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In the 7th century BCE, the Kushite king Tanwetamani commissioned his “Dream Stela”, which was to be erected in the Amun Temple of Jebel Barkal. The lunette of the stela features a dualistic artistic motif whose composition, meaning, and significance are understudied despite their potential to illuminate important aspects of royal Kushite ideology. On the lunette, there are two back-to-back offering scenes that appear at first glance to be nearly symmetrical, but that closer inspection reveals to differ in subtle but significant ways. Analysis of the iconographic and textual features of the motif reveals its rhetorical function in this royal context. The two strikingly similar but meaningfully different offering scenes represented the two halves of a Kushite “Double Kingdom” that considered Kush and Egypt together as a complementary geographic dual, with Tanwetamani presiding as king of both. This “Mirrored Motif” encapsulated the duality present in the Kushite ideology of kingship during the Twenty-Fifth Dynasty, which allowed Tanwetamani to reconcile the present imperial expansion of Kush with the history of Egyptian activity in Nubia. The lunette of the Dream Stela is therefore political art that serves to advance the Kushite imperial agenda.

Mixed Reality enables individuals to visualise and interact with artefacts and environments through a combination of physical and virtual assets. It has received increased interest from the design community as a means to accelerate, enrich and enhance prototyping activities. This article concerns MR’s ability to deceive an individual through the combination of virtual and physical assets and their underlying traits (e.g., mass, size), and a user’s cognitive ability to ‘join the dots’. If properly implemented, MR could save time and resources by reducing the required prototype fidelity and the need to fully realise variants. However, there is a gap in understanding how the traits of physical and virtual assets and cognition combine to form reality. This article presents a study investigated the role mass, virtual and physical model size played on users perception of an MR prototype. The relative impact of these factors was determined by varying these parameters and assessing the user’s perceived change. The key finding from this study was that the virtual model size had a far greater influence on prototype perceived by the user. This suggests that the required physical fidelity of an MR prototype can be lower than the virtual. Furthermore, exploring size design variants can be achieved exclusively through changes to the virtual model.

Abstract Over a five-month time window between March and July 2020, scientists deployed two small uncrewed aircraft systems (sUAS) to the central Arctic Ocean as part of legs three and four of the MOSAiC expedition. These sUAS were flown to measure the thermodynamic and kinematic state of the lower atmosphere, including collecting information on temperature, pressure, humidity and winds between the surface and 1 km, as well as to document ice properties, including albedo, melt pond fraction, and open water amounts. The atmospheric state flights were primarily conducted by the DataHawk2 sUAS, which was operated primarily in a profiling manner, while the surface property flights were conducted using the HELiX sUAS, which flew grid patterns, profiles, and hover flights. In total, over 120 flights were conducted and over 48 flight hours of data were collected, sampling conditions that included temperatures as low as −35 °C and as warm as 15 °C, spanning the summer melt season.

Resumo Fundamento A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. Objetivo Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. Métodos Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. Resultados Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). Conclusão Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

Abstract Aims Little is known about the association of temporal changes in inflammatory biomarkers and the risk of death and cardiovascular diseases. We aimed to evaluate the association between temporal changes in C‐reactive protein (CRP), fibrinogen, and interleukin‐6 (IL‐6) and risk of heart failure (HF), cardiovascular disease (CVD), and all‐cause mortality in individuals without a history of prior CVD. Methods and results Participants from the Multi‐Ethnic Study of Atherosclerosis (MESA) cohort with repeated measures of inflammatory biomarkers and no CVD event prior to the second measure were included. Quantitative measures, annual change, and biomarker change categories were used as main predictors in Cox proportional hazard models stratified based on sex and statin use. A total of 2258 subjects (50.6% female, mean age of 62 years) were studied over an average of 8.1 years of follow‐up. The median annual decrease in CRP levels was 0.08 mg/L. Fibrinogen and IL‐6 levels increased by a median of 30 mg/dL and 0.24 pg/mL annually. Temporal changes in CRP were positively associated with HF risk among females (HR: 1.18 per each standard deviation increase, P

Objective: To assess the incidence of contrast-associated acute kidney injury (CAAKI) after repeated exposure to contrast material for computed tomography (CT) and conventional coronary angiography within short intervals. Methods: We studied 651 patients enrolled in the CorE-64 (November 5, 2005–January 30, 2007) and CORE320 (October 21, 2009–August 17, 2011) multicenter studies. Participants with suspected obstructive coronary heart disease were referred for diagnostic cardiac catheterization and underwent coronary CT angiography for research before invasive angiography. Nonionic, low-osmolality iodinated contrast material was used for all imaging. Results: The median age of the patients was 62 years, and 190 (29%) were women. Major risk factors for acute kidney injury were present in 277 of 651 (43%) patients. The median interval between CT imaging and invasive angiography was 3.1 days (interquartile range, 0.9-8.0 days). The median volume of contrast material was 100 mL for each test. In 16 (2.5%) of 651 patients, CAAKI developed. Of these cases, 1 occurred after the CT scan, whereas 6 were documented after invasive angiography (compared with post-CT creatinine concentration assessment). In 9 patients, CAAKI was found in comparing creatinine concentration after completion of both tests with baseline values (but not compared with post-CT imaging). Conclusion: Acute kidney injury after repeated exposure to iodinated contrast media within a few days is uncommon even in a population of patients with highly prevalent risk factors. Withholding of clinically indicated contrast-enhanced imaging may therefore not be justified in this setting.

Abstract Aims The long‐term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. Methods and results We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long‐term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year‐25 exam (2010–2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year‐0 exam (1985–1986), 57.4% were women, and 41.9% were African‐American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of 4 cups/day with non‐coffee drinkers were β = −0.30%, P 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of 4 cups/day with non‐coffee drinkers were β = −0.29, P .05; and β = −0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (β = −1.69, P 0.05 for all). Conclusions Low‐to‐moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.

Abstract Background Critical illness increases the risk for poor mental health outcomes among both patients and their informal caregivers, especially their surrogate decision-makers. Surrogates who must make life-and-death medical decisions on behalf of incapacitated patients may experience additional distress. EMPOWER (Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience) is a novel cognitive-behavioral, acceptance-based intervention delivered in the intensive care unit (ICU) setting to surrogate decision-makers designed to improve both patients’ quality of life and death and dying as well as surrogates’ mental health. Methods Clinician stakeholder and surrogate participant feedback (n = 15), as well as results from an open trial (n = 10), will be used to refine the intervention, which will then be evaluated through a multisite randomized controlled trial (RCT) (n = 60) to examine clinical superiority to usual care. Feasibility, tolerability, and acceptability of the intervention will be evaluated through self-report assessments. Hierarchical linear modeling will be used to adjust for clustering within interventionists to determine the effect of EMPOWER on surrogate differences in the primary outcome, peritraumatic stress. Secondary outcomes will include symptoms of post-traumatic stress disorder, prolonged grief disorder, and experiential avoidance. Exploratory outcomes will include symptoms of anxiety, depression, and decision regret, all measured at 1 and 3 months from post-intervention assessment. Linear regression models will examine the effects of assignment to EMPOWER versus the enhanced usual care group on patient quality of life or quality of death and intensity of care the patient received during the indexed ICU stay assessed at the time of the post-intervention assessment. Participant exit interviews will be conducted at the 3-month assessment time point and will be analyzed using qualitative thematic data analysis methods. Discussion The EMPOWER study is unique in its application of evidence-based psychotherapy targeting peritraumatic stress to improve patient and caregiver outcomes in the setting of critical illness. The experimental intervention will be strengthened through the input of a variety of ICU stakeholders, including behavioral health clinicians, physicians, bereaved informal caregivers, and open trial participants. Results of the RCT will be submitted for publication in a peer-reviewed journal and serve as preliminary data for a larger, multisite RCT grant application. Trial registration ClinicalTrials.gov, NCT03276559. Retrospectively registered on 8 September 2017.

This study describes the primary and secondary partnerships of aging gay men participating in the Understanding Patterns of Healthy Aging Among Men Who Have Sex with Men substudy of the Multicenter AIDS Cohort Study and examines differences in the prevalence of these relationship structures by HIV status while adjusting for age, education, and race/ethnicity. Relationships were compared within the following structural categories: "only a primary partnership", "only a secondary partnership", "both a primary and secondary relationship", or "neither a primary nor secondary relationship". There were 1,054 participants (51.9% HIV negative/48.1% HIV positive) included in the study. Participants had a median age of 62.0 years (interquartile range: 56.0-67.0) and most reported being non-Hispanic white (74.6%) and college educated (88.0%). Of the 1,004 participants with available partnership status data, 384 (38.2%) reported no primary or secondary partnerships, 108 (10.8%) reported secondary-only partnership, 385 (38.3%) reported primary-only partnership, and 127 (12.6%) reported both primary and secondary partnerships. Of participants who reported primary partnerships only, the prevalence rates (PRs) were lower among those 62 years and older, HIV positive, black non-Hispanic and Hispanics. Of participants who reported only having a secondary partnership, the PRs were higher among those 62 years and older and HIV positive. Of participants who did not report having either a primary or secondary partnership, the PRs were higher among those 62 years and older, HIV positive, and black non-Hispanic compared with their respective referent groups. There was no significant difference in PRs of having both primary and secondary partnerships by age category, HIV status, race/ethnicity, and education. This study aimed to fill a knowledge gap in the literature regarding both primary and secondary supportive partnerships among aging HIV-positive and HIV-negative gay men.

Abstract The dusty regolith covering the surfaces of asteroids and planetary satellites differs in size, shape, and composition from terrestrial soil particles and is subject to environmental conditions very different from those found on Earth. This regolith evolves in a low ambient pressure and low-gravity environment. Its response to low-velocity impacts, such as those that may accompany human and robotic exploration activities, may be completely different than what is encountered on Earth. Experimental studies of the response of planetary regolith in the relevant environmental conditions are thus necessary to facilitate future Solar System exploration activities.We combined the results and provided new data analysis elements for a series of impact experiments into simulated planetary regolith in low-gravity conditions using two experimental setups and a range of microgravity platforms. The Physics of Regolith Impacts in Microgravity Experiment (PRIME) flew on several parabolic aircraft flights, enabling the recording of impacts into granular materials at speeds of ∼ 4–230 cm/s. The COLLisions Into Dust Experiment (COLLIDE) is conceptually close to the PRIME setup. It flew on the Space Shuttle in 1998 and 2001 and more recently on the Blue Origin New Shepard rocket, recording impacts into simulated regolith at speeds between 1 and 120 cm/s.Results of these experimental campaigns found that there is a significant change in the regolith behavior with the gravity environment. In a 10 −2 g environment (with g being the gravity acceleration at the surface of the Earth), only embedding of the impactor was observed and ejecta production was produced for most impacts at > 20 cm/s. Once at microgravity levels ( 10 cm/s. The measured ejecta speeds were somewhat lower than the ones measured at reduced-gravity levels, but the ejected masses were higher. In general, the mean ejecta velocity shows a power-law dependence on the impact energy with an index of ∼ 0.5. When projectile rebound occurred, we observed that its coefficients of restitution on the bed of regolith simulant decrease by a factor of 10 with increasing impact speeds from ∼ 5 up to 100 cm/s. We could also observe an increased cohesion between the JSC-1 grains compared to the quartz sand targets.

Objectives:. To identify actionable processes of care, quality indicators, or performance measures and their evidence base relevant to patients with persistent or chronic critical illness and their family members including themes relating to patient/family experience. Data Sources:. Two authors independently searched electronic, systemic review, and trial registration databases (inception to November 2016). Study Selection:. We included studies with an ICU length of stay of greater than or equal to 7 days as an inclusion criterion and reported actionable processes of care; quality improvement indicators, measures, or tools; or patient/family experience. We excluded case series/reports of less than 10 patients. Data Extraction:. Paired authors independently extracted data and performed risk of bias assessment. Data Synthesis:. We screened 13,130 references identifying 114 primary studies and 102 relevant reviews. Primary studies reported data on 24,252 participants; median (interquartile range) sample size of 70 (32–182). We identified 42 distinct actionable processes of care, the most commonly investigated related to categories of 1) weaning methods (21 studies; 27 reviews); 2) rehabilitation, mobilization, and physiotherapy (20 studies; 40 reviews); and 3) provision of information, prognosis, and family communication (14 studies; 11 reviews). Processes with limited evidence were generally more patient-centered categories such as communication, promotion of sleep, symptom management, or family support. Of the 21 randomized controlled trials, only two were considered at low risk of bias across all six domains, whereas just two cohort studies and one qualitative study were considered of high quality. Conclusions:. We identified 42 distinct actionable processes of care relevant to patients with persistent or chronic critical illness and their families, with most frequently studied processes relating to weaning, rehabilitation/mobilization, and family communication. Qualitative studies highlighted the need to address psychologic needs and distressing symptoms as well as enabling patient communication. Our findings are informative for clinicians and decision-makers when planning high-quality patient and family-focused care.

Background The predictive value of coronary artery calcium (CAC) has been widely studied; however, little is known about specific characteristics of CAC that are most predictive. We aimed to determine the independent associations of Agatston score, CAC volume, CAC area, CAC mass, and CAC density score with major adverse cardiac events in patients with suspected coronary artery disease. Methods and Results A total of 379 symptomatic participants, aged 45 to 85 years, referred for invasive coronary angiography, who underwent coronary calcium scanning and computed tomography angiography as part of the CORE320 (Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography) study, were included. Agatston score, CAC volume, area, mass, and density were computed on noncontrast images. Stenosis measurements were made on contrast‐enhanced images. The primary outcome of 2‐year major adverse cardiac events (30 revascularizations [>182 days of index catheterization], 5 myocardial infarctions, 1 cardiac death, 9 hospitalizations, and 1 arrhythmia) occurred in 32 patients (8.4%). Associations were estimated using multivariable proportional means models. Median age was 62 (interquartile range, 56–68) years, 34% were women, and 56% were white. In separate models, the Agatston, volume, and density scores were all significantly associated with higher risk of major adverse cardiac events after adjustment for age, sex, race, and statin use; density was the strongest predictor in all CAC models. CAC density did not provide incremental value over Agatston score after adjustment for diameter stenosis, age, sex, and race. Conclusions In symptomatic patients, CAC density was the strongest independent predictor of major adverse cardiac events among CAC scores, but it did not provide incremental value beyond the Agatston score after adjustment for diameter stenosis.

Dendritic cells (DCs) are pivotal in regulating tolerogenic as well as immunogenic responses against microorganisms by directing both the innate and adaptive immune response. In health, phenotypically different DC subsets found in the gut mucosa are maintained in their tolerogenic state but switch to a pro-inflammatory phenotype during infection or chronic autoinflammatory conditions such as inflammatory bowel disease (IBD). The mechanisms that promote the switch among the mucosal DCs from a tolerogenic to an immunogenic, pro-inflammatory phenotype are incompletely understood. We hypothesized that disabled homolog 2 (DAB2), recently described as a negative regulator of DC immunogenicity during their development, is regulated during intestinal inflammation and modulates mucosal DC function. We show that DAB2 is highly expressed in colonic CD11b+CD103− DCs, a subset known for its capacity to induce inflammatory Th1/Th17 responses in the colon, and is downregulated predominantly in this DC subset during adoptive T cell transfer colitis. Administration of Dab2-deficient DCs (DC2.4Dab2−/− cells) modulated the course of DSS colitis in wild-type mice, enhanced mucosal expression of Tnfa, Il6, and Il17a, and promoted neutrophil recruitment. In bone-marrow derived dendritic cells (BMDC), DAB2 expression correlated with CD11b levels and DAB2 was rapidly and profoundly inhibited by TLR ligands in a TRIF- and MyD88-dependent manner. The negative modulation of DAB2 was biphasic, initiated with a quick drop in DAB2 protein, followed by a sustained reduction in Dab2 mRNA. DAB2 downregulation promoted a more functional and activated DC phenotype, reduced phagocytosis, and increased CD40 expression after TLR activation. Furthermore, Dab2 knockout in DCs inhibited autophagy and promoted apoptotic cell death. Collectively, our results highlight the immunoregulatory role for DAB2 in the intestinal dendritic cells and suggest that DAB2 downregulation after microbial exposure promotes their switch to an inflammatory phenotype.

We investigated the diagnostic accuracy of computed tomography angiography (CTA) versus myocardial perfusion imaging (MPI) for detecting obstructive coronary artery disease (CAD) as defined by conventional quantitative coronary angiography (QCA). Sixty-three patients who were enrolled in the CorE-64 multicenter study underwent CTA, MPI, and QCA imaging. All subjects were referred for cardiac catheterization with suspected or known coronary artery disease. The diagnostic accuracy of quantitative CTA and MPI for identifying patients with 50% or greater coronary arterial stenosis by QCA was evaluated using receiver operating characteristic (ROC) analysis. Pre-defined subgroups were patients with known CAD and those with a calcium score of 400 or over. Diagnostic accuracy by ROC analysis revealed greater area under the curve (AUC) for CTA than MPI for all 63 patients: 0.95 [95% confidence interval (CI): 0.89-0.100] vs 0.65 (95%CI: 0.53-0.77), respectively (P

Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV) and hepatitis B virus (HBV); however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV) and influenza (flu). Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.

BACKGROUND:We characterized associations between smoking, alcohol, and recreational drug use and coronary plaque by HIV serostatus within the Multicenter AIDS Cohort Study (MACS). METHODS:MACS participants (N = 1005, 621 HIV+ and 384 HIV-) underwent non-contrast CT scanning to measure coronary artery calcium; 764 underwent coronary CT angiograms to evaluate plaque type and extent. Self-reported use of alcohol, tobacco, smoked/inhaled cocaine, methamphetamine, ecstasy, marijuana, inhaled nitrites, and erectile dysfunction drugs was obtained at semi-annual visits beginning 10 years prior to CT scanning. Multivariable logistic and linear regression models were performed, stratified by HIV serostatus. RESULTS:Among HIV+ men, current smoking, former smoking, and cumulative pack years of smoking were positively associated with multiple coronary plaque measures (coronary artery calcium presence and extent, total plaque presence and extent, calcified plaque presence, and stenosis >50%). Smoking was significantly associated with fewer plaque measures of comparable effect size among HIV- men; current smoking and calcified plaque extent was the only such association. Heavy alcohol use (>14 drinks/week) was associated with stenosis >50% among HIV+ men. Among HIV- men, low/moderate (1-14 drinks/week) and heavy alcohol use were inversely associated with coronary artery calcium and calcified plaque extent. Few significant associations between other recreational drug use and plaque measures were observed. CONCLUSION:Smoking is strongly associated with coronary plaque among HIV+ men, underscoring the value of smoking cessation for HIV+ persons. Alcohol use may protect against coronary artery calcium and calcified plaque progression in HIV- (but not HIV+) men. Few positive associations were observed between recreational drug use and coronary plaque measures.

OBJECTIVE:Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown. DESIGN:This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then ≥5 years later. METHODS:Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixed-model regression. RESULTS:We studied 270 HIV+ and 247 HIV- men. At baseline, ≥50% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p

Most HIV-seropositive subjects in western countries receive highly active antiretroviral therapy (HAART). Although many aspects of their health have been studied, little is known about their vestibular and balance function. The goals of this study were to determine the prevalences of vestibular and balance impairments among HIV-seropositive and comparable seronegative men and women and to determine if those groups differed.Standard screening tests of vestibular and balance function, including head thrusts, Dix-Hallpike maneuvers, and Romberg balance tests on compliant foam were performed during semiannual study visits of participants who were enrolled in the Baltimore and Washington, D. C. sites of the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study.No significant differences by HIV status were found on most tests, but HIV-seropositive subjects who were using HAART had a lower frequency of abnormal Dix-Hallpike nystagmus than HIV-seronegative subjects. A significant number of nonclassical Dix-Hallpike responses were found. Age was associated with Romberg scores on foam with eyes closed. Sex was not associated with any of the test scores.These findings suggest that HAART-treated HIV infection has no harmful association with vestibular function in community-dwelling, ambulatory men and women. The association with age was expected, but the lack of association with sex was unexpected. The presence of nonclassical Dix-Hallpike responses might be consistent with central nervous system lesions.

We have previously reported that Optisol, a commercially available medium (Chiron Vision, Irvine, CA), is a favorable fluid for the storage of neural retina. We now characterize the cell survival and histologic integrity of the tissue following storage and then transplantation. Neural retinas from human fetal eyes obtained within 1 h of pregnancy termination were stored in Optisol-GS medium (containing TC-199 and MEM medium, 2.5% chondroitin sulfate, 1% dextran, HEPES buffer, gentamicin sulfate, 0.1 mmol/L nonessential amino acids, sodium bicarbonate, 1 mmol/L sodium pyruvate, and additional antioxidants), at 4°C for the following time periods: 0, 1, 2, and 7 days, and then tested for viability. Retinas stored for 2 and 7 days were mechanically dissociated and grafted into the eyes of light-damaged Fischer 344 rats (17 animals, 28 eyes). Non-transplanted eyes received injections of vehicle only (5 animals, 6 eyes). All animals were immunosuppressed daily with cyclosporine (10 mg/kg). All experiments were conducted in strict accordance with institutional, federal, and ARVO guidelines. Cell viability averaged 94.8%, 90.2%, 83.2%, and 76.8% at 0, 1, 2, and 7 days storage, respectively. Light microscopy demonstrated that the fetal retina was preserved without evident changes for up to 48 h. Up to 7 days there was a good to very good preservation of the cells in the outer neuroblastic layer. One month after transplantation subretinal grafts of retinal tissue stored for 2 and 7 days in Optisol showed good integration with host retina and initial photoreceptor differentiation. Optisol is a widely used medium for the preservation of human corneas prior to transplantation. Our results show that this medium is also highly suitable for preserving human fetal retinas prior to transplantation.

Previously we have observed that fetal retinal cells grafted to the subretinal space of blind rats produced a functional recovery as determined by testing the visual inhibition of the startle response. Following those studies, we performed experiments to test whether the injection itself, cell by-products, or unrelated neural cells could also produce an effect. Visual function was tested by examining the inhibitory effect of a brief light flash (300 Ix) on the acoustic startle response to an immediately following intense noise burst in light blinded Fischer 344 rats. Animals were tested before and after grafts of fetal retinal cell homogenates, dissociated perinatal cerebellar cells, and sham injections in the subretinal space. Behavioral testing continued every 2 wk for 14 wk after the graft. In the pretests, the light flash inhibited the startle response, maximal at intervals of 40-70 ms with recovery thereafter. In contrast, after exposure for 4 wk to fluorescent light (300 lx) and a rest in a normal 12/12 h light/ dark environment the rats showed reflex facilitation to the light, maximal at an interval of 110 ms, followed by a late period of reflex inhibition. The light flash had no effect on other rats that had been blinded by bilateral enucleation. Light blinded animals receiving either cerebellar grafts or retinal cell homogenates were no different in performance from their sham injected control animals. The present data suggest that neither subretinal injections of neural cells nor nonspecific neurochemical factors are able to elicit a positive behavioral response in visually impaired animals.