct association with the severity of liver disease. In this regard, several recent studies have shown that clinical manifestations secondary to portal hypertension are good prognostic markers in cirrhotic patients and may add additional useful prognostic information to the current MELD. We review the feasibility of MELD score as a prognostic predictor in patients with liver cirrhosis-related complications.