Coupling mammalian cell surface display with somatic hypermutation for the discovery and maturation of human antibodies

A novel approach has been developed for the isolation and maturation of human antibodies that replicates key features of the adaptive immune system by coupling in vitro somatic hypermutation (SHM) with mammalian cell display. SHM is dependent on the action of the B cell specific enzyme, activation-induced cytidine deaminase (AID), and can be replicated in non-B cells through expression of recombinant AID. A library of human antibodies, based on germline V-gene segments with recombined human regions was used to isolate low-affinity antibodies to human β nerve growth factor (hβNGF). These antibodies, initially naïve to SHM, were subjected to AID-directed SHM in vitro and selected using the same mammalian cell display system, as illustrated by the maturation of one of the antibodies to low pM K_D. This approach overcomes many of the previous limitations of mammalian cell display, enabling direct selection and maturation of antibodies as full-length, glycosylated IgGs.     

Reviewing the role of donepezil in the treatment of Alzheimer's disease

Donepezil is a reversible, non-competitive piperidine-type acetylcholinesterase inhibitor (AChEI) that is structurally unique compared with other currently available AChEIs. It was developed as a symptomatic treatment to compensate for the progressive loss of cholinergic signal between neurons, a consequence of neuronal cell loss in the brains of patients with Alzheimer's disease (AD). Clinical trials conducted over the 15 years since the drug was first licensed and available for use in patients with mild to moderate AD (1997) have shown that donepezil is efficacious and well tolerated at all stages of AD, from patients with mild or moderate impairment to those with severe disease. The published literature contains nearly 2000 papers on donepezil, and more than 200 of these articles relate to randomized controlled clinical trials. Trials in patients with mild cognitive impairment (MCI) failed to meet all of their primary objectives, but provided insights into patient selection and the design of trials. Overall, more than a decade of donepezil research has gradually changed attitudes toward therapy of AD from a general belief that no clinically useful treatment exists to the present day understanding that symptomatic therapy may be effective across the spectrum of dementia stages.     

Validation of the treatment identification strategy of the HEDIS addiction quality measures: concordance with medical record review

Background  

Strategies to accurately identify the occurrence of specific health care events in administrative data is central to many quality improvement and research efforts. Many health care quality measures have treatment identification strategies based on diagnosis and procedure codes - an approach that is inexpensive and feasible but usually of unknown validity. In this study, we examined if the diagnosis/procedure code combinations used in the 2006 HEDIS Initiation and Engagement quality measures to identify instances of addiction treatment have high concordance with documentation of addiction treatment in clinical progress notes.     

Teen Use of Marijuana Edibles: A Focus Group Study of an Emerging Issue

Recent research indicates that marijuana-infused food product (i.e., edible) use is becoming nearly as common as smoking marijuana where medical marijuana is available. This study explores edible use among teens. We conducted four focus groups in the San Francisco Bay Area with youth, ages 15–17. The focus groups were divided by gender and whether they used marijuana. Some teens mentioned edible use at school. Youth reported that teens consume edibles, primarily to reduce the likelihood of getting caught. Edibles are also attractive to those who do not like to smoke or have concerns about smoking. Both male and female respondents suggested that females are more likely than males to prefer edibles over smoking, one reason for which may be to avoid smelling like marijuana smoke. For some young women, edibles may be a way to avoid publicly presenting themselves as marijuana users. Findings also suggest that youth have access to edibles through multiple sources. Youth reported that they can purchase edibles at school from other students who either make the edibles themselves or are reselling edibles obtained from dispensaries. Both users and non-users were aware of potentially negative consequences related to edible use. Some youth mentioned that they have heard of youth dying from edibles, and several reported being concerned about the high produced by edibles. Female non-users appeared to be more concerned than others about edibles and compared them to drinks that could be spiked with drugs. However, sentiment among some male marijuana users was that if you cannot handle edibles you should not be using them. These findings suggest that strategies to curb access to edibles and use among youth, such as restricting sales of edibles with strong youth appeal and educating youth on the risks of edibles, will need to be developed.