Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators. We show here that Tax activates the gene coding for coactivator-associated arginine methyltransferase 1 (CARM1), which epigenetically enhances gene expression through methylation of histones. Tax activated the Carm1 gene and increased protein expression, not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs). Tax increased R17-methylated histone H3 on the target gene IL-2Rα, concomitant with increased expression of CARM1. Short hairpin RNA (shRNA)-mediated knockdown of CARM1 decreased Tax-mediated induction of IL-2Rα and Cyclin D2 gene expression, reduced E2F activation and inhibited cell cycle progression. Tax acted via response elements in intron 1 of the Carm1 gene, through the NF-κB pathway. These results suggest that Tax-mediated activation of the Carm1 gene contributes to leukemogenic target-gene expression and cell cycle progression, identifying the first epigenetic target gene for Tax-mediated trans-activation in cell growth promotion.

Human T-cell leukemia virus type 1 (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL). Mutational analysis has demonstrated that the tumor suppressor, F-box and WD repeat domain containing 7 (FBXW7/FBW7/CDC4), is mutated in primary ATL patients. However, even in the absence of genetic mutations, FBXW7 substrates are stabilized in ATL cells, suggesting additional mechanisms can prevent FBXW7 functions. Here, we report that the viral oncoprotein Tax represses FBXW7 activity, resulting in the stabilization of activated Notch intracellular domain, c-MYC, Cyclin E, and myeloid cell leukemia sequence 1 (BCL2-related) (Mcl-1). Mechanistically, we demonstrate that Tax directly binds to FBXW7 in the nucleus, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 substrates. In support of the nuclear role of Tax, a non-degradable form of the nuclear factor kappa B subunit 2 (NFκB2/p100) was found to delocalize Tax to the cytoplasm, thereby preventing Tax interactions with FBXW7 and Tax-mediated inhibition of FBXW7. Finally, we characterize a Tax mutant that is unable to interact with FBXW7, unable to block FBXW7 tumor suppressor functions, and unable to effectively transform fibroblasts. These results demonstrate that HTLV-I Tax can inhibit FBXW7 functions without genetic mutations to promote an oncogenic state. These results suggest that Tax-mediated inhibition of FBXW7 is likely critical during the early stages of the cellular transformation process.
OBJECTIVE: F-box and WD repeat domain containing 7 (FBXW7), a critical tumor suppressor of human cancers, is frequently mutated or epigenetically suppressed. Loss of FBXW7 functions is associated with stabilization and increased expression of oncogenic factors such as Cyclin E, c-Myc, Mcl-1, mTOR, Jun, and Notch. In this study, we demonstrate that the human retrovirus human T-cell leukemia virus type 1 oncoprotein Tax directly interacts with FBXW7, effectively outcompeting other targets for binding to FBXW7, resulting in decreased ubiquitination and degradation of FBXW7 cellular substrates. We further demonstrate that a Tax mutant unable to interact with and inactivate FBXW7 loses its ability to transform primary fibroblasts. Collectively, our results describe a novel mechanism used by a human tumor virus to promote cellular transformation.

BACKGROUND: A high intake of sugar-sweetened beverages (SSBs) is associated with the risk of several chronic diseases, including ischemic heart disease (IHD) and stroke. This study aimed to model the impact of a 20% tax on all SSBs for IHD and stroke among Brazilian adults.
METHODS: This was an ex-ante risk comparative study. The model applied a 20% tax on SSBs and projected the incidence, prevalence and mortality of IHD and stroke over a 20-year period (2019-39). Using data on consumption, previously published cross- and own-price elasticities of SSBs, and relative risk, we estimated changes in IHD and stroke burden.
RESULTS: Our model predicts that a 20% SSB tax may reduce new cases of IHD by ~13%, especially among women, and avert ~8% of the deaths attributable to IHD over 20 years. These results represent a decrease of 19 543 new cases and 8466 and 7274 fewer deaths in the period for men and women, respectively. Estimates of reduction in incidence, prevalence and deaths from stroke were not significant over 20 years.
CONCLUSIONS: Even under conservative assumptions, our study found that a small reduction in SSB consumption led to a substantial decrease in IHD incidence and mortality in Brazil.

OBJECTIVE: We explored the early impact of changes to the UK alcohol tax system, implemented in August 2023, on the strength and price of alcoholic products available for sale on the website of the largest supermarket in England.
METHODS: Our comparative descriptive study using longitudinal brand-level data was not preregistered and should be considered exploratory.
METHODS: Data were collected weekly (May to October 2023) using automated web scraping tools. Outcomes were product strength (% alcohol by volume [ABV]) and price (per 10 mL of pure alcohol and per litre of product). We undertook paired t-tests, two-sample Kolmogorov-Smirnov tests, and quantile regression to compare outcomes before and after the tax changes. Beer, cider, spirits, and ready-to-drinks (RTDs) were analysed separately.
RESULTS: There was a reduction in the mean strength of beer, driven by manufacturers reformulating a small number of weaker beers, moving them into a lower tax band (<3.5%ABV). The mean price per 10 mL of alcohol and per litre of product was significantly higher after the new tax system for beer, cider, and spirits and significantly lower for RTDs. Increases in the price of beer tended to occur across the entire distribution, whereas increases in the price of cider occurred among more expensive products.
CONCLUSIONS: Changes to product strength tended to occur among weaker products near the new lowest tax band, suggesting tax bands may be a potential stimulus for change. Reformulation of stronger products would have better public health potential. Longer term monitoring, including data on purchasing/consumption, is required.

BACKGROUND: The WHO highlight alcohol, tobacco, unhealthy food, and sugar-sweetened beverage (SSB) taxes as one of the most effective policies for preventing and reducing the burden of non-communicable diseases. This umbrella review aimed to identify and summarise evidence from systematic reviews that report the relationship between price and demand or price and disease/death for alcohol, tobacco, unhealthy food, and SSBs. Given the recent recognition as gambling as a public health problem, we also included gambling.
METHODS: The protocol for this umbrella review was pre-registered (PROSPERO CRD42023447429). Seven electronic databases were searched between 2000-2023. Eligible systematic reviews were those published in any country, including adults or children, and which quantitatively examined the relationship between alcohol, tobacco, gambling, unhealthy food, or SSB price/tax and demand (sales/consumption) or disease/death. Two researchers undertook screening, eligibility, data extraction, and risk of bias assessment using the ROBIS tool.
RESULTS: We identified 50 reviews from 5,185 records, of which 31 reported on unhealthy food or SSBs, nine reported on tobacco, nine on alcohol, and one on multiple outcomes (alcohol, tobacco, unhealthy food, and SSBs). We did not identify any reviews on gambling. Higher prices were consistently associated with lower demand, notwithstanding variation in the size of effect across commodities or populations. Reductions in demand were large enough to be considered meaningful for policy.
CONCLUSIONS: Increases in the price of alcohol, tobacco, unhealthy food, and SSBs are consistently associated with decreases in demand. Moreover, increasing taxes can be expected to increase tax revenue. There may be potential in joining up approaches to taxation across the harm-causing commodities.

BACKGROUND: Open-system electronic cigarette (EC) product features, such as battery capacity, maximum output wattage, and so forth, are major components that drive product costs and may influence use patterns. Moreover, continued innovation and monitoring of product features and prices will provide critical information for designing appropriate taxation policies and product regulations.
OBJECTIVE: This study will examine how product features are associated with the prices of devices sold in web-based vape shops.
METHODS: We draw samples from 5 popular, US-based, web-based vape shops from April to August 2022 to examine starter kits, device-only products, and e-liquid container-only products. We implemented a linear regression model with a store-fixed effect to examine the association between device attributes and prices.
RESULTS: EC starter kits or devices vary significantly by type, with mod prices being much higher than pod and vape pen prices. The prices of mod starter kits were even lower than those of mod devices, suggesting that mod starter kits are discounted in web-based vape shops. The price of mod kits, mod device-only products, and pod kits increased as the battery capacity and output wattage increased. For vape pens, the price was positively associated with the volume size of the e-liquid container. On the other hand, the price of pod kits was positively associated with the number of containers.
CONCLUSIONS: A unit-based specific tax, therefore, will impose a higher tax burden on lower-priced devices such as vape pens or pod systems and a lower tax burden on mod devices. A volume- or capacity-based specific tax on devices will impose a higher tax burden on vape pens with a larger container size. Meanwhile, ad valorem taxes pegged to wholesale or retail prices would apply evenly across device types, meaning those with advanced features such as higher battery capacities and output wattage would face higher rates. Therefore, policy makers could manipulate tax rates by device type to discourage the use of certain device products.

Increasing concerns about the health impacts of sugar consumption has led to the proposition of a sugar-sweetened beverage (SSB) tax in Canada. However, competing concerns related to stigma and equity remain and have not been explored in a Canadian context. As part of a broader study examining the perspectives of various populations on SSB tax acceptability, we examined how residents of an upper-middle class neighborhood conceptualize SSB tax acceptability, and we explored the discourses that inform their discussion. We conducted and analyzed qualitative, semi-structured interviews with residents of an upper-middle class neighborhood in Winnipeg, Manitoba, Canada. Recruitment criteria were residence, adults, and English speaking. Critical discourse analysis methodology was used, and healthism (health moralism) and tax psychology informed the analysis. Eighteen participants volunteered: 15 females and 3 males; all self-identified as white, and all spoke about (grand)parenting. Healthist discourse was utilized in supportive discussion of SSB taxation. With the mobilization of healthism, ideal citizens and parents were described as \"health conscious\" and those who might be likely to reduce SSB intake because of taxation. Healthism also contributed to their identification of beverages targeted by a tax, versus those they deemed as having redeeming nutritional qualities. Limits to SSB tax support were expressed as fairness concerns, with a focus on the procedural justice of the tax. Participants supported SSB taxation and the discourses they employed suggested support for the tax was perceived as contributing to their construction of the kind of ideal, health-valuing citizens they hoped to embody. However, participants were also concerned about the fairness of implementation, although this did not outweigh the prioritization of good health.

BACKGROUND: Economic evaluations of public health interventions like sugar-sweetened beverage (SSB) taxes face difficulties similar to those previously identified in other public health areas. This stems from challenges in accurately attributing effects, capturing outcomes and costs beyond health, and integrating equity effects. This review examines how these challenges were addressed in economic evaluations of SSB taxes.
METHODS: A systematic review was conducted to identify economic evaluations of SSB taxes focused on addressing obesity in adults, published up to February 2021. The methodological challenges examined include measuring effects, valuing outcomes, assessing costs, and incorporating equity.
RESULTS: Fourteen economic evaluations of SSB taxes were identified. Across these evaluations, estimating SSB tax effects was uncertain due to a reliance on indirect evidence that was less robust than evidence from randomised controlled trials. Health outcomes, like quality-adjusted life years, along with a healthcare system perspective for costs, dominated the evaluations of SSB taxes, with a limited focus on broader non-health consequences. Equity analyses were common but employed significantly different approaches and exhibited varying degrees of quality.
CONCLUSIONS: Addressing the methodological challenges remains an issue for economic evaluations of public health interventions like SSB taxes, suggesting the need for increased attention on those issues in future studies. Dedicated methodological guidelines, in particular addressing the measurement of effect and incorporation of equity impacts, are warranted.

BACKGROUND: High consumption of red and processed meat contributes to both health and environmental harms. Warning labels and taxes for red meat reduce selection of red meat overall, but little is known about how these potential policies affect purchases of subcategories of red meat (e.g., processed versus unprocessed) or of non-red-meat foods (e.g., cheese, pulses) relevant to health and environmental outcomes. This study examined consumer responses to warning labels and taxes for red meat in a randomized controlled trial.
METHODS: In October 2021, we recruited 3,518 US adults to complete a shopping task in a naturalistic online grocery store. Participants were randomly assigned to one of four arms: control (no warning labels or tax), warning labels only (health and environmental warning labels appeared next to products containing red meat), tax only (prices of products containing red meat were increased 30%) or combined warning labels + tax. Participants selected items to hypothetically purchase, which we categorized into food groups based on the presence of animal- and plant-source ingredients (e.g., beef, eggs, pulses), meat processing level (e.g., processed pork versus unprocessed pork), and meat species (e.g., beef versus pork). We assessed the effects of the warning labels and tax on selections from each food group.
RESULTS: Compared to control, all three interventions led participants to select fewer items with processed meat (driven by reductions in processed pork) and (for the tax and warning labels + tax interventions only) fewer items with unprocessed meat (driven by reductions in unprocessed beef). All three interventions also led participants to select more items containing cheese, while only the combined warning labels + tax intervention led participants to select more items containing processed poultry. Except for an increase in selection of pulses in the tax arm, the interventions did not affect selections of fish or seafood (processed or unprocessed), eggs, or plant-based items (pulses, nuts & seeds, tofu, meat mimics, grains & potatoes, vegetables).
CONCLUSIONS: Policies to reduce red meat consumption are also likely to affect consumption of other types of foods that are relevant to both health and environmental outcomes.
BACKGROUND: NCT04716010 on www.
RESULTS: gov .

Revenues from international trade and transactions are crucial for the economic growth and macroeconomic activity of a country. For that reason, taxes from international trade and transactions are used to proxy revenues. Moreover, industrial production index is considered to be proxied for the economic growth. In this study, these variables are used monthly for the period of January 2006 and February 2022 for Turkey. First, different kinds of Fourier based unit root tests including flexibility and fractionality have been used to analyze the data structure. Then, linear VAR and Fourier VAR models have been estimated to reach and analyze the differences of the results of impulse responses between linear and trigonometric models. Finally, linear and Fourier term included Granger Causality tests have been used to question if there would be a difference or not. When the estimations and tests having Fourier structure have been established, the tests considering it have given more different results than linear models. Briefly, it has been shown that policy makers should shift their decisions to an alternative direction.