Developing Wolbachia-based disease interventions for an extreme environment.

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae. aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced egg hatch under a range of environmental conditions, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia-based disease interventions in harsh climates.

Characterising smoking and nicotine use behaviours among women of reproductive age: a 10-year population study in England.

BACKGROUND: Tobacco smoking affects women's fertility and is associated with substantial risks of adverse pregnancy outcomes. This study explored trends by socioeconomic position in patterns of smoking, use of non-combustible nicotine products, and quitting activity among women of reproductive age in England. METHODS: Data come from a nationally representative monthly cross-sectional survey. Between October 2013 and October 2023, 197,266 adults (≥ 18 years) were surveyed, of whom 44,052 were women of reproductive age (18-45 years). Main outcome measures were current smoking, vaping, and use of nicotine replacement therapy (NRT), heated tobacco products (HTPs), and nicotine pouches; mainly/exclusively smoking hand-rolled cigarettes and level of dependence among current smokers; past-year quit attempts among past-year smokers; and success of quit attempts among those who tried to quit. We modelled time trends in these outcomes, overall and by occupational social grade (ABC1 = more advantaged/C2DE = less advantaged). RESULTS: Smoking prevalence among women of reproductive age fell from 28.7% [95%CI = 26.3-31.2%] to 22.4% [19.6-25.5%] in social grades C2DE but there was an uncertain increase from 11.7% [10.2-13.5%] to 14.9% [13.4-16.6%] in ABC1. By contrast, among all adults and among men of the same age, smoking prevalence remained relatively stable in ABC1. Vaping prevalence among women of reproductive age more than tripled, from 5.1% [4.3-6.0%] to 19.7% [18.0-21.5%], with the absolute increase more pronounced among those in social grades C2DE (reaching 26.7%; 23.3-30.3%); these changes were larger than those observed among all adults but similar to those among men of the same age. The proportion of smokers mainly/exclusively smoking hand-rolled cigarettes increased from 40.5% [36.3-44.9%] to 61.4% [56.5-66.1%] among women of reproductive age; smaller increases were observed among all adults and among men of the same age. Patterns on other outcomes were largely similar between groups. CONCLUSIONS: Among women of reproductive age, there appears to have been a rise in smoking prevalence in the more advantaged social grades over the past decade. Across social grades, there have been substantial increases in the proportion of women of reproductive age who vape and shifts from use of manufactured to hand-rolled cigarettes among those who smoke. These changes have been more pronounced than those observed in the general adult population over the same period.

Changes in sex-specific incidence of lymphoid neoplasms across the lifespan.

Not available.

Sex differences in iron status during military training: a prospective cohort study of longitudinal changes and associations with endurance performance and musculoskeletal outcomes.

This study investigated sex differences in Fe status, and associations between Fe status and endurance and musculoskeletal outcomes, in military training. In total, 2277 British Army trainees (581 women) participated. Fe markers and endurance performance (2·4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased Hb in men and women (mean change (-0·1 (95 % CI -0·2, -0·0) and -0·7 (95 % CI -0·9, -0·6) g/dl, both P < 0·001) but more so in women (P < 0·001). Ferritin decreased in men and women (-27 (95 % CI -28, -23) and -5 (95 % CI -8, -1) µg/l, both P ≤ 0·001) but more so in men (P < 0·001). Soluble transferrin receptor increased in men and women (2·9 (95 % CI 2·3, 3·6) and 3·8 (95 % CI 2·7, 4·9) nmol/l, both P < 0·001), with no difference between sexes (P = 0·872). Erythrocyte distribution width increased in men (0·3 (95 % CI 0·2, 0·4)%, P < 0·001) but not in women (0·1 (95 % CI -0·1, 0·2)%, P = 0·956). Mean corpuscular volume decreased in men (-1·5 (95 % CI -1·8, -1·1) fL, P < 0·001) but not in women (0·4 (95 % CI -0·4, 1·3) fL, P = 0·087). Lower ferritin was associated with slower 2·4 km run time (P = 0·018), sustaining a lower limb overuse injury (P = 0·048), lower aBMD (P = 0·021) and higher beta C-telopeptide cross-links of type 1 collagen and procollagen type 1 N-terminal propeptide (both P < 0·001) controlling for sex. Improving Fe stores before training may protect Hb in women and improve endurance and protect against injury.

Trends in Exclusive Non-Cigarette Tobacco Smoking in England: A Population Survey 2013-2023.

INTRODUCTION: The UK Government intends to implement a "smokefree generation" policy prohibiting the sale of all tobacco products to people born after 2008. National surveys provide comprehensive data on cigarette smoking, but little is known about patterns of non-cigarette tobacco smoking across key population groups. AIMS AND METHODS: Using data from a nationally representative cross-sectional survey of adults in England, collected monthly between September 2013 and September 2023 (n = 196 721), we estimated time trends in exclusive non-cigarette tobacco (eg, cigar/pipe/shisha) smoking prevalence, overall and by age, gender, occupational social grade, region, ethnicity, and vaping status. Interviews were conducted face-to-face until March 2020 and via telephone thereafter. RESULTS: From September 2013 to September 2023, there was a non-linear increase in exclusive non-cigarette tobacco smoking prevalence (from 0.36% to 1.68%; prevalence ratio = 4.72 [95% CI = 3.43-6.48]). Prevalence was relatively stable up to February 2020 (at an average of 0.46%), then increased sharply at the start of the COVID-19 pandemic (at the same time as survey methods changed), to 0.90% (0.82%-0.99%) in March 2020. This was followed by a steadier rise, peaking at 1.97% in May 2022, before falling slightly to 1.68% by September 2023. In 2022/2023, 1 in 10 smokers (10.8% [9.64%-12.0%]) exclusively used non-cigarette tobacco. The rise in prevalence was observed across all subgroups but was most pronounced among younger adults (eg, reaching 3.21% of 18-year-olds vs. 1.09% of 65-year-olds). Prevalence was consistently higher among men and current vapers. CONCLUSIONS: Although exclusive use of non-cigarette combustible tobacco remains rare among adults in England, it has increased in recent years, particularly among younger ages. As of September 2023, there were approximately 772 800 adult exclusive non-cigarette tobacco smokers in England; around five times more than a decade earlier. IMPLICATIONS: The proportion of adults in England who do not use cigarettes at all but smoke other combustible tobacco products has increased substantially in recent years, with a particularly pronounced rise among young people. The inclusion of non-cigarette combustible tobacco products under the proposed "smokefree generation" policy is therefore likely to be important for achieving the greatest reduction in youth uptake of tobacco smoking, as it would ensure young people who are unable to legally buy cigarettes do not buy other combustible tobacco products that are similarly harmful to health.

Associations of Prevalence of E-cigarette Use With Quit Attempts, Quit Success, Use of Smoking Cessation Medication, and the Overall Quit Rate Among Smokers in England: A Time-Series Analysis of Population Trends 2007-2022.

INTRODUCTION: This study aimed to (1) provide up-to-date estimates of how changes in the prevalence of e-cigarette use have been associated with changes in smoking cessation activities and use of licensed treatments among smokers in England and (2) explore any changes in these associations over time. METHODS: Data were aggregated quarterly on 67 548 past-year smokers between Q1-2007 and Q4-2022. Explanatory variables were the prevalence of (1) current e-cigarette use among smokers and (2) e-cigarette use during a quit attempt. Outcomes were rates of quit attempts and overall quits among past-year smokers, and the quit success rate and use of licensed treatments among those who made a quit attempt. RESULTS: The success rate of quit attempts increased by 0.040% (95% CI 0.019; 0.062) for every 1% increase in the prevalence of e-cigarette use during a quit attempt. No clear evidence was found for an association between current e-cigarette use and the quit attempt rate (Badj = 0.008 [95% CI -0.045; 0.061]) or overall quit rate (Badj = 0.063 [-0.031; 0.158]); or between use of e-cigarettes during a quit attempt and the overall quit rate (Badj = 0.030 [-0.054; 0.114]), use of prescription medication (varenicline/bupropion/nicotine replacement therapy [NRT]: Badj = -0.036 [-0.175; 0.102]), or use of over-the-counter NRT (Badj = -0.052 [-0.120; 0.015]). There was no clear evidence this pattern of associations has changed substantially over time. CONCLUSIONS: Changes in the prevalence of e-cigarette use in England through 2022 have been positively associated with the success rate of quit attempts but not clearly associated with the quit attempt rate, overall quit rate, or use of licensed smoking cessation treatments. IMPLICATIONS: If the association between the increase in e-cigarette use and the quit success rate is causal, then the use of e-cigarettes in quit attempts has helped in the region of 30 000 to 50 000 additional smokers in England to successfully quit each year since they became popular in 2013, over and above the number who were quitting before the advent of e-cigarettes.

Evaluation of a regional tobacco control programme (Greater Manchester's Making Smoking History) on quitting and smoking in England 2014 to 2022: a time-series analysis.

INTRODUCTION: This study aimed to assess the impact of Greater Manchester's Making Smoking History programme - a region-wide smoking cessation programme launched in January 2018 - on key smoking and quitting outcomes. METHODS: Data were from a nationally-representative monthly survey, 2014-2022 (n=171,281). We used interrupted time-series analyses (Autoregressive Integrated Moving Average [ARIMA] and generalised additive models [GAM]) to examine regional differences between Greater Manchester and the rest of England, before and during the programme's first five years. Outcomes were rates of quit attempts and overall quits among smokers, quit success rates among smokers who tried to quit (pre-registered outcomes), and current smoking prevalence among adults (unregistered outcome). RESULTS: Results showed mixed effects of the programme on quitting. Primary ARIMA models showed comparative reductions in quit success rates (change in quarterly difference between regions = -11.03%; 95%CI -18.96;-3.11) and overall quit rates in Greater Manchester compared with the rest of England (-2.56%; 95%CI -4.95;-0.18), and no significant change in the difference in the quit attempt rate (+2.95%; 95%CI -11.64;17.54). These results were not consistently observed across sensitivity analyses or GAM analyses. Exploratory ARIMA models consistently showed smoking prevalence in Greater Manchester declined more quickly than in the rest of England following initiation of the programme (-2.14%; 95%CI -4.02;-0.27). CONCLUSIONS: The first five years of Greater Manchester's Making Smoking History programme did not appear to be associated with substantial increases in quitting activity. However, exploratory analyses showed a significant reduction in the regional smoking rate, over and above changes in the rest of England over the same period. IMPLICATIONS: Taken together, these results show a relative decline in smoking prevalence in Greater Manchester but equivocal data on quitting, introducing some uncertainty. It is possible the programme has reduced smoking prevalence in the absence of any substantial change in quitting activity by changing norms around smoking and reducing uptake, or by reducing the rate of late relapse. It is also possible that an undetected effect on quitting outcomes has still contributed to the programme's impact on reducing prevalence to some degree. It will be important to evaluate the overall impact of the programme over a longer timeframe.

Examining differences in real-world effectiveness of e-cigarettes for smoking cessation by source of purchase in England: an observational study of different contexts before and after the COVID-19 pandemic.

INTRODUCTION: The effectiveness of e-cigarettes for smoking cessation may differ by source of purchase. The changing influence of self-selection on purchase location caused by COVID-19 pandemic-related vape shop closures means we can examine the association between smoking abstinence e-cigarette use by purchase source and test for moderation of this association by the timing of the pandemic. METHODS: Repeat-cross-sectional nationally representative surveys, conducted between January-2017 and August-2023. Participants (N=1,284; ≥18y, 46.9% women) who made a past-year quit attempt, used an e-cigarette in their most recent attempt, currently vaping and provided data on the purchase source were included. The association between e-cigarette purchase source and continuous abstinence following the most recent quit attempt was assessed with adjusted regression, including an interaction between the timing of pandemic restrictions (March-2020 through January-2022). RESULTS: Overall, 48.1% usually purchasing their e-cigarettes from vape shops, declining from 53.6% pre-pandemic to 40.6% during the pandemic. There was inconclusive evidence that those purchasing from vape shops had greater odds of quitting smoking (ORadj=1.25, 95%CI 0.92-1.76). The association between purchase source and successful quitting did not depend upon whether purchasing occurred before or during the pandemic (F=0.08, pinteraction=0.774; pre-pandemic: ORadj=1.23, 0.79-1.91; and pandemic: ORadj=1.29, 0.81-2.06). CONCLUSIONS: More data are needed to conclusively determine whether purchasing from a specialist vape shop increases smoking cessation. Given the changing influence of self-selection on purchase location caused by the pandemic, the similar associations between purchase source and quit success across both periods suggests it is unlikely an artefact of unmeasured confounding. IMPLICATIONS: It is important to know if where e-cigarettes are purchased can increase their effectiveness for smoking cessation. While we found a positive association between purchasing from a specialist vape shop and abstinence rates, the results were inconclusive. Further studies are required to establish whether purchasing from specialist vape shops improves smoking cessation outcomes compared with other purchase sources.

Trends in Daily Cigarette Consumption Among Smokers: A Population Study in England, 2008-2023.

INTRODUCTION: This study aimed to estimate time trends in cigarette consumption among smokers in England between 2008 and 2023 and to explore differences by key potential moderators. AIMS AND METHODS: We used data from 57 778 adult cigarette smokers participating in a nationally representative monthly cross-sectional survey between January 2008 and September 2023. We estimated monthly time trends in mean daily consumption of (1) any, (2) manufactured, and (3) hand-rolled cigarettes among all smokers and by main type of cigarettes smoked, smoking frequency, age, gender, occupational social grade, region, nicotine replacement therapy use, and vaping status. RESULTS: Overall cigarette consumption fell from 13.6 [95% CI = 13.3 to 13.9] to 10.6 [10.5 to 10.8] per day between January 2008 and October 2019 (a 22% decrease), then remained stable up to September 2023. Over this period, the proportion mainly or exclusively smoking hand-rolled cigarettes increased (from 30.6% [29.1%-32.1%] in 2008 to 52.1% [49.7%-54.5%] in 2023). As a result, manufactured cigarette consumption fell by 47%, from 9.5 [9.2-9.8] per day in January 2008 to 5.0 [4.7-5.3] in September 2023, while hand-rolled cigarette consumption increased by 35%, from 4.2 [3.9-4.4] to 5.6 [5.3-5.9], respectively. The decline in overall cigarette consumption was observed across all subgroups, but was greater among non-daily smokers, younger smokers, and those who vaped. CONCLUSIONS: Over the last 15 years, the average number of cigarettes consumed each day by smokers in England has fallen by almost a quarter, but has plateaued since October 2019. There has been a sharp decline in the number of manufactured cigarettes consumed and an increase in the number of hand-rolled cigarettes consumed, as smokers have increasingly shifted towards using hand-rolled tobacco. IMPLICATIONS: While average cigarette consumption in England has fallen over the past 15 years, this declining trend has stalled (and reversed in some population groups) since 2019. The availability of cheap, hand-rolled tobacco appears to be undermining policies that aim to reduce smoking by raising the price of tobacco (eg, through taxation) and could be targeted to reignite the decline in cigarette consumption.

Are people more likely to vape or smoke indoors? A population survey of adults in England.

BACKGROUND: Increasingly, people smoke cigarettes outdoors and avoid exposing bystanders to harm. People may not have the same motivation to vape outdoors since e-cigarettes, unlike cigarettes, do not create side stream emissions and exhaled aerosol contains fewer toxicants than secondhand smoke. This study aims to estimate the prevalence and correlates of vaping and smoking indoors among adults in England. METHODS: Data came from the Health Survey for England 2019, a cross-sectional household survey. Adults who vape or smoke (N=1,530) were asked whether they had vaped or smoked indoors inside the home, car, or other places within the past seven days. Logistic regression was used to estimate prevalence and key correlates of indoor use, including age, sex, presence of adults/children in home, housing tenure and nicotine dependence. RESULTS: People who exclusively vaped were much more likely to use their product indoors than those who exclusively smoked (87.0% versus 52.0%; odds ratio [OR]=6.16, 95% confidence interval [CI]=4.09-9.28). Similarly, people who dual used had higher odds of vaping than smoking indoors (62.1% versus 44.3%; within-person OR=3.76, 95%CI=2.06-6.84). The preference for vaping over smoking indoors was found across different locations, including at home and in cars. Those who were older, highly dependent on nicotine, and lived alone were most prone to use any product indoors. While housing tenure was not strongly associated with vaping indoors, those living in social housing were much more likely to smoke indoors than homeowners. CONCLUSIONS: Adults in England are much more likely to vape than smoke indoors. Age, nicotine dependence, and living alone are strongly associated with both behaviours. IMPLICATIONS: Our results show that people have a strong preference for vaping over smoking indoors, including in the home. Given the high prevalence of vaping indoors, policymakers, landlords and businesses must weigh up the ethics, benefits, and harms of extending smoke-free laws to include e-cigarettes.

Impact of Standardised Packaging of Tobacco Products Regulations on cigarette consumption and youth smoking in England: interrupted time-series analysis.

BACKGROUND: In the UK in May 2016, standardised packaging of tobacco products was implemented, including minimum pack sizes of 20 sticks or 30 g loose tobacco. The change was intended to reduce uptake by increasing upfront costs to young people, but there was concern it may unintentionally increase consumption among people smoking. This study aimed to assess whether the introduction of the policy was associated with changes in (1) mean daily factory-made (FM)/roll-your-own (RYO) cigarettes consumption among people smoking predominantly (a) FM and (b) RYO cigarettes; and (2) current smoking prevalence among 16-24-year-olds. METHODS: Data (N=257 929) were from a representative monthly cross-sectional survey of adults (≥16 years) in England, collected between November 2007 and January 2020. Outcome measures were mean daily (FM/RYO) cigarette consumption among those smoking FM/RYO cigarettes, and prevalence of current smoking among 16-24-year-olds. Time-series analyses were conducted using Autoregressive Integrated Moving Average with Exogenous variables (ARIMAX) regression models including a gradual level change starting in June 2017 and ending in May 2018 for cigarette consumption and a step change in June 2016 for prevalence of current smoking. RESULTS: The ARIMAX model was not able to detect a change in mean daily cigarette consumption-for FM (Badj=-0.543, 95% CI -1.381 to 0.296) or RYO (Badj=0.002, 95% CI -0.518 to 0.522) following the implementation of standardised packaging. The unadjusted analysis suggested the implementation of standardised packaging was associated with a small (3%) decrease in smoking prevalence among 16-24-year-olds (Bunadj=-0.031, 95% CI -0.062 to 0.000), but this association was attenuated after adjustment for covariates (Badj=-0.010, 95% CI -0.039 to 0.019). CONCLUSIONS: The implementation of standardised packaging of tobacco products was not associated with a meaningful change in the mean number of FM or RYO cigarettes consumed by people smoking in England, suggesting the larger pack size has not had an unintended consequence of substantially increasing cigarette consumption. However, there was also little evidence that the policy substantially reduced smoking among 16-24-year-olds.

Anthropogenic lead pervasive in Canadian Arctic seawater.

Anthropogenic Pb is widespread in the environment including remote places. However, its presence in Canadian Arctic seawater is thought to be negligible based on low dissolved Pb (dPb) concentrations and proxy data. Here, we measured dPb isotopes in Arctic seawater with very low dPb concentrations (average ∼5 pmol ⋅ kg-1) and show that anthropogenic Pb is pervasive and often dominant in the western Arctic Ocean. Pb isotopes further reveal that historic aerosol Pb from Europe and Russia (Eurasia) deposited to the Arctic during the 20th century, and subsequently remobilized, is a significant source of dPb, particularly in water layers with relatively higher dPb concentrations (up to 16 pmol ⋅ kg-1). The 20th century Eurasian Pb is present predominantly in the upper 1,000 m near the shelf but is also detected in older deep water (2,000 to 2,500 m). These findings highlight the importance of the remobilization of anthropogenic Pb associated with previously deposited aerosols, especially those that were emitted during the peak of Pb emissions in the 20th century. This remobilization might be further enhanced because of accelerated melting of permafrost and ice along with increased coastal erosion in the Arctic. Additionally, the detection of 20th century Eurasian Pb in deep water helps constrain ventilation ages. Overall, this study shows that Pb isotopes in Arctic seawater are useful as a gauge of changing particulate and contaminant sources, such as those resulting from increased remobilization (e.g., coastal erosion) and potentially also those associated with increased human activities (e.g., mining and shipping).

Bromodomain proteins regulate human cytomegalovirus latency and reactivation allowing epigenetic therapeutic intervention.

Reactivation of human cytomegalovirus (HCMV) from latency is a major health consideration for recipients of stem-cell and solid organ transplantations. With over 200,000 transplants taking place globally per annum, virus reactivation can occur in more than 50% of cases leading to loss of grafts as well as serious morbidity and even mortality. Here, we present the most extensive screening to date of epigenetic inhibitors on HCMV latently infected cells and find that histone deacetylase inhibitors (HDACis) and bromodomain inhibitors are broadly effective at inducing virus immediate early gene expression. However, while HDACis, such as myeloid-selective CHR-4487, lead to production of infectious virions, inhibitors of bromodomain (BRD) and extraterminal proteins (I-BETs), including GSK726, restrict full reactivation. Mechanistically, we show that BET proteins (BRDs) are pivotally connected to regulation of HCMV latency and reactivation. Through BRD4 interaction, the transcriptional activator complex P-TEFb (CDK9/CycT1) is sequestered by repressive complexes during HCMV latency. Consequently, I-BETs allow release of P-TEFb and subsequent recruitment to promoters via the superelongation complex (SEC), inducing transcription of HCMV lytic genes encoding immunogenic antigens from otherwise latently infected cells. Surprisingly, this occurs without inducing many viral immunoevasins and, importantly, while also restricting viral DNA replication and full HCMV reactivation. Therefore, this pattern of HCMV transcriptional dysregulation allows effective cytotoxic immune targeting and killing of latently infected cells, thus reducing the latent virus genome load. This approach could be safely used to pre-emptively purge the virus latent reservoir prior to transplantation, thereby reducing HCMV reactivation-related morbidity and mortality.

Protocol and validity testing of femoroacetabular posterior translation with dynamic hip ultrasonography.

OBJECTIVE: To describe femoroacetabular posterior translation (FAPT) using dynamic hip ultrasonography (DHUS), and to determine the inter- and intra-rater reliability of hip ultrasound measurements of FAPT. MATERIALS AND METHODS: The study design was a feasibility study of 13 healthy young adults (26 hips) using test-retest analysis. The data was collected prospectively over a 2-week time period. Three DHUS measurements (posterior neutral (PN), flexion, adduction, and internal rotation (PFADIR), and stand and load (PStand) were measured by four independent raters (2 senior who divided the cohort, 1 intermediate, 1 junior) at two time points for bilateral hips of each participant. Reliability was assessed by calculating the intraclass correlation coefficient (ICC) along with 95% confidence intervals (CIs) for each rater and across all raters. RESULTS: A total of 468 US scans were completed. The mean age of the cohort was 25.7 years (SD 5.1 years) and 54% were female. The inter-rater reliability was excellent for PFADIR (ICC 0.85 95% CI 0.76-0.91), good for PN (ICC 0.69 95% CI 0.5-0.81), and good for PStand (ICC 0.72 95% CI 0.55-0.83). The intra-rater reliability for all raters was good for PFADIR (ICC 0.60 95% CI 0.44-0.73), fair for PN (ICC 0.42 95% CI 0.21-0.59), and fair for PStand (ICC 0.42 95% CI 0.22-0.59). CONCLUSION: This is the first study to present a protocol using dynamic ultrasonography to measure FAPT. DHUS measure for FAPT was shown to be reliable across raters with varying levels of ultrasound experience.

Epidemiology of reported cases of leptospirosis in the EU/EEA, 2010 to 2021.

BackgroundLeptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira. Humans are infected by exposure to animal urine or urine-contaminated environments. Although disease incidence is lower in Europe compared with tropical regions, there have been reports of an increase in leptospirosis cases since the 2000s in some European countries.AimWe aimed to describe the epidemiology of reported cases of leptospirosis in the European Union/European Economic Area (EU/EEA) during 2010-2021 and to identify potential changes in epidemiological patterns.MethodsWe ran a descriptive analysis of leptospirosis cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease during 2010-2021. We also analysed trends at EU/EEA and national level.ResultsDuring 2010-2021, 23 countries reported 12,180 confirmed leptospirosis cases corresponding to a mean annual notification rate of 0.24 cases per 100,000 population. Five countries (France, Germany, the Netherlands, Portugal and Romania) accounted for 79% of all reported cases. The highest notification rate was observed in Slovenia with 0.82 cases per 100,000 population. Overall, the notification rate increased by 5.0% per year from 2010 to 2021 (95% CI: 1.2-8.8%), although trends differed across countries.ConclusionThe notification rate of leptospirosis at EU/EEA level increased during 2010-2021 despite including the first 2 years of the COVID-19 pandemic and associated changes in population behaviours. Studies at (sub)national level would help broaden the understanding of differences at country-level and specificities in terms of exposure to Leptospira, as well as biases in diagnosis and reporting.

Who would be affected by a ban on disposable vapes? A population study in Great Britain.

OBJECTIVES: The UK government is consulting on banning disposable e-cigarettes. This study aimed to describe trends in disposable e-cigarette use among adults in Great Britain since 2021 and establish who would currently be affected by a ban on disposables. STUDY DESIGN: Nationally-representative monthly cross-sectional survey. METHODS: We analysed data from 69,973 adults surveyed between January 2021 and August 2023. We estimated monthly time trends in the weighted prevalence of current disposable e-cigarette use among adults and by sociodemographic characteristics and smoking status. RESULTS: From January 2021 to August 2023, the prevalence of disposable e-cigarette use grew from 0.1 % to 4.9 %. This rise was observed across all population subgroups but was most pronounced among younger adults (e.g. reaching 15.9 % of 18-year-olds compared with 1.3 % of 65-year-olds), those who currently smoke (16.3 %), and those who stopped smoking in the past year (18.2 %). Use among never smokers remained relatively rare (1.5 %), except among 18- to 24-year-olds (7.1 %). Use was significantly higher in England than Wales or Scotland (5.3 % vs. 2.0 % and 2.8 %) and among less (vs. more) advantaged social grades (6.1 % vs. 4.0 %), those with (vs. without) children (6.4 % vs. 4.4 %), and those with (vs. without) a history of mental health conditions (9.3 % vs. 3.1 %). CONCLUSIONS: A ban on disposable e-cigarettes would currently affect one in 20 adults in Great Britain (approximately 2.6 million people). The proportion who would be affected would be greatest among young people, including the 316,000 18-24 year-olds who currently use disposables but who have never regularly smoked tobacco, which may discourage uptake of vaping in this group. However, a ban would also affect 1.2 million people who currently smoke and a further 744,000 who previously smoked. It would also have a disproportionate impact on disadvantaged groups that have higher rates of smoking and typically find it harder to quit.

Cocaine-Induced Changes in Sperm Cdkn1a Methylation Are Associated with Cocaine Resistance in Male Offspring.

Paternal environmental perturbations can influence the physiology and behavior of offspring. For example, our previous work showed reduced cocaine reinforcement in male, but not female, progeny of rat sires that self-administered cocaine. The information transfer from sire to progeny may occur through epigenetic marks in sperm, encompassing alterations in small noncoding RNAs, including microRNAs (miRNAs) and/or DNA methylation. Here, no reliable changes in miRNAs in the sperm of cocaine- relative to saline-experienced sires were identified. In contrast, 272 differentially methylated regions were observed in sperm between these groups. Two hypomethylated promoter regions in the sperm of cocaine-experienced rats were upstream of cyclin-dependent kinase inhibitor 1a (Cdkn1a). Cdkn1a mRNA also was selectively increased in the NAc of cocaine-sired male (but not female) offspring. Cocaine self-administration also enhanced Cdkn1a expression in the accumbens of cocaine-sired rats. These results suggest that changes in Cdkn1a may play a role in the reduced cocaine reinforcing efficacy observed in cocaine-sired male rats. Introducing a 90 d delay between sire self-administration and breeding reversed both cocaine resistance and the increase in accumbens Cdkn1a mRNA in male offspring, indicating that cocaine-induced epigenetic modifications are eliminated with sperm turnover. Collectively, our results indicate that cocaine self-administration produces hypomethylation of Cdkn1a in sperm and a selective increase in the expression of this gene in the NAc of male offspring, which is associated with blunted cocaine reinforcement.SIGNIFICANCE STATEMENT The relatively new field of transgenerational epigenetics explores the effects of environmental perturbations on offspring behavior and physiology. Our prior work in rats indicated that male, but not female, progeny of sires that self-administered cocaine displayed reduced cocaine reinforcement. The information transfer from sire to progeny may occur through heritable epigenetic marks in sperm, including DNA methylation. The present findings revealed two hypomethylated promoter regions upstream of the Cdkn1a gene in sire sperm. Remarkably, Cdkn1a expression was selectively decreased in offspring NAc, a brain region that regulates cocaine reinforcement.

No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.

BACKGROUND: IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers. METHODS: We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies. RESULTS: We found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval, .76-1.11]), cytomegalovirus infection (0.94 [.71-1.24]), herpes simplex virus infection (1.37 [.68-2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count. CONCLUSIONS: The absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.

Have there been sustained impacts of the COVID-19 pandemic on trends in smoking prevalence, uptake, quitting, use of treatment, and relapse? A monthly population study in England, 2017-2022.

BACKGROUND: Studies conducted during the early stages of the pandemic documented mixed changes in smoking behaviour: more smokers quitting successfully but little change in prevalence. This study aimed to examine whether there have been sustained impacts of the COVID-19 pandemic on smoking patterns in England. METHODS: Data were from 101,960 adults (≥ 18 years) participating in the Smoking Toolkit Study, a monthly representative household survey, between June 2017 and August 2022. Interviews were conducted face-to-face until March 2020 and via telephone thereafter. Generalised additive models estimated associations of the pandemic onset (March 2020) with current smoking, uptake, cessation, quit attempts, and use of support. Models adjusted for seasonality, sociodemographic characteristics, and (where relevant) dependence and tobacco control mass-media expenditure. RESULTS: Before the COVID-19 pandemic, smoking prevalence fell by 5.2% per year; this rate of decline slowed to 0.3% per year during the pandemic (RRΔtrend = 1.06, 95% CI = 1.02, 1.09). This slowing was evident in more but not less advantaged social grades (RRΔtrend = 1.15, 1.08, 1.21; RRΔtrend = 1.00, 0.96, 1.05). There were sustained step-level changes in different age groups: a 34.9% (95% CI = 17.7, 54.7%) increase in smoking prevalence among 18-24-year-olds, indicating a potential rise in uptake, in contrast to a 13.6% (95% CI = 4.4, 21.9%) decrease among 45-65-year-olds. In both age groups, these step-level changes were followed by the pre-pandemic declines stopping, and prevalence remaining flat. There were sustained increases in quitting among past-year smokers, with a 120.4% (95% CI = 79.4, 170.9%) step-level increase in cessation and a 41.7% (95% CI = 29.7, 54.7%) increase in quit attempts. The main limitation was the change in modality of data collection when the pandemic started; while this may have contributed to the step-level changes we observed, it is unlikely to explain changes in the slope of trends. CONCLUSIONS: In England, the rate of decline in adult smoking prevalence stagnated during the COVID-19 pandemic through to 2022. At the start of the pandemic, a potential reduction in smoking prevalence among middle-aged adults and increases in quitting among smokers may have been offset by an increase in smoking among young adults. The slowing in the rate of decline was pronounced in more advantaged social grades.

Menopausal hormone therapy and risk of biliary tract cancers.

BACKGROUND AND AIMS: Gallbladder cancer (GBC) has a female predominance, whereas the other biliary tract cancers (BTCs) have a male predominance, suggesting that sex hormones may be involved in carcinogenesis. We sought to evaluate the association between menopausal hormone therapy (MHT) and the risk of BTC in women. APPROACH AND RESULTS: This nested case-control study was conducted in the UK Clinical Practice Research Datalink. Cases diagnosed between 1990 and 2017 with incident primary cancers of the gallbladder (GBC), cholangiocarcinoma (CCA), ampulla of Vater (AVC), and mixed type were matched to 5 controls on birth year, diagnosis year, and years in the general practice using incidence density sampling. Conditional logistic regression was used to calculate ORs and 95% CIs for associations between MHT use and BTC type. The sample consisted of 1,682 BTC cases (483 GBC, 870 CCA, 105 AVC, and 224 mixed) and 8,419 matched controls with a mean age of 73 (SD, 11) years. Combined formulations (estrogen-progesterone) were associated with an increased GBC risk (OR, 1.97; 95% CI, 1.08, 3.59). Orally administered MHT was associated with an increased GBC risk (OR, 2.28; 95% CI, 1.24, 4.17). Estrogen-only formulations (OR, 0.59; 95% CI, 0.34, 0.93) and cream or suppository administrations (OR, 0.57; 95% CI, 0.34, 0.95) were associated with decreased CCA risk. The number of prescriptions, dose, duration of use, and time since last use were not associated with GBC or CCA risk. MHT use was not associated with risk of AVC or mixed cancer. CONCLUSIONS: Combination MHT formulations and oral administrations were associated with increased GBC risk, whereas estrogen-only formulations were associated with a lower CCA risk. MHT formulation and administration should be carefully considered when prescribing.