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Potential long-term health effects from tobacco products can be estimated by measuring changes in biochemical indicators of disease mechanisms like inflammation. This study assesses the potential relationships between biomarkers of potential harm (BOPH) and biomarkers of cigarette smoke exposure (BOE) based on data from the NHANES (2007–2012,n = 17,293 respondents). Statistically significant relationships were observed between white blood cells (WBC) and high-density lipoprotein (HDL) and BOE; between WBC and high-sensitivity C-reactive protein and smoking status; and between WBC and HDL and smoking intensity. This analysis suggests that WBC and HDL are useful BOPH in studies assessing the health risks of cigarette smoking. [ABSTRACT FROM AUTHOR]

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser363 and Thr370, while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser356, Thr357 and Ser375. Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we show that, in vitro, purified G protein-coupled receptor kinase 2 (GRK2) phosphorylates Ser375, protein kinase C (PKC) phosphorylates Ser363, while CaMKII phosphorylates Thr370. Phosphorylation of the GST fusion protein of the C-terminal tail of MOPr enhanced its ability to bind arrestin-2 and -3. Hence, our study identifies both the basal and agonist-stimulated phospho-acceptor sites in the C-terminal tail of MOPr, and suggests that the receptor is subject to phosphorylation and hence regulation by multiple protein kinases. [ABSTRACT FROM AUTHOR]

We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y12 receptor (P2Y12R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y12R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y12R internalization. In vitro and prior to agonist stimulation P2Y12R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization. [ABSTRACT FROM AUTHOR]

Introduction: Routine human papillomavirus (HPV) vaccination in the US is recommended at ages 11 or 12 years and can be given at age 9. Vaccination completion rates among adolescents 13-15 years in the US remain below the 80% goal. This study evaluated the long-term effects of increasing proactive HPV vaccination initiation rates at age 9 years in completion rates of adolescents., Methods: An age-structured vaccination model was developed and parametrized based on the National Immunization Survey-Teen (NIS-Teen) survey data. The model projected vaccination coverage (by vaccination status and age group), for 20 years, for a routine initiation scenario (no increase in initiation rates of 9-year-olds) and different proactive initiation (increased age 9 initiation) scenarios. The time to reach a completion rate of 80% for 13-15-year-olds was estimated. The model also generated projections stratified for subgroups of interest., Results: Results indicated that vaccine completion rates of 80% in 13-15-year-olds may not be achieved by 2040 under current trends of routine initiation at ages 11 or 12 years. However, increasing initiation rates in 9-year-olds by 1% and 3% annually could shorten the time to achieve 80% completion by 4 and 8 years, respectively. Stratification analyses showed that increasing initiation rates in 9-year-olds can also reduce disparities across subgroups in the time to achieve vaccination completion targets., Discussion: Increasing HPV vaccination initiation rates in 9-year-olds by as little as 1%-3% annually may be an effective strategy to improve HPV vaccination completion rates in adolescents by age 15 and reach the Healthy People goal of 80% completion much earlier., Competing Interests: KS is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and owns stock in Merck & Co., Inc., Rahway, NJ, USA. OP-L, AG-L, and AZ are employees of Analysis Group, Inc., and received research funding from Merck and Co, Inc, Rahway, NJ to conduct this study. JC-E has received consultancy fees from Merck Sharp and Dohme LLC and the Foundation for Sarcoidosis Research. DK has received research grants from Merck Investigators Studies Program and consultancy fees from Merck Sharp and Dohme LLC. The authors declare that this study received funding from Merck Sharp & Dohme LLC. The study sponsors were involved in several aspects of the research, including the study design, interpretation of data, and writing of the manuscript., (© 2024 Saxena, Patterson-Lomba, Gomez-Lievano, Zion, Cunningham-Erves and Kepka.)

Competing Interests: None