Spontaneous Reattachment of a Detached Sutured Descemet-Stripping Automated Endothelial Keratoplasty Graft.

Introduction: This is a case report of a spontaneous reattachment of Descemet-stripping automated endothelial keratoplasty (DSAEK). This graft was primarily sutured, and 20% sulfur hexafluoride (SF6) was injected into the anterior chamber, followed by graft detachment and spontaneous reattachment, 3 months later. Case Presentation: A 78-year-old male presented with DSAEK graft detachment, which was the patient's second DSAEK (the first also did not adhere). During the second surgery, the DSAEK graft was sutured and 20% SF6 was injected intraoperatively. Graft reattachment occurred without any intervention or repositioning 3 months after the 2nd DSAEK surgery. Conclusion: Spontaneous DSEAK late graft reattachment is possible, particularly in the setting of an anchoring suture. In some patients, waiting can be an option that can spare the patient the possible risks of graft repositioning, rebubbling, or repeating the DSAEK. Suturing the DSAEK graft primarily may have served as an anchor to keep the graft approximate and aid in attachment. A graft suture can be considered in the setting of a previously failed DSAEK due to DSAEK graft detachment.

Diversity's Pandemic Distractions.

Pandemic diseases have a nasty history of racialization. COVID-19 is no exception. Beyond the obvious racist invocations of the "China virus" or the "Wuhan Flu" are subtler racializing dynamics that are often veiled in more benign motives but are nonetheless deeply problematic. The racialization of COVID-19 proceeded along two distinct trajectories each of which threatened to reinforce inaccurate biologized conceptions of race while diverting attention from the social, legal, and political forces historically structuring race-based health disparities. First, early on as significant racial disparities in disease incidence and mortality became evident, a frame of race-based genetic difference came to the fore as a possible explanation. Second, as vaccine development ramped up there came widespread calls for racially "diversifying" clinical trials for the vaccines being tested. The rationales for such diversification were varied but tended to reinforce genetic frames of racial difference. Most common was the assertion (without substantial evidence) that vaccines might work differently in Black or Brown bodies and so racial diversity in trials was imperative for reasons of safety and efficacy. Derrick Bell cautioned 20 years ago that "the concept of diversity … is a serious distraction in the ongoing efforts to achieve racial justice." (Derrick Bell, Diversity's Distractions, 103 Colum. L. Rev. 1622, 1622 (2003).) This article explores the dynamics of how the concept of "diversity" racialized responses to COVID-19 and considers their broader implications for understanding and responding to racial disparities in the face of pandemic emergencies and beyond. In the short term, vaccine developers did a decent job of enrolling minorities in their clinical trials and the vaccines have proven to have the same safety and efficacy across races. In the long term, diversity in the biomedical context of pandemic response not only distracts attention from important structural causes of health injustice, but it also focuses attention on the genetics of disparities in a manner that has the potential to reinforce pernicious and false ideas of essential biological difference among racial groups. This article argues that an uncritical embrace of the idea of diversity in analyzing and responding to emergent health crises has the potential to distract us from considering deeper historical and structural formations contributing to racial health disparities. It proceeds first by exploring the dynamics through which initial responses to racial disparities in COVID-19 became geneticized. It will then move on to unpack the rationales for such racialization, examine their merits (or lack thereof), and consider their implications for developing an equitable response to pandemic emergencies. The next section will examine the subsequent racialization of clinical trials for COVID-19 vaccines through the concept of "diversity." It then moves on to explore how the geneticization of COVID-19 racial disparities laid the foundations for a similar geneticization of race in vaccine development. It will argue that in failing to clearly distinguish social and biological rationales for diversity, such framings, while generally well-intentioned, are poorly supported and work in tandem with the geneticization of racial disparities in COVID-19 morbidity and mortality to locate the causes of disparities in the minds and bodies of minoritized populations; again this distracts attention from the historical and structural forces contributing to such disparities. The article concludes by recognizing a certain intractability to the problems of using race in biomedical research and practice, particularly in the context of public health emergencies. It offers modest suggestions for improvement that could have significant practical effects if taken to heart by researchers, clinicians, and policy makers.

SMRT Regulates Metabolic Homeostasis and Adipose Tissue Macrophage Phenotypes in Tandem.

The Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) is a nuclear corepressor, regulating the transcriptional activity of many transcription factors critical for metabolic processes. While the importance of the role of SMRT in the adipocyte has been well-established, our comprehensive understanding of its in vivo function in the context of homeostatic maintenance is limited due to contradictory phenotypes yielded by prior generalized knockout mouse models. Multiple such models agree that SMRT deficiency leads to increased adiposity, although the effects of SMRT loss on glucose tolerance and insulin sensitivity have been variable. We therefore generated an adipocyte-specific SMRT knockout (adSMRT-/-) mouse to more clearly define the metabolic contributions of SMRT. In doing so, we found that SMRT deletion in the adipocyte does not cause obesity-even when mice are challenged with a high-fat diet. This suggests that adiposity phenotypes of previously described models were due to effects of SMRT loss beyond the adipocyte. However, an adipocyte-specific SMRT deficiency still led to dramatic effects on systemic glucose tolerance and adipocyte insulin sensitivity, impairing both. This metabolically deleterious outcome was coupled with a surprising immune phenotype, wherein most genes differentially expressed in the adipose tissue of adSMRT-/- mice were upregulated in pro-inflammatory pathways. Flow cytometry and conditioned media experiments demonstrated that secreted factors from knockout adipose tissue strongly informed resident macrophages to develop a pro-inflammatory, MMe (metabolically activated) phenotype. Together, these studies suggest a novel role for SMRT as an integrator of metabolic and inflammatory signals to maintain physiological homeostasis.

Quantification of the Cost and Potential Environmental Effects of Unused Pharmaceutical Products in Cataract Surgery.

IMPORTANCE: Pharmaceutical products, including unused portions, may contribute to financial and environmental costs in the United States. Because cataract surgery is performed millions of times each year in the United States and throughout the rest of the world, understanding these financial and environmental costs associated with cataract surgery is warranted. OBJECTIVE: To investigate the financial and environmental costs of unused pharmaceutical products after phacoemulsification surgery. DESIGN, SETTING, AND PARTICIPANTS: This descriptive qualitative study included 4 surgical sites in the northeastern United States (a private ambulatory care center, private tertiary care center, private outpatient center, and federally run medical center for veterans). Prices and data for use of services and pharmaceuticals were obtained for the tertiary care and outpatient centers from January 1 through April 30, 2016; for the ambulatory care center from June 1, 2017, through March 31, 2018; and the federal medical center from November 1, 2017, through February 28, 2018. Data were collected from routine phacoemulsification surgical procedures without vitreous loss or other complications. Volume or weight of medications remaining after surgery was measured. Total and mean costs of medications per case and month were calculated. Environmental effects were estimated using economic input-output life cycle assessment methods. Data were analyzed from December 1, 2017, through June 30, 2018. MAIN OUTCOMES AND MEASURES: Cost of unused pharmaceutical products (in US dollars) and kilogram equivalents of carbon emissions (carbon dioxide [CO2-e]), air pollution (fine particulate matter emissions of ≤10 µm in diameter [PM10-e]), and eutrophication potential (nitrogen [N-e]). RESULTS: A total of 116 unique drugs were surveyed among the 4 centers. Assuming unmeasured medications had no materials left unused, a cumulative mean 83 070 of 183 304 mL per month (45.3%) of pharmaceuticals were unused by weight or volume across all sites. Annual unused product cost estimates reached approximately $195 200 per site. A larger percentage of eyedrops (65.7% by volume) were unused compared with injections (24.8%) or systemic medications (59.9%). Monthly unused quantities at the ambulatory care center (65.9% by volume [54 971 of 83 440 mL]), tertiary care center (21.3% [17 143 of 80 344 mL]), federal medical center (38.5% [265 of 689 mL]), and outpatient center (56.8% [10 691 of 18 832 mL]) resulted in unnecessary potential emissions at each center of 2135, 2498, 418, and 711 kg CO2-e/mo, respectively. Unnecessary potential air pollution between sites varied from 0.8 to 4.5 kg PM10-e/mo, and unnecessary eutrophication potential between sites varied from 0.07 to 0.42 kg N-e/mo. CONCLUSIONS AND RELEVANCE: This study suggests that unused pharmaceutical products during phacoemulsification result in relatively high financial and environmental costs. If these findings can be substantiated and shown to be generalizable in the United States or elsewhere, reducing these costs may be of value.

Infarcted Tarsal Pyogenic Granuloma Simulating Malignant Melanoma.

The authors describe a rapidly enlarging, pedunculated brown tarsal lesion in a 34-year-old man with a history of chalazia. Following excision, histopathologic analysis showed the features of a necrotic pyogenic granuloma. This unique case expands the differential diagnosis of conjunctival malignant melanoma.

Microarray Analysis of Gene Expression in Saccharomyces cerevisiae kap108Δ Mutants upon Addition of Oxidative Stress.

Protein transport between the nucleus and cytoplasm of eukaryotic cells is tightly regulated, providing a mechanism for controlling intracellular localization of proteins, and regulating gene expression. In this study, we have investigated the importance of nucleocytoplasmic transport mediated by the karyopherin Kap108 in regulating cellular responses to oxidative stress in Saccharomyces cerevisiae We carried out microarray analyses on wild-type and kap108 mutant cells grown under normal conditions, shortly after introduction of oxidative stress, after 1 hr of oxidative stress, and 1 hr after oxidative stress was removed. We observe more than 500 genes that undergo a 40% or greater change in differential expression between wild-type and kap108Δ cells under at least one of these conditions. Genes undergoing changes in expression can be categorized in two general groups: 1) those that are differentially expressed between wild-type and kap108Δ cells, no matter the oxidative stress conditions; and 2) those that have patterns of response dependent upon both the absence of Kap108, and introduction or removal of oxidative stress. Gene ontology analysis reveals that, among the genes whose expression is reduced in the absence of Kap108 are those involved in stress response and intracellular transport, while those overexpressed are largely involved in mating and pheromone response. We also identified 25 clusters of genes that undergo similar patterns of change in gene expression when oxidative stresses are added and subsequently removed, including genes involved in stress response, oxidation-reduction processing, iron homeostasis, ascospore wall assembly, transmembrane transport, and cell fusion during mating. These data suggest that Kap108 is important for regulating expression of genes involved in a variety of specific cell functions.

Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) regulates glucocorticoid action in adipocytes.

Local modulation of glucocorticoid action in adipocytes regulates adiposity and systemic insulin sensitivity. However, the specific cofactors that mediate glucocorticoid receptor (GR) action in adipocytes remain unclear. Here we show that the silencing mediator of retinoid and thyroid hormone receptors (SMRT) is recruited to GR in adipocytes and regulates ligand-dependent GR function. Decreased SMRT expression in adipocytes in vivo increases expression of glucocorticoid-responsive genes. Moreover, adipocytes with decreased SMRT expression exhibit altered glucocorticoid regulation of lipolysis. We conclude that SMRT regulates the metabolic functions of GR in adipocytes in vivo. Modulation of GR-SMRT interactions in adipocytes represents a novel approach to control the local degree of glucocorticoid action and thus influence adipocyte metabolic function.

The troubling persistence of race in pharmacogenomics.

This article is concerned about what may be happening to race and medicine in the "meantime" between today's clinical realities and the promised land of pharmacogenomics where the need for using race in medicine is supposed to fade away. It argues that previous debates over the use of race in medicine are being side-stepped as race is being reconfigured from a "crude surrogate" for genetic variation into a purportedly viable placeholder for variable drug response--to be used here and now until the specific genetic underpinnings of drug response are more fully understood. Embracing the trope of "promise" in pharmacogenomics alongside the idea of using race as a useful interim proxy for genetic variation raises concerns that new diagnostic and therapeutic interventions may reflect or be mapped upon existing social categories of race, class, gender, and ethnicity in a harmful or dangerous manner. At the most basic level, the politics of the meantime in pharmacogenomics may be promoting the scientifically unjustified and socially dangerous recasting of race as a social and historical construct into a reified genetic category.

Topography-guided hyperopic LASIK with and without high irradiance collagen cross-linking: initial comparative clinical findings in a contralateral eye study of 34 consecutive patients.

PURPOSE: To evaluate the safety and efficacy of intrastromally applied collagen cross-linking (CXL) in a comparative contralateral eye study of topography-guided femtosecond laser-assisted hyperopic LASIK. METHODS: Thirty-four consecutive patients with hyperopia and hyperopic astigmatism elected to have bilateral topography-guided LASIK and were randomized to receive a single drop of 0.1% sodium phosphate riboflavin solution under the flap followed by 3-minute exposure of 10 mW/cm2 ultraviolet A (UVA) light with the flap realigned in one eye (CXL group) and no intrastromal CXL in the contralateral eye (no CXL group). All eyes were treated with the WaveLight FS200 femtosecond laser and WaveLight EX500 excimer laser (Alcon Laboratories Inc). Refractive error and keratometric, topographic, and tomographic measurements were evaluated over mean follow-up of 23 months. RESULTS: Preoperatively, mean spherical equivalent refraction was +3.15 +/- 1.46 diopters (D) and +3.40 +/- 1.78 D with a mean cylinder of 1.20 +/- 1.18 D and 1.40 +/- 1.80 D and mean uncorrected distance visual acuity (UDVA) (decimal) of 0.1 +/- 0.26 and 0.1 +/-0.25 in the CXL and no CXL groups, respectively. At 2 years postoperatively, mean spherical equivalent refraction was -0.20 +/- 0.56 D and +0.20 +/- 0.40 D with mean cylinder of 0.65 +/- 0.56 D and 0.76 +/- 0.72 D and mean UDVA of 0.95 +/- 0.15 and 0.85 +/- 0.23 in the CXL and no CXL groups, respectively. Eyes with CXL demonstrated a mean regression from treatment of +0.22 +/- 0.31 D, whereas eyes without CXL showed a statistically significant greater regression of +0.72 +/- 0.19 D (P = .0001). CONCLUSIONS: Topography-guided hyperopic LASIK with or without intrastromal CXL is safe and effective, with greater long-term efficacy (less regression) in eyes with CXL. Our data suggest that the regression seen with hyperopic LASIK may be related to biomechanical changes in corneal shape over time.

Spectral-domain optical coherence tomography as a screening technique for chloroquine and hydroxychloroquine retinal toxicity.

BACKGROUND AND OBJECTIVE: To determine the effectiveness of spectral-domain optical coherence tomography (SD-OCT) as a screening tool for the evaluation of chloroquine or hydroxychloroquine retinal toxicity. PATIENTS AND METHODS: This is a prospective, case-control study. Subject eyes were divided into four groups (group I = eyes with bull's eye maculopathy, group II = eyes with early changes of toxicity, group III = eyes with exposure but no signs of toxicity, and group IV = eyes of age-matched controls). Retinal thickness was measured via SD-OCT 0.5 and 1.0 mm from the foveal center. RESULTS: Mean retinal thickness 1.0 mm from the fovea in group I eyes was significantly thinner when compared to group IV. Eyes in group II also showed retinal thinning 1.0 mm from the foveal center when compared to both groups III and IV. Mean retinal thickness 0.5 mm from the foveal center did not differ significantly between any groups. CONCLUSION: Significant retinal thinning occurred 1.0 mm, but not 0.5 mm, from the foveal center in patients with early and late chloroquine or hydroxychloroquine toxicity. Measuring retinal thickness 1.0 mm from the foveal center in patients receiving these medications may help screen for early toxicity.

The two (institutional) cultures: a consideration of structural barriers to interdisciplinarity.

C. P. Snow's famous Two Cultures essay has become a foil for decades of discussions over the relation between science and the humanities. The problem of the "two cultures" is often framed in terms of how the particular epistemological claims or general intellectual orientations of particular individuals on either side of this purported divide obstruct interdisciplinary dialogue or cooperation. This formulation, however, fails to consider the institutional frameworks within which such debates occur. This article examines the broader structural constraints that provide incentives, erect barriers, or otherwise shape the potential for interdisciplinary research and practice, with particular attention to work involving the life sciences. It argues that in order to understand the nature and scope of the problems facing interdisciplinary work, we must focus on the institutional constraints that shape how individuals frame questions, pursue investigations, develop careers, and collaborate.

Orbital dissemination of Lemierre syndrome from gram-positive septic emboli.

A 45-year-old patient presented with bilateral orbital abscesses. He was found to have Lemierre syndrome, a condition involving septic thrombophlebitis of the internal jugular vein. The patient developed severe proptosis, sepsis, and cavernous sinus thrombosis. Despite aggressive antibiotic and anticoagulation therapy, visual loss was rapid, and the patient ultimately died. Lemierre syndrome, previously thought to be rare, is now becoming more commonly reported. Its prompt diagnosis and treatment are essential for patient survival.

Race and ancestry in biomedical research: exploring the challenges.

The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms.