Optimization and validation of the NeuroLux wireless optoelectronics system for optogenetics

Utilizing light and genetic engineering, optogenetics permits the manipulation of events within cells via light using the light-sensitive properties of single-component microbial opsins. Microbial opsins are activated by a light source, such as lasers, light-emitting diodes, and incandescent sources that deliver light to the region of interest either directly or indirectly, such as through fiberoptics. In classical in vivo optogenetics, the wiring of optic fibers necessitates tethering of animals by the optic fiber to the light source. The novel NeuroLux wireless optoelectronic system for optogenetics circumvents issues pertaining to classical optogenetics by utilizing near-field power transfer via magnetic coil antennae to power miniature, subdermal, and flexible optoelectronic implants, including an LED light sources. Furthermore, features of the NeuroLux system overcome issues posed by other wireless systems, including interference. This preliminary study sought to validate and optimize the novel NeuroLux system setup by stimulating the cornu ammonis 2 (CA2) region of the hippocampus in transgenic mice that express Cre recombinase from the vasopressin 1b receptor promoter. Following experimentation, distinct stimulation, indicated by quantified cFos expression, was noted in the CA2 region, thereby validating the use of the NeuroLux wireless optoelectronics system for future optogenetics studies

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Comparison of Two Nasal Cell Collection Methods in Determining Cyclic Adenosine Monophosphate Levels and its Association with Olfaction: A Feasibility Study

Cyclic adenosine monophosphate (cAMP) is a second messenger that may be associated with olfactory function. No known studies have compared existing collection methods for determining nasal cAMP levels. This is a prospective study comparing the comfort and reliability of the nasal curette and cytobrush. A secondary outcome collected for feasibility testing was characterizing the association between cAMP and olfactory function. We enrolled 19 normal olfaction and 10 olfactory dysfunction subjects. Olfaction was measured by the University of Pennsylvania Smell Identification Test. Two samples were obtained from each nasal cavity at the initial visit and at 1 week follow-up. Comfort was measured by a visual analog scale (VAS). cAMP levels were determined by an enzyme immunoassay. For the curette and cytobrush, mean VAS scores were 03 and 0.7 cm (p = 0.48). Intraclass correlation coefficients were 0.81 (curette) and 0.65 (cytobrush) for the initial visit and 0.64 and 0.54 between the initial and follow-up visit. Using the curette, mean cAMP was 537 and 480 fmol/(mg/mL) for the normal and dysfunction cohorts (p = 0.18). Using the cytobrush, cAMP was 505 and 477, respectively (p = 0.65). The curette and cytobrush are both comfortable and reliable collection methods for determining nasal cAMP levels