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Despite decades of research and clinical trials, metastatic castration-resistant prostate cancer (mCRPC) remains incurable and typically fatal. Current treatments may provide modest increases in progression-free survival but can come with significant adverse effects and are disaggregated from the diagnostic imaging needed to fully assess the spread of metastatic disease. A theranostic approach, using radiolabeled ligands that target the cell surface protein PSMA, simplifies the visualization and disease treatment process by enabling both to use similar agents. Here, we describe an exemplary case wherein a gentleman in his 70s with mCRPC on diagnosis was treated with 177Lu–PSMA-617 and abiraterone, and remains disease-free to date, over five years later.

Nutrition knowledge, confidence, and skills are thought to be important elements in the role of healthcare professionals in obesity prevention and management. The Upstream Obesity Solutions curriculum goes upstream with a multidisciplinary approach to supplement nutrition education among health professional trainees. Educational strategies of didactics, teaching kitchens, and service-based learning were employed for medical, dental, and nursing students and resident physicians. Pre/post participation surveys assessed knowledge, attitude, and practices; lifestyle habits; and culinary skills among 75 trainees in this cross-sectional descriptive study. There was variability in statistically significant improvement in knowledge, attitudes, and practices about obesity management and nutrition education, lifestyle habits, and culinary skills among learner groups.

BackgroundOccupational health hazards are ubiquitously found in the operating room, guaranteeing an inevitable risk of exposure to the surgeon. Although provisions on occupational health and safety in healthcare exist, they do not address non-traditional hazards found in the operating room. In order to determine whether surgeons or trainees receive any form of occupational health training, we examine the associations between occupational health training and exposure rate.Study designA cross-sectional survey was distributed. Respondent characteristics included academic level, race/ethnicity, and gender. The survey evaluated seven surgical disciplines and 13 occupational hazards. Multivariable logistic regression was used to examine the association between academic level, surgical specialty, and exposure rate.ResultsOur cohort of 183 respondents (33.1% response rate) consisted of attendings (n = 72, 39.3%) and trainees (n = 111, 60.7%). Surgical trainees were less likely to have been trained in cytotoxic drugs (OR 0.22, pConclusionAlthough surgeon safety is not a domain in residency training, standardized efforts to educate and change the culture of safety in residency programs is warranted. Our study demonstrates a disparity between trainees and attendings with a recommendation to provide formal training to trainees independent of their anticipated risk of exposure.

Purpose: Improved graft reinnervation and functional recovery would greatly enhance the utility of vascularized composite allotransplantation (VCA). Pre-implantation of nerve grafts in a limb transplant recipient prior to transplantation to increase the length of the severed nerves in the amputation stump offers a novel, readily translatable approach to this problem. At the time of transplantation a pre-implanted nerve graft (PING) would be elevated from its wound bed in the amputated stump and unfurled distally into the transplanted limb, allowing for a more distal nerve coaptation. Methods: We used a reversed sciatic-tibial nerve isograft coapted end-to-end to a median nerve in a rat to: (1) determine viability of distal axons after elevating PINGs; and (2) assess for ischemic injury to axons in the distal PING following elevation from the wound bed. For axonal viability, grafts of varying lengths (2cm,3cm,4cm, n≥5/group) were left to regenerate for 8 weeks. The distal ends were then biopsied prior to elevation, and again one week after elevation. For ischemia assessment, blood flow along 4cm long PINGs was measured with laser doppler at multiple timepoints: baseline (at time of grafting), 8 weeks after grafting (before elevation), immediately after elevation, and 3 and 7 days post-elevation (n=8/timepoint). Means were compared with t-tests and ANOVA. A pig forelimb model was used to assess the functional impact of PINGs. A 6cm long reversed ulnar-PING was coapted to the proximally transected ulnar nerve. After 12 weeks of regeneration, the distal PING was transferred end-to-end to the median nerve just proximal to the elbow. A control group underwent ulnar-to-median nerve transfer 6cm proximal to the elbow (n=4 limbs/group). Hoof flexion force was measured every three weeks. Results Axonal viability: after 8 weeks, axons had regenerated into the distal grafts in all lengths: mean myelinated axon counts (±SD): 7043 (±790), 6066 (±1838), 6491 (±983) in 2cm,3cm,4cm grafts, with no differences between graft lengths (p=0.48). One week after elevation and unfurling, the number of myelinated axons was significantly decreased in all groups (p

Category: Ankle Arthritis Introduction/Purpose: Total ankle replacement (TAR) is common tool used by the foot and ankle specialist to treat end stage ankle arthritis. Current data about ankle motion following TAR is derived from gait analysis utilizing external markers. Utilizing Xray Reconstruction of Moving Morphology (XROMM), which combines 3-D mapping technology with biplanar fluoroscopy in vivo to visualize true skeletal motion, we can evaluate true motion of TAR implants. Current TAR replacement systems are either mobile bearing or fixed bearing. We hypothesized that subjects implanted with a fixed bearing prosthesis would exhibit less tibiotalar rotation and translation than subjects implanted with a mobile bearing prosthesis. Methods: Six subjects with total ankle replacement at least one-year post implantation gave informed consent before participating (IRB #H16496). Three subjects with a mobile bearing prosthesis with an average age 63.3+-11.1 yrs were compared to three matched subjects with a fixed bearing prosthesis with an average age of 64.7+-1.5 yrs. Utilizing 3D slicer software, lower body CT scans for each subject were evaluated to create 3D models of the foot and ankle bones and implant components. All subjects walked for several trials at a self-selected pace along a walkway while their foot and ankle motions were captured by a high-speed biplanar fluoroscopic x-ray motion analysis (XMA) system. The 3D models were combined with the x-ray images within a 3D animation platform and rotoscoped to resolve accurate kinematic motions at the tibiotalar joint during stance phase of gait. We examined for differences between the two groups using a two-sample t-test (p

Neurodegenerative diseases originate from neuronal loss in the central nervous system (CNS). These debilitating diseases progress with age and have become common due to an increase in longevity. The National Institute of Environmental Health Science’s 2021 annual report suggests around 6.2 million Americans are living with Alzheimer’s disease, and there is a possibility that there will be 1.2 million Parkinson’s disease patients in the USA by 2030. There is no clear-cut universal mechanism for identifying neurodegenerative diseases, and therefore, they pose a challenge for neurobiology scientists. Genetic and environmental factors modulate these diseases leading to familial or sporadic forms. Prior studies have shown that miRNA levels are altered during the course of the disease, thereby suggesting that these noncoding RNAs may be the contributing factor in neurodegeneration. In this review, we highlight the role of miRNAs in the pathogenesis of neurodegenerative diseases. Through this review, we aim to achieve four main objectives: First, we highlight how dysregulation of miRNA biogenesis led to these diseases. Second, we highlight the computational or bioinformatics tools required to identify the putative molecular targets of miRNAs, leading to biological molecular pathways or mechanisms involved in these diseases. Third, we focus on the dysregulation of miRNAs and their target genes leading to several neurodegenerative diseases. In the final section, we highlight the use of miRNAs as potential diagnostic biomarkers in the early asymptomatic preclinical diagnosis of these age-dependent debilitating diseases. Additionally, we discuss the challenges and advances in the development of miRNA therapeutics for brain targeting. We list some of the innovative strategies employed to deliver miRNA into target cells and the relevance of these viral and non-viral carrier systems in RNA therapy for neurodegenerative diseases. In summary, this review highlights the relevance of studying brain-enriched miRNAs, the mechanisms underlying their regulation of target gene expression, their dysregulation leading to progressive neurodegeneration, and their potential for biomarker marker and therapeutic intervention. This review thereby highlights ways for the effective diagnosis and prevention of these neurodegenerative disorders in the near future.

Purpose: Despite clinical concerns associated with traumatic brain injuries (TBIs), they remain grossly underreported: 46% of TBIs in adult craniomaxillofacial (CMF) trauma patients remained unrecorded at discharge. This has not been studied in the pediatric CMF trauma population. Consequently, this is the first retrospective study to characterize concomitant pediatric TBI and CMF trauma patients, including incidence, presentation, documentation, and outcomes. The authors hypothesize that TBI in pediatric CMF trauma is associated with worse prognosis and remains under-recorded. Methods: An IRB-approved retrospective cohort study was performed to identify all pediatric patients presenting with CMF fractures at a high volume, tertiary trauma center between January 1st, 1990 to December 31st, 2010. Patients were included if they were (1) age younger than 15 years and (2) confirmed presence of CMF injury by means of imaging, radiology report, and physical examination. Patient charts were reviewed for demographic information, dentition stage, CMF fracture patterns, mechanism of injury, presentation, need for operative management, length of stay, and mortality at 2 years. Charts were reviewed to identify concomitant TBIs, defined as intracranial injury, cerebral hemorrhage, brain concussion, epilepsy or seizures (post-traumatic), and traumatic brain injury (documented). Data was analyzed using two-tailed Student’s t-tests and chi square analysis. Point-biserial correlation coefficients were calculated between a continuous and dichotomous variable; Pearson correlation coefficients were calculated between continuous variables. A P value ≤ 0.05 was considered statistically significant. Results: Of the 2966 pediatric CMF trauma patients identified and included for analysis (mean age of 7 +/- 4.7 years old, predominantly white, 59.8%, and male, 64.0%), 809 had concomitant TBI (frequency of 27.3%). Only 13 of the 809 TBI cases were documented in charts (1.6%). Concomitant TBI with CMF trauma patients were more likely to be male (69.1% vs 62%, P < 0.05), and be caused by blunt injury (98.9% vs. 95.5%, P < 0.05), compared to CMF trauma patients without TBI. TBI patients had a higher mortality rate at two years (8.0% vs 4.8%, P < 0.05). Mortality at two years, length of stay in hospital, and time to follow up significantly increased from mild to severe TBIs. Concomitant TBI and CMF trauma patients were also more likely to present with skull & upper third fractures than CMF trauma without TBI (81.8% vs 61.1%, P < 0.05). Conclusion: In this 20-year retrospective review, concomitant TBI injuries were present in a significant number of pediatric CMF trauma cases (27.3%) but was not documented for most cases. Given the importance of initial management and long-term care in TBI patients, it is critical for clinicians to remain vigilant for and manage TBIs in pediatric CMF trauma patients in collaboration with appropriate neurology and/or neurosurgery teams. Future prospective studies are necessary to better characterize TBI patient injury patterns and outcomes to generate practice guiding recommendations for this patient population.

Purpose: There is poor functional recovery following delayed peripheral nerve repair since both muscle and Schwann cells (SC) undergo denervation atrophy. We investigated the specific temporal effect of nerve/SC denervation on recovery as well as changes in RNA expression in the nerves that may elucidate changes in recovery potential. We hypothesized that functional recovery would be worse after prolonged nerve/SC denervation and that the expression profiles would differ. Methods: Our study was conducted using a forelimb model in adult Lewis rats. Each animal underwent unilateral forelimb denervation of 8, 12, 16, or 24 weeks duration. In the functional recovery arm of the study, the ulnar nerve was denervated proximally or a sham surgery was performed. After the denervation period had elapsed, an in situ nerve transfer of median to ulnar to median nerve was performed. Functional recovery was then measured by stimulated grip strength weekly for 12 weeks. In the RNA expression arm, median and ulnar nerves were denervated. The same time points were used with the addition of a 1-week denervation group. After the denervation period, the median and ulnar nerves were harvested bilaterally. To create a comprehensive RNA-Seq dataset, the median nerve, with an average length of 3 cm, was homogenized and RNA was purified. RNA-sequencing was carried out using TrueSeq RiboZero gold kit. Samples were analyzed through FastQC, aligned to reference genome using STAR and quantified as transcripts per million (TPM) using Salmon. Principle component analysis was performed, followed by differential gene analysis using a linear mixed effects model to control for the control nerves being from the same animals. Results: Functional recovery was statistically significantly different depending on the duration of nerve/SC denervation (P0.05, we identified 1624 genes differentially expressed, of which 327 genes were upregulated and rest (1297 genes) downregulated with denervation. Conclusions: Prolonged nerve/SC denervation of more than 12 weeks resulted in significantly worse functional recovery. RNA sequencing demonstrated that not only were there many genes differentially expressed, but these appear to vary with duration of denervation as well. Further investigation into the specific genes and their changes over time will allow us to know why recovery potential is decreased and targets for interventions to improve recovery.

Recently, some polysaccharides showed therapeutic potentials for the treatment of neurodegenerative diseases while the most important property, their permeability to the blood brain barrier (BBB) that sheathes the brain and spinal cord, is not yet determined. The determination has been delayed by the difficulty in tracking a target polysaccharide among endogenous polysaccharides in animal. We developed an easy way to examine the BBB-permeability and, possibly, tissue distribution of a target polysaccharide in animal. We tagged a polysaccharide with fluorescent 8-aminonaphthalene-1,3,6-trisulfonic acid disodium salt (ANTS) for tracking. We also developed a simple method to separate ANTS-tagged polysaccharide from unconjugated free ANTS using 75% ethanol. After ANTS-polysaccharide was intra-nasally administered into animals, we could quantify the amounts of ANTS-polysaccharide in the brain and the serum by fluorocytometry. We could also separate free ANTS-polysaccharide from serum proteins using trichloroacetic acid (TCA) and 75% ethanol. Our method will help to track a polysaccharide in animal easily. • ANTS-labeling is less tedious than but as powerful as radiolabeling for tracking a target polysaccharide in animal. • Our simple method can separate structurally intact ANTS-polysaccharide from animal serum and tissues. • This method is good for the fluorometry-based measurement of ANTS-conjugated macromolecules in tissues.

Measurements of nuclear organization in asymmetric nuclei in 2D images have traditionally been manual. This is exemplified by attempts to measure chromosome position in sperm samples, typically by dividing the nucleus into zones, and manually scoring which zone a fluorescence in-situ hybridisation (FISH) signal lies in. This is time consuming, limiting the number of nuclei that can be analyzed, and prone to subjectivity. We have developed a new approach for automated mapping of FISH signals in asymmetric nuclei, integrated into an existing image analysis tool for nuclear morphology. Automatic landmark detection defines equivalent structural regions in each nucleus, then dynamic warping of the FISH images to a common shape allows us to generate a composite of the signal within the entire cell population. Using this approach, we mapped the positions of the sex chromosomes and two autosomes in three mouse lineages (Mus musculus domesticus, Mus musculus musculus and Mus spretus). We found that in all three, chromosomes 11 and 19 tend to interact with each other, but are shielded from interactions with the sex chromosomes. This organization is conserved across 2 million years of mouse evolution.

This chapter reflects on how the Michigan Center for Student Success (MCSS) has leveraged its position within a membership organization for community college presidents and trustees to engage in statewide student success efforts in a state with a unique higher education governance structure. With no formal higher education governing body to set policy or coordinate initiatives, the MCSS has relied on individual leaders and practitioners within institutions to create a coalition of the willing who have worked to move the student success agenda forward. The article provides a political and historical context for the center's founding, explores the center's accomplishments, and concludes by discussing considerations for coalition leaders in other states.

While visiting Erica's tenth-grade classroom, Jen approached Cameron (student names are pseudonyms), asking him what he was going to write about for his social justice research paper. Cameron briefly looked [...]

This case describes a strategic planning process initiated by the division of student affairs at a small, private college. It presents several issues related to institutional identity, strategic planning initiative development, faculty and staff buy-in and stay-in, and the changing landscape of higher education. The case is designed for usage in educational leadership programs and is particularly pertinent to provoke discussions regarding leading from the middle, leadership for institutional change, and moral and ethical leadership. Students in educational leadership enrolled in student affairs leadership and administration courses, budgeting or strategic planning, or organizational theory courses can engage in discussion using multiple aspects of the case.

This study uses fixed-effects panel data techniques to estimate the elasticity of community college enrollment demand relative to local unemployment rates. The findings suggest that community college enrollment demand is counter-cyclical to changes in the labor market, as enrollments rise during periods of weak economic conditions. Using national data for the years 1990 through 2009, we find that a one percentage-point change in unemployment is associated with 1.1-3.3% increases in enrollment demand. We disaggregate the analysis by total full-time and part-time enrollment, concluding that high levels of unemployment are also associated with greater demand for full-time attendance. Additionally, enrollments are slightly more responsive to unemployment in metropolitan (rather than micropolitan) areas. Informed by enrollment demand theory, our analysis provides an update to the "unemployment elasticity" literature and could aid in current enrollment planning, economic development, and public policy efforts to educate students on the margin between college and work.