PGC-1α repression dysregulates lipid metabolism and induces lipid droplet accumulation in retinal pigment epithelium.

Drusen, the yellow deposits under the retina, are composed of lipids and proteins, and represent a hallmark of age-related macular degeneration (AMD). Lipid droplets are also reported in the retinal pigment epithelium (RPE) from AMD donor eyes. However, the mechanisms underlying these disease phenotypes remain elusive. Previously, we showed that Pgc-1α repression, combined with a high-fat diet (HFD), induce drastic AMD-like phenotypes in mice. We also reported increased PGC-1α acetylation and subsequent deactivation in the RPE derived from AMD donor eyes. Here, through a series of in vivo and in vitro experiments, we sought to investigate the molecular mechanisms by which PGC-1α repression could influence RPE and retinal function. We show that PGC-1α plays an important role in RPE and retinal lipid metabolism and function. In mice, repression of Pgc-1α alone induced RPE and retinal degeneration and drusen-like deposits. In vitro inhibition of PGC1A by CRISPR-Cas9 gene editing in human RPE (ARPE19- PGC1A KO) affected the expression of genes responsible for lipid metabolism, fatty acid ß-oxidation (FAO), fatty acid transport, low-density lipoprotein (LDL) uptake, cholesterol esterification, cholesterol biosynthesis, and cholesterol efflux. Moreover, inhibition of PGC1A in RPE cells caused lipid droplet accumulation and lipid peroxidation. ARPE19-PGC1A KO cells also showed reduced mitochondrial biosynthesis, impaired mitochondrial dynamics and activity, reduced antioxidant enzymes, decreased mitochondrial membrane potential, loss of cardiolipin, and increased susceptibility to oxidative stress. Our data demonstrate the crucial role of PGC-1α in regulating lipid metabolism. They provide new insights into the mechanisms involved in lipid and drusen accumulation in the RPE and retina during aging and AMD, which may pave the way for developing novel therapeutic strategies targeting PGC-1α.

A retrospective comparison of mechanically vs. kinematically aligned unicompartmental knee arthroplasties.

Background: Unicompartmental Knee Arthroplasties (UKAs) treat unicompartmental arthritic degeneration. Traditionally, they are placed in a mechanical alignment with bone cuts perpendicular to the leg's mechanical axis. Kinematic alignment, an alternative, considers the patient's pre-arthritic alignment. Methods: A retrospective study at Medstar Washington Hospital Center from 2015 to 2022 identified 72 UKA patients. Among them, 53 had mechanical alignments, and 20 had kinematic alignments. Using the Forgotten Joint Score (FJS) and Oxford Knee Score (OKS), Patient Reported Outcome Measures for these surgeries were recorded. Individuals were additionally analyzed post-surgically for Coronal Plane Alignment of the Knee (CPAK). Analysis was performed within the post-operative joint imaging, where mechanical medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA) were measured. The arithmetic hip knee ankle angle (aHKA) and joint line obliquity (JLO) were calculated according to the results of MPTA-LDFA and MPTA + LDFA respectively and grouped in accordance with the CPAK classification. Results: Overall, there was a statistically significant response rate of 51% (>50%). According to the FJS, the mechanical cohort averaged a score of 39.1 (±33.8), while the kinematical cohort averaged 56.5 (±35.2). A two-sample t-test of this data demonstrated a statistically insignificant p-value of 0.1537. According to the OKS, the mechanical cohort averaged a score of 29.1 (±10) and the kinematical cohort averaged 38.4 (±8). A two-sample t-test of this data demonstrated a statistically significant p-value of <0.001. Of note, 7 patients had to undergo revisions in the mechanical alignment cohort compared to 0 in the kinematic alignment cohort due to aseptic loosening. Conclusion: This study demonstrates the potential benefit in patient outcomes for individuals who undergo a kinematic rather than mechanical alignment of their UKAs. The results of the CPAK data with the significance of LDFA are consistent with the goals of the mechanical and kinematic alignment respectively.

Which Hospitals Promote a Sleep-Friendly Patient Experience?

The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey measures patient perceptions of hospital experience to determine the annual Center for Medicare and Medicaid Services (CMS) reimbursement. This study focuses on the "Quiet at Night" variable and identifies institutions with the highest scores to determine characteristics that facilitate patient sleep. The key findings were as follows: CMS Top Rated Hospitals have a mean score of 5 on the "Quiet at Night" variable.US News Honor Roll Hospitals have a mean score of 2.67, with a statistically significant difference of P < .001 between the groups.The key characteristics of the CMS Hospitals are that they are predominantly privately owned, specialized, surgical facilities with few total hospital beds.Knowing that HCAHPS scores directly impact and reflect patient experience, the objective of this study was to better understand the hospital practices that facilitate a high score on the "Quiet at Night" question to empower low scoring hospitals to improve their sleep practices at night and to score higher on the HCAHPS survey.

Defining existing practices to support the sleep of hospitalized patients: A mixed-methods study of top-ranked hospitals.

The objective of this study was to understand the existing practices and attitudes regarding inpatient sleep at the 2020 US News and World Report (USNWR) Honor Roll pediatric (n = 10) and adult (n = 20) hospitals. Section chiefs of Hospital Medicine from these institutions were surveyed and interviewed between June and August 2021. Among 23 of 30 surveyed physician leaders (response rate = 77%), 96% (n = 22) rated patient sleep as important, but only 43% (n = 10) were satisfied with their institutions' efforts. A total of 96% (n = 22) of institutions lack sleep equity practices. Fewer than half (48%) of top hospitals have sleep-friendly practices, with the most common practices including reducing overnight vital sign monitoring (43%), decreasing ambient light in the wards (43%), adjusting lab and medication schedules (35%), and implementing quiet hours (30%). Major themes from qualitative interviews included: importance of universal sleep-friendly cultures, environmental changes, and external incentives to improve patient sleep.

Racial and ethnic distribution of US randomized controlled trials in obstetrics: a retrospective review.

OBJECTIVES: To determine the racial and ethnic compositions of the participants in obstetric randomized controlled trials (RCTs) and compare them to the US general population. METHODS: RCTs published in two premier US journals, American Journal of Obstetrics and Gynecology, Obstetrics and Gynecology from January 2010 to April 2020 were analyzed. The racial and ethnic distributions of the study participants were extracted and expressed as percentages for each article. Obstetrics articles were selected and then further divided into subcategories. Statistical analyses were performed on racial and ethnicity representation in each subcategory compared to a US population norm. RESULTS: Overall, a wide variation of racial and ethnic distribution was noted among studies. However, statistically significant overrepresentation of Non-Hispanic Black population and underrepresentation of White and Asian races were noted while Hispanic population's representation was comparable to the US general population. This observation was persistent across most of the subcategories. CONCLUSIONS: RCTs in the field of Obstetrics showed an overrepresentation of Black population. This observation was unique when we consider the previous reports in other fields of medicine. These findings should be taken into consideration when interpreting the results of RCTs conducted in US.