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Unsticking Shame: Considering Lived Experience and Processes of Overcoming
No full textTaking the Braving Body Shame conference, which featured women discussing their experiences with shame, as a case study, this paper addresses what women do with their affective experiences. The paper examines videos from the Braving Body Shame conference to discuss how participants frame shame as a generative, recursive process of overcoming that stems from a recognition of their subjectivity. This paper offers one way of complicating our scholarly understanding of shame to avoid the flattening of affect and highlights the manifold ways individuals cope and seek empowerment within oppressive system
Utilization and Perceptions of a Novel Cervical Visualization Tool, The Callascope, For Home-Based Self-Cervical Examinations
No full textPostoperative pyoderma gangrenosum after spinal fusion with instrumentation: case report.
No full textPyoderma gangrenosum (PG) is a rare inflammatory dermatosis that is most often associated with inflammatory bowel disease, but which can occur as a pathergic reaction around surgical incisions. The authors report the case of a patient who developed postoperative PG over the course of several months after undergoing extensive spinal instrumentation between the T4 and iliac levels. This is only the second such case occurring after spine surgery to be reported. The authors additionally review the literature to characterize treatment approaches and outcomes for this condition. The case highlights a potentially severe adverse effect of surgery that can be difficult to recognize and causes delays in effective treatment. It also demonstrates the importance of multidisciplinary collaboration in the effective care of patients
Antithrombotic therapy in patients with COVID-19: indications, pharmacotherapy and controversy
No full textBest Practices for Modernizing Integrated Public Benefits Applications
No full textMany state agencies around the country are trying to modernize applications for public benefits programs in their state. This work often involves developing an integrated application for two or more public benefits, and then engineering an online portal on which to host the integrated application. Because most state agencies lack the technological expertise to do this work in-house, they hire third party vendors and consulting firms to help. This report thus seeks to answer the question: What can be learned about best practices for equitable applications, from states that have modernized their remote integrated benefits applications for Medicaid, Supplemental Nutrition Assistance Program (SNAP) and/or Temporary Assistance for Needy Families (TANF) programs since the Affordable Care Act? To answer this question, the researcher conducted 24 interviews with Subject Matter Experts involved in designing, building, launching, administering, and/or researching integrated benefits applications. Findings include best practices for the processes of hiring, building, launching, and conducting outreach related to integrated benefits applications. States must also ensure that the benefits applications are human-centered, meaning that the features and capabilities of the application facilitate equitable access and successful enrollment by applicants with diverse backgrounds, identities, and needs
I. Development of sulfonyl piperazine LpxH inhibitors against multi-drug resistant Gram-negative bacteria II. Exploration towards new TRPM8 agonists for dry eye disease
No full textThe discovery of new drug scaffolds is a time-consuming and costly process. As new technologies are developed and implemented into the drug discovery process, these costs are being lessened. Of these methods, computer-aided drug discovery is the most widely implemented as it reduces the number of compounds that need to be explored synthetically. Computer-aided drug discovery has also become a powerful tool as it envelops a wide range of computational methods that can be used to identify or optimize lead compounds for various disease states or drug targets.The first part of the dissertation presents the design, synthesis, and biological evaluation of sulfonyl piperazine LpxH inhibitors. The emergence of widespread antibiotic resistance among Gram-negative pathogens has led to an urgent need for a new class of antibiotics to fight multidrug-resistant Gram-negative bacteria. Lipid A is a critical component of lipopolysaccharides present on the outer membrane of Gram-negative bacteria that prevents penetration of the membrane by external detergents and antibiotics. The biosynthesis of lipid A occurs through the Raetz pathway via 9 distinct enzymes, one of which is known as LpxH. The dual mechanism of cell killing due to the inhibition of LpxH and its presence in the majority of Gram-negative bacteria makes it an attractive target for novel antibiotics. Based on the structure of AZ1, a small molecule inhibitor of LpxH identified by AstraZeneca, we have synthesized and evaluated a series of sulfonyl piperazine LpxH inhibitors. Our study allowed for the establishment of a comprehensive structure-activity relationship of the various components of AZ1. We also obtained the first crystal structure of Klebsiella pneumoniae LpxH in complex with a sulfonyl piperazine LpxH inhibitor which illuminated how this class of LpxH inhibitors fits into the binding pocket of LpxH and guided the design of inhibitors with increased potency. Our findings will be instrumental in the discovery of new antibiotics against multidrug-resistant Gram-negative pathogens.
The second part of the dissertation describes the modification of existing TRPM8 ligands and the search for alternative scaffolds towards the development of a new TRPM8 agonist for the treatment of dry eye disease. As the use of technology continues to increase, so does the incidence of dry eye disease, especially in younger individuals. Modulation of the transient receptor potential cation channel TRPM8 has been implicated as a route for the treatment of dry eye disease as TRPM8 plays a critical role in basal tear production, eye blinking, and is the sensor for eye dryness. Current well-known modulators of TRPM8 such as menthol, icilin, and WS-12, are not suitable for ocular use as they have undesirable physical properties and have off-target effects on other transient receptor potential channels. The recently discovered small molecule cryosim-3 which was identified as a TRPM8 specific agonist provides a good starting point for the development of a new agonist suitable for ocular studies. Through the use of cryo-electron microscopy, molecular docking, and virtual screening, we have begun to understand the different binding orientations of various TRPM8 ligands. This information has aided us in probing new chemical space for the identification of a TRPM8 agonist with improved potency, selectivity, and physical properties over existing agonists.
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Vocal Fold Paralysis/Paresis as a Marker for Poor Swallowing Outcomes After Thoracic Surgery Procedures.
No full text(1) To examine the association between vocal fold paresis/paralysis (VFP) and poor swallowing outcomes in a thoracic surgery cohort at the population level, and (2) to assess utilization of ENT/speech-language pathology intervention in these cases. The National Inpatient Sample (NIS) represents a 20% stratified sample of discharges from US hospitals. Using ICD-9 codes, discharges undergoing general thoracic surgical procedures between 2008 and 2013 were identified in the NIS. Sub-cohorts of discharges with VFP and those who utilized ENT/SLP services were also identified. Weighted logistic regression models were used to compare binary outcomes such as dysphagia, aspiration pneumonia, and other complications; generalized linear models with generalized estimating equations (GEE) were used to compare total hospital costs and length of stay (LOS). We identified a weighted estimate of 673,940 discharges following general thoracic surgery procedures. The weighted frequency of VFP was 3738 (0.55%). Compared to those without VFP, patients who discharged with VFP had increased odds of dysphagia (6.56, 95% CI 5.07-8.47), aspiration pneumonia (2.54, 95% CI 1.74-3.70), post-operative tracheotomy (3.10, 95% CI 2.16-4.45), and gastrostomy tube requirement (2.46, 95% CI 1.66-3.64). Discharges with VFP also had a longer length of stay and total hospital costs. Of the discharges with VFP, 15.7% received ENT/SLP intervention. VFP after general thoracic procedures is associated with negative swallowing-related health outcomes and higher costs. Despite these negative impacts, most patients with VFP do not receive ENT/SLP intervention, identifying a potential opportunity for improving adverse swallowing-related outcomes
Sexual Dysfunction: Prevalence and Prognosis in Patients Operated for Degenerative Lumbar Spondylolisthesis.
No full textBackgroundThere is a paucity of investigation on the impact of spondylolisthesis surgery on back pain-related sexual inactivity.ObjectiveTo investigate predictors of improved sex life postoperatively by utilizing the prospective Quality Outcomes Database (QOD) registry.MethodsA total of 218 patients who underwent surgery for grade 1 degenerative lumbar spondylolisthesis were included who were sexually active. Sex life was assessed by Oswestry Disability Index item 8 at baseline and 24-mo follow-up.ResultsMean age was 58.0 ± 11.0 yr, and 108 (49.5%) patients were women. At baseline, 178 patients (81.7%) had sex life impairment. At 24 mo, 130 patients (73.0% of the 178 impaired) had an improved sex life. Those with improved sex lives noted higher satisfaction with surgery (84.5% vs 64.6% would undergo surgery again, P = .002). In multivariate analyses, lower body mass index (BMI) was associated with improved sex life (OR = 1.14; 95% CI [1.05-1.20]; P ConclusionOver 80% of patients who present for surgery for degenerative lumbar spondylolisthesis report a negative effect of the disease on sex life. However, most patients (73%) report improvement postoperatively. Sex life improvement was associated with greater satisfaction with surgery. Lower BMI was predictive of improved sex life. In older patients-in addition to lower BMI-lower ASA grade and higher education were predictive of improvement
A single-center retrospective analysis of 3- or 4-level anterior cervical discectomy and fusion: surgical outcomes in 66 patients.
No full textObjectiveAnterior cervical discectomy and fusion (ACDF) is a safe and effective intervention to treat cervical spine pathology. Although these were originally performed as single-level procedures, multilevel ACDF has been performed for patients with extensive degenerative disc disease. To date, there is a paucity of data regarding outcomes related to ACDFs of 3 or more levels. The purpose of this study was to compare surgical outcomes of 3- and 4-level ACDF procedures.MethodsThe authors performed a retrospective chart review of patients who underwent 3- and 4-level ACDF at the University of Virginia Health System between January 2010 and December 2017. In patients meeting the inclusion/exclusion criteria, demographics, fusion rates, time to fusion, and reoperation rates were evaluated. Fusion was determined by ResultsSixty-six patients (47 with 3-level and 19 with 4-level ACDFs) met the inclusion/exclusion criteria of having at least one lateral flexion/extension radiograph series ≥ 12 months after surgery. Seventy percent of 3-level patients and 68% of 4-level patients had ≥ 24 months of follow-up. Ninety-four percent of 3-level patients and 100% of 4-level patients achieved radiographic fusion for at least 1 surgical level. Eighty-eight percent and 82% of 3- and 4-level patients achieved fusion at C3-4; 85% and 89% of 3- and 4-level patients achieved fusion at C4-5; 68% and 89% of 3- and 4-level patients achieved fusion at C5-6; 44% and 42% of 3- and 4-level patients achieved fusion at C6-7; and no patients achieved fusion at C7-T1. Time to fusion was not significantly different between levels. Revision was required in 6.4% of patients with 3-level and in 16% of patients with 4-level ACDF. The mean time to revision was 46.2 and 45.4 months for 3- and 4-level ACDF, respectively. The most common reason for revision was worsening of initial symptoms.ConclusionsThe authors' experience with long-segment anterior cervical fusions shows their fusion rates exceeding most of the reported fusion rates for similar procedures in the literature, with rates similar to those reported for short-segment ACDFs. Three-level and 4-level ACDF procedures are viable options for cervical spine pathology, and the authors' analysis demonstrates an equivalent rate of fusion and time to fusion between 3- and 4-level surgeries
Clinically Adjudicated Reference Standards for Evaluation of Infectious Diseases Diagnostics.
No full textLack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an imperfect reference, rather than correctness, because the right answer is unknown. Solutions consist of multitest comparators, including those that involve a test under evaluation if multiple new tests are being evaluated together, using latent class modeling, and clinically adjudicated reference standards. Clinically adjudicated reference standards may be considered as comparator methods when no predefined test or composite of tests is sufficiently accurate; they emulate clinical practice in that multiple data pieces are clinically assessed together