Naturally leading: a content analysis of terms, themes and word associations in Natural American Spirit advertising, 2000–2020

BackgroundNatural American Spirit (NAS) is a cigarette brand distinguished by supposed ‘natural’, ‘additive-free’ characteristics, marketing of which is tied to misperceptions of reduced harm. In 2017, NAS’s manufacturer agreed (with the Food and Drug Administration) to remove ‘natural’/‘additive-free’ from US marketing. Prior research has explored NAS marketing immediately post-agreement. This study sought to identify prominent post-agreement terms and themes and analyse how they had been used in pre-agreement ads.MethodsWe conducted a content analysis of NAS ads from 2000 to 2020 (N=176), documenting prominent pre-agreement and post-agreement terms/themes and examining how they are used in NAS ads. We coded for descriptors, themes, imagery and promotions, and extended prior research by analysing how leading post-agreement terms were used in conjunction and thematically associated with ‘additive-free’ and ‘natural’ before the agreement.ResultsResults indicated ‘tobacco and water’ and ‘Real. Simple. Different.’ increased post-agreement, as did environmental imagery. ‘Organic’ was prominent pre-agreement and post-agreement. The descriptors used most often in post-agreement ads almost always appeared in conjunction with (and were thematically linked to) ‘natural’ and ‘additive-free’ in pre-agreement ads.ConclusionsIn the years since the agreement, NAS ads have heavily relied on still-allowable descriptors that may invite reduced risk misperceptions. Notably, these descriptors were consistently used alongside the banned terminology before the agreement and presented as if affiliated conceptually, possibly prompting similar connotations. Findings indicate a continuing need for research into NAS advertising effects and a potential role for additional regulatory action.

Exploring Indicators of Hepatotoxicity-Related Post-Marketing Regulatory Actions: A Retrospective Analysis of Drug Approval Data

<b><i>Background:</i></b> Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders such as drug regulatory authorities. <b><i>Objective:</i></b> To explore the potential of drugs, pre-approval regulatory factors as predictors for the occurrence of hepatotoxicity-related post-marketing regulatory actions. Pre-approval factors were specified as: (a) Hy’s Law hepatotoxicity grade ≥3, (b) accelerated approval status, and (c) labeled hepatic adverse effects and regulatory actions at approval. <b><i>Methods:</i></b> Using publicly accessible FDA data, we examined clinical review documents for drugs approved in the USA during the period from 2011 to 2016 to evaluate their hepatic safety profile, identifying the 3 specified indicators for analysis. <b><i>Predictors (Covariates):</i></b> We assessed whether these medications meet: (a) Hy’s Law hepatotoxicity grade ≥3, (b) accelerated approval status, and (c) labeled hepatic adverse effects and regulatory actions at approval. <b><i>Outcome (Dependent Variable):</i></b> Post-marketing regulatory action related to hepatotoxicity including products withdrawal and updates to either warning, precaution or adverse effects sections. <b><i>Statistical Analysis:</i></b> Drugs that were approved between 2011 and 2016 were included in the analysis with follow-up time from the date of approval until end of December 2019 or the date of first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. <b><i>Results:</i></b> A total of 192 medications were included in the study. We classified 48 drugs with grade ≥3 hepatotoxicity, 43 with accelerated approval status, and 74 with labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17–2.23), 0.92 (95% CI, 0.29–2.93) for drug approved via accelerated approval program, and 0.91 (95% CI, 0.33–2.56) for drugs with labeled hepatotoxicity information at approval time. <b><i>Conclusion:</i></b> Hy’s Law with hepatotoxicity grade ≥3, accelerated approval, and label information on hepatotoxicity were not identified as predictors for post-marketing additional regulatory actions concerning liver adverse effects. However, the evidence is inconclusive due to small sample size and potential channeling bias.

The PACAP/PAC1 Receptor System and Feeding

Pituitary adenylyl cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily. PACAP is present in two forms (PACAP-38 and PACAP-27) and binds to three guanine-regulatory (G) protein-coupled receptors (PAC1, VPAC1, and VPAC2). PACAP is expressed in the central and peripheral nervous systems, with high PACAP levels found in the hypothalamus, a brain region involved in feeding and energy homeostasis. PAC1 receptors are high-affinity and PACAP-selective receptors, while VPAC1 and VPAC2 receptors show a comparable affinity to PACAP and VIP. PACAP and its receptors are expressed in the central and peripheral nervous systems with moderate to high expression in the hypothalamus, amygdala, and other limbic structures. Consistent with their expression, PACAP is involved in several physiological responses and pathological states. A growing body of literature suggests that PACAP regulates food intake in laboratory animals. However, there is no comprehensive review of the literature on this topic. Thus, the purpose of this article is to review the literature regarding the role of PACAP and its receptors in food intake regulation and to synthesize how PACAP exerts its anorexic effects in different brain regions. To achieve this goal, we searched PubMed and reviewed 68 articles regarding the regulatory action of PACAP on food intake. Here, we present the literature regarding the effect of exogenous PACAP on feeding and the role of endogenous PACAP in this process. We also provide evidence regarding the effect of PACAP on the homeostatic and hedonic aspects of food intake, the neuroanatomical sites where PACAP exerts its regulatory action, which PACAP receptors may be involved, and the role of various signaling pathways and neurotransmitters in hypophagic effects of PACAP.

The PACAP/PAC1 Receptor System and Feeding

Pituitary adenylyl cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily. PACAP is present in two forms, PACAP-38 and PACAP-27, and binds to three guanine-regulatory (G) protein-coupled receptors (PAC1, VPAC1, and VPAC2). PACAP is expressed in the central and peripheral nervous systems with high PACAP levels found in the hypothalamus, a brain region involved in feeding and energy homeostasis. PAC1 receptors are high-affinity and PACAP-selective receptors, while VPAC1 and VPAC2 receptors show a comparable affinity to PACAP and VIP. PACAP and its receptors are expressed in the central and peripheral nervous systems, with moderate to high expression in the hypothalamus, amygdala, and other limbic structures. Consistent with their expression, PACAP is involved in several physiological responses and pathological states. A growing body of literature suggests that PACAP regulates food intake in laboratory animals. However, there is no comprehensive review of the literature on this topic. Thus, the purpose of this article is to review the literature regarding the role of PACAP and its receptors in food intake regulation and to synthesize how PACAP exerts its anorexic effects in different brain regions. To achieve this goal, we searched PubMed and reviewed 68 articles regarding the regulatory action of PACAP on food intake. Here, we present the literature regarding the effect of exogenous PACAP on feeding and the role of endogenous PACAP in this process. We also provide evidence regarding the effect of PACAP on the homeostatic and hedonic aspects of food intake, the neuroanatomical sites where PACAP exerts its regulatory action, which PACAP receptors may be involved, and the role of various signaling pathways and neurotransmitters in hypophagic effects of PACAP.

Research on Action of Bone Marrow Stromal Cells (BMSC) Modified by Toll-Like Receptor for Myocardial Function of Rats with Myocardial Infarction (MI)

MI could affect myocardial function seriously. The action and mechanism of BSMC modified by the transplantation of Toll-like receptor on myocardial function of rats with MI was studied. The sixty SD rats were divided into sham-operation group and model group randomly. The isolated and cultivated BMSC was divided into three groups such as group with added by TLR4 agonist, group with added by TLR-4 antagonist as TAK-242, group with only BMSC. The model of rats with MT was established in model group. BMSC in different group was transplanted into rats respectively. The cardiac function of rats in sham-operation group and model group was observed. The distribution condition of surface molecule in BMSC was detected by FCM. There was expression CD44 (+), CD54 (+), CD90 (+), no expression CD34 (−) from results. It could indicated that BMSCs with high purity was cultivated successfully. The high MT expression was affected by TLR-4 generally which could also illustrate the degree of deformation and necrosis of cardiac muscle cell, could be enhanced in established rat model because of negative regulatory action. The zone of MI in rats could be amplified by TLR-4. The cytobiological function of BMSC could be adjusted by TLR-4 through the transplantation of TLR-4 after there was MI in rats. The cytobiological function of BMSC could be adjusted by TLR-4 through modification of the transplantation of TLT-4 in rats after there was MI in rats. The BMSCs modified by high TLR-4 expression had negative regulatory action on the treatment on MI.

Digital Arenas: The regulatory framework and other relevant issues on eSports online betting

The contribution of technological development, in an essential and user-friendly way, to the transition of many aspects of the real world to the digital environment, is constantly creating new habits and new fields of activity. This transition, without any shadow of doubt, leads to new and unknown realities, which, apart from the interest they present, they call for thorough investigation and further regulation, where it is needed. The cases of eSports and online gaming, although not new to the user of the digital age, are of high importance to the investment and commercial world, in terms of their further development and exploitation. In this context, although online betting in eSports has been introduced to the Greek market a few years ago, it is unlikely to be developed according to its dynamics, since issues of legal nature are not settled yet. In order to ensure a secure landscape for eSports online betting, the necessity for transparency and integrity and their protection through regulatory action becomes imperative.

Regulatory Standards, Legitimate Authority and the Adjudicatory Role

Part V contains two chapters, Chapter Nine and Chapter Ten. These chapters return to the conceptual questions raised by the emergence of global regulatory standards in international courts and tribunals. Chapter Nine evaluates overall how the standards preserve, enhance or undermine international law’s claim to legitimate authority. Broadly, the standards appear to strengthen traditional procedural justifications of authority. However, substantively they contribute only partially to an ideal balancing of international interests and do not promise the co-ordination between domestic and international legal orders needed for international law better to serve its subjects by better balancing competing global interests. More is not to be expected, though. International courts and tribunals remain formally and socially constrained; inter alia the parties’ pleadings are often influential. Greater international political involvement in the development of global regulatory standards would be appropriate, especially in relation to the possible future adoption of regulatory coherence tests that might require proportionality in regulatory action.