Professional Development for Graphing Calculators

The implementation of higher standards and the use of graphing calculators as changed the mathematical pedagogy for New York State teachers. This study was conducted because of poor achievement results and a lack of graphing calculator use at East High School in the Rochester City School District. The teachers at East High School did not feel comfortable or knowledgeable enough on their own use of graphing calculators to implement the calculators into their lessons. The decision was made that an effective professional development plan needed to be conducted. An effective professional development would be on-going rather than a one-time workshop, conducted at a pace that makes the participants comfortable, and with relevant curriculum that the teachers will use in their classroom lessons. The professional development made a positive impact on how comfortable and knowledgeable the participants now feel with use of graphing calculators

Editorial: The CB2 cannabinoid system: A new strategy in neurodegenerative disorder and neuroinflammation

Editorial for Frontiers journal without abstrac

Automated synthesis, preclinical toxicity, and radiation dosimetry of [F-18]MC225 for clinical use:a tracer for measuring P-glycoprotein function at the blood-brain barrier

Introduction: [18F]MC225 is a selective substrate for P-glycoprotein (P-gp) that has good metabolic stability and shows higher baseline uptake compared with other P-gp substrates such as (R)-[11C]Verapamil. Prior to clinical translation, it is necessary to perform process validation of the radiosynthesis, assessment of preclinical toxicity, and radiation dosimetry. Methods: The production of [18F]MC225 was automated on a CFN-MPS200 multipurpose synthesizer. The acute toxicity of MC225 was evaluated at a dose of 2.5 mg/kg bodyweight, which is more than 10,000-fold the postulated maximum clinical dose of [18F]MC225. The acute toxicity of [18F]MC225 injection at a 200-fold dose, to administer a postulated dose of 185 MBq of [18F]MC225, was also evaluated after the decay-out of 18F. The mutagenicity of MC225 was studied by a reverse mutation test using Salmonella typhimurium and Escherichia coli (Ames test). In vivo biodistribution and dosimetry studies of [18F]MC225 were carried out in normal mice. Human dosimetry was estimated using OLINDA software. Results: The mean decay-corrected yields of [18F]MC225 at end of synthesis were 13%, with > 99% radiochemical purity, > 1000 GBq/!mol molar activity, and ! 1.5 !g/185 MBq of total chemical contents. All process validation batches complied with the product specifications and the process was confirmed to be appropriate for the production of [18F]MC225. No acute toxicity of MC225 or [18F]MC225 injection was found. No mutagenic activity was observed for MC225. The biodistribution study demonstrated both hepatobiliary and renal excretion of radioactivity. The most critical organ was the pancreas, with (63.8 !Gy/MBq) or without urination (63.9 !Gy/MBq) at 360 min after injection. The estimated effective dose (!Sv/MBq) with and without urination at 360 min after injection was calculated as 15.7 and 16.9, respectively. Conclusion: [18F]MC225 shows acceptable pharmacological safety at the dose required for adequate PET imaging. The potential risk associated with [18F]MC225 PET imaging is well within acceptable dose limits

Arylpiperazine agonists of the serotonin 5-HT1A receptor preferentially activate cAMP signaling versus recruitment of β-arrestin-2

G protein-coupled receptors (GPCRs) mediate biological signal transduction through complex molecular pathways. Therapeutic effects of GPCR-directed drugs are typically accompanied by unwanted side effects, owing in part to the parallel engagement of multiple signaling mechanisms. The discovery of drugs that are ‘functionally selective’ towards therapeutic effects, based on their selective control of cellular responses through a given GPCR, is thus a major goal in pharmacology today. In the present study, we show that several arylpiperazine ligands of the serotonin 5-HT1A receptor (5-HT1AR) preferentially activate 3',5'-cyclic adenosine monophosphate (cAMP) signaling versus b-arrestin-2 recruitment. The pharmacology of these compounds is thus qualitatively different from the endogenous agonist serotonin, indicating functional selectivity of 5-HT1AR-mediated response pathways. Preliminary evidence suggests that phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) downstream of 5-HT1AR is a substrate of functionally selective signaling by partial agonists. We propose that the compounds described in the present study are useful starting points for the development of signaling pathway-selective drugs targeting 5-HT1AR

First clinical assessment of [ 18 F]MC225, a novel fluorine-18 labelled PET tracer for measuring functional P-glycoprotein at the blood-brain barrier

Objective: 5-(1-(2-[18F]fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen ([18F]MC225) is a selective substrate for P-glycoprotein (P-gp), possessing suitable properties for measuring overexpression of P-gp in the brain. This is the first-in-human study to examine safety, radiation dosimetry and P-gp function at the blood-brain barrier (BBB) of [18F]MC225 in healthy subjects. Methods: [18F]MC225 biodistribution and dosimetry were determined in 3 healthy male subjects, using serial 2 h and intermittent 4 and 6 h whole-body PET scans acquired after [18F]MC225 injection. Dynamic [18F]MC225 brain PET (90 min) was obtained in 5 healthy male subjects. Arterial blood was sampled at various time intervals during scanning and the fraction of unchanged [18F]MC225 in plasma was determined. T1-weighted MRI was performed for anatomical coregistration. Total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1-TCM and 2-TCM, respectively). VT was also estimated using the Logan graphical method (Logan plot) (t* = 20 min). Surrogate parameters without blood sampling (area-under the curve [AUC] of regional time-activity curves [TACs] and negative slope of calculated TACs) were compared with the VT values. Results: No serious adverse events occurred throughout the study period. Although biodistribution implied hepatobiliary excretion, secretion of radioactivity from liver to small intestine through the gallbladder was very slow. Total renal excreted radioactivity recovered during 6 h after injection was 0.9). AUCs of TACs were positively correlated with VT (2-TCM) values (r2: AUC0-60 min = 0.61, AUC0-30 min = 0.62, AUC30-60 min = 0.59, p < 0.0001). Negative slope of SUV TACs was negatively correlated with VT (2-TCM) values (r2 = 0.53, p < 0.0001). Conclusions: This initial evaluation indicated that [18F]MC225 is a suitable and safe PET tracer for measuring P-gp function at the BBB. Keywords: Blood–Brain barrier; Dosimetry; First-in-human; P-glycoprotein; Positron emission tomography

Glycated Albumin, An Early Biomarker of Several Pathologies

The role of glycated albumin is determinant for early diagnosis in several pathologies. Obviously, it is with glycated hemoglobin elective for Diabetes diagnosis but the ratio albumin glycated and hemoglobin glycated could support the in vitro diagnosis in several pathologies of CNS such as Parkinson Alzheimer diseases and Epilepsy