The WRAIR Projectile Concussive Impact Model of Mild Traumatic Brain Injury: Re-design,Testing and Preclinical Validation

The WRAIR projectile concussive impact (PCI) model was developed for preclinical study of concussion. It represents a truly non-invasive closed-head injury caused by a blunt impact. The original design, however, has several drawbacks that limit the manipulation of injury parameters. The present study describes engineering advancements made to the PCI injury model including helmet material testing, projectile impact energy/head kinematics and impact location. Material testing indicated that among the tested materials, ‘fiber-glass/carbon’ had the lowest elastic modulus and yield stress for providing an relative high percentage of load transfer from the projectile impact, resulting in significant hippocampal astrocyte activation. Impact energy testing of small projectiles, ranging in shape and size, showed the steel sphere produced the highest impact energy and the most consistent impact characteristics. Additional tests confirmed the steel sphere produced linear and rotational motions on the rat’s head while remaining within a range that meets the criteria for mTBI. Finally, impact location testing results showed that PCI targeted at the temporoparietal surface of the rat head produced the most prominent gait abnormalities. Using the parameters defined above, pilot studies were conducted to provide initial validation of the PCI model demonstrating quantifiable and significant increases in righting reflex recovery time, axonal damage and astrocyte activation following single and multiple concussions.     

A one-pot synthesis of N2,6-diaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines and systematic evaluation of their ability to host ethanol in crystals

A convenient one-pot method for the preparation of N²,6-diaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines was developed using a three-component synthesis of 1,6-diaryl-1,6-dihydro-1,3,5-triazine-2,4-diamines followed by their Dimroth rearrangement to the desired products. The prepared compounds crystallized from ethanol as ethanol clathrates (1 : 1). X-ray crystallography on several products confirmed the adoption of 5,6-dihydro-tautomer. The thermal analysis and powder X-ray diffraction experiments on selected compounds suggested that thermal desolvation of crystals was irreversible.

One-pot synthesis and analysis of stable dihydrotriazine-EtOH clathrates.     

Localization and characterization of val‐opsin isoform‐expressing cells in the brain of adult zebrafish

In addition to vision, light information is used to regulate a range of animal physiology. Such nonimage‐forming functions of light are mediated by nonvisual photoreceptors expressed in distinct neurons in the retina and the brain in most vertebrates. A nonvisual photoreceptor vertebrate ancient long opsin (VAL‐opsin) possesses two functional isoforms in the zebrafish, encoded by valopa and valopb, which has received little attention. To delineate the neurochemical identities of valop cells and to test for colocalization of the valop isoforms, we used in situ hybridization to characterize the expression of the valop genes along with that of neurotransmitters and a neuropeptide known to be present at the sites of valop expression. Double labeling showed that the thalamic valop population coexpresses valopa and valopb. All the thalamic valop cells overlapped with a GABAergic cell mass that continues from the anterior nucleus to the intercalated thalamic nucleus. A novel valopa cell population found in the superior raphe was serotonergic in nature. A valopb cell population in the Edinger‐Westphal nucleus was identified as containing thyrotropin‐releasing hormone. Valopb cells localized in the hindbrain intermediate reticular formation were noncholinergic in nature (nonmotorneurons). Thus, the presence of valop cell populations in different brain regions with coexpression of neurotransmitters and neuropeptides and the colocalization of valop isoforms in the thalamic cell population indicate regulatory and functional complexity of VAL‐opsin in the brain of the zebrafish. J. Comp. Neurol. 522:3847–3860, 2014. © 2014 Wiley Periodicals, Inc.     

The effectiveness of an integrated pain management program for older persons and staff in nursing homes

This study examined the effects of an 8-week integrated pain management program (IPMP) on enhancing the knowledge and attitude toward pain management among staff; and improving the pain, quality of life, physical and psychosocial functions, and use of non-drug therapies for the elderly in nursing homes. Nursing home staff (N=147) and residents (N=535) were recruited from ten nursing homes. Nursing homes were randomly assigned into an experimental group (N=296) with IPMP or control group (N=239) without IPMP. The IPMP consisted of pain education for staff and physical exercise and multisensory stimulation art and craft therapy for residents. Data were collected before and after the IPMP. The staff demonstrated a significant improvement in knowledge and attitude to pain management, with the survey score increasing from 8.46±3.74 to 19.43±4.07 (p<0.001). Among the residents, 74% had experienced pain within the previous 6 months, with pain intensity of 4.10±2.20. Those in the experimental group showed a significantly better reduction in pain scores than the control group, from 4.19±2.25 to 2.67±2.08 (p<0.001). Group differences were also found in psychological well-being, including happiness, loneliness, life satisfaction and depression (p<0.05), and the use of non-drug methods (p<0.05). These results suggested that IPMP is beneficial for staff, and is effective in reducing geriatric pain and negative impacts. Management support and staff involvement in the program are important for its long-term continuation.