Comprehensive Evaluation of Peripheral Nerve Regeneration in the Acute Healing Phase Using Tissue Clearing and Optical Microscopy in a Rodent Model

Peripheral nerve injury (PNI), a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout nerves in a PNI model. The methods developed in this study could advance PNI research allowing both researchers and clinicians to further understand the individual events of axonal degeneration and regeneration on a multifaceted level

Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly

Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is currently lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this dataset reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome likely represents a core cell adhesion machinery, centred around four axes comprising ILK-PINCH-kindlin, FAK-paxillin, talin-vinculin and α-actinin-zyxin-VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community

Painful bruising: Gynecology, hematology, or just pill bias? A case report

A 23-year-old woman, G0, presented to the emergency department with painful bruising of the legs shortly after starting an oral contraceptive pill. The presumed diagnosis was pill-induced ecchymosis, and she was instructed to discontinue the medication. Her bruising resolved. However, the working diagnosis was later questioned as the patient had used other oral contraceptive pills in the past without any adverse reaction. In addition, there is robust literature associating these medications with thrombosis, not bruising.The patient later disclosed that she had concomitantly started an oral hair supplement along with her oral contraceptive pill. Analysis of the supplement contents revealed that it contained extract of Aesculus hippocastanum, a herbal anticoagulant, making this a much more plausible explanation for the ecchymosis. She then resumed the original oral contraceptive pill alone without any reaction.The case highlights how cognitive bias resulted in a misdiagnosis. Specifically, this case introduces the concept of pill bias, as the patient's unexplained bruising was presumed to be a result of her use of an oral contraceptive despite the lack of evidence to support this claim. This bias has the potential to impact clinical decision-making and lead to clinical errors

Use of a Mandibular Plate to Maintain Intergonial Width in a Partially Edentulous Patient Undergoing Mandibular Symphysis Reconstruction

Photograph of a scene on the Lake of the Arbuckles

Thermal Injury to Reconstructed Breasts from Commonly Used Warming Devices: A Risk for Reconstructive Failure

Background: Sensation is decreased or absent after breast reconstruction. This leaves reconstructed breasts vulnerable to injury from common household thermal sources such as heating pads and hot water bottles. We sought to categorize these injuries, provide a treatment plan, and prevent these injuries in the future. Methods: A retrospective review of patients who had sustained burns to reconstructed breasts with household devices was performed at a single institution. A PubMed search was performed to identify and summarize articles cataloguing patients who had suffered burns to breast reconstructions. Results: Five patients in our practice were affected. Fifteen articles were identified in the literature search. A total of 40 patients had sustained thermal injury to reconstructed breasts, with the majority being full thickness burns (67.5%). Patients who sustained full thickness burns to reconstructed breasts were more likely to require an operative procedure compared with patients who sustained partial thickness burns (P = 0.0076). Conclusions: Reconstructed breasts are at risk for injury from commonly used household warming devices and ambient heat from the sun. As a result, patients should be counseled about these risks accordingly, to avoid injury or loss of reconstruction. These injuries require immediate vigilant treatment

How the CHI community got its groove: and changed the world!

In its 35 years, the CHI Community's remarkable research success has enabled an astonishing worldwide cultural transformation. CHI research on graphical user interfaces, touchscreens, hypertext, mobile devices, and social media have dramatically changed family/friend relationships, business, medical care, education, and much more. Many of the changes are for good, but disruptive changes and destructive forces have also been unleashed. This session will track the history of the CHI community's dramatic growth, changing research methods, and substantial impact across disciplines, industries, and cultures. It will focus on some key personalities, while also drawing on my career, which includes being a founder of the CHI conference and a participant throughout. I will also present a fresh vision of research from my book "The New ABCs of Research: Achieving Breakthrough Collaborations.