It's addiction at this Point": A qualitative examination of youth E-cigarette use trajectory in the United States.

E-cigarettes (electronic cigarettes) have been the most used tobacco product among US youth since 2014, reaching a plateau during the COVID-19 pandemic. Youth e-cigarette use is associated with negative health consequences such as impaired cognitive functioning. For many, the COVID-19 pandemic altered social interactions, harm perceptions, and product availability. This changed the frequency and locations in which youth use e-cigarettes. To better understand youth e-cigarette use, we need more information on factors that can alter e-cigarette use, specifically, how the pandemic changed e-cigarette use among youth. In 2020-2021, we conducted online, individual interviews with 19 youth (aged 13-17) e-cigarette users living in the US to explore how COVID-19 impacted their e-cigarette use. Youth described a progression of e-cigarette use from initial experimentation, regular social use, and ultimately to nicotine addiction demonstrated by individual use in isolation. Many youth initiated e-cigarette use due to influences by friends or family members. Youth discussed progression to social use, with social interactions as an important reason for use and an avenue for expanding one's knowledge of e-cigarettes. After a period of time, youth began to recognize that the social interactions mattered less, suggesting to them that they had become addicted. This realization became more apparent during COVID-19, which changed how youth used e-cigarettes, especially around where use was occurring, health concerns, and use behavior and frequency. In our interviews, youth trajectory began with an initiation with family and friends, progressed to social use, and eventually developed to addiction, at which point social use was no longer the primary motivation for e-cigarette use. Understanding the trajectory of e-cigarette use will allow for effective interventions that reduce harm to youth from e-cigarette use.

"I Get the Flavors and It Makes Me Love Vaping More": How and Why Youth Users Modify Electronic Nicotine Delivery Systems.

INTRODUCTION: Youth in the United States are using electronic nicotine delivery systems (ENDS) at a high rate. Modifications to ENDS by youth can introduce additional health hazards which have not been previously considered. To better understand these risks, we need more information on what these modifications are, the motivations behind them, and the sources of information on modifications. AIMS AND METHODS: Utilizing a trained moderator, in 2020-2021, we conducted one-on-one interviews with 19 youth ENDS users aged 16-17 living in the United States and analyzed their responses using a qualitative description approach. RESULTS: The most prominent modification was to the e-liquid; youth indicated they mixed e-juices to create new flavors and added substances not intended for vaping, including illicit drugs such as cannabis and cocaine. Few youths from our sample were interested in achieving a specific nicotine level to vape, and modifications to the battery, coil and wick were less frequently mentioned. Some of these modifications were motivated by a desire to achieve specific experiences with their device. At other times, modifications were made due to necessity because of limited access to ENDS devices and supplies. YouTube and peers were the main sources of information about modifying. CONCLUSIONS: Youth are making modifications that are both intended and unintended by the manufacturer. Adding illicit drugs and other substances not made for vaping is of particular concern. Understanding how youth modify ENDS and how that changes their use is important to guide regulatory policy intended to reduce harm to youth from ENDS use. IMPLICATIONS: Youth from our study indicated that they make modifications to the ENDS devices, specifically to the e-liquid. These modifications are both intended by the manufacturer, such as changing the e-liquid and replacing coils, and unintended, such as adding substances not meant for vaping. Future policies aimed at reducing youth ENDS use should consider mandating better safeguards against modifications that appeal to youth.

Cancer detection in clinical practice and using blood-based liquid biopsy: A retrospective audit of over 350 dogs.

BACKGROUND: Guidelines-driven screening protocols for early cancer detection in dogs are lacking, and cancer often is detected at advanced stages. HYPOTHESIS/OBJECTIVES: To examine how cancer typically is detected in dogs and whether the addition of a next-generation sequencing-based "liquid biopsy" test to a wellness visit has the potential to enhance cancer detection. ANIMALS: Client-owned dogs with definitive cancer diagnoses enrolled in a clinical validation study for a novel blood-based multicancer early detection test. METHODS: Retrospective medical record review was performed to establish the history and presenting complaint that ultimately led to a definitive cancer diagnosis. Blood samples were subjected to DNA extraction, library preparation, and next-generation sequencing. Sequencing data were analyzed using an internally developed bioinformatics pipeline to detect genomic alterations associated with the presence of cancer. RESULTS: In an unselected cohort of 359 cancer-diagnosed dogs, 4% of cases were detected during a wellness visit, 8% were detected incidentally, and 88% were detected after the owner reported clinical signs suggestive of cancer. Liquid biopsy detected disease in 54.7% (95% confidence interval [CI], 49.5%-59.8%) of patients, including 32% of dogs with early-stage cancer, 48% of preclinical dogs, and 84% of dogs with advanced-stage disease. CONCLUSIONS/CLINICAL IMPORTANCE: Most cases of cancer were diagnosed after the onset of clinical signs; only 4% of dogs had cancer detected using the current standard of care (i.e., wellness visit). Liquid biopsy has the potential to increase detection of cancer when added to a dog's wellness visit.

Stakeholder-led design of a mobile HIV clinic model to enhance engagement and retention in HIV care in the Southern United States.

To foster retention of people living with HIV (PLWH) in HIV care in the Southern United States, we aimed to develop a stakeholder-driven mobile HIV clinic (MHC) model. From June 2019 to May 2021 we conducted a mixed-methods study: 50 surveys with out-of-care PLWH and 41 in-depth interviews with PLWH, HIV clinic staff, city officials, AIDS service organizations, and mobile clinics to examine preferences for MHC implementation. Survey data was analyzed descriptively, and interview transcripts were coded thematically. Participants recommended the MHC: (1) have nondescript exterior and HIV services nested in non-HIV care to foster confidentiality, (2) be located along public transportation and have extended hours to promote accessibility, (3) have established protocols addressing security, biosafety, and data safety; (4) provide comprehensive clinical and support services to address retention barriers; and (5) be integrated within the health system, use low-cost, diverse staffing, and establish appointment notification systems. By informing MHC design, these findings add to the toolbox of strategies that can render HIV care more accessible.

PP2ACdc55 dephosphorylates Pds1 and inhibits spindle elongation in S. cerevisiae.

PP2ACdc55 (the form of protein phosphatase 2A containing Cdc55) regulates cell cycle progression by reversing cyclin-dependent kinase (CDK)- and polo-like kinase (Cdc5)-dependent phosphorylation events. In S. cerevisiae, Cdk1 phosphorylates securin (Pds1), which facilitates Pds1 binding and inhibits separase (Esp1). During anaphase, Esp1 cleaves the cohesin subunit Scc1 and promotes spindle elongation. Here, we show that PP2ACdc55 directly dephosphorylates Pds1 both in vivo and in vitro Pds1 hyperphosphorylation in a cdc55 deletion mutant enhanced the Pds1-Esp1 interaction, which played a positive role in Pds1 nuclear accumulation and in spindle elongation. We also show that nuclear PP2ACdc55 plays a role during replication stress to inhibit spindle elongation. This pathway acted independently of the known Mec1, Swe1 or spindle assembly checkpoint (SAC) checkpoint pathways. We propose a model where Pds1 dephosphorylation by PP2ACdc55 disrupts the Pds1-Esp1 protein interaction and inhibits Pds1 nuclear accumulation, which prevents spindle elongation, a process that is elevated during replication stress.

Proteasomal regulation of the hypoxic response modulates aging in C. elegans.

The Caenorhabditis elegans von Hippel-Lindau tumor suppressor homolog VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the hypoxic response by promoting ubiquitination and degradation of the hypoxic response transcription factor HIF-1. Here, we report that loss of VHL-1 significantly increased life span and enhanced resistance to polyglutamine and beta-amyloid toxicity. Deletion of HIF-1 was epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to modulate aging and proteotoxicity. VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway.