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Few studies have investigated risk factors for recurrence of blunt traumatic abdominal wall hernias (TAWH).Twenty trauma centers identified repaired TAWH from January 2012 to December 2018. Logistic regression was used to investigate risk factors for recurrence.TAWH were repaired in 175 patients with 21 (12.0%) known recurrences. No difference was found in location, defect size, or median time to repair between the recurrence and non-recurrence groups. Mesh use was not protective of recurrence. Female sex, injury severity score (ISS), emergency laparotomy (EL), and bowel resection were associated with hernia recurrence. Bowel resection remained significant in a multivariable model.Female sex, ISS, EL, and bowel resection were identified as risk factors for hernia recurrence. Mesh use and time to repair were not associated with recurrence. Surgeons should be mindful of these risk factors but could attempt acute repair in the setting of appropriate physiologic parameters.

Quantitative phase analysis (QPA) of slags is complex due to the natural richness of phases and variability in sample composition. The number of phases frequently exceeds 10, with certain slag types (EAF, BOF, blends, stainless) having extreme peak overlap, making identification difficult. Another convolution arises from the variable crystallite sizes of phases found in slag, as well as the mixture of crystalline and amorphous components specific to each slag type. Additionally, polymorphs are common because of the complexity of the steelmaking and slag cooling processes, such as the cation-doped calcium aluminum silicate (Ca3Al2O6, C3A, Z = 24) supercell in LMF slag. References for these doped variants may not exist or in many cases are not known in advance, therefore it is incumbent on the analyzer to be aware of such discrepancies and choose the best available reference. All issues can compound to form a highly intricate QPA and have prevented previous methods of QPA from accurately measuring phase components in slag. QPA was performed via the internal standard method using 8 wt% ZnO as the internal standard and JADE Pro's Whole Pattern Fitting analysis. For each phase, five variables (lattice parameters, preferred orientation, scale factor, temperature factor, and crystallite size) must be accounted for during quantitation, with a specific emphasis on not refining crystallite sizes for iron oxides and trace phases as they are inclined to over-broaden and interact with the background to improve the goodness of fit (R/E value). Preliminary investigations show somewhat reliable results with the use of custom file sets created within PDF-4+ specifically targeted toward slag minerals to further regulate and normalize the analysis process. The objective of this research is to provide a standard protocol for collecting data, as well as to update methodologies and databases for QPA, to the slag community for implementation in a conventional laboratory setting. Currently, Whole Pattern Fitting “Modified” Rietveld block refinement coupled with the addition of a ZnO internal standard gives the most accurate QPA results, though further research is needed to improve upon the complex issues found in this study of the QPA of slags.

Communication deficits have a substantial impact on quality of life for individuals with Angelman syndrome (AS) and their families, but limited qualitative work exists to support the necessary content of measures aiming to assess communication for these individuals. Following best practices for concept elicitation studies, we conducted individual qualitative interviews with caregivers and clinicians to elicit meaningful aspects of communication for individuals with AS. Caregivers were able to discuss their child's specific communication behaviors within a large number of expressive, receptive, and pragmatic functions via numerous symbolic and non-symbolic modalities. These results aligned well with published literature on communication in AS and will be used to inform the design of a novel caregiver-reported measure. Future studies on communication in individuals with AS should focus on gathering quantitative data from large samples of diverse caregivers, which would allow for estimations of the frequency of specific behaviors across the population.

Introduction: Pregnant leukemia patients should be offered continuation or termination of pregnancy. Treatment of leukemia in reproductive-age patients includes consideration of contraception. Hormonal intrauterine devices (IUDs) prevent pregnancy and decrease menstrual bleeding. Despite safety data for IUDs in immunocompromised patients, infection and vaginal bleeding concerns may inhibit their placement. Case Report: We report a case of a 28-year-old female at 13 weeks 4 days gestation with acute promyelocytic leukemia (APL) who presented with coagulopathy. When stabilized, dilation and evacuation (D and E) with levonorgestrel IUD placement was performed. The postoperative course was uncomplicated. Despite chemotherapy and neutropenia, this APL patient tolerated D and E with levonorgestrel IUD placement well with only routine preoperative antibiotics. Conclusion: Comprehensive options counseling for pregnant patients with new APL diagnoses are imperative, and interdisciplinary consideration of risks for individual patient concerns of pregnancy prevention during treatment with teratogenic potential, avoidance of combined hormonal contraception (CHC) coagulopathy risk, and menstrual bleeding reduction in the setting of pancytopenia with levonorgestrel IUD contraception management in immunocompromised patients may be considered.

Purpose: This study utilized the control-value theory of achievement emotions to investigate relationships between retroactive physical education (PE) beliefs and emotions with adulthood physical activity (PA) attitudes and behaviors. Method: An exploratory structural equation model was employed to evaluate participants’ (N = 381) PE emotions, antecedents, and outcomes. Results: Control, intrinsic value, and extrinsic value antecedents predicted several emotions. PE enjoyment facilitated positive PA attitudes, whereas boredom and shame predicted negative PA attitudes. Shame predicted lower physical self-concept in students. Moderate to vigorous PA was traced positively with enjoyment and negatively from relief. Several indirect relationships were also observed that further support the control-value theory of achievement emotions. Conclusions: Emotions are a response to learning and finding value in PE, which clearly impacts PA-related beliefs and behaviors into adulthood. Considerations on the externally driven nature of PE outcomes (i.e., standards/performance) are needed given the juxtaposition for also targeting suggested goals like intrinsic value and enjoyment.

This article discusses a resurgent banking concept of education laid bare by the coronavirus pandemic. It uses the theories of Paulo Freire, Mark Fisher, Michel Foucault, and Saidiya Hartman to articulate how learning-management systems undermine literary study's problem-posing educational paradigm and how to retain it amid increasing technocratic pressures.

This essay explores the potential for literary history to be useful as a part of epidemiological sleuthing. It considers how an imperative to employ social determinants of health frameworks incites movement away from epidemiological plots, particularly the forward trajectory of the outbreak narrative and its privileging of containment as the solution to emerging infections. Instead, opportunities arise to explore how data about the history of present-day structural inequities offer better ways to combat the deleterious effects of outbreaks. Through an analysis of Harriet Wilson’s novel Our Nig, this essay lays out provisional ways in which literary history and those with expertise in it may prove an untapped resource for increasing our knowledge of how to prevent disproportionate risk of disease, debility, and death for people of color.

Introduction: As the population ages, the prevalence of cognitive impairment is expanding. Given the recent pandemic, there is a need for remote testing modalities to assess cognitive deficits in individuals with neurological disorders. Self-administered, remote, tablet-based cognitive assessments would be clinically valuable if they can detect and classify cognitive deficits as effectively as traditional in-person neuropsychological testing. Methods: We tested whether the Miro application, a tablet-based neurocognitive platform, measured the same cognitive domains as traditional pencil-and-paper neuropsychological tests. Seventy-nine patients were recruited and then randomized to either undergo pencil-and-paper or tablet testing first. Twenty-nine age-matched healthy controls completed the tablet-based assessments. We identified Pearson correlations between Miro tablet-based modules and corresponding neuropsychological tests in patients and compared scores of patients with neurological disorders with those of healthy controls using t tests. Results: Statistically significant Pearson correlations between the neuropsychological tests and their tablet equivalents were found for all domains with moderate (r > 0.3) or strong (r > 0.7) correlations in 16 of 17 tests (p < 0.05). All tablet-based subtests differentiated healthy controls from neurologically impaired patients by t tests except for the spatial span forward and finger tapping modules. Participants reported enjoyment of the tablet-based testing, denied that it provoked anxiety, and noted no preference between modalities. Conclusions: This tablet-based application was found to be widely acceptable to participants. This study supports the validity of these tablet-based assessments in the differentiation of healthy controls from patients with neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies.

Necrotizing fasciitis travels along the fascial plane and surrounding soft tissue, leading to ischemia and necrosis. Fournier’s gangrene is a type of necrotizing fasciitis invading the deep and superficial planes of the perineal/genital region. It is rapidly progressive in nature and may have life-threatening consequences. Fournier’s often exhibits a misleading clinical presentation and can be mistaken for other conditions, such as hematoma, phlebitis, cellulitis, or septic arthritis. Since the ramifications of delayed diagnosis can be clinically significant, recognition of potential mimics is important to prevent morbidity or mortality. We report a case of Fournier’s gangrene mimicking a second-degree burn, an exceedingly rare presentation.

Background: The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear. Methods: We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders. Results: Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46–0.90]) or apixaban (HR, 0.40 [95% CI, 0.19–0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47–1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91–3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58–0.82]), apixaban (HR, 0.60 [95% CI, 0.46–0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62–1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18–2.14]). Conclusions: Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.

Evaluating population health initiatives at the community level necessitates valid counterfactual communities, which includes having similar population composition, health care access, and health determinants. Estimating appropriate county counterfactuals is challenging in states with large intercounty variation. We describe an application ofWe described counties by using indicators from the American Community Survey, Area Health Resources Files, University of Wisconsin Population Health Institute County Health Rankings, and vital records for Michigan Medicaid-insured births for 2009, the year the intervention began (or the closest available year). We ran analyses of 1000 iterations with random starting cluster values for each of a range of number of clusters from 3 to 10 with commonly used variability and reliability measures to identify the optimal number of clusters.The use of unstandardized features resulted in the grouping of 1 county with the intervention county in all solutions for all iterations and the frequent grouping of 2 additional counties with the intervention county. Standardized features led to no solution, and other distance measures gave mixed results. However, no county was ideal for all subpopulation analyses.Although the

Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease with a treatment goal of controlling symptoms and limiting disease burden. While endoscopic sinus surgery is effective for removing polyps and aerating sinuses, proper medical management remains necessary for reducing inflammation and limiting polyp recurrence. Objective This article aims to summarize the literature regarding medical treatment of chronic rhinosinusitis with nasal polyposis, with a specific focus on developments in the past 5 years. Methodology We conducted a literature review using PubMed to identify studies assessing medical treatment strategies for patients with CRSwNP. Articles focusing on chronic rhinosinusitis without nasal polyposis were excluded unless specifically stated. Surgical treatment and biologic therapies for CRSwNP will be covered in subsequent chapters and are therefore not included. Results Intranasal saline irrigations and topical steroids are mainstays of CRSwNP treatment in the pre-surgical, post-surgical, and maintenance phases of the disease. Alternative steroid delivery methods and adjunctive treatments with antibiotics, anti-leukotrienes, and other topical therapies have been investigated and may benefit certain patient populations, but convincing evidence does not exist to warrant addition of these treatments to the standard of care for CRSwNP. Conclusions Topical steroid therapy is clearly effective for CRSwNP, and recent studies demonstrate the safety and efficacy of high-dose nasal steroid rinses. Alternate delivery methods for local steroids may be useful for patients who are not responding to or who are noncompliant with conventional intranasal corticosteroid sprays and rinses. Future studies are needed to clarify if oral or topical antibiotics, oral anti-leukotrienes, or other novel therapies are significantly effective in decreasing symptoms and improving the quality of life in patients with CRSwNP.

White matter deficits are a common neuropathologic finding in neurologic disorders, including HIV-associated neurocognitive disorders (HAND). In HAND, the persistence of white matter alterations despite suppressive antiretroviral (ARV) therapy suggests that ARVs may be directly contributing to these impairments. Here, we report that a frontline ARV, bictegravir (BIC), significantly attenuates remyelination following cuprizone-mediated demyelination, a model that recapitulates acute demyelination, but has no impact on already formed mature myelin. Mechanistic studies in vitro revealed that treatment with BIC leads to significant decrease in mature oligodendrocytes accompanied by lysosomal de-acidification and impairment of lysosomal degradative capacity with no alterations in lysosomal membrane permeability or total lysosome number. Activation of the endolysosomal cation channel TRPML1 prevents both lysosomal de-acidification and impairment of oligodendrocyte differentiation by BIC. Lastly, we show that de-acidification of lysosomes by compounds that raise lysosomal pH is sufficient to prevent maturation of oligodendrocytes. Overall, this study has uncovered a critical role for lysosomal acidification in modulating oligodendrocyte function and has implications for neurologic diseases characterized by lysosomal dysfunction and white matter abnormalities.Table of ContentsMain PointsThe antiretroviral, bictegravir, inhibited remyelination through OPC differentiation blockade and had no effect on mature myelinBictegravir inhibits oligodendrocyte differentiation through de-acidification of lysosomes and this was prevented via activation of the lysosomal channel TRPML1De-acidification of lysosomes by other drugs (e.g. bafilomycin A) is sufficient to inhibit oligodendrocyte maturationTable of Contents Image

Background Somatic copy number alterations (sCNAs) acquired during the evolution of breast cancer provide valuable prognostic and therapeutic information. Here we present a workflow for screening sCNAs using picogram amounts of cell-free DNA (cfDNA) and single circulating tumor cells (CTCs). Methods We repurposed the Ion ReproSeq PGS™ preimplantation genetic testing kit to perform shallow whole genome sequencing on 178 cfDNA samples (300 pg) and individual CTCs from 10 MBC patients with metastatic breast cancer (MBC) recovered by CellSearch®/DEPArray™. Results were analyzed using a tailored ichorCNA workflow. Results sCNAs were detected in cfDNA of 41/105 (39%) patients with MBC and 3/23 (13%) primary breast cancers on follow-up (PBC FU), all of whom subsequently relapsed. In 8 of 10 MBCs, individual CTCs had a higher copy number count than matched cfDNA. The median tumor fraction detected by ichorCNA was 0.34 (range 0.17–0.58) for MBC and 0.36 (range 0.31–0.37) for PBC FU. Patients with detectable tumor fraction (≥ 0.1) and TFx and OncomineTM variants had significantly lower overall survival rates (P values P = 0.002 and P < 0.0001 for the log-rank test, respectively). Conclusions The ReproSeq PGS assay is rapid, at approximately $120 per sample, providing both a sCNA profile and estimation of the tumor DNA fraction from limiting cfDNA template (300pg) and individual CTCs. The approach could be used to examine the copy number landscape over time to guide treatment decisions, support future trial designs, and be applied to low volume blood spot samples enabling remote monitoring.

PURPOSE: To describe psychological outcomes among people with recurrent anomalous pregnancies pursuing trio-exome sequencing (exome sequencing (ES)) compared to those with one affected. METHODS: We analyzed data from a prospective ES cohort, enrolling patients with major fetal anomaly and normal microarray. Participants completed validated scales before and after ES. We (1) compared responses of those with multiple anomalous pregnancies to those with one affected and (2) conducted linear regression to examine associations between multiple affected pregnancies and post-ES constructs. RESULTS: Of 166 trios, 61 (37%) received results from ES. Forty (24%) had more than one affected pregnancy and 45% of those received a result explaining the fetal phenotype. All participants had clinically significant presequencing generalized psychological distress. For the 93 who completed the post-ES surveys, those with multiple affected pregnancies had higher psychological adaptation scores but worse test related distress scores (9.3 (6.2) versus 7.1(5.6), p = 0.12) and (14.3 (1.5) versus 15.4 (1.4), p = 0.01). In linear regression models, there were no significant differences in post-ES constructs after adjusting for clinically relevant covariates. CONCLUSIONS: All individuals experienced significant generalized psychological distress in the pre-ES period, extending our knowledge of how pregnancy history contributes to parental sequencing outcomes.

Purpose: Grounded in Control-Value Theory, this study aimed to investigate the relationships between emotional antecedents (control-value beliefs) and emotions with students' perceived self-esteem and physical activity intention. In addition, the potential differences in antecedents, emotions, and outcomes by gender were explored. Method: Multivariate analysis of variance and multiple hierarchical regressions were used to explore self-reported responses from middle school students (N = 247; 51% male, 49% female). Results: Preliminary analysis showed males reporting higher levels of intrinsic value, enjoyment, and self-esteem, while females reported more boredom and shame in PE. Control beliefs and intrinsic value were maintained as positive significant predictors (p Discussion/Conclusion: Emotions and their antecedents need consideration for understanding student motivation, particularly for female students who are more vulnerable to negative PE experiences.

Despite virologic suppression, people living with HIV (PLWH) remain at risk for developing cognitive impairment, with aberrations in motor control being a predominant symptom leading to functional dependencies in later life. While the neuroanatomical bases of motor dysfunction have recently been illuminated, the underlying molecular processes remain poorly understood. Herein, we evaluate the predictive capacity of the mitochondrial redox environment on sensorimotor brain-behavior dynamics in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art approaches, including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance spectroscopy to measure superoxide levels, antioxidant activity assays and dynamic magnetoencephalographic imaging to quantify sensorimotor oscillatory dynamics. We observed differential modulation of sensorimotor brain-behavior relationships by superoxide and hydrogen peroxide-sensitive features of the redox environment in PLWH, while only superoxide-sensitive features were related to optimal oscillatory response profiles and better motor performance in controls. Moreover, these divergent pathways may be attributable to immediate, separable mechanisms of action within the redox environment seen in PLWH, as evidenced by mediation analyses. These findings suggest that mitochondrial redox parameters are important modulators of healthy and pathological oscillations in motor systems and behavior, serving as potential targets for remedying HIV-related cognitive-motor dysfunction in the future.

In my first years of contingency, I began having anxiety-ridden dreams. The most prominent one featured me with shattered mirror skin. As I removed the shards, I felt the pain of each one tearing away. In this article, I consider how my whiteness and my neurodivergency intersect to impact how I feel about my position as a contingent faculty. Within the whiteness of academia, my white skin provides me with solace, but when my neurodivergency or precarious position reveal themselves, my investment in whiteness becomes harmful. These tensions pull at me. As I pull each shard off, my body tries to mold into an academic. In Disidentifications, José Esteban Muñoz writes, “disidentification is a step further than cracking open the code of the majority; it proceeds to use this code as raw material for representing a disempowered politics or positionality that has been rendered unthinkable by the dominant culture.”1 As I reflect on the tensions between whiteness, neurodivergency, and contingency, I find ways to disidentify as a means of survival in an academia that has little room for neurodivergency.

Molecular testing improves the diagnostic accuracy of thyroid cancer. Whether specific molecular testing results are associated with tumor phenotype or provide prognostic information needs further delineation.Consecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into 3 molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural.Of 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group-low, molecular risk group-intermediate, and molecular risk group-high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group-low, molecular risk group-intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group-intermediate, molecular risk group-high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In multivariable analysis, recurrence was more likely in molecular risk group-high cancers than in molecular risk group-intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9-8.6; P.001) and more likely in molecular risk group-intermediate than in molecular risk group-low (hazard ratio = 5.0; 95% confidence interval, 2.0-12.5; P.001).Using modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into 3 novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up.

Liquid chromatography coupled to electrospray ionisation high resolution mass spectrometry is an extremely powerful technique for both targeted and non-targeted analysis of organic aerosol.

Wearing slogan T-shirts largely began in the United States in the mid-twentieth century with the rise of various social movements. Considering the persistence of slogan T-shirts as a component of commodity activism, we theoretically engage with the ways twenty-first century organizations produce slogan T-shirts within the fashion system, with heightened attention to white progressive politics. We examine two Midwestern organizations in the United States: Raygun, which approaches T-shirt activism as a for-profit business and For Everyone Co., which approaches T-shirt activism as a not-for-profit collective. We conduct a case study to examine the nuance of how and why these collective and for-profit businesses use T-shirt activism, drawing upon multiple theoretical concepts to critically interpret the production and distribution of these products within the fashion system and offering theoretical implications for future study. We conduct a close reading of T-shirt texts and images, the organizations’ biographical information, and their reported philanthropic actions to construct and interpret their public-facing narratives engaging with fashion and activism. Examining T-shirt activism, as both an ‘artivist’ practice and a commodity, requires a critical analysis of how organizations capitalize on consumers’ desire and instances wherein white progressive politics prioritize the appearance of equity and justice or ambiguous fashion activism, over meaningful social-action centred fashion. Our work offers implications for the production, distribution and consumption of these products within the fashion system.

UV-4 (N-(9-methoxynonyl)-1-deoxynojirimycin) is a host-targeted antiviral agent, which targets mammalian proteins (endoplasmic reticulum glucosidases) rather than virally encoded proteins. This mechanism confers both broad-spectrum activity and low potential for generation of viral drug resistance mutations. Reproductive and developmental studies of UV-4 evaluated effects on fertility and early embryonic development in rats, embryo-fetal development in rats and rabbits, and pre- and postnatal development including maternal function in rats. All reproductive and developmental studies conducted achieved dose levels where parental toxicity (generally decreased body weight, decreased food consumption and adverse clinical signs) were observed. Toxicokinetic evaluations confirmed UV-4 crossed the placenta exposing fetal rats and rabbits in utero. Adverse findings in reproductive and developmental studies included decreases in sperm motility with histopathology correlates, visceral and skeletal malformations, changes in eye opening, air drop reflex, vaginal opening and preputial separation. The combined results of the fertility and early embryonic developmental study and pre- and postnatal study suggested that there may be an increased risk for male fertility. These effects are similar to those reported in pre-clinical studies of the structurally related drug Miglustat (N-butyl-1-deoxynojirimycin), therefore UV-4 may have risk of developmental or reproductive adverse outcomes in humans similar to existing approved agents in this drug class.