Explore the vast range of titles available.

Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D microarchitectures essential for guiding cell growth and promoting tissue maturation 1 . 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (μCPP) to create a complex CNS structure for regenerative medicine applications in the spinal cord. μCPP can print 3D biomimetic hydrogel scaffolds tailored to the dimensions of the rodent spinal cord in 1.6 s and is scalable to human spinal cord sizes and lesion geometries. We tested the ability of µCPP 3D-printed scaffolds loaded with neural progenitor cells (NPCs) to support axon regeneration and form new ‘neural relays’ across sites of complete spinal cord injury in vivo in rodents 1 , 2 . We find that injured host axons regenerate into 3D biomimetic scaffolds and synapse onto NPCs implanted into the device and that implanted NPCs in turn extend axons out of the scaffold and into the host spinal cord below the injury to restore synaptic transmission and significantly improve functional outcomes. Thus, 3D biomimetic scaffolds offer a means of enhancing CNS regeneration through precision medicine. Fast scalable 3D bioprinting generates biocompatible and biomimetic scaffolds to precisely fit the geometries of spinal cord lesions, promote axonal regeneration, and support stem cell grafts to promote recovery from spinal cord injury in rodents.

Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.

Neural stem cells (NSCs) differentiate into both neurons and glia, and strategies using human NSCs have the potential to restore function following spinal cord injury (SCI). However, the time period of maturation for human NSCs in adult injured CNS is not well defined, posing fundamental questions about the design and implementation of NSC-based therapies. This work assessed human H9 NSCs that were implanted into sites of SCI in immunodeficient rats over a period of 1.5 years. Notably, grafts showed evidence of continued maturation over the entire assessment period. Markers of neuronal maturity were first expressed 3 months after grafting. However, neurogenesis, neuronal pruning, and neuronal enlargement continued over the next year, while total graft size remained stable over time. Axons emerged early from grafts in very high numbers, and half of these projections persisted by 1.5 years. Mature astrocyte markers first appeared after 6 months, while more mature oligodendrocyte markers were not present until 1 year after grafting. Astrocytes slowly migrated from grafts. Notably, functional recovery began more than 1 year after grafting. Thus, human NSCs retain an intrinsic human rate of maturation, despite implantation into the injured rodent spinal cord, yet they support delayed functional recovery, a finding of great importance in planning human clinical trials.

Background: Professional identity formation (PIF), a foundational process in becoming a physician, includes establishment of values, moral principles, and self-awareness. The purpose of this report is to examine challenges in establishing the validity of measures of identity fusion as one facet of PIF. Method: Utilizing the modern approach of validity as a unitary concept, the authors generated six hypotheses to examine the evidence for the construct validity of the scores of Physician Professional Identity (PPI) and Identity Integration (IdIn), considering relationships of these measures with each other, year of training and data from a larger survey. Results: Responses from 3473 students at 8 medical schools revealed a weak association between the measures with distributions varying by cohort. PPI had a stronger relationship to cohort and IdIn was moderately associated with students' attitudes relevant to social media use. Responses were independent of response format and evidence supported the interpretation of scores for IdIn as indications of integration of identity. Discussion : Sufficient evidence was found to suggest that these measures assess aspects of PIF. Use of these measures as part of a multidimensional, longitudinal approach to refining understanding of the construct of PIF and developing effective assessment strategies.

ABSTRACT The unicellular green alga, Oophila amblystomatis, populates egg capsules of the spotted salamander Ambystoma maculatum. This nutrient-exchange mutualism is widely perceived as a bipartite interaction, but the presence and contributing effects of bacteria to this symbiosis are unknown. We used standard cultivation techniques and amplicon sequencing of the V4/V5 region of 16S rRNA gene to identify and compare diversity of bacterial taxa in embryonic capsules with that in the aquatic breeding habitat. Our sampling regime allowed us to investigate diversity among individual capsules of an egg mass and between two ponds and sampling years. Capsules contain much lower diversity of bacteria than pond water, and spatial and temporal variation in intracapsular and pond bacterial diversity was observed. Despite this variation, sequences corresponding to species in the orders Burkholderiales and Oligoflexales were either prevalent or abundant, or both. Isolates most commonly recovered from capsules were closely related to species in the genus Herbaspirillum (Burkholderiaceae); other isolates were pseudomonads, but in all cases are closely related to known vascular plant-associated species. We conclude that, despite observed variation, there are bacterial taxa whose presence is held in common spatially and temporally among capsules and that the symbiosis between O. amblystomatis and A. maculatum may involve these taxa. Egg capsules of the spotted salamander: an increasingly tangled (micro)bank.

The unicellular green alga, Oophila amblystomatis, populates egg capsules of the spotted salamander Ambystoma maculatum. This nutrient-exchange mutualism is widely perceived as a bipartite interaction, but the presence and contributing effects of bacteria to this symbiosis are unknown. We used standard cultivation techniques and amplicon sequencing of the V4/V5 region of 16S rRNA gene to identify and compare diversity of bacterial taxa in embryonic capsules with that in the aquatic breeding habitat. Our sampling regime allowed us to investigate diversity among individual capsules of an egg mass and between two ponds and sampling years. Capsules contain much lower diversity of bacteria than pond water, and spatial and temporal variation in intracapsular and pond bacterial diversity was observed. Despite this variation, sequences corresponding to species in the orders Burkholderiales and Oligoflexales were either prevalent or abundant, or both. Isolates most commonly recovered from capsules were closely related to species in the genus Herbaspirillum (Burkholderiaceae); other isolates were pseudomonads, but in all cases are closely related to known vascular plant-associated species. We conclude that, despite observed variation, there are bacterial taxa whose presence is held in common spatially and temporally among capsules and that the symbiosis between O. amblystomatis and A. maculatum may involve these taxa.

Integrating interprofessional education (IPE) activities and curricular components in health professions education has been emphasized recently by the inclusion of accreditation standards across disciplines. The Interprofessional Education Collaborative (IPEC) established IPE competencies in 2009, but evaluating how activities link to competencies has not been investigated in depth. The purpose of this project is to investigate how well two IPE activities align with IPEC competencies. To evaluate how our IPE activities met IPEC competencies, we developed a checklist and an observation instrument. A brief description of each is included as well as the outcomes. We analyzed Disaster Day, a simulation exercise that includes participants from Nursing, Medicine, and Pharmacy, and Interprofessional Healthcare Ethics (IPHCE), a course that introduced medical, nursing, and pharmacy students to ethical issues using didactic sessions and case discussions. While both activities appeared to facilitate the development of IPE competencies, Disaster Day aligned more with IPEC competencies than the IPHCE course and appears to be a more comprehensive way of addressing IPEC competencies. However, offering one IPE activity or curricular element is not sufficient. Having several IPE options available, utilizing the tools we developed to map the IPE curriculum and evaluating competency coverage is recommended.

Previously, we and others have shown that rodent neural progenitor cells (NPCs) can support functional recovery after cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral midcervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived multi-potent NPCs were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts. The NPCs differentiated into all three neural lineages (neurons, astrocytes, oligodendrocytes) and robustly extended axons into the host spinal cord caudal and rostral to the lesion. Graft-derived axons grew into host gray matter and expressed synaptic proteins in juxtaposition with host neurons. Animals that received NPC grafts exhibited significant recovery of forelimb motor function compared with the two control groups (analysis of variance p < 0.05). Thus, NPC grafts improve forelimb motor outcomes after clinically relevant cervical contusion injury. These benefits are observed when grafts are placed two weeks after injury, a time point that is more clinically practical than acute interventions, allowing time for patients to stabilize medically, simplifying enrollment in clinical trials, and enhancing predictability of spontaneous improvement in control groups.

Bone marrow stromal cells (BMSCs) have been reported to exert potential neuroprotective properties in models of neurotrauma, although precise mechanisms underlying their benefits are poorly understood. Despite this lack of knowledge, several clinical trials have been initiated using these cells. To determine whether local mechanisms mediate BMSC neuroprotective actions, we grafted allogeneic BMSCs to sites of severe, compressive spinal cord injury (SCI) in Sprague-Dawley rats. Cells were administered 48 h after the original injury. Additional animals received allogeneic MSCs that were genetically modified to secrete brain-derived neurotrophic factor (BDNF) to further determine whether a locally administered neurotrophic factor provides or extends neuroprotection. When assessed 2 months post-injury in a clinically relevant model of severe SCI, BMSC grafts with or without BDNF secretion failed to improve motor outcomes. Thus, allogeneic grafts of BMSCs do not appear to act through local mechanisms, and future clinical trials that acutely deliver BMSCs to actual sites of injury within days are unlikely to be beneficial. Additional studies should address whether systemic administration of BMSCs alter outcomes from neurotrauma.