Did Edgar Degas have Stargardt disease?

Renowned French painter Edgar Degas suffered of progressive light sensitivity and blurred central vision in both eyes, which affected his life and art in many ways. A first cousin from his mother's side, Estelle Musson of New Orleans also lost vision in a similar fashion at a comparable age. We postulated that Edgar and Estelle shared the same retinal pathology that possibly developed in a hereditary fashion, and we were interested whether any of their living family descendants might carry ABCA4 mutations to test the possibility that Edgar Degas may have had Stargardt disease.Edgar was never married and had no children, but Estelle had five children, four of whom from her marriage to Edgar's younger brother, and there are several descendants still living in New Orleans area. Genetic testing on five of Estelle's great grandchildren (Edgar's great grandnieces) were performed searching for ABCA4 mutations.We could not document any disease-causing variations in the ABCA4 gene in any of the descendants and therefore concluded that Edgar Degas most likely did not have Stargardt disease. Estelle and Edgar may have shared a different hereditary disease or have had two different retinal dystrophies or had another eye disease, including the unlikely possibility of inflammatory disease.

Quality improvement tool for rapid identification of risk factors for SARS-CoV-2 infection among healthcare workers.

The rapid growth of the coronavirus disease 2019 (COVID-19) pandemic, limited availability of personal protective equipment, and uncertainties regarding transmission modes of severe acute respiratory syndrome coronavirus-2 have heightened concerns for the safety of healthcare workers (HCWs). Systematic studies of occupational risks for COVID-19 in the context of community risks are difficult and have only recently started to be reported. Ongoing quality improvement studies in various locales and within many affected healthcare institutions are needed. A template design for small-scale quality improvement surveys is proposed. Such surveys have the potential for rapid implementation and completion, are cost-effective, impose little administrative or workforce burden, can reveal occupational risks while taking community risks into account, and can be repeated easily with short time intervals between repetitions. This article describes a template design and proposes a survey instrument that is easily modifiable to fit the particular needs of various healthcare institutions in the hope of beginning a collaborative effort to refine the design and instrument. These methods, along with data management and analytic techniques, can be widely useful and shared globally. The authors' goal is to facilitate quality improvement surveys aimed at reducing the risk of occupational infection of HCWs during the COVID-19 pandemic.

Retinal remodeling in human retinitis pigmentosa.

Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

Vision, eye disease, and art: 2015 Keeler Lecture.

The purpose of this study was to examine normal vision and eye disease in relation to art. Ophthalmology cannot explain art, but vision is a tool for artists and its normal and abnormal characteristics may influence what an artist can do. The retina codes for contrast, and the impact of this is evident throughout art history from Asian brush painting, to Renaissance chiaroscuro, to Op Art. Art exists, and can portray day or night, only because of the way retina adjusts to light. Color processing is complex, but artists have exploited it to create shimmer (Seurat, Op Art), or to disconnect color from form (fauvists, expressionists, Andy Warhol). It is hazardous to diagnose eye disease from an artist's work, because artists have license to create as they wish. El Greco was not astigmatic; Monet was not myopic; Turner did not have cataracts. But when eye disease is documented, the effects can be analyzed. Color-blind artists limit their palette to ambers and blues, and avoid greens. Dense brown cataracts destroy color distinctions, and Monet's late canvases (before surgery) showed strange and intense uses of color. Degas had failing vision for 40 years, and his pastels grew coarser and coarser. He may have continued working because his blurred vision smoothed over the rough work. This paper can barely touch upon the complexity of either vision or art. However, it demonstrates some ways in which understanding vision and eye disease give insight into art, and thereby an appreciation of both art and ophthalmology.

How placement affects force and contact pressure between a volar plate of the distal radius and the flexor pollicus longus tendon: a biomechanical investigation.

Open reduction and internal fixation of a distal radius fracture can leave a volar plate in close proximity or touching the tendons of the wrist. This cadaveric study examines the how volar plate position changes contact pressure and force against the flexor pollicis longus (FPL) tendon in multiple wrist extension positions. This study suggests that moving the plate from an ideal position (distal edge at the watershed line) to a malposition (5 mm distal to the watershed line) significantly increased the force by 72.7% and contact pressure by 33.5% on the FPL. Multiple clinical case reports have described rupture of the flexor tendons associated with distally positioned plates or protruding screw heads, creating prominent or sharp edges. This study illustrates that in order to minimize contact pressure on the flexor tendons, plating distal to the watershed line should be avoided when possible.

Cementless fixation in total knee arthroplasty: down the boulevard of broken dreams - opposes.

In this study we present our experience with four generations of uncemented total knee arthroplasty (TKA) from Smith & Nephew: Tricon M, Tricon LS, Tricon II and Profix, focusing on the failure rates correlating with each design change. Beginning in 1984, 380 Tricon M, 435 Tricon LS, 305 Tricon 2 and 588 Profix were implanted by the senior author. The rate of revision for loosening was 1.1% for the Tricon M, 1.1% for the Tricon LS, 0.5% for the Tricon 2 with a HA coated tibial component, and 1.3% for the Profix TKA. No loosening of the femoral component was seen with the Tricon M, Tricon LS or Tricon 2, with no loosening seen of the tibial component with the Profix TKA. Regarding revision for wear, the incidence was 13.1% for the Tricon M, 6.6% for the Tricon LS, 2.3% for the Tricon 2, and 0% for the Profix. These results demonstrate that improvements in the design of uncemented components, including increased polyethylene thickness, improved polyethylene quality, and the introduction of hydroxyapatite coating, has improved the outcomes of uncemented TKA over time.

A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0.02% tretinoin product regimen.

BACKGROUND: Tretinoin is considered the benchmark prescription topical therapy for improving fine facial wrinkles, but skin tolerance issues can affect patient compliance. In contrast, cosmetic antiwrinkle products are well tolerated but are generally presumed to be less efficacious than tretinoin. OBJECTIVES: To compare the efficacy of a cosmetic moisturizer regimen vs. a prescription regimen with 0.02% tretinoin for improving the appearance of facial wrinkles. METHODS: An 8-week, randomized, parallel-group study was conducted in 196 women with moderate to moderately severe periorbital wrinkles. Following 2 weeks washout, subjects on the cosmetic regimen (n = 99) used a sun protection factor (SPF) 30 moisturizing lotion containing 5% niacinamide, peptides and antioxidants, a moisturizing cream containing niacinamide and peptides, and a targeted wrinkle product containing niacinamide, peptides and 0.3% retinyl propionate. Subjects on the prescription regimen (n = 97) used 0.02% tretinoin plus moisturizing SPF 30 sunscreen. Subject cohorts (n = 25) continued treatment for an additional 16 weeks. Changes in facial wrinkling were assessed by both expert grading and image analysis of digital images of subjects' faces and by self-assessment questionnaire. Product tolerance was assessed via clinical erythema and dryness grading, subject self-assessment, and determinations of skin barrier integrity (transepidermal water loss) and stratum corneum protein changes. RESULTS: The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks. The cosmetic regimen was significantly better tolerated than tretinoin through 8 weeks by all measures. CONCLUSIONS: An appropriately designed cosmetic regimen can improve facial wrinkle appearance comparably with the benchmark prescription treatment, with improved tolerability.

Effect of shape and coating of a subretinal prosthesis on its integration with the retina.

Retinal stimulation with high spatial resolution requires close proximity of electrodes to target cells. This study examines the effects of material coatings and 3-dimensional geometries of subretinal prostheses on their integration with the retina. A trans-scleral implantation technique was developed to place microfabricated structures in the subretinal space of RCS rats. The effect of three coatings (silicon oxide, iridium oxide and parylene) and three geometries (flat, pillars and chambers) on the retinal integration was compared using passive implants. Retinal morphology was evaluated histologically 6 weeks after implantation. For 3-dimensional implants the retinal cell phenotype was also evaluated using Computational Molecular Phenotyping. Flat implants coated with parylene and iridium oxide were generally well tolerated in the subretinal space, inducing only a mild gliotic response. However, silicon-oxide coatings induced the formation of a significant fibrotic seal around the implants. Glial proliferation was observed at the base of the pillar electrode arrays and inside the chambers. The non-traumatic penetration of pillar tips into the retina provided uniform and stable proximity to the inner nuclear layer. Retinal cells migrated into chambers with apertures larger than 10 mum. Both pillars and chambers achieved better proximity to the inner retinal cells than flat implants. However, isolation of retinal cells inside the chamber arrays is likely to affect their long-term viability. Pillars demonstrated minimal alteration of the inner retinal architecture, and thus appear to be the most promising approach for maintaining close proximity between the retinal prosthetic electrodes and target neurons.

ISCEV Standard for full-field clinical electroretinography (2008 update).

This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical electroretinography (ERG). The parameters for flash stimulation and background adaptation have been tightened, and responses renamed to indicate the flash strength (in cd x s x m(-2)). The ISCEV Standard specifies five responses: (1) Dark-adapted 0.01 ERG (rod response); (2) Dark-adapted 3.0 ERG (combined rod-cone response); (3) Dark-adapted 3.0 oscillatory potentials; (4) Light-adapted 3.0 ERG (cone response); (5) Light-adapted 3.0 flicker (30 Hz flicker). An additional Dark-adapted 10.0 ERG or Dark-adapted 30.0 ERG response is recommended.

Resistance to HIV infection.

The biological correlates of an effective immune response that could contain or prevent HIV infection remain elusive despite substantial scientific accomplishments in understanding the interactions among the virus, the individual and the community. The observation that some individuals appear to possess resistance to HIV infection or its consequences has generated a host of epidemiologic investigations to identify biological or behavioral characteristics of these individuals. These data might hold the keys to developing appropriate strategies for mimicking the effective responses of those who appear immune. In this paper we review genetic mechanisms including the role of chemokines and their receptors, cytokines, host genetic immune response to HIV infection, local immune response correlating with behavioral variables, co-infection and immune based mechanisms that have been elucidated so far. We offer suggestions for how to use these observations as platforms for future research to further understand natural resistance to HIV infection through cohort studies, population genotype sampling, mathematical modeling of virus-host interactions and behavioral analyses.

Pulsed electron avalanche knife (PEAK) for intraocular surgery.

PURPOSE: To develop a better and more economical instrument for precise, tractionless, "cold" cutting during intraocular surgery. The use of highly localized electric fields rather than laser light as the means of tissue dissection was investigated. METHODS: A high electric field at the tip of a fine wire can, like lasers, initiate plasma formation. Micrometer-length plasma streamers are generated when an insulated 25 micron (microm) wire, exposed to physiological medium at one end, is subjected to nanosecond electrical pulses between 1 and 8 kV in magnitude. The explosive evaporation of water in the vicinity of these streamers cuts soft tissue without heat deposition into surrounding material (cold cutting). Streamers of plasma and the dynamics of water evaporation were imaged using an inverted microscope and fast flash photography. Cutting effectiveness was evaluated on both polyacrylamide gels, on different tissues from excised bovine eyes, and in vivo on rabbit retina. Standard histology techniques were used to examine the tissue. RESULTS: Electric pulses with energies between 150 and 670 microJ produced plasma streamers in saline between 10 and 200 microm in length. Application of electric discharges to dense (10%) polyacrylamide gels resulted in fracturing of the gel without ejection of bulk material. In both dense and softer (6%) gels, layer by layer shaving was possible with pulse energy rather than number of pulses as the determinant of ultimate cutting depth. The instrument made precise partial or full-thickness cuts of retina, iris, lens, and lens capsule without any evidence of thermal damage. Because different tissues require distinct energies for dissection, tissue-selective cutting on complex structures can be performed if the appropriate pulse energies are used; for example, retina can be dissected without damage to the major retinal vessels. CONCLUSIONS: This instrument, called the Pulsed Electron Avalanche Knife (PEAK), can quickly and precisely cut intraocular tissues without traction. The small delivery probe and modest cost make it promising for many ophthalmic applications, including retinal, cataract, and glaucoma surgery. In addition, the instrument may be useful in nonophthalmic procedures such as intravascular surgery and neurosurgery.

Acute effects of sildenafil on the electroretinogram and multifocal electroretinogram.

PURPOSE: To evaluate the acute effects of sildenafil (Viagra; Pfizer, Inc, New York, New York) on the electroretinogram and multifocal electroretinogram. METHODS: Eighteen healthy individuals (ages 21-49 years) were studied; 14 were given 200 mg sildenafil orally and four were given only water. All subjects were tested before sildenafil and 1 hour after sildenafil (or water) with a desaturated Panel D-15 color test, a full-field standard electroretinogram, and a multifocal electroretinogram using the VERIS system; five subjects were also tested 5 hours after sildenafil. RESULTS: Responses from the subjects who received sildenafil were compared with those from the control subjects. At 1 hour after sildenafil, photopic single-flash waveforms were attenuated by 9% and scotopic maximal response amplitudes were increased slightly. Photopic and 30-Hz flicker electroretinogram responses were delayed; multifocal electroretinogram waveforms were delayed (5%-9%) and attenuated (14%-22%) across the posterior pole. These changes did not resolve by 5 hours. Nine of the subjects who had received sildenafil (64%) reported visual or systemic symptoms, including one who reported bluish vision. Ten of those subjects (71%) showed a slight increase in color test errors 1 hour after sildenafil. CONCLUSIONS: For at least 5 hours after taking 200 mg of sildenafil, cone function was slightly depressed in the macula and periphery, as measured by full-field electroretinogram and multifocal electroretinogram recordings. However, the affected electroretinogram and multifocal electroretinogram parameters still remained within normal limits.

Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection.

OBJECTIVE: To investigate evidence for resistance to HIV-1 infection associated with the heterozygous genotype CCR5-+/Delta32 and with the homozygous genotype CCR5-Delta32/Delta32, which results in a nonfunctional CCR5 receptor. DESIGN: Cohort study of initially HIV-seronegative high-risk individuals from eight different cities. Enrollment data were analyzed to investigate the association of demographic factors and risk behaviors with CCR5 genotypes on the assumption that increased genotype prevalence among persons with histories of longer or more intensive exposure to HIV would indicate HIV resistance associated with that genotype. Longitudinal data were analyzed to investigate the association of HIV seroincidence with CCR5 genotypes. The cohort of 2996 individuals included 1892 men who have sex with men (MSM), 474 male injection drug users (IDUs), 347 women at heterosexual risk, and 283 female IDUs. MEASUREMENTS: CCR5 genotype, HIV serostatus, demographic factors, and risk behaviors during the 6 months before enrollment, followed by measurement of HIV seroincidence during the subsequent 18 months (for men) and 24 months (for women). RESULTS: Forty (1.3%) subjects were homozygous CCR5-Delta32/Delta32 and 387 (12.9%) were heterozygous CCR5-+/Delta32. All but 1 CCR5-Delta32/Delta32 individuals and 51 CCR5-+/Delta32 individuals were Caucasian. Among 1531 Caucasian MSM, CCR5-+/Delta32 individuals were present more frequently (22.3%) among those reporting unprotected receptive anal intercourse than among those not reporting this risk (15.9%) (p =.002), suggesting a selective advantage of the heterozygous genotype. CCR5-+/Delta32 individuals also had a significantly reduced relative risk of HIV seroconversion adjusted for unprotected receptive anal intercourse compared with CCR5-/+ individuals (relative risk = 0.30, 95% confidence interval [CI]: 0.08-0.97). CCR5-Delta32/Delta32 prevalence among Caucasian MSM was significantly associated with age among subjects recruited from high HIV seroprevalence cities (New York City and San Francisco) (odds ratio [OR] for each decade increase in age = 2.57, CI: 1.56-4.21) but not among those recruited from lower HIV prevalence sites (Boston, Chicago, Philadelphia, Seattle, and Providence/Pawtucket, Rhode Island) (OR = 1.20, CI: 0.75-1.89). CONCLUSIONS: Cross-sectional and longitudinal analyses indicated that among high-risk HIV seronegative MSM, CCR5-+/Delta32 and CCR5-Delta32/Delta32 are associated with protection against HIV infection. These findings imply that strategies aimed at reducing susceptibility to HIV infection by blocking CCR5 receptor sites need not seek blockage of all receptor sites to achieve an imperfect but substantial degree of protection.

Role for lipid rafts in regulating interleukin-2 receptor signaling.

Lipid rafts are plasma membrane microdomains characterized by a unique lipid environment enriched in gangliosides and cholesterol, leading to their insolubility in nonionic detergents. Many receptors are constitutively or inducibly localized in lipid rafts, which have been shown to function as platforms coordinating the induction of signaling pathways. In this report, the first evidence is provided for a role of these lipid microdomains in regulating interleukin-2 receptor (IL-2R) signaling. It is demonstrated that antibody- or ligand-mediated immobilization of components of lipid rafts, glycosyl-phosphatidyl-inositol-anchored proteins, and the GM1 ganglioside, respectively, inhibit IL-2-induced proliferation in T cells. IL-2Ralpha is shown to be constitutively enriched in rafts and further enriched in the presence of immobilized anti-Thy-1. In contrast, IL-2Rbeta and IL-2Rgamma, as well as JAK1 and JAK3, are found in soluble membrane fractions, and their localization is not altered by anti-Thy-1. IL-2-mediated heterotrimerization of IL-2R chains is shown to occur within soluble membrane fractions, exclusively, as is the activation of JAK1 and JAK3. As predicted by these results, the disruption of lipid raft integrity did not impair IL-2-induced signaling. Thus, the sequestration of IL-2Ralpha within lipid microdomains restricts its intermolecular interactions and regulates IL-2R signaling through impeding its association with IL-2Rbeta and IL-2Rgamma.

Are US populations appropriate for trials of human immunodeficiency virus vaccine? The HIVNET Vaccine Preparedness Study.

Questions exist about whether testing of preventive human immunodeficiency virus (HIV)-1 vaccines, which will require rapid recruitment and retention of cohorts with high HIV-1 seroincidence, is feasible in the United States. A prospective cohort study was conducted in 1995-1997 among 4,892 persons at high risk for HIV infection in nine US cities. At 18 months, with an 88% retention rate, 90 incident HIV-1 infections were observed (1.31/100 person-years (PY), 95% confidence interval (CI): 1.06, 1.61). HIV-1 seroincidence rates varied significantly by baseline eligibility criteria--1.55/100 PY among men who had sex with men, 0.38/100 PY among male intravenous drug users, 1.24/100 PY among female intravenous drug users, and 1.13/100 PY among women at heterosexual risk-and by enrollment site, from 0.48/100 PY to 2.18/100 PY. HIV-1 incidence was highest among those men who had sex with men who reported unprotected anal intercourse (2.01/100 PY, 95% CI: 1.54, 2.63), participants who were definitely willing to enroll in an HIV vaccine trial (1.96/100 PY, 95% CI: 1.41, 2.73), and women who used crack cocaine (1.62/100 PY, 95% CI: 0.92, 2.85). Therefore, cohorts with HIV-1 seroincidence rates appropriate for HIV-1 vaccine trials can be recruited, enrolled, and retained.

Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus Type 1 vaccine with or without gp120: a phase 2 study in higher- and lower-risk volunteers.

Live attenuated viral vectors that express human immunodeficiency virus (HIV) antigens are being developed as potential vaccines to prevent HIV infection. The first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55, and protease) was conducted in 435 volunteers with and without gp120 boosting, to expand the safety database and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection. Neutralizing antibodies to the MN strain were stimulated in 94% of volunteers given vCP205 plus gp120 and in 56% of volunteers given vCP205 alone. CD8(+) cytotoxic T lymphocyte cells developed at some time point in 33% of volunteers given vCP205, with or without gp120. Phase 3 field trials with these or similar vaccines are needed, to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study.

The dilemma of color deficiency and art.

No "major" painter is known to be color deficient. Are there truly no color deficient artists, or have they not been recognized? The historical literature cites criteria for recognizing color deficiency in artists, but they are hard to apply without knowing the intentions of an artist. The work and commentary of a color-deficient artist who works currently in Paris are presented as an example. He uses a limited palette of colors, based on advice from colleagues as much as his own perceptions, and he uses colors in ways that do not always fit with expectations for color deficiency. Biographies of earlier painters suggest that there were a few whose color sense was poor, but these painters used assistants to help. The color sense of others, such as the English landscape painter John Constable (1776-1837), has been questioned because of a preponderance of suspicious color, such as murky green. However, there are good reasons to doubt that Constable was color deficient. It is instructive to know how proven color deficiency has influenced an artist's style. When medical information is unavailable, the best advice for the diagnostically-inclined observer is just to enjoy the art.

Slow diffusion of home HIV-specimen collection: provider concerns at odds with client preferences.

BACKGROUND: Home specimen collection and telephone counseling (HSCTC) may be a convenient new method for detection of HIV infection among cohorts at high-risk for HIV. GOAL: To evaluate attitudes about HSCTC among participants, HIV counselors, and community advisory board members associated with a national multisite study of persons at high risk for HIV. STUDY DESIGN: Twelve focus groups and surveys were conducted at six sites among 126 counselors, community advisory board members, and cohort participants. RESULTS: Staff and community advisory board members raised concerns about the acceptability, feasibility, safety, and effectiveness of HSCTC. In contrast, participants (92%) reported a willingness to collect blood and oral samples on a frequent basis, and preferred telephone (73%) to office-based counseling. CONCLUSION: Home specimen collection and telephone counseling appear to be preferred by study participants at high risk of HIV infection. Staff and community advisory board members had stronger reservations than prospective users.