Nicotine pouch use by sex, school type and tobacco product use among Finnish adolescents during the 2023 change in regulatory scheme with deregulated sales.

BACKGROUND AND AIMS: In Finland, nicotine pouches entered the national market abruptly in 2023, following a change in April 2023 from medicinal product classification into less regulated tobacco surrogate status. This study aimed to measure adolescent nicotine pouch use and associated characteristics. DESIGN AND SETTING: A cross-sectional, nationwide school-based survey among students in comprehensive schools (COMP), general upper secondary schools (GEN) and vocational institutes (VOC) in 2023 in Finland. PARTICIPANTS: A total of 151 224 respondents aged 14-20 years (mean age 16.18 years, standard deviation 1.20 years). MEASUREMENTS: Nicotine pouch use was used as the outcome variable. Demographics included age, sex, school type and tobacco product use (smoking, snus use and e-cigarette use). Covariates included parental education and parental smoking. All measures were self-reported. FINDINGS: Unadjusted results showed that current nicotine pouch use was more common among boys (11.3%) than among girls (3.3%), adolescents in VOC (15.4%) compared with COMP (6.8%) and GEN (4.3%), whereas daily use of other tobacco and nicotine products was associated with current nicotine pouch use compared with never using such products and the association was especially strong for snus use. The fully adjusted estimates of current nicotine pouch use remained strong for daily use of other tobacco and nicotine products (snus use: adjusted prevalence ratio [aPR] = 74.95, 95% confidence interval [CI] = 65.65-84.25; smoking: aPR = 1.43, 95% CI = 1.36-1.50; e-cigarette use: aPR = 2.15, 95% CI = 2.04-2.27) and for sex (boys aPR = 1.53, 95% CI = 1.48-1.57). There was no clear evidence of differences in current nicotine pouch use by school type, age or parental factors in the fully adjusted model. CONCLUSIONS: In Finland in 2023, during which the availability of nicotine pouches became less regulated, nicotine pouch use appeared to be more common among boys and adolescents who used other nicotine products.

Genetic drivers and cellular selection of female mosaic X chromosome loss.

Mosaic loss of the X chromosome (mLOX) is the most common clonal somatic alteration in leukocytes of female individuals1,2, but little is known about its genetic determinants or phenotypic consequences. Here, to address this, we used data from 883,574 female participants across 8 biobanks; 12% of participants exhibited detectable mLOX in approximately 2% of leukocytes. Female participants with mLOX had an increased risk of myeloid and lymphoid leukaemias. Genetic analyses identified 56 common variants associated with mLOX, implicating genes with roles in chromosomal missegregation, cancer predisposition and autoimmune diseases. Exome-sequence analyses identified rare missense variants in FBXO10 that confer a twofold increased risk of mLOX. Only a small fraction of associations was shared with mosaic Y chromosome loss, suggesting that distinct biological processes drive formation and clonal expansion of sex chromosome missegregation. Allelic shift analyses identified X chromosome alleles that are preferentially retained in mLOX, demonstrating variation at many loci under cellular selection. A polygenic score including 44 allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile. Our results support a model in which germline variants predispose female individuals to acquiring mLOX, with the allelic content of the X chromosome possibly shaping the magnitude of clonal expansion.

Tobacco endgame goals and measures in Europe: current status and future directions.

The European Union (EU) aims for a tobacco use prevalence of less than 5% by 2040 with its Tobacco-Free Generation goal, aligning with the tobacco endgame approach. In the Joint Action on Tobacco Control 2 (JATC-2) -project, we examined adopted and planned endgame goals and measures as well as preparedness to counter tobacco industry interference in the process. We surveyed key informants in 24 out of 50 countries in the WHO European Region (19 of the 27 EU Member States, MS). Altogether, eight countries (7 EU MS) had official governmental endgame goals, and an additional six EU MS had similar proposals from government, civil society or research entities. Movement towards tobacco endgame was most evident in retail-oriented and consumer-oriented policies. These include restricting the sales of tobacco and related products and raising the age limit above 18 years. Product standards were used especially to regulate flavours but no measures to substantially reduce addictiveness were reported. Market-oriented measures that tap into industry profits were predominantly missing, and countries often lacked concrete tools to prevent industry interference. Respondents' concerns around tobacco endgame were related to high smoking prevalence in some population groups, non-combustible and new nicotine products, cross-border marketing, political will, challenges with the existing regulations and industry interference. Results indicate both momentum and challenges in adopting and disseminating measures that facilitate achieving tobacco endgame goals. The EU goal can be used to advocate for national endgame goals and measures, and for the strengthened implementation of the WHO Framework Convention on Tobacco Control.

Patterns and Determinants of Exclusive Smokeless Tobacco (Snus) Use, Exclusive Smoking and Dual Use in General Population During 20 Years.

BACKGROUND: We investigate smokeless tobacco (snus) use and its correlates over 20 years in a country where selling snus is prohibited but a large import quota and illicit market exists. METHODS: Repeated cross-sectional population-based surveys during 2000 to 2020 in Finland, including N = 57 111 adults aged 20 to 64 years. The outcome measures were current tobacco use (exclusive snus use, dual use, exclusive smoking, no tobacco use) and snus use (daily, occasional, no snus use). Study years, gender, age, education, marital status, self-rated health, body mass index, and binge drinking were used as explanatory variables. RESULTS: Exclusive snus use and dual use increased 3.6% units and 2.6% units from 2000 to 2005 and from 2018 to 2020, respectively. Overall decrease of tobacco use was led by decreasing exclusive smoking from 30.1% to 18.2%. The shared risk factors for snus use and dual use were male gender, age group 20 to 34 years, and binge drinking. The increases in snus and dual use over time were also most prevalent among these groups. Among men, occasional smoking increased the likelihood of daily (relative risk ratio [RRR] 2.38, 95% confidence interval [CI] 1.42, 3.99) and occasional (RRR 3.11, 95% CI 1.93, 5.03) snus use. CONCLUSIONS: Snus use has increased among the general adult population in Finland during 2000 to 2020 yet remains less common than smoking. Snus use and dual use share some common risk factors. Snus use should be considered in cessation services, with support for quitting developed and targeted predominantly for men, younger adults, and persons drinking to intoxication.

Proteogenomic analyses identify coagulation factor XI as a thromboinflammatory mediator of long COVID.

SARS-CoV-2 infection can result in long COVID, characterized by post-acute symptoms from multiple organ systems. Current hypotheses on mechanisms underlying long COVID include persistent inflammation and dysregulated coagulation; however, precise mechanisms and causal mediators remain unclear. Here, we tested the associations of genetic instruments for 49 complement and coagulation factors from the UK Biobank ( N =34,557) with long COVID in the Long COVID Host Genetics Initiative ( N =997,600). Primary analyses revealed that genetically predicted higher factor XI increased long COVID risk (odds ratio, 1.17 [95% confidence interval, 1.08-1.27] per standard deviation; P =1.7×10 -4 ). This association was robust to sensitivity analyses using pleiotropy-robust methods and different genetic instruments and was replicated using proteogenomic data from an Icelandic cohort. Genetically predicted factor XI was also associated with venous thromboembolism, but not with acute COVID-19 or long COVID-resembling conditions. Collectively, these findings provide genetic evidence implicating factor XI in the biology of long COVID.

Tobacco endgame measures and their adaptation in selected European countries: A narrative review synthesis.

Due to the continued detrimental effects of tobacco use, a growing number of countries are embracing the idea of tobacco endgame, meaning ending the tobacco epidemic instead of controlling it. This narrative review aims to synthesize and update the evidence from earlier scientific reviews on effective tobacco endgame measures, as well as to assess their integration to current national strategies among European countries with official tobacco endgame goals. The synthesis of the prior scientific literature found most evidence on product-focused and some evidence for supply-focused policies. Little evidence was detected for user- and institutional-focused measures. An update for the tobacco-free generation measure showed uncertainty in reducing smoking prevalence, especially for adolescents' reactions to age-restrictive laws. All the countries that established a tobacco endgame strategy have included product standards in their measures, predominantly based on European Union regulations on conventional tobacco products, yet standards above this level and considering other products were also common. Cessation measures were given strong emphasis in strategies, yet none of the countries linked these to specific endgame measures. Despite commonly mentioning vulnerable groups, such as youth and pregnant women, adoption of measures to reduce tobacco use among these groups was scarce. Lastly, the decline in tobacco use seems to be modest, implying challenges in meeting the endgame goals. To meet these goals, European countries should reinforce the implementation of known effective tobacco control measures such as tax increases. Furthermore, new innovative strategies and measures to meet the objective of an endgame should be explored.

SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease.

Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.

Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.

BACKGROUND: Congenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. They exhibit low penetrance and non-Mendelian patterns of inheritance as varied and complex traits. While genetic factors are known to play an important role in the development of CHD, the specific genetics remain unknown for the majority of patients. To elucidate the underlying genetic risk, we performed a genome wide association study (GWAS) of CHDs in general and specific CHD subgroups using the FinnGen Release 10 (R10) (N > 393,000), followed by functional fine-mapping through eQTL and co-localization analyses using the GTEx database. RESULTS: We discovered three genome-wide significant loci associated with general CHD. Two of them were located in chromosome 17: 17q21.32 (rs2316327, intronic: LRRC37A2, Odds ratio (OR) [95% Confidence Interval (CI)] = 1.17[1.12-1.23], p = 1.5 × 10-9) and 17q25.3 (rs1293973611, nearest: BAHCC1, OR[95%CI] = 4.48[2.80-7.17], p = 7.0 × 10-10), respectively, and in addition to general CHD, the rs1293973611 locus was associated with the septal defect subtype. The third locus was in band 1p21.2 (rs35046143, nearest: PALMD, OR[95%CI] = 1.15[1.09-1.21], p = 7.1 × 10-9), and it was associated with general CHD and left-sided lesions. In the subgroup analysis, two additional loci were associated with septal defects (rs75230966 and rs6824295), and one with left-sided lesions (rs1305393195). In the eQTL analysis the variants rs2316327 (general CHD), and rs75230966 (septal defects) both located in 17q21.32 (with a LD r2 of 0.41) were both predicted to significantly associate with the expression of WNT9B in the atrial appendage tissue category. This effect was further confirmed by co-localization analysis, which also implicated WNT3 expression in the atrial appendage. A meta-analysis of general CHD together with the UK Biobank (combined N = 881,678) provided a different genome-wide significant locus in LRRC37A2; rs16941382 (OR[95%CI] = 1.15[1.11-1.20], p = 1.5 × 10-9) which is in significant LD with rs2316327. CONCLUSIONS: Our results of general CHD and different CHD subcategories identified a complex risk locus on chromosome 17 near BAHCC1 and LRRC37A2, interacting with the genes WNT9B, WNT3 and MYL4, may constitute potential novel CHD risk associated loci, warranting future experimental tests to determine their role.

Nightmares share genetic risk factors with sleep and psychiatric traits.

Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e-06), depressive (rg = 0.562, p = 1.282e-07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e-07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual's liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts.

Genetic Analysis of Obstructive Sleep Apnea and Its Relationship with Severe COVID-19.

Rationale: Although patients with obstructive sleep apnea (OSA) have a higher risk for coronavirus disease (COVID-19) hospitalization, the causal relationship has remained unexplored. Objectives: To understand the causal relationship between OSA and COVID-19 by leveraging data from vaccination and electronic health records, genetic risk factors from genome-wide association studies, and Mendelian randomization. Methods: We elucidated genetic risk factors for OSA using FinnGen (total N = 377,277), performing genome-wide association. We used the associated variants as instruments for univariate and multivariate Mendelian randomization (MR) analyses and computed absolute risk reduction against COVID-19 hospitalization with or without vaccination. Results: We identified nine novel loci for OSA and replicated our findings in the Million Veteran Program. Furthermore, MR analysis showed that OSA was a causal risk factor for severe COVID-19 (P = 9.41 × 10-4). Probabilistic modeling showed that the strongest genetic risk factor for OSA at the FTO locus reflected a signal of higher body mass index (BMI), whereas BMI-independent association was seen with the earlier reported SLC9A4 locus and a MECOM locus, which is a transcriptional regulator with 210-fold enrichment in the Finnish population. Similarly, multivariate MR analysis showed that the causality for severe COVID-19 was driven by BMI (multivariate MR P = 5.97 × 10-6, ß = 0.47). Finally, vaccination reduced the risk for COVID-19 hospitalization more in the patients with OSA than in the non-OSA controls, with respective absolute risk reductions of 13.3% versus 6.3%. Conclusions: Our analysis identified novel genetic risk factors for OSA and showed that OSA is a causal risk factor for severe COVID-19. The effect is predominantly explained by higher BMI and suggests BMI-dependent effects at the level of individual variants and at the level of comorbid causality.

An immunogenetic basis for lung cancer risk.

Cancer risk is influenced by inherited mutations, DNA replication errors, and environmental factors. However, the influence of genetic variation in immunosurveillance on cancer risk is not well understood. Leveraging population-level data from the UK Biobank and FinnGen, we show that heterozygosity at the human leukocyte antigen (HLA)-II loci is associated with reduced lung cancer risk in smokers. Fine-mapping implicated amino acid heterozygosity in the HLA-II peptide binding groove in reduced lung cancer risk, and single-cell analyses showed that smoking drives enrichment of proinflammatory lung macrophages and HLA-II+ epithelial cells. In lung cancer, widespread loss of HLA-II heterozygosity (LOH) favored loss of alleles with larger neopeptide repertoires. Thus, our findings nominate genetic variation in immunosurveillance as a critical risk factor for lung cancer.

Cross-sectional study of the associations between the implementation of the WHO FCTC tobacco advertising, promotion and sponsorship bans and current e-cigarette use among youth from countries with different income levels.

BACKGROUND: The WHO Framework Convention on Tobacco Control (WHO FCTC) Article 13 requires countries to ban tobacco advertising, promotion and sponsorship (TAPS), and bans are recommended to cover electronic cigarettes (e-cigarettes). We examined youth e-cigarette prevalence by TAPS regulations in countries with different income levels. METHODS: We analysed data on 165 299 respondents from 48 countries with 2016/2018 WHO FCTC implementation reports and 2016-2019 Global Youth Tobacco Survey. We used multilevel logistic regressions to examine associations between TAPS regulations and current e-cigarette use, stratified by country income. RESULTS: About 1 in 10 respondents was currently using e-cigarettes. Respondents in countries with TAPS bans on the internet were less likely to use e-cigarettes (adjOR=0.58; 95% CI 0.39 to 0.86) than youth in countries without such bans. In lower middle-income and low-income countries, bans on displaying tobacco products at the point of sale (adjOR=0.55; 95% CI 0.34 to 0.90), bans on product placement (adjOR=0.44; 95% CI 0.28 to 0.69) and strength of additional TAPS measures were associated with lower prevalence of e-cigarette use among students. Being taught about the dangers of the use of tobacco in school was associated with lower odds of e-cigarette use. No differences in the use of e-cigarettes were observed by types of TAPS among respondents in high-income countries. CONCLUSIONS: Strengthening implementation of TAPS policies and assuring they cover new and emerging products, online channels and points of sales are essential, especially in lower income countries. Maintaining tobacco health education is also important to protect youth from e-cigarette use.

Have there been changes in daily smoking and cigarette consumption among adolescents? Investigation between 1999 and 2019 among Finnish adolescents.

BACKGROUND AND AIMS: It is postulated that due to decreased smoking rates and increased denormalisation of smoking, those who start and maintain smoking have more socially disadvantaged characteristics and are more dependent on nicotine than those who do not (the so-called 'hardening' hypothesis). The aim of this study was to measure changes in daily smoking and cigarette consumption among Finnish adolescents according to background factors. DESIGN AND SETTING: A repeated cross-sectional study using data from European School Survey Project on Alcohol and other Drugs (ESPAD) on six representative cross-sections of 15- to 16-year-old students between 1999 and 2019 in Finland. PARTICIPANTS: A total of 11 377 males and 12 247 females. MEASUREMENTS: The outcome measures included the proportion of daily smokers among current smokers, daily smoking and the estimated mean number of smoked cigarettes per day (CPD). Substance use, parental monitoring and school performance were used as independent variables. All measures were self-reported. FINDINGS: Daily smoking decreased over time and daily smokers constituted a smaller part of current smokers in 2019 compared with 1999 (the ratio among boys 0.68 and 0.43, respectively; among girls 0.59 and 0.43). Boys using cannabis (interaction between cannabis*survey year: P = 0.020; in 2019 odds ratio [OR]: 3.68, 95% confidence interval [CI] 2.23-6.08) and girls with heavy episodic drinking (interaction between heavy episodic drinking*survey year: P = 0.006, in 2019 OR: 9.00, 95% CI 5.61-14.42) had elevated adjusted odds for daily smoking over time. The estimated mean number of CPD decreased among daily smokers from 9.0 in 1999 to 7.2 in 2019 (P = 0.0002) and the differences diminished between groups based on gender, snus/alcohol use and parental monitoring. The between-group differences remained with regard to cannabis use (P = 0.0233 in 2019) and school performance (P = 0.0111 in 2019). CONCLUSIONS: Among currently smoking Finnish adolescents, the proportion of daily smokers decreased between 1999 and 2019, as did the number of cigarettes smoked per day (CPD) among daily smokers, suggesting an absence of 'hardening' in this group. However, differences were observed related to the odds of daily smoking and the mean number of CPD, indicating the change has been less favorable among some adolescent groups than others.

Genetics of sleep medication purchases suggests causality from sleep problems to psychiatric traits.

STUDY OBJECTIVES: Over 10% of the population in Europe and in the United States use sleep medication to manage sleep problems. Our objective was to elucidate genetic risk factors and clinical correlates that contribute to sleep medication purchase and estimate the comorbid impact of sleep problems. METHODS: We performed epidemiological analysis for psychiatric diagnoses, and genetic association studies of sleep medication purchase in 797 714 individuals from FinnGen Release 7 (N = 311 892) and from the UK Biobank (N = 485 822). Post-association analyses included genetic correlation, co-localization, Mendelian randomization (MR), and polygenic risk estimation. RESULTS: In a GWAS we identified 27 genetic loci significantly associated with sleep medication, located in genes associated with sleep; AUTS2, CACNA1C, MEIS1, KIRREL3, PAX8, GABRA2, psychiatric traits; CACNA1C, HIST1H2BD, NUDT12. TOPAZ1 and TSNARE1. Co-localization and expression analysis emphasized effects on the KPNA2, GABRA2, and CACNA1C expression in the brain. Sleep medications use was epidemiologically related to psychiatric traits in FinnGen (OR [95% (CI)] = 3.86 [3.78 to 3.94], p < 2 × 10-16), and the association was accentuated by genetic correlation and MR; depression (rg = 0.55 (0.027), p = 2.86 × 10-89, p MR = 4.5 × 10-5), schizophrenia (rg = 0.25 (0.026), p = 2.52 × 10-21, p MR = 2 × 10-4), and anxiety (rg = 0.44 (0.047), p = 2.88 × 10-27, p MR = 8.6 × 10-12). CONCLUSIONS: These results demonstrate the genetics behind sleep problems and the association between sleep problems and psychiatric traits. Our results highlight the scientific basis for sleep management in treating the impact of psychiatric diseases.

Implementation of the Article 13 WHO FCTC measures and changes in cigarette smoking among youth in 42 countries.

INTRODUCTION: Despite a decline in global smoking prevalence among adolescents, around 21 million youth report current cigarette smoking. Exposure to tobacco advertising, promotion and sponsorship (TAPS) is a risk factor for smoking initiation, and therefore the Article 13 of the WHO Framework Convention on Tobacco Control (WHO FCTC) requires comprehensive TAPS bans. We examined the associations between changes in youth cigarette smoking and implementation of Article 13. METHODS: We used two rounds of cross-sectional data from the Global Youth Tobacco Survey (GYTS) for 42 countries: first between 2006 and 2015, and second between 2017 and 2020. The GYTS data were linked with the WHO FCTC implementation reports from 2016 and 2018. The outcome was current smoking. Multilevel binary logistic regression models, stratified by country income level, were used to test the prevalence differences between the latest and previous GYTS rounds and their associations with TAPS bans with postestimations using marginal analyses. RESULTS: The percentage of students currently smoking decreased from 10.0% (95% CI 8.0 to 12.1) to 7.7% (95% CI 6.1 to 9.3) from first to second GYTS rounds (p<0.001), adjusting for country clustering. In low-income and lower-middle-income countries, the degree of decrease significantly differed between countries with versus without bans on display, partial internet TAPS ban, ban on depiction of tobacco products and by number of TAPS measures, adjusting for age and sex of the respondents. In high-income and upper-middle-income countries, the degree of decrease significantly differed by presence (or absence) of partial or full internet TAPS ban, ban on product placement and by number of TAPS measures. CONCLUSION: Implementation of TAPS bans is associated with decreased smoking among adolescents both in high-income and low-income countries. Enhanced and continuous efforts are necessary to protect youth from the promotion of tobacco and nicotine products.

Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases.

BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9 hours), short (<6 hours), and long (>9 hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355 901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted ß=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.

SIRPα controls CD47-dependent platelet clearance in mice and humans.

Over the last decade, more data has revealed that increased surface expression of the "don't eat me" CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 is critical in regulating cell homeostasis and clearance, as binding of CD47 to the inhibitory receptor SIRPα can prevent phagocytosis and macrophage-mediated cell clearance. The purpose of this study was to examine the role of the CD47-SIRPα signal in platelet homeostasis and clearance. Therapeutic reagents targeting the CD47-SIRPα axis are very promising for treatment of hematologic malignancies and solid tumors, but lead to transient anemia or thrombocytopenia in a subset of patients. We found that platelet homeostatic clearance is regulated through the CD47-SIRPα axis and that therapeutic blockade to disrupt this interaction in mice and in humans has a significant impact on platelet levels. Furthermore, we identified genetic variations at the SIRPA locus that impact platelet levels in humans such that higher SIRPA gene expression is associated with higher platelet levels. SIRPA expression at either end of the normal range may affect clinical outcomes of treatment with anti-CD47 therapy.

Associations between sleep medication use and alcohol consumption over 36 years in Finnish twins.

BACKGROUND: Sleep medication use is an indicator of underlying sleep problems that might be induced by various factors such as alcohol use. However, the longitudinal relationship between drinking and sleep problems remains poorly understood. We investigated associations between sleep medication and alcohol use throughout adulthood, and examined the role of familial and potential confounding factors contributing to these associations. METHODS: We used information of zygosity and self-report questionnaire data over a follow-up period of 36 years from the Older Finnish Twin Cohort (N=13,851). RESULTS: Logistic regression analyses suggested consistent associations between sleep medication use and heavy/binge drinking at all four time points (OR range =1.36-3.18, P <0.05), implying that increased drinking is associated with increased sleep medication use over time. Cross-lagged path analyses suggested that moderate/heavy and binge drinking predict sleep medication use at most time points (OR range = 1.15-1.94, P <0.05), whilst sleep medication use predicts subsequent abstaining from alcohol (OR range =2.26-2.47, P <0.05). Within-pair analyses implied that familial factors play a role, and quantitative genetic modelling estimated genetic factors to explain approximately 80% of the lifetime association of sleep medication use with moderate/heavy and binge drinking. CONCLUSIONS: Drinking is associated with sleep medication use throughout adulthood. Further, our results suggest that drinking is likely to predict sleep medication use, thereby potentially constituting a risk factor for sleep problems, and that genetic factors contribute to the association. These findings are important in terms of better understanding the development of sleep and alcohol use disorders.

Tobacco endgame in the WHO European Region: Feasibility in light of current tobacco control status.

INTRODUCTION: To assess the feasibility of developing World Health Organization (WHO) European Region countries' goals and measures in line with tobacco endgame objectives, information on the current tobacco control context and capacity is needed. The aim of this study was to assess the implementation of the Framework Convention on Tobacco Control (WHO FCTC) and MPOWER measures in the region. METHODS: In this cross-sectional study we used data from the WHO FCTC implementation reports and MPOWER from 2020 in 53 WHO European Region countries. Six domains (i.e. capacity, taxation and price policies, other national key regulations, public awareness raising and communication, tobacco use cessation, and monitoring) were formed. Subsequently, available indicators under these domains were scored and the level of implementation was computed for each country. Mann-Whitney tests were carried out to compare the scores between the group of countries with and without official endgame goals. RESULTS: Overall, implementation of the WHO FCTC with the selected indicators at the country level ranged from 28% to 86%, and of MPOWER from 31% to 96%. Full implementation was achieved by 28% of WHO FCTC Parties in the region in taxation and price policies, 12% in public awareness raising and communication, and 42% in monitoring. In capacity, tobacco use cessation and other national key regulations, none of the Parties in the region reached full implementation. Overall median WHO FCTC scores were significantly higher in countries with official endgame goals than in those without (p<0.001). CONCLUSIONS: There is unequal implementation of both WHO FCTC and MPOWER measures among WHO European Region countries. MPOWER and WHO FCTC provide all the measures for the necessary first steps, followed by innovative measures, to accomplish tobacco endgame goals.