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Formation of transport vesicles requires the coordinate activity of the coating machinery that selects cargo into the nascent vesicle and the membrane bending machinery that imparts curvature to the forming bud. Vesicle coating at the trans -Golgi Network (TGN) involves AP1, GGA2 and clathrin, which are recruited to membranes by activated ARF GTPases. The ARF activation at the TGN is mediated by the BIG1 and BIG2 guanine nucleotide exchange factors (GEFs). Membrane deformation at the TGN has been shown to be mediated by lipid flippases, including ATP8A1, that moves phospholipids from the inner to the outer leaflet of the TGN membrane. We probed a possible coupling between the coating and deformation machineries by testing for an interaction between BIG1, BIG2 and ATP8A1, and by assessing whether such an interaction may influence coating efficiency. Herein, we document that BIG1 and BIG2 co-localize with ATP8A1 in both, static and highly mobile TGN elements, and that BIG1 and BIG2 bind ATP8A1. We show that the interaction involves the catalytic Sec7 domain of the GEFs and the cytosolic C -terminal tail of ATP8A1. Moreover, we report that the expression of ATP8A1, but not ATP8A1 lacking the GEF-binding cytosolic tail, increases the generation of activated ARFs at the TGN and increases the selective recruitment of AP1, GGA2 and clathrin to TGN membranes. This occurs without increasing BIG1 or BIG2 levels at the TGN, suggesting that the binding of the ATP8A1 flippase tail to the Sec7 domain of BIG1/BIG2 increases their catalytic activity. Our results support a model in which a flippase component of the deformation machinery impacts the activity of the GEF component of the coating machinery. [Display omitted] • The lipid flippase ATP8A1 interacts with the Guanine Nucleotide Exchange Factors BIG1/BIG2 at the trans-Golgi network (TGN) in mammalian cells. • ATP8A1 and BIG1/BIG2 interaction stimulates activated ARFs at the TGN, recruiting AP1, GGA2, and clathrin. • ATP8A1 co-localizes with BIG1/BIG2 in static and mobile TGN elements, linking membrane deformation with coating processes. [ABSTRACT FROM AUTHOR]

Objective: Identify contemporary noise exposures and hearing protection use among adults.Study Design: Cross-sectional analysis of national health survey.Methods: Adult respondents in the 2014 National Health Interview Series hearing survey module were analyzed. Potentially harmful exposures to occupational and recreational noises in the past 12 months were extracted and quantified. Patterns of hearing protection use also were analyzed.Results: Among 239.7 million adults, "loud" and "very loud" occupational noise exposures were reported by 5.3% and 21.7%, respectively. Of those exposed to "loud" or "very loud" sounds at work, only 18.7% and 43.6%, respectively, always used hearing protection. A total of 38.2% (1.9 million) of those with "very loud" occupational exposures never used hearing protection. Frequent (> 10/year) "loud" and "very loud" recreational noise exposures were reported by 13.9% and 21.1%, respectively, most commonly to lawn mowers (72.6% and 55.2%, respectively). When exposed to recreational "loud/very loud" noise, only 11.4% always used hearing protection, whereas 62.3% (6.3 million) never used any protection. Lifetime exposure to firearm noise was reported by 36.6% of adults, 11.5% of whom had used firearms in the prior 12 months. Of those, only 58.5% always used hearing protection, whereas 21.4% (7.4 million) never used hearing protection.Conclusion: Substantial noise exposures with potentially serious long-term hearing health consequences frequently are occurring in occupational and recreational settings, and with the use of firearms. Only a minority of those exposed consistently are using hearing protection. Healthcare providers should actively identify and encourage the use of hearing protection with those patients at risk.Level Of Evidence: 4. Laryngoscope, 127:E340-E346, 2017. [ABSTRACT FROM AUTHOR]

The human mitochondrial heat shock protein 60 (hsp60) is a tetradecameric chaperonin that folds proteins in the mitochondrial matrix. An hsp60 D3G mutation leads to MitCHAP-60, an early onset neurodegenerative disease while hsp60 V72I has been linked to SPG13, a form of hereditary spastic paraplegia. Previous studies have suggested that these mutations impair the protein folding activity of hsp60 complexes but the detailed mechanism by which these mutations lead the neuromuscular diseases remains unknown. It is known, is that the β-subunit of the human mitochondrial ATP synthase co-immunoprecipitates with hsp60 indicating that the β-subunit is likely a substrate for the chaperonin. Therefore, we hypothesized that hsp60 mutations cause misfolding of proteins that are critical for aerobic respiration. Negative-stain electron microscopy and DLS results suggest that the D3G and V72I complexes fall apart when treated with ATP or ADP and are therefore unable to fold denatured substrates such as α-lactalbumin, malate dehydrogenase (MDH), and the β-subunit of ATP synthase in in-vitro protein-folding assays. These data suggests that hsp60 plays a crucial role in folding important players in aerobic respiration such as the β-subunit of the ATP synthase. The hsp60 mutations D3G and V72I impair its ability to fold mitochondrial substrates leading to abnormal ATP synthesis and the development of the MitCHAP-60 and SPG13 neuromuscular degenerative disorders. [ABSTRACT FROM AUTHOR]

This article discusses the importance of promoting health equity in the U.S. workforce, particularly in relation to COVID-19 and cardiovascular disease. It highlights the economic and social costs of health inequities and introduces the Health Equity in the Workforce initiative led by the American Heart Association. The initiative aims to improve health outcomes for 10 million U.S. workers by 2025 through strategic relationships, empowering employers, embedding in communities, measuring impact, and recognizing achievement. The article also discusses the efforts of the American Heart Association, Deloitte Health Equity Institute, and the SHRM Foundation in addressing health disparities and promoting diversity and inclusion. These organizations provide actionable strategies for employers to prioritize health equity in the workplace and believe that it is essential for creating a healthier and more equitable future for all. [Extracted from the article]

Rethinking Community Benefit Programs - A New Vision for Hospital Investment in Community Health Over the past decade, hospitals have been tasked with a growing responsibility to address the social determinants of health. This requires (1) policy reforms that incentivize investments in community health, (2)hospital-community partnerships, and (3) a renewed focus on the "investment" in community investment. [Extracted from the article]

A letter to the editor is presented in response to the article {Population Health, Public Health, and Accountable Care: Emerging Roles and Relationships" by Richard C. Ingram, Julia F. Costich, and F. Douglas Scutchfield, along with a response from the authors.

The effectiveness of a Cidex-based decontamination protocol was analyzed for its effectiveness in cleaning various components of a flexible fiberoptic laryngoscope (FFL), including the handle, eyepiece, and detachable light cable. A random microbiological sampling and aerobic bacterial culture analysis of 6 FFL eyepieces, 6 FFL driver handles, and 5 light cables prior to patient use was performed. Of 17 samples collected, 7 (41%) were contaminated with bacterial organisms. Organisms recovered represented both environmental organisms from skin and oral flora origin. This study demonstrates that potential contaminants may be present on FFL eyepieces and light cables, which are commonly overlooked in the cleaning protocols of a standard otolaryngology clinic. [ABSTRACT FROM PUBLISHER]