Automated synthesis of (R)-[18F]MH.MZ on the iPhase Flexlab reaction platform

(R)-[¹⁸F]MH.MZ ([¹⁸F]MH.MZ) is a promising positron emission tomography (PET) radiotracer for in vivo study of the 5-HT_2A receptor. To facilitate clinical trials, a fully automated radiosynthesis procedure for [¹⁸F]MH.MZ was developed using commercially available materials on the iPhase Flexlab module. The overall synthesis time was 100 min with a radiochemical yield of 7 ± 0.9% (n = 3). The radiochemical purity was greater than 99% for [¹⁸F]MH.MZ with a molar activity of 361 ± 57 GBq/μmol (n = 3). The protocol described herein reliably provides [¹⁸F]MH.MZ that meets all relevant release criteria for a GMP radiopharmaceutical.     

Realizing Present and Future Promise of DIY Biology and Medicine through a Trust Architecture

The speed and scale of the COVID-19 pandemic has highlighted the limits of current health systems and the potential promise of non-establishment research such as “DIY” research. We consider one example of how DIY research is responding to the pandemic, discuss the challenges faced by DIY research more generally, and suggest that a “trust architecture” should be developed now to contribute to successful future DIY efforts.     

Explained and unexplained racial and regional inequality in obesity prevalence in the United States

ABSTRACT

Objective: There are substantial racial and regional disparities in obesity prevalence in the United States. This study partitioned the mean Body Mass Index (BMI) and obesity prevalence rate gaps between non-Hispanic blacks and non-Hispanic whites into the portion attributable to observable obesity risk factors and the remaining portion attributable to unobservable factors at the national and the state levels in the United States (U.S.) in 2010.

Design: This study used a simulated micro-population dataset combining common information from the Behavioral Risk Factor Surveillance System and the U.S. Census data to obtain a reliable, large sample representing the adult populations at the national and state levels. It then applied a reweighting decomposition method to decompose the black-white mean BMI and obesity prevalence disparities at the national and state levels into the portion attributable to the differences in distribution of observable obesity risk factors and the remaining portion unexplainable with risk factors.

Results: We found that the observable differences in distribution of known obesity risk factors explain 18.5% of the mean BMI difference and 20.6% of obesity prevalence disparities between non-Hispanic blacks and non-Hispanic whites. There were substantial variations in how much the differences in distribution of known obesity risk factors can explain black-white gaps in mean BMI (?67.7% to 833.6%) and obesity prevalence (?278.5% to 340.3%) at the state level.

Conclusion: The results from this study demonstrate that known obesity risk factors explain a small proportion of the racial, ethnic and between-state disparities in obesity prevalence in the United States. Future etiologic studies are required to further understand the causal factors underlying obesity and racial, ethnic and geographic disparities.     

Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival

Journal of Neuro-Oncology - Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT)...     

Biologic adjuvants and bone: current use in orthopedic surgery

Normal bone healing is a complex process that eventually restores original structure and function to the site of trauma. However, clinical circumstances such as nonunion, critical-sized defects, systemic bone disease, and fusion procedures have stimulated a search for ways to enhance this normal healing process. Biologics are an important part of this search and many, including bone marrow aspirate concentrate, demineralized bone matrix, platelet-rich plasma, bone morphogenic proteins, and platelet-derived growth factor, are currently in clinical use. Many others, including mesenchymal stem cells, parathyroid hormone, and Nel-like molecule-1 (NELL-1) will likely be in use in the future depending on the results of preclinical and clinical trials.     

Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.