Custom-engineered hydrogels for delivery of human iPSC-derived neurons into the injured cervical spinal cord.

Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties. In vitro studies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord.

Computer-generated photorealistic hologram using ray-wavefront conversion based on the additive compressive light field approach.

The conventional computer-generated hologram reconstructing photorealistic three-dimensional (3D) images based on ray-wavefront conversion has the disadvantage of spatio-angular resolution trade-off. In this Letter, we propose for the first time, to the best of our knowledge, a computer-generated photorealistic hologram without spatio-angular resolution trade-off based on the additive compressive light field (CLF) approach. The original light field is compressed into multiple layer images through numerical optimization based on the additive light field principle. Then, by independently calculating the wave propagation from each layer image to the hologram plane and adding them together, a CLF hologram is generated. Since the CLF information is presented through a holographic method, the advantage of high resolution in CLF is preserved while the limitation of the number of physically stacked layers (such as liquid crystal displays) is removed, leading to higher quality, larger depth of field, and higher brightness compared with a conventional CLF display. The proposed method is verified with a photorealistic optical experiment.

Long-term denosumab treatment restores cortical bone loss and reduces fracture risk at the forearm and humerus: analyses from the FREEDOM Extension cross-over group.

Upper limb fractures (including wrist, forearm, and humerus) represent a significant burden among postmenopausal women with osteoporosis. Up to 7 years of treatment with denosumab resulted in an increase in bone mineral density and decrease in fractures in upper limb sites. INTRODUCTION: Upper limb (wrist, forearm, and humerus) fractures are a significant burden in osteoporosis, associated with significant morbidity and mortality. Denosumab, a monoclonal antibody against RANK ligand, increases bone mineral density (BMD) and decreases vertebral, nonvertebral, and hip fractures. Here, we evaluated the long-term effect of denosumab treatment on upper limb fracture risk and BMD. METHODS: In the FREEDOM trial, subjects were randomized 1:1 to receive every-6-month denosumab 60 mg or placebo subcutaneously for 3 years, after which all subjects could receive denosumab for up to 7 years (Extension). Among placebo subjects who completed FREEDOM and enrolled in the Extension, wrist, forearm, humerus, and upper limb fracture rates and rate ratios between different time periods (FREEDOM years 1-3, Extension years 1-3, and Extension years 4-7) were computed. BMD at the ultradistal radius, 1/3 radius, and total radius was analyzed in a subset of subjects in a BMD substudy. RESULTS: This analysis included 2207 subjects (116 in the BMD substudy). Fracture rates decreased over the 7-year Extension; fracture rate ratios between Extension years 4-7 (denosumab) and FREEDOM years 1-3 (placebo) reduced significantly for the wrist (0.57), forearm (0.57), humerus (0.42), and upper limb (0.52; p < 0.05 for all). Percentage increase in BMD from Extension baseline at the ultradistal radius, 1/3 radius, and total radius was significant by Extension year 7 (p < 0.05 for all). CONCLUSIONS: Long-term treatment with denosumab decreases upper limb fracture risk and increases forearm BMD, suggesting beneficial effects on both cortical and trabecular bone accruing over time.

Resolution priority holographic stereogram based on integral imaging with enhanced depth range.

Conventional holographic stereogram (HS) can be generated through fast Fourier transforming parallax images into hogels. Conventional HS uses multiple plane waves to reconstruct 3D images with low resolution and is similar to the principle of depth priority integral imaging (II). We proposed the concept of resolution priority HS for the first time, which is based on the principle of resolution priority II, by adding a quadratic phase term on the conventional Fourier transform. In the proposed resolution priority HS, the resolution of reconstructed 3D images is much better than conventional HS, but the depth range is limited. To enhance the depth range, a multi-plane technique was used to present multiple central depth planes simultaneously. The proposed resolution priority HS with high resolution and enhanced depth range was verified by both simulation and optical experiment.

Brief Report: Sensory Reactivity in Children with Phelan-McDermid Syndrome.

Phelan-McDermid syndrome (PMS), a monogenic form of autism spectrum disorder (ASD), results from deletion or mutation of the SHANK3 gene. Atypical sensory reactivity is now included in the diagnostic criteria for ASD. Examining the sensory phenotype in monogenic forms of ASD, such as PMS, may help identify underlying mechanisms of sensory reactivity. Using the Short Sensory Profile, the current study compared sensory reactivity in 24 children with PMS to 61 children with idiopathic ASD (iASD). Results suggest that children with PMS show more low energy/weak symptoms and less sensory sensitivity as compared to children with iASD. This study is the first to demonstrate differences in sensory reactivity between children with PMS and iASD, helping to refine the PMS phenotype.

Simulation training for breast and pelvic physical examination: a systematic review and meta-analysis.

BACKGROUND: Breast and pelvic examinations are challenging intimate examinations. Technology-based simulation may help to overcome these challenges. OBJECTIVE: To synthesise the evidence regarding the effectiveness of technology-based simulation training for breast and pelvic examination. SEARCH STRATEGY: Our systematic search included MEDLINE, EMBASE, CINAHL, PsychINFO, Scopus, and key journals and review articles; the date of the last search was January 2012. SELECTION CRITERIA: Original research studies evaluating technology-enhanced simulation of breast and pelvic examination to teach learners, compared with no intervention or with other educational activities. DATA COLLECTION AND ANALYSIS: The reviewers evaluated study eligibility and abstracted data on methodological quality, learners, instructional design, and outcomes, and used random-effects models to pool weighted effect sizes. MAIN RESULTS: In total, 11 272 articles were identified for screening, and 22 studies were eligible, enrolling 2036 trainees. In eight studies comparing simulation for breast examination training with no intervention, simulation was associated with a significant improvement in skill, with a pooled effect size of 0.86 (95% CI 0.52-1.19; P < 0.001). Four studies comparing simulation training for pelvic examination with no intervention had a large and significant benefit, with a pooled effect size of 1.18 (95% CI 0.40-1.96; P = 0.003). Among breast examination simulation studies, dynamic models providing feedback were associated with improved outcomes. In pelvic examination simulation studies, the addition of a standardised patient to the simulation model and the use of an electronic model with enhanced feedback improved outcomes. AUTHOR'S CONCLUSIONS: In comparison with no intervention, breast and pelvic examination simulation training is associated with moderate to large effects for skills outcomes. Enhanced feedback appears to improve learning.

Electron paramagnetic resonance and nanosecond fluorescence depolarization studies on creatine-phosphokinase interaction with myosin and its fragments.

Recent reports in the literature have indicated a physical association of creatine-phosphokinase (CPK) with the tail portion of the myosin molecule. The present paper describes further studies on the interaction of CPK with myosin and myosin fragments, using the techniques of electron paramagnetic resonance (EPR) and nanosecond fluorescence depolarization. From EPR work, spin-labeled CPK appears to interact with myosin, tail-less myosin (heavy meromyosin [HMM]), and myosin heads (subfragment-1 [S1]), the extent of interaction being proportional to the S1 content of myosin or its fragments. Spin-labeled CPK did not evidence interaction with the headless myosin "rods," with myosin tails (light meromyosin [LMM]), with S2 necks (which connect S1 to the rest of the myosin molecule), or with actin. When a fluorescent dye is directed to the essential epsilon-amino group of CPK, nanosecond fluorescence depolarization studies indicate a substantial interaction with myosin, HMM, and S1, but very little with F-actin. When the "fast-reacting" thiol of the S1 moiety or the "essential thiol" of CPK was labeled with either a fluorescent dye or a spin label, no interaction between CPK and myosin (or S1) was detected.