Safety and Effectiveness of Stoss Therapy in Children with Vitamin D Deficiency

Objectives: Paediatric vitamin D (25-hydroxyvitamin D - 25OHD) deficiency can lead to nutritional rickets and extra-skeletal complications. Compliance with daily therapy can be difficult, making high dose, short-term vitamin D (stoss) therapy attractive to correct vitamin D deficiency. We compared the effectiveness and safety of standard versus stoss therapy in treating childhood 25OHD deficiency. Study Design: Children aged 2 - 16 years with 25OHD \u3c50nmol/L were randomized to either standard (5,000IU daily for 80 days) or stoss (100,000 IU weekly for 4 weeks) cholecalciferol. Participants underwent evaluation of effectiveness and safety. 25OHD, random spot calcium: creatinine ratio (Ca:Cr) and compliance were measured at 12 weeks. Results: 151 children were enrolled in the study (68 standard and 83 stoss), median age 9 years (IQR: 6 - 12 years). Baseline 25OHD levels were 26 nmol/L (IQR: 19 - 35 nmol/L) and 32 nmol/L (IQR: 24 - 39 nmol/L) in the standard and stoss groups respectively. At 12 weeks, the median 25OHD level was significantly greater in the standard vs. stoss group (81 vs. 67 nmol/L; p=0.005), however, \u3e80% of participants in both groups achieved sufficiency (25OHD\u3e50nmol/L) and had normal urinary Ca:Cr, with no significant difference seen between groups. Compliance was similar in the two groups. Conclusion: Compared to stoss, standard therapy achieved higher 25OHD levels at 12 weeks; however, in both groups there were a similar proportion of participants who achieved 25OHD sufficiency, with no evidence of toxicity. Unlike other studies, simplifying the treatment regimen did not improve compliance. These results support stoss therapy as an effective and safe alternative therapy for the treatment of paediatric vitamin D deficiency

Attenuated AMPA Receptor Expression Allows Glioblastoma Cell Survival in Glutamate-Rich Environment

Background: Glioblastoma multiforme (GBM) cells secrete large amounts of glutamate that can trigger AMPA-type glutamate receptors (AMPARs). This commonly results in Na+ and Ca2+-permeability and thereby in excitotoxic cell death of the surrounding neurons. Here we investigated how the GBM cells themselves survive in a glutamate-rich environment. Methods and Findings: In silico analysis of published reports shows down-regulation of all ionotropic glutamate receptors in GBM as compared to normal brain. In vitro, in all GBM samples tested, mRNA expression of AMPAR subunit GluR1, 2 and 4 was relatively low compared to adult and fetal total brain mRNA and adult cerebellum mRNA. These findings were in line with primary GBM samples, in which protein expression patterns were down-regulated as compared to the normal tissue. Furthermore, mislocalized expression of these receptors was found. Sequence analysis of GluR2 RNA in primary and established GBM cell lines showed that the GluR2 subunit was found to be partly unedited. Conclusions: Together with the lack of functional effect of AMPAR inhibition by NBQX our results suggest that down-regulation and afunctionality of AMPARs, enable GBM cells to survive in a high glutamate environment without going into excitotoxic cell death themselves. It can be speculated that specific AMPA receptor inhibitors may protect normal neurons against the high glutamate microenvironment of GBM tumor

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Gene Therapy: Charting a Future Course—Summary of a National Institutes of Health Workshop, April 12, 2013

Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities, brought together early and mid-career researchers to discuss the key scientific challenges and opportunities, ethical and communication issues, and NIH and foundation resources available to facilitate further clinical advances

Statut bucco-dentaire au sein d’une population gériatrique libanaise : étude pilote

According to the World Health Organization (WHO), oral health status represents an indicator of the physical and psychological general state of a person, especially among the elderly. Many epidemiological studies have studied oral health among the geriatric population. In Lebanon, the lack of publications related to this subject encouraged us to realize a pilot study in order to evaluate oral health status among a Lebanese geriatric sample from low socioeconomic class. This study was conducted in a volunteer associational center (“Resto du Coeur”), by the Department of ediatric and community dentistry, in collaboration with the Department of prosthodontics of the Faculty of Dental Medicine, at Saint-Joseph University, Lebanon. This activity included the oral health evaluation of 51 geriatric persons along with educational oral health promotion.The oral exam of the participants showed a high prevalence of edentulism, a poor oral hygiene as well as multiple periodontal and dental problems

Effect of surface chemistry on the electrical double layer in a long-chain ionic liquid

International audienceRoom temperature ionic liquids (ILs) can create a strong accumulation of charges at solid interfaces by forming a very thin and dense electrical double layer (EDL). The structure of this EDL has important consequences in numerous applications involving ILs, for example in supercapacitors, sensors and lubricants, by impacting the interfacial capacitance, the charge carrier density of semiconductors , as well as the frictional properties of the interfaces. We have studied the interfacial structure of a long chain imidazolium-based IL (1-octyl-3-methylimidazolium dicyanamide) on several substrates: mica, silica, silicon and molybdenum disulfide (MoS 2), using atomic force microscopy (AFM) experiments and molecular dynamics (MD) simulations. We have observed 3 types of interfacial structures for the same IL, depending on the chemistry of the substrate and the water content, showing that the EDL structure is not an intrinsic property of the IL. We evidenced that at a low water content, neutral and apolar (thus hydrophobic) substrates promote a thin layer structure, where the ions are oriented parallel to the substrate and cations and anions are mixed in each layer. In contrast, a strongly charged (thus hydrophilic) substrate yield an extended structuration into several bilayers, while a heterogeneous layering with loose bilayer regions was observed on an intermediate polar and weakly charged substrate and on an apolar one at a high bulk water content. In the latter case, water contamination favors the formation of bilayer patches by promoting the segregation of the long chain IL into polar and apolar domains