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IntroductionThe vertebrate retinal pigment epithelium (RPE) lies adjacent to the photoreceptors and is responsible for the engulfment and degradation of shed photoreceptor outer segment fragments (POS) through receptor-mediated phagocytosis. Phagocytosis of POS is critical for maintaining photoreceptor function and is a key indicator of RPE functionality. Popular established methods to assess RPE phagocytosis rely mainly on quantifying POS proteins, especially their most abundant protein rhodopsin, or on fluorescent dye conjugation of bulk, unspecified POS components. While these approaches are practical and quantitative, they fail to assess the fate of POS lipids, which make up about 50% of POS by dry weight and whose processing is essential for life-long functionality of RPE and retina.MethodsWe have developed a novel very-long-chain polyunsaturated fatty acids (VLC-PUFA)-based approach for evaluating RPE phagocytic activity by primary bovine and rat RPE and the human ARPE-19 cell line and validated its results using traditional methods.Results and discussionThis new approach can be used to detect in vitro the dynamic process of phagocytosis at varying POS concentrations and incubation times and offers a robust, unbiased, and reproducible assay that will have utility in studies of POS lipid processing.

Lipids participate in all cellular processes. Diverse methods have been developed to investigate lipid composition and distribution in biological samples to understand the effect of lipids across an organism’s lifespan. Here, we summarize the advanced techniques for studying lipids, including mass spectrometry-based lipidomics, lipid imaging, chemical-based lipid analysis and lipid engineering and their advantages. We further discuss the limitation of the current methods to gain an in-depth knowledge of the role of lipids in aging, and the possibility of lipid-based therapy in aging-related diseases.

Adiponectin receptor 1 (ADIPOR1) is a lipid and glucose metabolism regulator that possesses intrinsic ceramidase activity. Mutations of the ADIPOR1 gene have been associated with nonsyndromic and syndromic retinitis pigmentosa. Here, we show that the absence of AdipoR1 in mice leads to progressive photoreceptor degeneration, significant reduction of electroretinogram amplitudes, decreased retinoid content in the retina, and reduced cone opsin expression. Single-cell RNA-Seq results indicate that ADIPOR1 encoded the most abundantly expressed ceramidase in mice and one of the 2 most highly expressed ceramidases in the human retina, next to acid ceramidase ASAH1. We discovered an accumulation of ceramides in the AdipoR1–/– retina, likely due to insufficient ceramidase activity for healthy retina function, resulting in photoreceptor death. Combined treatment with desipramine/L-cycloserine (DC) lowered ceramide levels and exerted a protective effect on photoreceptors in AdipoR1–/– mice. Moreover, we observed improvement in cone-mediated retinal function in the DC-treated animals. Lastly, we found that prolonged DC treatment corrected the electrical responses of the primary visual cortex to visual stimuli, approaching near-normal levels for some parameters. These results highlight the importance of ADIPOR1 ceramidase in the retina and show that pharmacological inhibition of ceramide generation can provide a therapeutic strategy for ADIPOR1-related retinopathy.

Abstract Epithelial ovarian cancer (EOC) research has become more complex as researchers try to fully understand the metastatic process. Especially as we delve into the concept of tumour dormancy, where cells transition between proliferative and dormant states to survive during disease progression. Thus, the in vitro models used to conduct this research need to reflect this vast biological complexity. The innovation behind the many three-dimensional (3D) spheroid models has been refined to easily generate reproducible spheroids so that we may understand the various molecular signaling changes of cells during metastasis and determine therapeutic efficacy of treatments. This ingenuity was then used to develop the 3D ex vivo patient-derived organoid model, as well as multiple co-culture model systems for EOC research. Although, researchers need to continue to push the boundaries of these current models for in vitro and even in vivo work in the future. In this review, we describe the 3D models already in use, where these models can be developed further and how we can use these models to gain the most knowledge on EOC pathogenesis and discover new targeted therapies.

Background: Medication-related problems (MRPs) occur across the continuum of emergency department (ED) care: they may contribute to ED presentation, occur in the ED/short-stay unit (SSU), at hospital admission, or shortly after discharge to the community. This project aimed to determine predictors for MRPs across the continuum of ED care and incorporate these into screening tools (one for use at ED presentation and one at ED/SSU discharge), to identify patients at greatest risk, who could be targeted by ED pharmacists.Methods: A prospective, observational, multicenter study was undertaken in nine EDs, between July 2016 and August 2017. Blocks of ten consecutive adult patients presenting at pre-specified times were identified. Within 1 week of ED discharge, a pharmacist interviewed patients and undertook a medical record review to determine a medication history, patient understanding of treatment, risk factors for MRPs and to manage the MRPs. Logistic regression was undertaken to determine predictor variables. Multivariable regression beta coefficients were used to develop a scoring system for the two screening tools.Results: Of 1,238 patients meeting all inclusion criteria, 904 were recruited. Characteristics predicting MRPs related to ED presentation were: patient self-administers regular medications (OR = 7.95, 95%CI = 3.79–16.65), carer assists with medication administration (OR = 15.46, 95%CI = 6.52–36.67), or health-professional administers (OR = 5.01, 95%CI = 1.77–14.19); medication-related ED presentation (OR = 9.95, 95%CI = 4.92–20.10); age ≥80 years (OR = 3.63, 95%CI = 1.96–6.71), or age 65–79 years (OR = 2.01, 95%CI = 1.17–3.46); potential medication adherence issue (OR = 2.27, 95%CI = 1.38–3.73); medical specialist seen in past 6-months (OR = 2.02, 95%CI = 1.42–2.85); pharmaceutical benefit/pension/concession cardholder (OR = 1.89, 95%CI = 1.28–2.78); inpatient in previous 4-weeks (OR = 1.60, 95%CI = 1.02–2.52); being male (OR = 1.48, 95%CI = 1.05–2.10); and difficulties reading labels (OR = 0.63, 95%CI = 0.40–0.99). Characteristics predicting MRPs related to ED discharge were: potential medication adherence issue (OR = 6.80, 95%CI = 3.97–11.64); stay in ED > 8 h (OR = 3.23, 95%CI = 1.47–7.78); difficulties reading labels (OR = 2.33, 95%CI = 1.30–4.16); and medication regimen changed in ED (OR = 3.91, 95%CI = 2.43–6.30). For ED presentation, the model had a C-statistic of 0.84 (95% CI 0.81–0.86) (sensitivity = 80%, specificity = 70%). For ED discharge, the model had a C-statistic of 0.78 (95% CI 0.73–0.83) (sensitivity = 82%, specificity = 57%).Conclusion: Predictors of MRPs are readily available at the bedside and may be used to screen for patients at greatest risk upon ED presentation and upon ED/SSU discharge to the community. These screening tools now require external validation and implementation studies to evaluate the impact of using such tools on patient care outcomes.

Background Vaccines are effective in preventing Coronavirus Disease 2019 (COVID-19). Vaccine hesitancy defined as delay of acceptance or refusal of the vaccine is a major barrier to effective implementation. Methods Participants were recruited statewide through an English and Spanish social media marketing campaign conducted by a local news station during a one-month period as vaccines were becoming available in Rhode Island (from December 21, 2020 to January 22, 2021). Participants completed an online survey about COVID-19 vaccines and vaccine hesitancy with constructs and items adopted from the Health Belief Model. Results A total of 2,007 individuals completed the survey. Eight percent (n = 161) reported vaccine hesitancy. The sample had a median age of 58 years (interquartile range [IQR]: 45, 67), were majority female (78%), White (96%), Non-Hispanic (94%), employed (58%), and reported an annual individual income of $50,000 (59%). COVID-19 vaccine hesitancy was associated with attitudes and behaviors related to COVID-19. A one unit increase in concern about COVID-19 was associated with a 69% (Adjusted Odds Ratio: 0.31, 95% CI: 0.26–0.37) decrease in vaccine hesitancy. A one-level increase in the likelihood of getting influenza vaccine was associated with a 55% (AOR: 0.45 95% CI: 0.41–0.50) decrease in vaccine hesitancy. Conclusions COVID-19 vaccine hesitancy was relatively low in a state-wide survey in Rhode Island. Future research is needed to better understand and tailor messaging related to vaccine hesitancy.

As with previous global public health emergencies, the COVID-19 pandemic has had distinct and disproportionate impacts on women and their health and livelihoods. As the leader in global public health, it is incumbent upon the World Health Organization (WHO) to ensure gender is prioritized in pandemic response. We conducted a policy analysis of 338 WHO COVID-19 documents and found that only 20% explicitly discuss gender and over half do not mention women, gender, or sex at all. Considering the well documented gendered effects of pandemics and the WHO’s commitment to gender mainstreaming, this paper: 1) asks to what degree and how the WHO incorporates a gender inclusive approach; 2) maps where and how gender considerations are included; and 3) analyses what this suggests about WHO’s commitment to gender mainstreaming within its COVID-19 response and beyond. We demonstrate that WHO should increase its gender mainstreaming efforts and incorporate gender considerations related to health emergencies more often and in more policy areas.

The clinical role of catheter ablation using radiofrequency or cryothermal energy has become an important therapy in the management of patients with recurrent or persistent tachyarrhythmia that is refractory to medical therapy. It is regarded as a safe and reliable procedure and is performed routinely in health care facilities across the country. Like all procedures, there are associated risks and benefits. Development of an esophageal–atrial fistula is a rare but often-fatal complication of radiofrequency ablation. It is the second most frequent cause of death caused by the procedure, with mortality rates in excess of 70%. Death usually occurs as a result of cerebral or myocardial air embolism, endocarditis, massive gastrointestinal bleeding, and/or septic shock. Electrophysiologists have instituted a number of safeguard techniques to diminish the risk of developing esophageal–atrial fistula. Despite these measurements, instances of fistulous development still occur. Herein, we report a case of a 74-year-old male who presented with chest pain secondary to esophageal–pericardial fistula 19 days after pulmonary vein isolation using radiofrequency energy for atrial fibrillation in order to illustrate the clinical variability and diagnostic challenges associated with this dreaded gastrointestinal complication.

Background: End-stage renal disease patients experience increased prevalence of cardiovascular disease. Heart-artery interaction may be shifted, impacting blood pressure lability, and exercise tolerance. The coupling ratio consists of the ratio of indexed arterial elastance (EaI, arterial load) to ElvI, a measure of cardiac contractility or stiffness. Our purpose was to explore the relationship between elastances and functional capacity. We hypothesized that arterial stiffness (central pulse wave velocity, PWV) and elastances would be correlated to shuttle walk time. Methods: We used applanation tonometry, ultrasonography, and a shuttle walk test to evaluate our hypothesis. Spearman's correlations were used to assess relationships between variables. Block regression was also performed. Results: Forty-two subjects on maintenance hemodialysis participated. Average age=44±5 years, body surface area=2.01 kg/m2. Mean EaI=4.45 and mean ElvI=6.89; the coupling ratio=0.82. Mean aortic pulse pressure=51 mmHg and PWV=9.6 m/s. PWV(r=-0.385) and EaI (r=-0.424) were significantly and inversely related to walking time while stroke volume index (SVI) was positively correlated to shuttle walk time (r=0.337), pConclusions: We conclude that, like other clinical populations, both arterial and heart function predict walking ability and represent potential targets for intervention; arterial stiffness and SVI are strongly related to shuttle walk time in patients with ESRD.