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The objective of this scoping review is to systematically map the extent and nature of the literature on the use of imaging for assessing cervicothoracic junction anatomical variation in patients with neurogenic thoracic outlet syndrome. Neurogenic thoracic outlet syndrome is a complex, disputed diagnosis that lacks a definitive gold-standard test, despite being the most common thoracic outlet syndrome subtype. Imaging is essential for identifying anatomical variations, such as cervical ribs, and excluding competing diagnoses. This review aims to clarify how imaging modalities are utilized to describe, classify, and assess these anatomical variations, and how these findings are explicitly linked to diagnosis or management. This review will consider studies that include patients with neurogenic thoracic outlet syndrome and evaluate the role of imaging in assessing anatomical variations at the cervicothoracic junction. All study designs, including reviews, quantitative, and descriptive studies, will be considered. This review will exclude studies where the primary focus is the diagnosis of arterial or venous thoracic outlet syndrome using vascular imaging modalities. The search strategy will employ a three-step process, developed in consultation with a medical librarian, utilizing a final comprehensive search across multiple major databases (e.g., MEDLINE, CINAHL, Embase, Scopus) and gray literature sources. Studies published in the English language and from database inception will be included. Following screening by two independent reviewers, data will be extracted, synthesized descriptively, and presented in tabular and narrative format to map the identified evidence. Open Science Framework https://osf.io/hybg2.

Nerve regeneration is a key biological process in those recovering from neural trauma. From animal models it is known that the regenerative capacity of the peripheral nervous system (PNS) relies heavily on the remarkable ability of Schwann cells to undergo a phenotypic shift from a myelinating phenotype to one that is supportive of neural regeneration. In rodents, a great deal is known about the molecules that control this process, such as the transcription factors c-Jun and early growth response protein 2 (EGR2/KROX20), or mark the cells and cellular changes involved, including SOX10 and P75 neurotrophin receptor (p75NTR). However, ethical and practical challenges associated with studying human nerve injury have meant that little is known about human nerve regeneration. The present study addresses this issue, analysing 34 denervated and five healthy nerve samples from 27 patients retrieved during reconstructive nerve procedures. Using immunohistochemistry and Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), the expression of SOX10, c-Jun, p75NTR and EGR2 was assessed in denervated samples and compared to healthy nerve. Nonparametric smoothing linear regression was implemented to better visualise trends in the expression of these markers across denervated samples. It was found, first, that two major genes associated with repair Schwann cells in rodents, c-Jun and p75NTR, are also up-regulated in acutely injured human nerves, while the myelin associated transcription factor EGR2 is down-regulated, observations that encourage the view that rodent models are relevant for learning about human nerve injury. Second, as in rodents, the expression of c-Jun and p75NTR declines during long-term denervation. In rodents, diminishing c-Jun and p75NTR levels mark the general deterioration of repair cells during chronic denervation, a process thought to be a major obstacle to effective nerve repair. The down-regulation of c-Jun and p75NTR reported here provides the first molecular evidence that also in humans, repair cells deteriorate during chronic denervation.

In 1917, we split the atom and released an incredible force for destruction. In 2019, we split the DMAIC and released an even bigger force for improvement.There is no doubt that the various improvement methods work. Whether it is PDCA or 7-Step problem-solving or A3 or IIs Not or DMAIC or any other tool, it has been used to great success in many organizations stretching back over decades. But why have some organizations been wildly successful with these and others not?The reason is that much of today's continuous improvement (CI) training is focused on tools. Training includes days or even weeks working through every possible tool a practitioner of CI might need. But rather than teach people about a set of tools that they might or might not use, why not teach them how to accomplish a specific objective? Why not give them a path for solving a particular type of problem that works most of the time? This way, anyone anywhere can make CI work by splitting the DMAIC.This book shows four typical paths through the DMAIC process to accomplish four different objectives: Reduce variability of a characteristic Reduce failures of a machine Reduce waste in a process Reduce the frequency of a defectFor each path, the following is presented: -an overview of the purpose and actual steps through the DMAIC process for that path. -Step Details-a detailed description of each step including specific tools used. -Checklist-a simple one-page sheet that anyone can use as a guide along the path. Think of these as a new app called DMAIC Maps, which helps people get around the DMAIC world the same way Google Maps helps in the real world.Project selection and team management are also discussed, since the choice of projects is crucial to creating context and therefore success.

Peripheral Nerve Injury (PNI) is common following blunt or penetrating trauma with an estimated prevalence of 2% among the trauma population. The resulting economic and societal impacts are significant. Nerve regeneration is a key biological process in those recovering from neural trauma. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and RNA sequencing (RNA seq) are investigative methods that are often deployed by researchers to characterize the cellular and molecular mechanisms that underpin this process. However, the ethical and practical challenges associated with studying human nerve injury have meant that studies of nerve injury have largely been limited to rodent models of renervation. In some circumstances it is possible to liberate human nerve tissue for study, for example during reconstructive nerve repair. This complex surgical environment affords numerous challenges for optimizing the yield of RNA in sufficient quantity and quality for downstream RT-qPCR and/or RNA seq applications. This study characterized the effect of: (1) Time delays between surgical liberation and cryopreservation and (2) contact with antiseptic surgical reagents, on the quantity and quality of RNA isolated from human and rodent nerve samples. It was found that time delays of greater than 3 min between surgical liberation and cryopreservation of human nerve samples significantly decreased RNA concentrations to be sub-optimal for downstream RT-qPCR/RNA seq applications (<5 ng/μl). Minimizing the exposure of human nerve samples to antiseptic surgical reagents significantly increased yield of RNA isolated from samples. The detrimental effect of antiseptic reagents on RNA yield was further confirmed in a rodent model where RNA yield was 8.3-fold lower compared to non-exposed samples. In summary, this study has shown that changes to the surgical tissue collection protocol can have significant effects on the yield of RNA isolated from nerve samples. This will enable the optimisation of protocols in future studies, facilitating characterisation of the cellular and molecular mechanisms that underpin the regenerative capacity of the human peripheral nervous system.

Muscle spindles are sensory organs that detect and mediate both static and dynamic muscle stretch and monitor muscle position, through a specialised cell population, termed intrafusal fibres. It is these fibres that provide a key contribution to proprioception and muscle spindle dysfunction is associated with multiple neuromuscular diseases, aging and nerve injuries. To date, there are few publications focussed on de novo generation and characterisation of intrafusal muscle fibres in vitro. To this end, current models of skeletal muscle focus on extrafusal fibres and lack an appreciation for the afferent functions of the muscle spindle. The goal of this study was to produce and define intrafusal bag and chain myotubes from differentiated C2C12 myoblasts, utilising the addition of the developmentally associated protein, Neuregulin 1 (Nrg-1). Intrafusal bag myotubes have a fusiform shape and were assigned using statistical morphological parameters. The model was further validated using immunofluorescent microscopy and western blot analysis, directed against an extensive list of putative intrafusal specific markers, as identified in vivo . The addition of Nrg-1 treatment resulted in a 5-fold increase in intrafusal bag myotubes (as assessed by morphology) and increased protein and gene expression of the intrafusal specific transcription factor, Egr3. Surprisingly, Nrg-1 treated myotubes had significantly reduced gene and protein expression of many intrafusal specific markers and showed no specificity towards intrafusal bag morphology. Another novel finding highlights a proliferative effect for Nrg-1 during the serum starvation-initiated differentiation phase, leading to increased nuclei counts, paired with less myotube area per myonuclei. Therefore, despite no clear collective evidence for specific intrafusal development, Nrg-1 treated myotubes share two inherent characteristics of intrafusal fibres, which contain increased satellite cell numbers and smaller myonuclear domains compared with their extrafusal neighbours. This research represents a minimalistic, monocellular C2C12 model for progression towards de novo intrafusal skeletal muscle generation, with the most extensive characterisation to date. Integration of intrafusal myotubes, characteristic of native, in vivo intrafusal skeletal muscle into future biomimetic tissue engineered models could provide platforms for developmental or disease state studies, pre-clinical screening, or clinical applications.

Title page -- CIP data -- Contents -- List of Figures and Tables -- Foreword -- Preface -- Introduction -- Splitting the DMAIC -- HOW TO READ THIS BOOK -- Brief History of CI -- The Paths -- Reducing Variability Path -- METHODOLOGY -- STEP DETAILS -- CHECKLIST -- Reducing Failures Path -- METHODOLOGY -- STEP DETAILS -- CHECKLIST -- Reducing Waste Path -- METHODOLOGY -- INVENTORY (AND OVERPRODUCTION) -- TRANSPORTATION (AND MOTION) -- WAITING -- MACHINE IDLE TIME -- PEOPLE IDLE TIME -- OVER PROCESSING -- DEFECTS -- Reducing Defects Path -- METHODOLOGY -- STEP DETAILS -- CHECKLIST -- What Comes Next? How Can You Do This? -- LOOSEN THE BELTS -- QUALITY KATAS -- THE DOING -- CHARTERING -- ROLES/COACHING -- TRAINING -- COMMUNICATION AND RECOGNITION -- REVIEWS -- Digitalization -- Summary and Conclusions -- References -- Index.

To establish a sustainable model for a \"Surgical Shadowing Scheme\" (SSS) and assess how this affects undergraduate attitudes to surgical careers. Surgeons at university teaching hospitals associated with UCL Medical School and UCL Partners, United Kingdom, were approached for their willingness to participate in the scheme. Medical students were then invited to apply for the scheme, where students were individually matched to operating theater sessions with surgeons in their specialty of choice. Feedback was subsequently obtained, evaluating experiences of the placement and the effect this had on future career aspirations. After running for four consecutive years, approximately 220 students have participated in the scheme across a range of surgical units and specialties. A total of 91.5% of the students were pre-clinical (years 1-3), whilst the remainder were clinical (years 4-6). Fifty-four percent were female and 46% male. Eighty-three percent of the students did not have any previous experience of the specialty that they shadowed, and 67% agreed that participating in the scheme had either \"increased\" or \"strongly increased\" their desire to pursue a surgical career. Ninety-four percent said they would \"recommend\" or \"strongly recommend\" the SSS to a peer. Over a third of students reported scrubbing-up during their placements and 35% of these directly assisted the lead surgeon. Traditionally male-dominated surgical sub-specialties recruited a high proportion of female students. This is the first published example of an established \"Surgical Shadowing Scheme\" for medical undergraduates. Our SSS has been highly valued by students and indicates that even a single high-quality surgical exposure is sufficient to increase the desire of undergraduates to pursue a surgical career. We hope that this SSS will act as a blueprint for other centers to develop their own shadowing schemes, in turn helping to ensure that surgery continues to inspire and attract the very best candidates for the future.

The development of outcome measures that can track the recovery of reinnervated muscle would benefit the clinical investigation of new therapies which hope to enhance peripheral nerve repair. The primary objective of this study was to assess the validity of volumetric Magnetic Resonance Imaging (MRI) as an outcome measure of muscle reinnervation by testing its reproducibility, responsiveness and relationship with clinical indices of muscular function. Over a 3-year period 25 patients who underwent nerve transfer to reinnervate elbow flexor muscles were assessed using intramuscular electromyography (EMG) and MRI (median post-operative assessment time of 258 days, ranging from 86 days pre-operatively to 1698 days post- operatively). Muscle power (Medical Research Council (MRC) grade) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) assessment was also recorded for all patients. Sub-analysis of peak volitional force (PVF), muscular fatigue and co-contraction was performed in those patients with MRC > 3. The responsiveness of each parameter was compared using Pearson or Spearman correlation. A Hierarchical Gaussian Process (HGP) was implemented to determine the ability of volumetric MRI measurements to predict the recovery of muscular function. Reinnervated muscle volume per unit Body Mass Index (BMI) demonstrated good responsiveness (R 2  = 0.73, p  < 0.001). Using the temporal and muscle volume per unit BMI data, a HGP model was able to predict MRC grade and SPONEA with a mean absolute error (MAE) of 0.73 and 1.7 respectively. Muscle volume per unit BMI demonstrated moderate to good positive correlations with patient reported impairments of reinnervated muscle; co- contraction (R 2  = 0.63, p  = 0.02) and muscle fatigue (R 2  = 0.64, p  = 0.04). In summary, volumetric MRI analysis of reinnervated muscle is highly reproducible, responsive to post-operative time and demonstrates correlation with clinical indices of muscle function. This encourages the view that volumetric MRI is a promising outcome measure for muscle reinnervation which will drive advancements in motor recovery therapy.

Glucagon like-peptide 1 receptor (GLP-1R) agonists diminish appetite and may contribute to the weight loss in inflammatory bowel disease (IBD). The aim of this study was to determine, for the first time, the expression of GLP-1R by colon nerve fibres in patients with IBD, and functional effects of its agonists in cultured rat and human sensory neurons. GLP-1R and other nerve markers were studied by immunohistochemistry in colon biopsies from patients with IBD (n = 16) and controls (n = 8), human dorsal root ganglia (DRG) tissue, and in GLP-1R transfected HEK293 cells. The morphological effects of incretin hormones oxyntomodulin, exendin-4 and glucagon were studied on neurite extension in cultured DRG neurons, and their functional effects on capsaicin and ATP signalling, using calcium imaging. Significantly increased numbers of colonic mucosal nerve fibres were observed in IBD biopsies expressing GLP-1R (p = 0.0013), the pan-neuronal marker PGP9.5 (p = 0.0008), and sensory neuropeptide CGRP (p = 0.0014). An increase of GLP-1R positive nerve fibres in IBD colon was confirmed with a different antibody to GLP-1R (p = 0.016). GLP-1R immunostaining was intensely positive in small and medium-sized neurons in human DRG, and in human and rat DRG cultured neurons. Co-localization of GLP-1R expression with neuronal markers in colon and DRG confirmed the neural expression of GLP-1R, and antibody specificity was confirmed in HEK293 cells transfected with the GLP-1R. Treatment with oxyntomodulin, exendin-4 and GLP-1 increased neurite length in cultured neurons compared with controls, but did not stimulate calcium influx directly, or affect capsaicin responses. However, exendin-4 significantly enhanced ATP responses in human DRG neurons. Our results show that increased GLP-1R innervation in IBD bowel could mediate enhanced visceral afferent signalling, and provide a peripheral target for therapeutic intervention. The differential effect of GLP-1R agonists on capsaicin and ATP responses in neurons suggest they may not affect pain mechanisms mediated by the capsaicin receptor TRPV1, but may enhance the effects of purinergic agonists.