Change, Adversity, and Adaptation: Young People's Experience of the COVID-19 Pandemic Expressed through Artwork and Semi-Structured Interviews.

This study explores how young people's mental health was affected by the COVID-19 pandemic using artwork and semi-structured interviews. The mental health impacts of the pandemic are important to understand so that policy and practice professionals can support those affected, prepare and respond to future crises, and support young people who are isolated and restricted in other contexts. Co-designed participatory art workshops and interviews were conducted with 16-18-year-olds (n = 21, 62% female) from the London-based Longitudinal cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP). Artworks and interview transcripts were qualitatively co-and analysed with young people. From interviews, six themes were identified: adaptation, restriction, change, challenges, overcoming adversity, and lockdown life. From the artwork, four themes were identified: trapped, negative mental wellbeing, positive emotions, and technology. Everyday factors such as home environment, social support, hobbies, habits, and online education were key determinants of how challenged and restricted participants felt, and their capacity to overcome this. This demonstrates the importance of wider (social and environmental) determinants and supports a systems-level public health approach to young people's mental health. For example, young people's mental health services should collaborate with other sectors to address such determinants in a holistic way. Clearer guidance and support with occupation, relationships, environment, routine and activities could mitigate the negative mental health impacts of major environmental changes on young people.

Development of Simplified and Efficient Sample Preparation Methods for the Analysis of Problem Material within the Diesel Fuel Delivery System.

A new approach for the analysis of diesel engine fuel filters has been developed. This method involves minimal to no sample preparation, allowing rapid and unbiased analysis of diesel fuel filters. In recent years, diesel fuel filter plugging incidences have increased in parallel with changing emissions legislation. Fuel filter blockages can result in increased emissions, reduced efficiency, and engine failure. It is not fully understood why fuel filter blockages occur; as a result, there has been an international increase in research into the cause of fuel filter plugging. The method discussed in this paper utilizes a thermal desorption (TD) style sample introduction technique that can be used in conjunction with gas chromatography-mass spectrometry (GC-MS) and presents a fast, simple, and more sustainable approach to the analysis of fuel filters. When required, an efficient and straightforward sample cleanup process was developed and was used to simplify and improve confidence in the data identification and assignment; this method is up to three orders of magnitude faster than some procedures adopted in the literature. Further complementary analytical techniques, such as ultrahigh-performance supercritical fluid chromatography-mass spectrometry (UHPSFC-MS) and high-resolution GC-MS, were used to access additional sample-specific information. This new approach has been successful in the identification of problematic materials deposited on blocked fuel filters, concurrent with recent research. This information can aid in the development of mitigation strategies to combat fuel filter plugging.

Fractal analysis: Left ventricular trabecular complexity cardiac MRI adds independent risks for heart failure with preserved ejection fraction in participants with end-stage renal disease.

PURPOSE: To measure left ventricular (LV) trabecular complexity by fractal dimension (FD) in patients with end-stage renal disease (ESRD), and assess whether FD was an independent risk factor for heart failure with preserved ejection fraction (HFpEF), or a significant predictor for adverse outcome in this population. METHODS: The study retrospectively enrolled 104 participants with ESRD who underwent 3.0 T cardiac magnetic resonance imaging (MRI) from June 2018 to November 2020. LV trabeculation was quantified with fractal analysis of short-axis cine slices to estimate the FD. Logistic regression analyses were used to evaluate FD and cardiac MRI parameters and to find independent risk predictors. Cox proportional hazard regression was used to investigate the association between FD and MACE. RESULTS: LV FD was higher in in the HFpEF group than those in the non-HFpEF group, with the greatest difference near the base of the ventricle. Age, minimum left atrial volume index, and LV mean basal FD were independent predictors for HFpEF in patients with ESRD. Combining the mean basal FD with typical predictive factors resulted in a C-index (0.902 vs 0.921), which was not significantly higher. Same improvements were found for net reclassification improvement [0.642; 95% confidence interval (CI), 0.254-1.029] and integrated discrimination index (0.026; 95% CI, 0.008-0.061). Participants with a LV global FD above the cutoff value (1.278) had higher risks of MACE in ESRD patients. CONCLUSIONS: LV trabecular complexity measured by FD was an independent risk factor for HFpEF, and a significant predictor for MACE among patients with ESRD.

BMI1 is required for melanocyte stem cell maintenance and hair pigmentation.

The epigenetic repressor BMI1 plays an integral role in promoting the self-renewal and proliferation of many adult stem cell populations, and also tumor types, primarily through silencing the Cdkn2a locus, which encodes the tumor suppressors p16Ink4a and p19Arf . However, in cutaneous melanoma, BMI1 drives epithelial-mesenchymal transition programs, and thus metastasis, while having little impact on proliferation or primary tumor growth. This raised questions about the requirement and role for BMI1 in melanocyte stem cell (McSC) biology. Here, we demonstrate that murine melanocyte-specific Bmi1 deletion causes premature hair greying and gradual loss of melanocyte lineage cells. Depilation enhances this hair greying defect, accelerating depletion of McSCs in early hair cycles, suggesting that BMI1 acts to protect McSCs against stress. RNA-seq of McSCs, harvested before onset of detectable phenotypic defects, revealed that Bmi1 deletion derepresses p16Ink4a and p19Arf , as observed in many other stem cell contexts. Additionally, BMI1 loss downregulated the glutathione S-transferase enzymes, Gsta1 and Gsta2, which can suppress oxidative stress. Accordingly, treatment with the antioxidant N-acetyl cysteine (NAC) partially rescued melanocyte expansion. Together, our data establish a critical function for BMI1 in McSC maintenance that reflects a partial role for suppression of oxidative stress, and likely transcriptional repression of Cdkn2a.

Texture analysis of native T1 images as a novel method for non-invasive assessment of heart failure with preserved ejection fraction in end-stage renal disease patients.

OBJECTIVES: To explore the diagnostic potential of texture analysis applied to native T1 maps obtained from cardiac magnetic resonance (CMR) images for the assessment of heart failure with preserved ejection fraction (HFpEF) among patients with end-stage renal disease (ESRD). METHODS: This study, conducted from June 2018 to November 2020, included 119 patients (35 on hemodialysis, 55 on peritoneal dialysis, and 29 with kidney transplants) in Renji Hospital. Native T1 maps were assessed with texture analysis, using a freely available software package, in participants who underwent cardiac MRI at 3.0 T. Four texture features, selected by dimension reduction specific to the diagnosis of HFpEF, were analyzed. Multivariate logistic regression was performed to examine the independent association between the selected features and HFpEF in ESRD patients. RESULTS: Seventy-six of 119 patients were diagnosed with HFpEF. Demographic, laboratory, cardiac MRI, and echocardiogram characteristics were compared between HFpEF and non-HFpEF groups. The four texture features that were analyzed showed statistically significant differences between groups. In multivariate analysis, age, left atrial volume index (LAVI), and sum average 4 (SA4) turned out to be independent predictors for HFpEF in ESRD patients. Combining the texture feature, SA4, with typical predictive factors resulted in higher C-index (0.923 vs. 0.898, p = 0.045) and a sensitivity and specificity of 79.2% and 95.2%, respectively. CONCLUSIONS: Texture analysis of T1 maps adds diagnostic value to typical clinical parameters for the assessment of heart failure with preserved ejection fraction in patients with end-stage renal disease. KEY POINTS: • Non-invasive assessment of HFpEF can help predict prognosis in ESRD patients and help them take timely preventative measures. • Texture analysis of native T1 maps adds diagnostic value to the typical clinical parameters for the assessment of HFpEF in patients with ESRD.

Bad mommies: socio-cognitive judgments of single mothers with alcohol use disorder.

Gender disparity persists in the United States; women are still paid less than men and are also subject to discrimination in the workplace based on the fact that they may become mothers. Further, there is evidence to indicate that single mothers are judged more harshly than their married mother counterparts and single fathers. As a form of amelioration, some women self medicate with alcohol and according to the CDC), alcohol use disorder (AUD) is on the rise for women. Although there is research on gender disparity, the motherhood penalty, and AUD, there are no experiments testing socio-cognitive judgments on those combined factors and specifically examining what we term "the single motherhood penalty". Therefore, in two experiments using between-participants designs, participants rated a picture of a person (female or male) paired with a brief description where marital status (single or married) and type of ailment (alcohol or physical) was manipulated. In Experiment 1, a passive AUD manipulation did not show a clear single motherhood penalty. In Experiment 2, the results of an active AUD manipulation supported the predicted single motherhood penalty (Experiment 2a), but did not show an analogous single fatherhood penalty (Experiment 2 b). These findings are the first to offer empirical evidence that socio-cognitive judgments might perpetuate the interplay of the single motherhood penalty and AUD.

Lead Levels in Spices From Market Basket and Home Lead Investigation Samples in North Carolina.

OBJECTIVES: Lead investigators in North Carolina found evidence that contaminated spices may contribute to children's elevated blood lead levels. We compared lead levels in samples of spices and other consumable products by country of purchase to inform consumer safety interventions and regulations. METHODS: From February 1, 2011, through October 22, 2020, North Carolina lead investigators sampled spices and other consumable products from 103 homes of children with confirmed elevated blood lead levels. In 2017, the study team purchased 50 products frequently sampled during lead investigations, as a "market basket" sample, from local stores in or near Raleigh, North Carolina. The State Laboratory of Public Health analyzed 423 product samples using mass spectrometry. We extracted environmental sample results from lead investigations from the North Carolina Electronic Lead Surveillance System. RESULTS: The median market basket lead result was 0.07 mg/kg (SD = 0.17); the maximum lead result was 0.88 mg/kg. The median home lead investigation sample result was 0.26 mg/kg (SD = 489.44); the maximum lead result was 6504.00 mg/kg in turmeric purchased in India. Among all samples, products purchased in India had more than triple the median lead levels (0.71 mg/kg) of those purchased in the United States (0.19 mg/kg). CONCLUSIONS: Purchasing spices in the United States is an action that consumers can take that may reduce their lead poisoning risk. Regulatory agencies should consider a lead limit of <1 mg/kg as attainable for spices sold in US stores and for ingredients of any foods that may be consumed by children.

Genome-wide CRISPR screen identifies PRC2 and KMT2D-COMPASS as regulators of distinct EMT trajectories that contribute differentially to metastasis.

Epithelial-mesenchymal transition (EMT) programs operate within carcinoma cells, where they generate phenotypes associated with malignant progression. In their various manifestations, EMT programs enable epithelial cells to enter into a series of intermediate states arrayed along the E-M phenotypic spectrum. At present, we lack a coherent understanding of how carcinoma cells control their entrance into and continued residence in these various states, and which of these states favour the process of metastasis. Here we characterize a layer of EMT-regulating machinery that governs E-M plasticity (EMP). This machinery consists of two chromatin-modifying complexes, PRC2 and KMT2D-COMPASS, which operate as critical regulators to maintain a stable epithelial state. Interestingly, loss of these two complexes unlocks two distinct EMT trajectories. Dysfunction of PRC2, but not KMT2D-COMPASS, yields a quasi-mesenchymal state that is associated with highly metastatic capabilities and poor survival of patients with breast cancer, suggesting that great caution should be applied when PRC2 inhibitors are evaluated clinically in certain patient cohorts. These observations identify epigenetic factors that regulate EMP, determine specific intermediate EMT states and, as a direct consequence, govern the metastatic ability of carcinoma cells.

An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis.

The epithelial-mesenchymal transition (EMT) and primary ciliogenesis induce stem cell properties in basal mammary stem cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis upon entry into intermediate EMT states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote ubiquitination and inactivation of a transcriptional repressor, GLIS2, which localizes to the ciliary base. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the mammary tumor­initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC stemness, mammary gland development, and claudin-low breast cancer formation.

The Effects of Sex, Oral Contraception, and Menstrual Cycle Phase on Intraocular Pressure, Central Corneal Thickness, and Foveal Thickness: A Descriptive Analysis.

The primary goal of this study was to investigate the effects of sex, oral contraceptive (OC) use, and menstrual cycle phase on common ocular parameters assessed during ophthalmic evaluations, namely intraocular pressure (IOP), central corneal thickness (CCT), and foveal thickness (FT), in young healthy adults. We measured IOP, CCT, and FT in 60 participants (16 men, 16 contraceptive users, and 28 cycling women) over two sessions that characterized the menstrual cycle phase in women. For men in our study, two sessions were separated by two weeks. For women, the two sessions were scheduled during the follicular and luteal phases of the menstrual cycle. There was a trend towards higher IOP in men, and the difference was significant for white, non-Hispanic subjects and for white subjects considered separately. There was also a trend for thicker corneas in women, but men had significantly thicker foveae. CCT and FT were not different between men and OC-users, hinting at a moderating hormonal effect of oral contraceptive use. We found that IOP, CCT, and FT were equivalent between the follicular and luteal phases, which may be owing to the timing of our sessions. However, our findings strongly suggest that clinicians should consider contraceptive use during routine ophthalmic evaluations, as it could inform glaucomatous risk in women.

Macular pigment optical density and visual quality of life

PURPOSE: There is robust evidence that higher macular pigment concentrations help reduce both veiling and discomfort glare in patients with or without ocular disease. We investigated whether there was also a relationship between macular pigment optical density (MPOD) and patient surveys about glare or ocular discomfort. METHODS: We measured MPOD psychophysically in 23 healthy subjects and administered the National Eye Institute Visual Functioning Questionnaire (VFQ-25). Responses for each survey question were sorted from low (no limitation) to high (very severe limitation). The median response for each question was determined, and independent t-tests were performed on the mean MPOD values for survey responses above and below the median. We also performed a non-parametric correlation analysis between MPOD and survey responses. RESULTS: While the median response was "no limitation" for most (22 of 25) survey questions, responses were slightly higher for two questions concerning ocular discomfort and one question related to driving at night. MPOD levels were significantly higher in subjects that reported no discomfort in or around their eyes than in those that reported mild discomfort. There was also a trend toward higher MPOD levels in subjects who reported that pain in or around their eyes never limited their activity as well as in subjects who reported no difficulty driving at night. CONCLUSION: These preliminary findings are consistent with the well-established discomfort and glare hypotheses for MPOD. The current findings on subjective ocular discomfort in the absence of glare deserve further study

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Model for Teaching the Helping Babies Survive Course Series and Advanced Life Support in Obstetrics Workshops to Rural Skilled Birth Attendants in Uganda.

Background: Uganda, like much of Sub-Saharan Africa and other underserved regions continues to face the challenge of high neonatal and maternal mortality. The Helping Babies Survive (HBS) course and the Advanced Life Support in Obstetrics (ALSO) provide hands on education to train providers in key life-saving interventions. A uterine balloon tamponade (UBT) procedure can be life-saving in the event of uterine bleeding. The purpose of this implementation research is to gain more insight into the effectiveness of a tailored down 5-day combined HBS-ALSO-UBT course. In this study, we found that a tailored down 5-day combined HBS-ALSO-UBT could be performed with significantly improved self-assessment in diagnosing and managing a wide range of peripartum conditions.

Macular pigment optical density and visual quality of life.

PURPOSE: There is robust evidence that higher macular pigment concentrations help reduce both veiling and discomfort glare in patients with or without ocular disease. We investigated whether there was also a relationship between macular pigment optical density (MPOD) and patient surveys about glare or ocular discomfort. METHODS: We measured MPOD psychophysically in 23 healthy subjects and administered the National Eye Institute Visual Functioning Questionnaire (VFQ-25). Responses for each survey question were sorted from low (no limitation) to high (very severe limitation). The median response for each question was determined, and independent t-tests were performed on the mean MPOD values for survey responses above and below the median. We also performed a non-parametric correlation analysis between MPOD and survey responses. RESULTS: While the median response was "no limitation" for most (22 of 25) survey questions, responses were slightly higher for two questions concerning ocular discomfort and one question related to driving at night. MPOD levels were significantly higher in subjects that reported no discomfort in or around their eyes than in those that reported mild discomfort. There was also a trend toward higher MPOD levels in subjects who reported that pain in or around their eyes never limited their activity as well as in subjects who reported no difficulty driving at night. CONCLUSION: These preliminary findings are consistent with the well-established discomfort and glare hypotheses for MPOD. The current findings on subjective ocular discomfort in the absence of glare deserve further study.

Emerging Mechanisms by which EMT Programs Control Stemness.

Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain cancers depends on a subset of tumor cells, called cancer stem cells (CSCs), with SC-like properties. In addition to being responsible for tumorigenesis, CSCs exhibit elevated resistance to therapy and thus drive tumor relapse post-treatment. The epithelial-mesenchymal transition (EMT) programs promote SC and CSC stemness in many epithelial tissues. Here, we provide an overview of the mechanisms underlying the relationship between stemness and EMT programs, which may represent therapeutic vulnerabilities for the treatment of cancers.

Catalyzing sustainable fisheries management through behavior change interventions.

Small-scale fisheries are an important livelihood and primary protein source for coastal communities in many of the poorest regions in the world, yet many are overfished and thus require effective and scalable management solutions. Positive ecological and socioeconomic responses to management typically lag behind immediate costs borne by fishers from fishing pressure reductions necessary for fisheries recovery. These short-term costs challenge the long-term success of these interventions. However, social marketing may increase perceptions of management benefits before ecological and socioeconomic benefits are fully realized, driving new social norms and ultimately long-term sustainable behavior change. By conducting underwater visual surveys to quantify ecological conditions and by conducting household surveys with community members to quantify their perceptions of management support and socioeconomic conditions, we assessed the impact of a standardized small-scale fisheries management intervention that was implemented across 41 sites in Brazil, Indonesia, and the Philippines. The intervention combines TURF reserves (community-based territorial use rights for fishing coupled with no-take marine reserves) with locally tailored social-marketing behavior change campaigns. Leveraging data across 22 indicators and 4 survey types, along with data from 3 control sites, we found that ecological and socioeconomic impacts varied and that communities supported the intervention and were already changing their fishing practices. These results suggest that communities were developing new social norms and fishing more sustainably before long-term ecological and socioeconomic benefits of fisheries management materialized.

Catalización del Manejo de Pesquerías Sustentables por medio de Intervenciones de Cambio de Comportamiento Resumen Las pesquerías a pequeña escala son un sustento importante y la principal fuente de proteína para las comunidades costeras en muchas de las regiones más pobres del mundo, sin embargo, muchas sufren de sobrepesca y por lo tanto requieren soluciones de manejo efectivas y escalables. Las respuestas ecológicas y socioeconómicas positivas al manejo generalmente se retrasan con respecto a los costos inmediatos asumidos por los pescadores a partir de las reducciones de la presión ocasionada por la pesca necesarias para la recuperación de la pesquería. Estos costos a corto plazo son un reto para el éxito a largo plazo de las intervenciones. Sin embargo, la mercadotecnia social puede incrementar las percepciones de los beneficios del manejo antes de que se conozcan por completo los beneficios ecológicos y socioeconómicos, lo que genera nuevas normas sociales y finalmente un cambio en el comportamiento a largo plazo. Realizamos censos submarinos visuales para cuantificar las condiciones ecológicas y censos domésticos a los miembros de la comunidad para cuantificar sus percepciones del apoyo al manejo y de las condiciones socioeconómicas. Con esto, evaluamos el impacto de la intervención de manejo para pesquerías estandarizadas a pequeña escala que fue implementada en 41 sitios de Brasil, Indonesia y las Filipinas. La intervención combina las reservas TURF (derechos de uso de pesca territorial basados en la comunidad acoplados con reservas marinas con restricción de pesca) con campañas de mercadotecnia social para el cambio de comportamiento ajustadas al contexto local. Con la movilización de datos a lo largo de 22 indicadores y cuatro tipos de censos, junto con los datos de tres sitios de control, encontramos que los impactos ecológicos y socioeconómicos variaron y que las comunidades apoyaban la intervención y ya se encontraban cambiando sus prácticas de pesca. Estos resultados sugieren que las comunidades ya estaban desarrollando nuevas normas sociales y pescando de manera más sustentable antes de que los beneficios ecológicos y socioeconómicos a largo plazo del manejo de las pesquerías se materializaran.

Characterization of Human iPSC-RPE on a Prosthetic Bruch's Membrane Manufactured From Silk Fibroin.

Purpose: RPE cell transplantation as a potential treatment for AMD has been extensively investigated; however, in AMD, ultrastructural damage affects both the RPE and its underlying matrix support, the Bruch's membrane (BrM). An RPE monolayer supported by a surrogate scaffold could thus provide a more effective approach to cell-based therapy for AMD. Toward this goal, we aimed to establish a functional human induced pluripotent stem cell-derived (hiPSC)-RPE monolayer on a Bombyx mori silk fibroin (BMSF) scaffold. Methods: RPE differentiated from five distinct hiPSC lines were cultured on BMSF membrane coated with extracellular matrix (ECM, COL1), and either regular tissue culture plastic or Transwell coated with ECM (LAM-TCP). Morphologic, gene and protein expression, and functional characteristics of the hiPSC-RPE cultured on different membranes were compared in longitudinal experiments spanning 1 day to ≥3 months. Results: The hiPSC-RPE monolayers on ECM-coated BMSF and TCP could be maintained in culture for ≥3 months and displayed RPE-characteristic morphology, pigmentation, polarity, and expression of RPE signature genes and proteins. Furthermore, hiPSC-RPE on both ECM-coated BMSF and TCP displayed robust expression and secretion of several basement membrane proteins. Importantly, hiPSC-RPE cells on COL1-BMSF and LAM-TCP showed similar efficacy in the phagocytosis and degradation of photoreceptor outer segments. Conclusions: A biomaterial scaffold manufactured from silk fibroin supports the maturation and long-term survival of a functional hiPSC-RPE monolayer. This has significant implications for both in vitro disease modeling and in vivo cell replacement therapy.

The Effects of Alcohol on Self-Regulation of Sexual Arousal in Sexually Compulsive Men Who Have Sex with Men.

Individuals who meet criteria for sexual compulsivity tend to be more likely to engage in behaviors that may have negative consequences. Despite the clear public health relevance, however, little is known about the determinants of sexual compulsivity. This psychophysiological study examined self-regulation of sexual arousal in men high and low in sexual compulsivity, when sober and after alcohol consumption. A total of 43 men who have sex with men (MSM) participated and were presented with a series of erotic film clips. Two clips were presented after alcohol consumption (BAL .06), two other film clips were viewed when sober. Within alcohol conditions, one of the two films was combined with a suppression, the other with a no-suppression instruction. Genital responses were lower in the high sexual compulsivity group and higher during no-suppression conditions. The suppression instruction was not effective under sober conditions but impacted responses after alcohol consumption. This effect was more pronounced for the low compulsivity group. The findings suggest that sexually compulsive men are less successful in inhibiting their sexual responses, but only after alcohol consumption. The findings also suggest that sexually compulsive men may be less responsive to (researcher-selected) erotic stimuli.

Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration.

Degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is essential for vision, and studies have implicated altered POS processing in the pathogenesis of some retinal degenerative diseases. Consistent with this concept, a recently established hiPSC-RPE model of inherited macular degeneration, Best disease (BD), displayed reduced rates of POS breakdown. Herein we utilized this model to determine (i) if disturbances in protein degradation pathways are associated with delayed POS digestion and (ii) whether such defect(s) can be pharmacologically targeted. We found that BD hiPSC-RPE cultures possessed increased protein oxidation, decreased free-ubiquitin levels, and altered rates of exosome secretion, consistent with altered POS processing. Application of valproic acid (VPA) with or without rapamycin increased rates of POS degradation in our model, whereas application of bafilomycin-A1 decreased such rates. Importantly, the negative effect of bafilomycin-A1 could be fully reversed by VPA. The utility of hiPSC-RPE for VPA testing was further evident following examination of its efficacy and metabolism in a complementary canine disease model. Our findings suggest that disturbances in protein degradation pathways contribute to the POS processing defect observed in BD hiPSC-RPE, which can be manipulated pharmacologically. These results have therapeutic implications for BD and perhaps other maculopathies.