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Introduction The e-cigarette market has expanded considerably in recent years, resulting in changes in availability and use of e-cigarettes with varying characteristics. Aims and Methods This study assessed trends in sales and prices of e-cigarettes by nicotine strength level, including by product type and flavor, during January 2017–March 2022. US e-cigarette retail sales data were licensed from IRI company. Nicotine strength was categorized as: Results During January 2017–March 2022, the unit share of products containing ≥5% nicotine strength increased by 1486.3%, while the dollar share increased by 1345.5%. By March 2022, 80.9% of total unit sales were composed of products containing ≥5% nicotine strength. By flavor, the percentage of units sold with ≥5% nicotine strength was 61.3% of tobacco-flavor sales, 79.3% of menthol sales, 87.4% of mint sales, and 96.1% of other flavor sales. By product type, the percentage of units sold with ≥5% nicotine strength was 90.6% of disposable e-cigarette sales and 74.2% of prefilled cartridge sales. During January 2017–March 2022, the price of low-nicotine strength e-cigarettes increased, while the price of high-nicotine products either decreased or did not change. Conclusions Sales of high nicotine-strength e-cigarettes have dominated the US e-cigarette market. Limiting the nicotine strength of e-cigarettes could be considered as part of a comprehensive tobacco control strategy to reduce youth access to and use of these products. Implications The findings from this study indicate that previously reported increases in e-cigarette nicotine strength during 2013–2018 have continued through 2022. The US e-cigarette market sales continue to be dominated by relatively high-nicotine products. Strategies to address factors that make these products, particularly appealing to youth, including flavors and product innovations, are critical. Such strategies are important—as part of a comprehensive approach alongside other evidence-based population-level actions—to address youth e-cigarette use. Importantly, actions to reduce e-cigarette use among youth are not mutually exclusive from actions to maximize the potential benefits of e-cigarettes for increasing smoking cessation among adults.

P2Y receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on P2Y Receptors [3, 5, 189]) are activated by the endogenous ligands ATP, ADP, UTP, UDP, UDP-glucose and adenosine. The eight mammalian P2Y receptors are activated by distinct nucleotides: P2Y1, P2Y11, P2Y12 and P2Y13 are activated by adenosine-nucleotides; P2Y2, P2Y4 can be activated by both adenosine and uridine nucleotides, with some species-specific differences; P2Y6 is mainly activated by UDP; P2Y14 is preferentially activated by sugar-uracil nucleotides. The missing numbers in the receptor nomenclature refer either to non-mammalian orthologs or receptors having some sequence homology to P2Y receptors but for which there is no functional evidence of responsiveness to nucleotides [380]. Based on their G protein coupling P2Y receptors can be divided into two subfamilies: P2Y1, P2Y2, P2Y4, P2Y6 and P2Y11 receptors couple via Gq proteins to stimulate phospholipase C followed by increases in inositol phosphates and mobilization of Ca2+ from intracellular stores. P2Y11 receptors couple in addition to Gs proteins followed by increased adenylate cyclase activity. In contrast, P2Y12, P2Y13, and P2Y14 receptors signal primarily through activation of Gi proteins and inhibition of adenylate cyclase activity or control of ion channel activity [380]. Clinically used drugs acting on these receptors include the dinucleoside polyphosphate diquafosol, agonist of the P2Y2 receptor subtype, approved in Japan and South Korea for the management of dry eye disease [238], and the P2Y12 receptor antagonists prasugrel, ticagrelor and cangrelor, all approved as antiplatelet drugs [52, 320].

P2X receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on P2X Receptors [49, 146]) have a trimeric topology [118, 128, 144, 197] with two putative TM domains per P2X subunit, gating primarily Na+, K+ and Ca2+, exceptionally Cl-. The Nomenclature Subcommittee has recommended that for P2X receptors, structural criteria should be the initial basis for nomenclature where possible. X-ray crystallography indicates that functional P2X receptors are trimeric and three agonist molecules are required to bind to a single trimeric assembly in order to activate it [118, 144, 95, 103, 177]. Native receptors may occur as either homotrimers (e.g. P2X1 in smooth muscle) or heterotrimers (e.g. P2X2:P2X3 in the nodose ganglion [280], P2X1:P2X5 in mouse cortical astrocytes [162], and P2X2:P2X5 in mouse dorsal root ganglion, spinal cord and mid pons [53, 234]. P2X2, P2X4 and P2X7 receptor activation can lead to influx of large cationic molecules, such as NMDG+, Yo-Pro, ethidium or propidium iodide [211]. The permeability of the P2X7 receptor is modulated by the amount of cholesterol in the plasma membrane [193]. The hemi-channel pannexin-1 was initially implicated in the action of P2X7 [212], but not P2X2, receptors [41], but this interpretation is probably misleading [215]. Convincing evidence now supports the view that the activated P2X7 receptor is immediately permeable to large cationic molecules, but influx proceeds at a much slower pace than that of the small cations Na+, K+, and Ca2+ [66].

The Southern Ocean upper-layer freshwater balance exerts a global climatic influence by modulating density stratification and biological productivity, and hence the exchange of heat and carbon between the atmosphere and the ocean interior. It is thus important to understand and quantify the time-varying freshwater inputs, which is challenging from measurements of salinity alone. Here we use seawater oxygen isotopes from samples collected between 2016 and 2021 along a transect spanning the Scotia and northern Weddell Seas to separate the freshwater contributions from sea ice and meteoric sources. The unprecedented retreat of sea ice in 2016 is evidenced as a strong increase in sea ice melt across the northern Weddell Sea, with surface values increasing approximately two percentage points between 2016 and 2018 and column inventories increasing approximately 1 to 2 m. Surface meteoric water concentrations exceeded 4% in early 2021 close to South Georgia due to meltwater from the A68 megaberg; smaller icebergs may influence meteoric water at other times also. Both these inputs highlight the importance of a changing cryosphere for upper-ocean freshening; potential future sea ice retreats and increases in iceberg calving would enhance the impacts of these freshwater sources on the ocean and climate. This article is part of a discussion meeting issue ‘Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities’.

Purpose We examined associations between academic grades and positive health behaviors, individually and collectively, among U.S. high school students. Design Cross-sectional study design. Setting: Data were from the 2017 national Youth Risk Behavior Survey. Response rates were 75% for schools, 81% for students, and 60% overall (n = 14,765 students). Subjects Youth in grades 9th–12th. Measures We focused on youth behaviors that can prevent or delay the onset of chronic health conditions. Seven dietary, 3 physical activity, 2 sedentary screen time, and 4 tobacco product use behaviors were assessed. Variables were dichotomized (0/1) to indicate that a score was given to the positive health behavior response (e.g.,, did not smoke cigarettes = 1). A composite score was created by summing each positive health behavior response among 16 total health behaviors. Analysis Multivariable logistic regression analyses for each individual health behavior, and a multivariable negative binomial regression for the composite score, were conducted with self-reported academic grades, controlling for sex, grade in school, race/ethnicity, and body mass index (BMI) categories. Results Controlling for covariates, students who reported mostly A’s had 2.0 ( P < .001) more positive health behaviors; students who reported mostly B’s had 1.3 ( P < .001) more positive health behaviors; and students who reported mostly C’s had .78 ( P < .001) more positive health behaviors, compared to students who reported mostly D’s/F’s. Conclusions Higher academic grades are associated with more positive individual and cumulative health behaviors among high school students. Understanding these relationships can help inform efforts to create a healthy and supportive school environment and strive for health equity.

Introduction Cigar smoking has increased in recent decades as the cigar product landscape has diversified. This study assessed trends in US cigar sales during 2016–2020. Aims and Methods Unit sales and average unit price for cigars were assessed during January 3, 2016–June 13, 2020, overall and by product and flavor type, for the 48 contiguous US states and D.C. Assessed cigar types were large cigars, little cigars, and cigarillos; assessed flavor types were tobacco/unflavored, candy/sweets, fruit, menthol, alcohol, coffee, other flavors, and no flavor stated. A joinpoint regression model was used to assess the magnitude and significance of sales trends. Results During January 3, 2016–June 13, 2020, unit sales of cigarillos increased (average monthly percentage change [AMPC] = 0.7%, p < .001), while unit sales of large cigars (AMPC = −0.8%, p < .001) and little cigars decreased (AMPC = −0.2%, p < .001). The average price of cigarillos gradually decreased since mid-August 2017 (AMPC = −0.1%, p < .001), and the average price of little cigars decreased from mid-June 2016 to mid-June 2019 (AMPC = −0.3%, p < .001). In contrast, the average price of large cigars increased during the entire study period (AMPC = 0.6%, p < .001). Irrespective of cigar type, tobacco-flavored/unflavored products were the most commonly sold cigars during the assessed period; however, sales of other flavors varied by cigar type. Conclusions Cigar sales and price vary by type over time in the United States, including sales of cigarillos (94.2% of unit sales) increasing as their prices have decreased in recent years. Public health strategies are warranted to address the full scope of cigar types being used in the United States. Implications Surveillance of cigar sales data, including product characteristics, can provide a timely complement to self-reported survey data of cigar use. This study assessed trends in US cigar sales during 2016–2020, including by product and flavor type. The findings indicate that sales of cigarillos, which comprise most cigar sales in the United States during the assessed period, increased as their prices decreased. Sales of certain flavors, such as candy/sweet cigarillos and coffee large cigars, increased significantly. These findings reinforce the importance of evidence-based strategies, including increasing price and restricting flavors, to reduce the affordability and consumption of cigars in the United States.

Scientists who plan to publish in the British Journal of Pharmacology (BJP) should read this article before undertaking studies utilising anaesthetics in mammalian animals. This editorial identifies certain gaps in the reporting of details on the use of anaesthetics in animal research studies published in the BJP. The editorial also provides guidance, based upon current best practices, for performing in vivo experiments that require anaesthesia. In addition, mechanisms of action and physiological impact of specific anaesthetic agents are discussed. Our goal is to identify best practices and to provide guidance on the information required for manuscripts submitted to the BJP that involve the use of anaesthetic agents in studies with experimental animals.

Objective: High-quality scientific evidence underpins public health decision making. The Centers for Disease Control and Prevention (CDC) agency provides scientific data, including during public health emergencies. To understand CDC’s contributions to COVID-19 science, we conducted a bibliometric evaluation of publications authored by CDC scientists from January 20, 2020, through January 20, 2022, by using a quality improvement approach (SQUIRE 2.0). Methods: We catalogued COVID-19 articles with ≥1 CDC-affiliated author published in a scientific journal and indexed in the World Health Organization’s COVID-19 database. We identified priority topic areas from the agency’s COVID-19 Public Health Science Agenda by using keyword scripts in EndNote and then assessed the impact of the published articles by using Scopus and Altmetric. Results: During the first 2 years of the agency’s pandemic response, CDC authors contributed to 1044 unique COVID-19 scientific publications in 208 journals. Publication topics included testing (n = 853, 82%); prevention strategies (n = 658, 63%); natural history, transmission, breakthrough infections, and reinfections (n = 587, 56%); vaccines (n = 567, 54%); health equity (n = 308, 30%); variants (n = 232, 22%); and post–COVID-19 conditions (n = 44, 4%). Publications were cited 40 427 times and received 81 921 news reports and 1 058 893 social media impressions. As the pandemic evolved, CDC adapted to address new scientific questions, including vaccine effectiveness, safety, and access; viral variants, including Delta and Omicron; and health equity. Conclusion: The agency’s COVID-19 Public Health Science Agenda helped guide impactful scientific activities. CDC continues to evaluate COVID-19 priority topic areas and contribute to development of new scientific work. CDC is committed to monitoring emerging issues and addressing gaps in evidence needed to improve health.

According to the WHO, the Region of the Americas has the second lowest tobacco use prevalence of any WHO region.1 WHO projections based on trends since 2000 indicate that the Region of the Americas, which includes both North and South America, is the only region expected to achieve a 30% relative reduction in tobacco use by 2025.1 However, there are approximately 127 million persons who report smoking tobacco in the Americas Region,2 a majority of whom reside in North America.3 North America consists of 23 countries with a combined population of nearly 600 million people, or approximately 7.5% of the world’s population in 2019.4 Among North American countries, data from 2017 for persons aged 15 years or older show current tobacco smoking prevalence ranged from 6.0% in Panama to 27.8% in Cuba.5 Among students aged 13–15 years old in North American countries with available data through 2017, current tobacco smoking prevalence ranged from 4.4% in Dominican Republic to 18.1% in Mexico.5 Tobacco smoking among adults is higher among males than females across North America. However, the difference in prevalence between sexes in the Region of the Americas is among the lowest of any WHO region5; this pattern is particularly pronounced among youth, where tobacco smoking among girls is similar to or higher among boys in most countries.2 5 Despite lower tobacco use relative to other regions, and future projected reductions,1 challenges remain to combating the tobacco epidemic in North America, including diversification of the product landscape, tobacco industry interference and uneven application of evidence-based strategies. This commentary discusses these challenges, as well as opportunities for future action to reduce the burden of tobacco use in North America. Over the past decade and a half, the tobacco and nicotine product landscape has evolved …

OBJECTIVE Fetal repair of an open neural tube defect (ONTD) by open hysterotomy has been shown to reduce the need for ventriculoperitoneal shunting and improve motor outcomes for infants, but increases the risk of Cesarean section and prematurity. Fetoscopic repair is an alternative approach that may confer similar neurological benefits but allows for vaginal delivery and reduces the incidence of hysterotomy-related complications. We sought to compare the costs of care from fetal surgery until neonatal discharge, as well as the clinical outcomes, associated with each surgical approach. METHODS This was a retrospective cohort study of patients who underwent prenatal ONTD repair, using either the open-hysterotomy or the fetoscopic approach, at a single institution between 2012 and 2018. Clinical outcomes were collected by chart review. A cost-consequence analysis was conducted from the hospital perspective, and included all inpatient and ambulatory hospital and physician costs incurred for the care of mothers and their infants, from the time of maternal admission for fetal ONTD repair up to postnatal maternal and infant discharge. Costs were estimated using cost-to-charge ratios for hospital billing and the Medicare physician fee schedule for physician billing. RESULTS Seventy-eight patients were included in the analysis, of whom 47 underwent fetoscopic repair and 31 underwent open-hysterotomy repair. In the fetoscopic-repair group, compared with the open-repair group, fewer women underwent Cesarean section (53% vs 100%; P

The ocean absorbs approximately a quarter of the carbon dioxide currently released to the atmosphere by human activities (Canth). A disproportionately large fraction accumulates in the North Atlantic due to the combined effects of transport by the Atlantic Meridional Overturning Circulation (AMOC) and air–sea exchange. However, discrepancies exist between modelled and observed estimates of the air–sea exchange due to unresolved ocean transport variability. Here we quantify the strength and variability of Canth transports across 26.5° N in the North Atlantic between 2004 and 2012 using circulation measurements from the RAPID mooring array and hydrographic observations. Over this period, decreasing circulation strength tended to decrease northward Canth transport, while increasing Canth concentrations (preferentially in the upper limb of the overturning circulation) tended to increase northward Canth transport. These two processes compensated each other over the 8.5-year period. While ocean transport and air–sea Canth fluxes are approximately equal in magnitude, the increasing accumulation rate of Canth in the North Atlantic combined with a stable ocean transport supply means we infer a growing contribution from air–sea Canth fluxes over the period. North Atlantic Canth accumulation is thus sensitive to AMOC strength, but growing atmospheric Canth uptake continues to significantly impact Canth transports. Slowdown of the Atlantic Meridional Overturning Circulation from 2004 to 2012 led to a decrease in its relative contribution to North Atlantic carbon accumulation, while the supply from air–sea fluxes increased, according to an analysis of ocean mooring circulation observations.

Algorithms that quantify the similarity between two sequences of data date back to the mid 20th century. Sequence comparison continues to be active area of research in mathematics, statistics, and ...

ObjectiveCreate a prioritization framework for value-based improvement in neonatal care.Study designA retrospective cohort study of very low birth weight (ResultsResource categories with the greatest cost, patient exposure, and inter-hospital variability were parenteral nutrition, hematology (lab testing), and anticoagulation (for central venous access and therapy), respectively. Based on our prioritization score, parenteral nutrition was identified as the highest priority overall.ConclusionsWe report the development of a prioritization score for potential value-based improvement in neonatal care. Our findings suggest that parenteral nutrition, central venous access, and high-volume laboratory and imaging modalities should be priorities for future comparative effectiveness and quality improvement efforts.

Introduction Nicotine pouch products, oral smokeless products that contain nicotine but no tobacco leaf material, have recently entered the US marketplace. Available data indicate sales of these products in the United States have increased since 2018; however, the extent of use among US youth and adults is uncertain. Methods To assay the chemistry of these emerging tobacco products, we analyzed 37 nicotine pouch brands from six total manufacturers. Almost all of the products had flavor descriptors (36 of 37), such as mint, licorice, coffee, cinnamon, and fruit. The amount of free nicotine, the form most easily absorbed, was calculated for each product using total nicotine, product pH, the appropriate pKa, and the Henderson–Hasselbalch equation. Results Nicotine pouch products varied in pouch content mass, moisture content (1.12%‒47.2%), alkalinity (pH 6.86‒10.1), and % free nicotine (7.7%‒99.2%). Total nicotine content ranged from 1.29 to 6.11 mg/pouch, whereas free nicotine ranged from 0.166 to 6.07 mg/pouch. These findings indicate that nicotine and pH levels found in some of these nicotine pouches are similar to conventional tobacco products, such as moist snuff and snus, and that most of these pouch products are flavored. Conclusions Although these products likely lack many tobacco-related chemicals, each product analyzed contained nicotine, which is both addictive and can harm human health. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, it is important to include these emerging tobacco products in tobacco control research, policy, and practice. Implications These “tobacco-free” nicotine pouches have similar pH and nicotine content to conventional tobacco products, such as moist snuff and snus. Although they lack many tobacco-related chemicals, most are highly flavored which could increase experimentation from new users. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, in terms of their flavors and nicotine content, it is important to examine and include these emerging tobacco products as they relate to tobacco control research, policy, and practice.

Estimate hospital variation in echocardiography (echo) among very preterm infants.Retrospective cohort study of very preterm (32 weeks) infants discharged between 2012 and 2019 from US children's hospitals. Echo exposure was identified using daily billing, and hospital variation was estimated after adjustment for illness severity. Variation in very early echo use (3 days of life) was compared to exposure to treatment of a patent ductus arteriosus (PDA), and other practice patterns.27,498 subjects across 39 children's hospitals were included. Very early echo use had the greatest hospital variation (3-34%). Increasing very early echo use was not associated with PDA treatment (p = 0.93), but was associated with nitric oxide (p 0.01) and vasoactive medications (p 0.01).Hospital variation in echo use among preterm infants was greatest in the first few days of life and was associated with increasing nitric oxide and vasoactive medication use. The impact of this variation on clinical outcomes is uncertain and warrants further investigation.

Background In June 2020, Massachusetts implemented a law prohibiting the sale of all flavored tobacco products, including menthol cigarettes. This law was associated with significant declines in overall cigarette and menthol cigarette sales in Massachusetts, however it is unknown whether the law has increased cross-border sales in neighboring states where menthol cigarettes are still sold. Methods U.S. cigarette retail scanner data were licensed from the IRi Company. Cigarette pack sales were summed in 4-week periods during January 2020-December 2021 (n = 832). Outcomes were state-level pack sales per 1000 population, overall and by flavor status (menthol and non-flavored). A difference-in-differences analysis was used to examine adjusted sales for Massachusetts border states (New Hampshire, Connecticut, Vermont, and Rhode Island) before (January 2020-May 2020) and after (June 2020-December 2021) the Massachusetts’s law, compared to 28 non-border states. Control variables included state and time fixed effects; real price per pack; tobacco control policies; COVID-19 cases and deaths, and related statewide closure; and state sociodemographic characteristics. Results Following the law, unadjusted sales of menthol, non-flavored, and overall cigarettes trended upward in border states; however, these increases were not statistically significant or different from sales patterns in non-border states. This finding persisted after accounting for product prices, tobacco control policies, the COVID-19 pandemic, sociodemographic factors, and fixed effects. Conclusion Laws prohibiting the sale of flavored tobacco products, including menthol products, reduce access to these products, while having no significant impact on cross-border sales in neighboring states where menthol cigarettes are sold.

Introduction About 80% of the 1.1 billion people who smoke tobacco worldwide reside in low- and middle-income countries. Evidence-based approaches to promote cessation include brief advice from health professionals and referrals through quitlines. This study assesses cessation behaviors and the use of cessation services in the past 12 months among current tobacco smokers in 31 countries who attempted to quit. Methods Data came from the Global Adult Tobacco Survey, a household-based survey of non-institutionalized adults aged ≥15 years. Surveys were conducted in 31 countries during 2008–2018; sample sizes ranged from 4,250 (Malaysia) to 74,037 (India), and response rates ranged from 64.4% (Ukraine) to 98.5% (Qatar). In 2019, data from the 31 countries were assessed in June 2019, and indicators included self-reported current (daily or less than daily) tobacco smoking, past-year quit attempts, and cessation methods used in the past 12 months. Results Current tobacco smoking prevalence ranged from 3.7% (Ethiopia) to 38.2% (Greece). Overall, an estimated 176.8 million adults from the 31 countries made a quit attempt in the past 12 months, with country-level prevalence ranging from 16.4% (Greece) to 54.7% (Botswana). Most individuals who made a quit attempt did so without assistance (median=74.4%). Other methods were less prevalent, including quitlines (median=0.2%) and counseling (median=7.2%). Conclusions In the assessed countries, the majority of those who currently smoked tobacco and made a quit attempt did so without assistance; very few reported using quitlines, partly because of the lack of quitlines in some countries. In resource-limited settings, quitlines can play a greater role in helping people quit smoking as part of a comprehensive approach.

Objective Studies examining the use of smoking cessation treatment and related spending among enrollees with employer-sponsored health insurance are dated and limited in scope. We assessed changes in annual receipt of and spending on cessation medications approved by the US Food and Drug Administration (FDA) among tobacco users with employer-sponsored health insurance from 2010 to 2017. Methods We analyzed data on 439 865 adult tobacco users in 2010 and 344 567 adult tobacco users in 2017 from the IBM MarketScan Commercial Database. We used a negative binomial regression to estimate changes in receipt of cessation medication (number of fills and refills and days of supply). We used a generalized linear model to estimate spending (total, employers’, and out of pocket). In both models, covariates included year, age, sex, residence, and type of health insurance plan. Results From 2010 to 2017, the percentage of adult tobacco users with employer-sponsored health insurance who received any cessation medication increased by 2.4%, from 15.7% to 16.1% ( P < .001). Annual average number of fills and refills per user increased by 15.1%, from 2.5 to 2.9 ( P < .001) and days of supply increased by 26.4%, from 81.9 to 103.5 ( P < .001). The total annual average spending per user increased by 53.6%, from $286.40 to $440.00 ( P < .001). Annual average out-of-pocket spending per user decreased by 70.9%, from $70.80 to $20.60 ( P < .001). Conclusions Use of smoking cessation medications is low among smokers covered by employer-sponsored health insurance. Opportunities exist to further increase the use of cessation medications by promoting the use of evidence-based cessation treatments and reducing barriers to coverage, including out-of-pocket costs.

This Viewpoint from leadership at the US Food and Drug Administration (FDA) proposes the creation of a comprehensive “care package” framework of resources to help maximize cessation of tobacco use, including components focused on strategies at the individual, health system, and population levels.

To rank clinician-driven tests and treatments (CTTs) by their total cost during the birth hospitalization for preterm infants. Retrospective cohort of very low birth weight (

Summary Background Since August, 2019, US public health officials have been investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). A spectrum of histological patterns consistent with acute to subacute lung injury has been seen in biopsies; however, autopsy findings have not been systematically characterised. We describe the pathological findings in autopsy and biopsy tissues submitted to the US Centers for Disease Control and Prevention (CDC) for the evaluation of suspected EVALI. Methods Between Aug 1, 2019, and Nov 30, 2019, we examined lung biopsy (n=10 individuals) and autopsy (n=13 individuals) tissue samples received by the CDC, submitted by 16 US states, from individuals with: a history of e-cigarette, or vaping, product use; respiratory, gastrointestinal, or constitutional symptoms; and either pulmonary infiltrates or opacities on chest imaging, or sudden death from an undetermined cause. We also reviewed medical records, evaluated histopathology, and performed infectious disease testing when indicated by histopathology and clinical history. Findings 21 cases met surveillance case definitions for EVALI, with a further two cases of clinically suspected EVALI evaluated. All ten lung biopsies showed histological evidence of acute to subacute lung injury, including diffuse alveolar damage or organising pneumonia. These patterns were also seen in nine of 13 (69%) autopsy cases, most frequently diffuse alveolar damage (eight autopsies), but also acute and organising fibrinous pneumonia (one autopsy). Additional pulmonary pathology not necessarily consistent with EVALI was seen in the remaining autopsies, including bronchopneumonia, bronchoaspiration, and chronic interstitial lung disease. Three of the five autopsy cases with no evidence of, or a plausible alternative cause for acute lung injury, had been classified as confirmed or probable EVALI according to surveillance case definitions. Interpretation Acute to subacute lung injury patterns were seen in all ten biopsies and most autopsy lung tissues from individuals with suspected EVALI. Acute to subacute lung injury can have numerous causes; however, if it is identified in an individual with a history of e-cigarette, or vaping, product use, and no alternative cause is apparent, a diagnosis of EVALI should be strongly considered. A review of autopsy tissue pathology in suspected EVALI deaths can also identify alternative diagnoses, which can enhance the specificity of public health surveillance efforts. Funding US Centers for Disease Control and Prevention.

Cigarette smoking remains the leading cause of preventable disease and death in the United States (1). Although the percentage of all U.S. adults who smoke cigarettes has declined substantially since the mid-1960s (1,2), marked disparities persist, and declines have not been consistent across population groups (1,2). Studies have shown that cigarette smoking is as common, and sometimes more so, among adults with a history of epilepsy compared with those without a history of epilepsy, but reasons for this are unclear (3-6). Compared with adults without epilepsy, adults with epilepsy report lower household income, more unemployment and disability, worse psychological health, and reduced health-related quality of life (3,4,6,7). Trends in cigarette smoking among U.S. adults with epilepsy have not been previously assessed. CDC analyzed National Health Interview Survey (NHIS) data among 121,497 U.S. adults from 2010, 2013, 2015, and 2017 to assess current cigarette smoking by epilepsy status. From 2010 through 2017, the age-standardized percentages of current smoking were 24.9% among adults with active epilepsy, 25.9% among adults with inactive epilepsy, and 16.6% among adults with no history of epilepsy. After accounting for differences in data collection intervals and patterns in smoking status among subgroups, CDC found that current cigarette smoking declined significantly from 2010 to 2017 among adults with no history of epilepsy (19.3% to 14.0% [p

The synaptic event called the inhibitory junction potential (IJP) was arguably one of the more important discoveries made by Burnstock and arguably one of his finer legacies. The discovery of the IJP fundamentally changed how electromechanical coupling was visualised in gastrointestinal smooth muscle. Its discovery also set in motion the search for novel inhibitory neurotransmitters in the enteric nervous system, eventually leading to proposal that ATP or a related nucleotide was a major inhibitory transmitter. The subsequent development of purinergic signalling gave impetus to expanding the classification of surface receptors for extracellular ATP, not only in the GI tract but beyond, and then led to successive phases of medicinal chemistry as the P2 receptor field developed. Ultimately, the discovery of the IJP led to the successful cloning of the first P2Y receptor (chick P2Y1) and expansion of mammalian ATP receptors into two classes: metabotropic P2Y receptors (encompassing P2Y1, P2Y2, P2Y4, P2Y6, P2Y11–14 receptors) and ionotropic P2X receptors (encompassing homomeric P2X1–P2X7 receptors). Here, the causal relationship between the IJP and P2Y1 is explored, setting out the milestones reached and achievements made by Burnstock and his colleagues.

Pennsylvania has one of the highest opioid overdose rates in the US; however, since 2018 approximately 80% of people who experienced an opioid overdose in the state survived. More attention has been paid to opioid overdose mortality despite notable individual and geographic differences in overdose survival. Naloxone is an essential tool in increasing chances of survival after opioid overdose, but its availability and the rate at which it is administered differs by county in Pennsylvania and nationally.We use 2018-2020 Pennsylvania Overdose Information Network data on opioid incidents and where they occurred, combined with 2015-2019 American Community Survey data, to evaluate opioid overdose survival and naloxone administration by county over a three-year period.Individuals who received at least one dose of naloxone following overdose had 11 times greater odds of survival. White, middle-aged men were least likely to survive opioid overdose. Both survival and naloxone administration rates differed by county with lower rates in less populated counties.Expanding naloxone distribution and administration and ensuring proper education about standing orders for naloxone administration are important tools for addressing opioid overdose mortality.

e-Cigarettes are the most commonly used tobacco product among US youths. Flavors are among the most cited reasons for use of e-cigarettes among youths, and therefore, some states have imposed restrictions on flavored e-cigarette sales. To our knowledge, no study has compared e-cigarette sales between states with statewide flavored e-cigarette restrictions and states without such restrictions while controlling for co-occurring events.To assess whether implementation of statewide restrictions on flavored e-cigarette sales in Massachusetts, New York, Rhode Island, and Washington was associated with a reduction in total e-cigarette unit sales from 2014 to 2020.This cross-sectional study with difference-in-differences analysis used e-cigarette retail sales data from Massachusetts, Rhode Island, and Washington, which implemented restrictions on flavored e-cigarette sales in October 2019; New York, which implemented these restrictions in May 2020; and 35 states without these restrictions (control states). Sales were summed into 4-week periods from August 24, 2014, to December 27, 2020, for a total of 2988 state-period observations.A difference-in-differences analysis was conducted to compare e-cigarette unit sales in the 4 states with flavor restrictions (before and after implementation) with those in the 35 control states. The model controlled for other population-based policies and emergent events (eg, the COVID-19 pandemic). Data on 4-week e-cigarette unit sales were sorted into 4 flavor categories (tobacco, menthol, mint, and other). Unit sales were standardized to reflect the most common package sizes for each product type.Statewide restrictions on non-tobacco-flavored e-cigarette sales were associated with the following reductions in mean 4-week total e-cigarette sales in intervention states compared with control states from October 2019 to December 2020: 30.65% (95% CI, 24.08%-36.66%) in New York, 31.26% (95% CI, 11.94%-46.34%) in Rhode Island, and 25.01% (95% CI, 18.43%-31.05%) in Washington. In Massachusetts, the comprehensive sales prohibition of all e-cigarette products was associated with a 94.38% (95% CI, 93.37%-95.23%) reduction in 4-week sales compared with control states. Except in Massachusetts, where all sales of flavored e-cigarettes decreased, reductions were found only for non-tobacco-flavored e-cigarette sales in the other states with restrictions. Among control states, mean sales decreased by 28.4% from August 2019 to February 2020 but then increased by 49.9% from February through December 2020.In this cross-sectional study, statewide restrictions on the sale of flavored e-cigarettes in Massachusetts, New York, Rhode Island, and Washington were associated with a reduction in total e-cigarette sales. These findings suggest that not all e-cigarette users who purchased non-tobacco-flavored e-cigarettes switched to purchasing tobacco-flavored e-cigarettes after policy implementation.

Development of recombinant enzymes as industrial biocatalysts or metabolic pathway elements requires soluble expression of active protein. Here we present a two-step strategy, combining a directed evolution selection with an enzyme activity screen, to increase the soluble production of enzymes in the cytoplasm of E. coli. The directed evolution component relies on the innate quality control of the twin-arginine translocation pathway coupled with antibiotic selection to isolate point mutations that promote intracellular solubility. A secondary screen is applied to ensure the solubility enhancement has not compromised enzyme activity. This strategy has been successfully applied to increase the soluble production of a fungal endocellulase by 30-fold in E. coli without change in enzyme specific activity through two rounds of directed evolution.

Over the last 55 years, cigarette smoking rates in the U.S. have declined considerably among adults, reaching the lowest level ever recorded (12.5 percent) in 2020. This represents one of the greatest public health achievements of the past century, resulting in millions of lives saved. Similarly, cigarette smoking has declined considerably among U.S. youth, with rates peaking in the mid-1990s and declining steadily ever since. However, among persons who smoke, progress hasn’t been experienced equitably. Smoking disproportionately affects communities including, but not limited to, certain racial and ethnic populations, low-income populations, people living with mental health conditions, and LGBTQI+ individuals.

Tobacco product use is the leading cause of preventable disease, disability, and death in the United States. This report used data from the 2019 Youth Risk Behavior Survey to assess the following among U.S. high school students: ever use of cigarettes and electronic vapor products, current use (≥1 day during the 30 days before the survey) of tobacco products, frequent use (≥20 days during the 30 days before the survey) among current users of tobacco products, trends in use over time, and usual source of electronic vapor products among current electronic vapor product users. In 2019, a total of 50.1% of U.S. high school students had ever used electronic vapor products, and 24.1% had ever tried cigarette smoking. Current electronic vapor product use was 32.7%, current cigarette smoking was 6.0%, current cigar smoking was 5.7%, and current smokeless tobacco use was 3.8%. Approximately 36.5% of students were current users of any tobacco product, and 8.2% were current users of two or more tobacco products. Frequent use among users of individual products was 32.6% for electronic vapor products, 28.5% for smokeless tobacco, 22.2% for cigarettes, and 18.4% for cigars. Among current electronic vapor product users who were aged ≤17 years, the most commonly reported source was borrowing them from someone else (42.8%). Significant decreases occurred in current cigarette smoking (1991: 27.5%; 2019: 6.0%), cigar smoking (1997: 22.0%; 2019: 5.7%), and smokeless tobacco use (2017: 5.5%; 2019: 3.8%). However, significant increases occurred in current electronic vapor product use (2015: 24.1%; 2019: 32.7%) and any tobacco product use (2017: 19.5%; 2019: 36.5%). Although current cigarette smoking, cigar smoking, and smokeless tobacco use has decreased among high school students, the increased prevalence of electronic vapor product use among youths is concerning. Continued surveillance for all tobacco product use is warranted for guiding and evaluating public health policy at the local, state, tribal, and national levels.

The sponsoring of mega-events enables organizations to capitalize on the power of sport to stimulate passionate brand identifications among attendees. However, a critical issue that has not been addressed by scholars is whether the effects of sponsoring mega-events such as the Olympics by a foreign brand will resemble the equivalent sponsorship by a domestic counterpart. In particular, few scholars have investigated attendee perceptions of congruities between event sponsor and self-sponsor brand favorability emanating from an overseas country with where there are longstanding tensions and from home. This study investigated attendees at the 2014 Summer Youth Olympic Games in Nanjing, China, a city with a long history of patriotic nationalism directed against Japan. The researchers identify that self-domestic sponsor congruity mediates the impact of patriotism among domestic attendees on their favorability toward domestic brands. Self-foreign sponsor congruity moderates the impact of event liking on favorability, even in the case of sponsors from a country with hostile connotations. The study has managerial implications for targeting and localization strategies by sponsor brands both domestic and overseas. It is proposed that foreign brand sponsors of mega-events should pursue local brand adaption through the incorporation local narratives with which residents can identify.

Artificial neural networks have been used for time series modeling and forecasting in many domains. However, they are often limited in their handling of nonlinear and chaotic data. More recently, reservoir-based recurrent neural net systems, most notably echo state networks (ESN), have made substantial improvements for time series modeling. Their shallow nature lends themselves to an efficient training method, but has limitations on nonstationary, nonlinear chaotic time series, particularly large, multidimensional time series. In this paper, we propose a novel approach for forecasting time series data based on an additive decomposition (AD) applied to the time series as a preprocessor to a deep echo state network. We compare the performance of our method, AD-DeepESN, on popular neural net architectures used for time series prediction. Stationary and nonstationary data sets are used to evaluate the performance of the methods. Our results are compelling, demonstrating that AD-DeepESN has superior performance, particularly on the most challenging time series that exhibit non-stationarity and chaotic behavior compared to existing methods.

E-cigarettes are battery-operated devices that heat a liquid and deliver an aerosolized product to the user. Pulmonary illnesses related to e-cigarette use have been reported, but no large series has been described. In July 2019, the Wisconsin Department of Health Services and the Illinois Department of Public Health received reports of lung injury associated with the use of e-cigarettes (also called vaping) and launched a coordinated public health investigation.We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes. Medical record abstraction and case patient interviews were conducted with the use of standardized tools.There were 98 case patients, 79% of whom were male; the median age of the patients was 21 years. The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%). All case patients had bilateral infiltrates on chest imaging. A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported. A total of 89% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported. Syndromic surveillance data from Illinois showed that the mean monthly rate of visits related to severe respiratory illness in June through August of 2019 was twice the rate that was observed in the same months in 2018.Case patients presented with similar clinical characteristics. Although the definitive substance or substances contributing to injury have not been determined, this initial cluster of illnesses represents an emerging clinical syndrome or syndromes. Additional work is needed to characterize the pathophysiology and to identify the definitive causes.

Raising the minimum legal sales age (MLSA) for tobacco products to 21 years (T21) is a strategy to help prevent and delay the initiation of tobacco product use (1). On December 20, 2019, Congress raised the federal MLSA for tobacco products from 18 to 21 years. Before enactment of the federal T21 law, localities, states, and territories were increasingly adopting their own T21 laws as part of a comprehensive approach to prevent youth initiation of tobacco products, particularly in response to recent increases in use of e-cigarettes among youths (2). Nearly all tobacco product use begins during adolescence, and minors have cited social sources such as older peers and siblings as a common source of access to tobacco products (1,3). State and territorial T21 laws vary widely and can include provisions that might not benefit the public's health, including penalties to youths for purchase, use, or possession of tobacco products; exemptions for military populations; phase-in periods; and preemption of local laws. To understand the landscape of U.S. state and territorial T21 laws before enactment of the federal law, CDC assessed state and territorial laws prohibiting sales of all tobacco products to persons aged

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders continue to investigate a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). EVALI patients in Illinois, Utah, and Wisconsin acquired tetrahydrocannabinol (THC)-containing products primarily from informal sources (2,3). This report updates demographic characteristics and self-reported sources of THC- and nicotine-containing e-cigarette, or vaping, products derived from EVALI patient data reported to CDC by state health departments. As of January 7, 2020, among 1,979 (76%) patients with available data on substance use, a total of 1,620 (82%) reported using any THC-containing products, including 665 (34%) who reported exclusive THC-containing product use. Use of any nicotine-containing products was reported by 1,128 (57%) patients, including 264 (13%) who reported exclusive nicotine-containing product use. Among 809 (50%) patients reporting data on the source of THC-containing products, 131 (16%) reported acquiring their products from only commercial sources (i.e., recreational dispensaries, medical dispensaries, or both; vape or smoke shops; stores; and pop-up shops), 627 (78%) from only informal sources (i.e., friends, family, in-person or online dealers, or other sources), and 51 (6%) from both types of sources. Among 613 (54%) EVALI patients reporting nicotine-containing product use with available data on product source, 421 (69%) reported acquiring their products from only commercial sources, 103 (17%) from only informal sources, and 89 (15%) from both types of sources. Adolescents aged 13-17 years were more likely to acquire both THC- and nicotine-containing products from informal sources than were persons in older age groups. The high prevalence of acquisition of THC-containing products from informal sources by EVALI patients reinforces CDC's recommendation to not use e-cigarette, or vaping, products that contain THC, especially those acquired from informal sources. Although acquisition of nicotine-containing products through informal sources was not common overall, it was common among persons aged

Purpose Using cross-sectional data, we measured the association between electronic cigarette (e-cigarette) use and subsequent initiation and sustained use of cigarettes among U.S. youth. Methods Data were pooled from the 2015–2017 National Youth Tobacco Survey, a school-based survey of U.S. students in grades 6–12. Questions on current age and age of first use of different tobacco products (cigarettes, e-cigarettes, cigars, and smokeless tobacco) were used to ascertain the temporal sequence of tobacco product use. The pooled study population was 52,579 youth who 5 years before the survey had never smoked cigarettes. E-cigarette users were defined as those who used e-cigarettes before or without ever smoking cigarettes. Cigarette smoking was assessed with the following measures: ever smoking a cigarette at any time within the past 5 years and sustained smoking (smoked ≥1 year ago and within past 30 days). Adjusted odds ratios (AORs) were calculated, controlling for other tobacco product use and sociodemographics. Results Among never cigarette smokers as of 5 years before the survey, 17.4% used e-cigarettes, and 15.6% first smoked within the past 5 years. Compared with those who did not use e-cigarettes, those who used e-cigarettes had higher odds of ever smoking cigarettes within the past 5 years (AOR = 2.73) and had higher odds of sustained smoking (AOR = 1.55; all p Conclusions E-cigarette use is associated with subsequent initiation and sustained use of cigarettes among youth. Efforts are warranted to reduce youth use of all tobacco products, including e-cigarettes.