Longitudinal Evaluation of Reproductive Endocrine Function in Men with ACTH-Dependent Cushing Syndrome.

CONTEXT: Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences. OBJECTIVE: To determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause. DESIGN: Post-hoc analyses of prospective cohort studies. SETTING: Clinical research center. PATIENTS: Men with ACTH-dependent CS. Cohort 1 (C1) (n=8, age 32.5±12 y; studied 1985-1989); Cohort 2 (C2) (n=44, 42.7 ± 15.1 y; studied 1989-2021). INTERVENTIONS: C1: Every 20-minute blood sampling for 24h before and 1-40 months after surgical cure. Three subjects underwent GnRH stimulation tests pre- and post-surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post-cure. MAIN OUTCOME MEASURES: C1: LH, FSH, LH pulse frequency and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, fT4, T3, TSH and UFC levels and frequency of hypogonadism pre- and post-surgery. RESULTS: C1: mean LH and LH pulse frequency increased after surgery (p < 0.05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and SHBG increased at 6M and 12M post surgery, but hypogonadism persisted in 51% at 6M and in 26% at 12M. CONCLUSION: Hypogonadism in men with CS is widely prevalent but reversible in ∼75% of patients one year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.

Predicting nutrition and environmental factors associated with female reproductive disorders using a knowledge graph and random forests.

OBJECTIVE: Female reproductive disorders (FRDs) are common health conditions that may present with significant symptoms. Diet and environment are potential areas for FRD interventions. We utilized a knowledge graph (KG) method to predict factors associated with common FRDs (for example, endometriosis, ovarian cyst, and uterine fibroids). MATERIALS AND METHODS: We harmonized survey data from the Personalized Environment and Genes Study (PEGS) on internal and external environmental exposures and health conditions with biomedical ontology content. We merged the harmonized data and ontologies with supplemental nutrient and agricultural chemical data to create a KG. We analyzed the KG by embedding edges and applying a random forest for edge prediction to identify variables potentially associated with FRDs. We also conducted logistic regression analysis for comparison. RESULTS: Across 9765 PEGS respondents, the KG analysis resulted in 8535 significant or suggestive predicted links between FRDs and chemicals, phenotypes, and diseases. Amongst these links, 32 were exact matches when compared with the logistic regression results, including comorbidities, medications, foods, and occupational exposures. DISCUSSION: Mechanistic underpinnings of predicted links documented in the literature may support some of our findings. Our KG methods are useful for predicting possible associations in large, survey-based datasets with added information on directionality and magnitude of effect from logistic regression. These results should not be construed as causal but can support hypothesis generation. CONCLUSION: This investigation enabled the generation of hypotheses on a variety of potential links between FRDs and exposures. Future investigations should prospectively evaluate the variables hypothesized to impact FRDs.

Questionnaire-based exposome-wide association studies for common diseases in the Personalized Environment and Genes Study.

The exposome collectively refers to all exposures, beginning in utero and continuing throughout life, and comprises not only standard environmental exposures such as point source pollution and ozone levels but also exposures from diet, medication, lifestyle factors, stress, and occupation. The exposome interacts with individual genetic and epigenetic characteristics to affect human health and disease, but large-scale studies that characterize the exposome and its relationships with human disease are limited. To address this gap, we used extensive questionnaire data from the diverse North Carolina-based Personalized Environment and Genes Study (PEGS, n = 9, 429) to evaluate exposure associations in relation to common diseases. We performed an exposome-wide association study (ExWAS) to examine single exposure models and their associations with 11 common complex diseases, namely allergic rhinitis, asthma, bone loss, fibroids, high cholesterol, hypertension, iron-deficient anemia, ovarian cysts, lower GI polyps, migraines, and type 2 diabetes. Across diseases, we found associations with lifestyle factors and socioeconomic status as well as asbestos, various dust types, biohazardous material, and textile-related exposures. We also found disease-specific associations such as fishing with lead weights and migraines. To differentiate between a replicated result and a novel finding, we used an AI-based literature search and database tool that allowed us to examine the current literature. We found both replicated findings, especially for lifestyle factors such as sleep and smoking across diseases, and novel findings, especially for occupational exposures and multiple diseases.

Public support for tobacco endgame policies in South Korea: Findings from the 2020 International Tobacco Control Korea Survey.

BACKGROUND: Strong public support can increase the likelihood of adopting tobacco control policies. We assessed support for six commercial tobacco endgame policies in South Korea: limiting the nicotine in cigarettes, banning all additives in cigarettes, restricting the number of places where cigarettes are sold, and banning the manufacture and sales of cigarettes (unconditionally, with the provision of cessation support and with alternative tobacco products available). METHODS: Data were obtained from 4740 adults who completed the 2020 International Tobacco Control Korea Survey. Participants were categorised based on their nicotine use: (1) did not use any products, (2) vaped and/or used heated tobacco products (HTPs) but did not smoke cigarettes, (3) smoked cigarettes only and (4) smoked cigarettes and vaped and/or used HTPs. Attitudes towards the policies were classified as supportive, undecided or opposed. Weighted multinomial logistic regression models assessed support levels according to nicotine use. RESULTS: Support was highest for limiting the nicotine content in cigarettes (68.4%; 95% CI 64.6% to 72.3%) and restricting the number of retailers (68.1%; 95% CI 64.5% to 71.7%), and lowest for banning cigarette sales if alternative products are made available (45.0%; 95% CI 40.9% to 49.1%). People who did not use any products were most likely to support endgame policies, except for banning cigarette sales with alternatives available. The proportion of undecided participants exceeded 10% (range 13%-25%) for all policies. CONCLUSION: There is a strong public support for tobacco endgame policies in South Korea. Further research should prioritise the development of strategies to ensure the effective implementation of highly supported policies.

Illicit cigarette purchasing after implementation of menthol cigarette bans in Canada: findings from the 2016-2018 ITC Four Country Smoking and Vaping Surveys.

OBJECTIVE: To examine the impact of menthol cigarette bans on use and purchasing of illicit cigarettes among menthol and non-menthol smokers in seven Canadian provinces. METHODS: Data from 1098 non-menthol smokers and 138 menthol smokers in Canada who completed the ITC Four Country Smoking and Vaping Survey in 2016 (pre-ban) and 2018 (post-ban). Brand validation analysis was conducted to (1) compare self-reported use of menthols versus actual use of menthols as regular brand, and verify self-reported purchasing of menthols among pre-ban menthol smokers at post-ban; and (2) assess pre-post ban changes in purchasing of illicit cigarettes from First Nations reserves among non-menthol smokers and menthol smokers. RESULTS: Among the subset of 138 pre-ban menthol smokers, 36 (19.5%) reported smoking menthols at post-ban. Brand validation analyses showed that 19 (9.0%) were actually using a non-menthol brand; of the 17 (10.5%) who were actually using a menthol brand, 13 (7.9%) bought a menthol brand at last purchase, and 4 (2.6%) bought a non-menthol brand. Among the full sample of smokers who purchased cigarettes from First Nations reserves at both pre-ban and post-ban, there was no change in purchasing of menthols (n=9 menthol smokers; 51.2% vs 51.2%, p=1.00), non-menthols (n=1024 non-menthol smokers; 9.1% vs 8.7%, p=0.69) or all cigarettes (menthol+non-menthol) (n=1086 smokers; 9.7% vs 9.2%, p=0.56). CONCLUSIONS: Actual rates of brand-verified menthol smoking were substantially lower than self-reported rates at post-ban. After Canada's menthol ban, there was no increase in illicit purchasing of menthol or non-menthol cigarettes from First Nations reserves.

Optimising a product standard for banning menthol and other flavours in tobacco products.

In this paper, we highlight key issues that policymakers should consider when developing a product standard banning menthol and other flavours in tobacco products based on research evidence and experiences learnt from other countries. A flavour product standard may be optimised by (1) having a clear and comprehensive definition of flavour that includes a complete ban on additives that have flavour properties and/or evoke sensory/cooling effects (ie, menthol analogues and synthetic coolants that stimulate the cooling receptor of the brain) rather than only as a 'characterising flavour' and (2) applying the standard to all tobacco product categories as well as all components or parts of the tobacco product (ie, the tobacco, filter, wrapper or paper), including separate flavourings that can be added to the product.

Application of machine learning and artificial intelligence in the diagnosis and classification of polycystic ovarian syndrome: a systematic review.

Introduction: Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and remains widely underdiagnosed leading to significant morbidity. Artificial intelligence (AI) and machine learning (ML) hold promise in improving diagnostics. Thus, we performed a systematic review of literature to identify the utility of AI/ML in the diagnosis or classification of PCOS. Methods: We applied a search strategy using the following databases MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science, and the IEEE Xplore Digital Library using relevant keywords. Eligible studies were identified, and results were extracted for their synthesis from inception until January 1, 2022. Results: 135 studies were screened and ultimately, 31 studies were included in this study. Data sources used by the AI/ML interventions included clinical data, electronic health records, and genetic and proteomic data. Ten studies (32%) employed standardized criteria (NIH, Rotterdam, or Revised International PCOS classification), while 17 (55%) used clinical information with/without imaging. The most common AI techniques employed were support vector machine (42% studies), K-nearest neighbor (26%), and regression models (23%) were the commonest AI/ML. Receiver operating curves (ROC) were employed to compare AI/ML with clinical diagnosis. Area under the ROC ranged from 73% to 100% (n=7 studies), diagnostic accuracy from 89% to 100% (n=4 studies), sensitivity from 41% to 100% (n=10 studies), specificity from 75% to 100% (n=10 studies), positive predictive value (PPV) from 68% to 95% (n=4 studies), and negative predictive value (NPV) from 94% to 99% (n=2 studies). Conclusion: Artificial intelligence and machine learning provide a high diagnostic and classification performance in detecting PCOS, thereby providing an avenue for early diagnosis of this disorder. However, AI-based studies should use standardized PCOS diagnostic criteria to enhance the clinical applicability of AI/ML in PCOS and improve adherence to methodological and reporting guidelines for maximum diagnostic utility. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022295287.

Illicit purchasing and use of flavour accessories after the European Union menthol cigarette ban: findings from the 2020-21 ITC Netherlands Surveys.

BACKGROUND: The 2020 European Union (EU) menthol cigarette ban increased quitting among pre-ban menthol smokers in the Netherlands, but some reported continuing to smoke menthol cigarettes. This study examined three possible explanations for post-ban menthol use-(i) illicit purchasing, (ii) use of flavour accessories and (iii) use of non-menthol replacement brands marketed for menthol smokers. METHODS: Data were from the ITC Netherlands Cohort Surveys among adult smokers before the menthol ban (Wave 1: February-March 2020, N = 2067) and after the ban (Wave 2: September-November 2020, N = 1752; Wave 3: June-July 2021, N = 1721). Bivariate, logistic regression and generalized estimating equation model analyses were conducted on weighted data. RESULTS: Illicit purchasing remained low from pre-ban (2.4%, 95% CI: 1.8-3.2, Wave 1) to post-ban (1.7%, 1.2-2.5%, Wave 3), with no difference between menthol and non-menthol smokers from Wave 1 to Wave 3. About 4.4% of post-ban menthol smokers last purchased their usual brand outside of the EU and 3.6% from the internet; 42.5% of post-ban menthol smokers and 4.4% of smokers overall reported using flavour accessories, with greater odds among those aged 25-39 years vs. 55+ (aOR = 3.16, P = 0.002). Approximately 70% of post-ban smokers who reported using a menthol brand were actually using a non-menthol replacement brand. CONCLUSIONS: There was no increase in illicit purchasing or of smuggling outside the EU among menthol and non-menthol smokers in the Netherlands 1 year after the EU menthol cigarette ban. Use of flavour accessories and non-menthol replacement brands best explain post-ban menthol use, suggesting the need to ban accessories and ensure industry compliance.

Predicting nutrition and environmental factors associated with female reproductive disorders using a knowledge graph and random forests.

Objective: Female reproductive disorders (FRDs) are common health conditions that may present with significant symptoms. Diet and environment are potential areas for FRD interventions. We utilized a knowledge graph (KG) method to predict factors associated with common FRDs (e.g., endometriosis, ovarian cyst, and uterine fibroids). Materials and Methods: We harmonized survey data from the Personalized Environment and Genes Study on internal and external environmental exposures and health conditions with biomedical ontology content. We merged the harmonized data and ontologies with supplemental nutrient and agricultural chemical data to create a KG. We analyzed the KG by embedding edges and applying a random forest for edge prediction to identify variables potentially associated with FRDs. We also conducted logistic regression analysis for comparison. Results: Across 9765 PEGS respondents, the KG analysis resulted in 8535 significant predicted links between FRDs and chemicals, phenotypes, and diseases. Amongst these links, 32 were exact matches when compared with the logistic regression results, including comorbidities, medications, foods, and occupational exposures. Discussion: Mechanistic underpinnings of predicted links documented in the literature may support some of our findings. Our KG methods are useful for predicting possible associations in large, survey-based datasets with added information on directionality and magnitude of effect from logistic regression. These results should not be construed as causal, but can support hypothesis generation. Conclusion: This investigation enabled the generation of hypotheses on a variety of potential links between FRDs and exposures. Future investigations should prospectively evaluate the variables hypothesized to impact FRDs.

The Thyroid Hormone Axis and Female Reproduction.

Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and polycystic ovarian syndrome. Thus, the complex molecular interplay between hormones involved in thyroid and reproductive functions is further compounded by the association of certain common autoimmune states with disorders of the thyroid and the HPG axes. Furthermore, in prepartum and intrapartum states, even relatively minor disruptions have been shown to adversely impact maternal and fetal outcomes, with some differences of opinion in the management of these conditions. In this review, we provide readers with a foundational understanding of the physiology and pathophysiology of thyroid hormone interactions with the female HPG axis. We also share clinical insights into the management of thyroid dysfunction in reproductive-aged women.

Support for pictorial health warning labels on cigarette packages in the United States among adults who currently smoke or quit smoking: Findings from the ITC US Smoking and Vaping Surveys.

INTRODUCTION: In March 2020, the US Food and Drug Administration (FDA) finalized new pictorial health warnings (PHWs), covering 50% of the front and back of the pack; however, legal challenges from cigarette manufacturers have prevented the new warnings from being implemented. About 70% of adults in the general US population support PHWs. This study assessed support for PHWs in 2016, 2018 and 2020 among US adults (aged ≥18 years) who currently smoke or formerly smoked cigarettes. We also assessed factors related to support. METHODS: Respondents included adults who currently or formerly smoked cigarettes and participated in at least one wave of the US ITC Smoking and Vaping Surveys: Wave 1 (2016, n=2557); Wave 2 (2018, n=2685); and Wave 3 (2020, n=1112). We assessed changes in support for PHWs between 2016 and 2020, and assessed factors related to support (support vs oppose/don't know). Analyses were conducted on weighted data. RESULTS: Overall, 38.0% of respondents supported PHWs in 2016, with a significant increase to 44.7% in 2018 (p<0.001), and leveling off to 45.0% in 2020 (2018 vs 2020, p=0.91). Support was highest among former smokers and lowest among daily smokers in all three survey years. Support for PHWs at all survey years was significantly higher among those who formerly smoked, were younger (aged 18-39 vs ≥40 years), those who identified as Black (vs White), and planned to quit smoking (vs not planning to quit). There were no differences by income level, education level, or sex. CONCLUSIONS: Nearly half of US adults who smoke cigarettes or quit smoking supported PHWs in 2020, with support being higher among younger adults, ethnic minorities, and those who formerly smoked. Support increased between 2016 and 2018, but not between 2018 and 2020. Similar to other studies, fewer current and former smokers supported PHWs compared to the US adult general population.

Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress.

NLRP3 is a pattern recognition receptor with a well-documented role in inducing inflammasome assembly in response to cellular stress. Deregulation of its activity leads to many inflammatory disorders including gouty arthritis, Alzheimer disease, and cancer. Whereas its role in the context of cancer has been mostly explored in the immune compartment, whether NLRP3 exerts functions unrelated to immunity in cancer development remains unexplored. Here, we demonstrate that NLRP3 interacts with the ATM kinase to control the activation of the DNA damage response, independently of its inflammasome activity. NLRP3 down-regulation in both broncho- and mammary human epithelial cells significantly impairs ATM pathway activation, leading to lower p53 activation, and provides cells with the ability to resist apoptosis induced by acute genotoxic stress. Interestingly, NLRP3 expression is down-regulated in non-small cell lung cancers and breast cancers, and its expression positively correlates with patient overall survival. Our findings identify a novel non-immune function for NLRP3 in maintaining genome integrity and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways to maintain cell integrity.

Evaluating the impact of plain packaging among Canadian smokers: findings from the 2018 and 2020 ITC Smoking and Vaping Surveys.

BACKGROUND: In February 2020, Canada implemented plain packaging without any changes to the size and content of health warning labels (HWLs), which were last updated in 2012 (pictorial HWLs on 75% of the pack front and back). This pre-post evaluation study assessed the impact of plain packaging in Canada on: (1) pack appeal; (2) HWL effectiveness; and (3) support for plain packaging. Additionally, a quasi-experimental design was used to assess the Canadian results relative to two comparator countries: Australia, where plain packaging (with new larger HWLs) was implemented in 2012, and the United States (USA), where plain packaging has not been implemented and the same text warnings have appeared on cigarette packs since 1985. METHODS: Data are from adult smokers who participated in the 2018 and/or 2020 International Tobacco Control Smoking and Vaping Surveys in Canada (n=4600), Australia (n=1834) and the USA (n=3046). Online surveys were conducted before (February to July 2018) and after (February to June 2020) the implementation of plain packaging in Canada. Adjusted regression analyses were conducted on weighted data. RESULTS: Plain packaging was associated with a significant increase in the percentage of Canadian smokers who did not like the look of their cigarette pack (2018: 28.6% vs 2020: 44.7%, p<0.001), whereas no change in pack appeal was observed among smokers in Australia and the USA over the same period. Plain packaging was not associated with changes in HWL effectiveness in Canada. Support for plain packaging increased significantly among Canadian smokers (2018: 25.6% vs 2020: 33.7%, p<0.001). CONCLUSIONS: Plain packaging in Canada substantially reduced pack appeal and increased support for the policy among adult smokers; however, there was no increase in the effectiveness of Canada's 8-year-old HWLs. The impact of plain packaging on health warning effectiveness may depend on the design of the warnings and length of time since implementation.

Impact of Canada's menthol cigarette ban on quitting among menthol smokers: pooled analysis of pre-post evaluation from the ITC Project and the Ontario Menthol Ban Study and projections of impact in the USA.

INTRODUCTION: Between 2015 and 2018, Canada banned menthol cigarettes. This study pooled data from two pre-post cohort studies (the Ontario Menthol Ban Study, and the International Tobacco Control Policy Evaluation (ITC) Canada Survey, conducted in seven provinces) to derive more precise estimates of the impact of Canada's menthol ban on quitting and to apply these estimates to project the impact of a menthol ban in the USA. METHODS: Weighted multivariable logistic analyses compared post-ban quit success of menthol smokers with non-menthol smokers (for daily smokers and for all (daily + non-daily) smokers), controlling for sex, age, ethnicity, education, baseline smoking status, baseline cigarettes per day and study regions. Projections to the USA were created by multiplying the effect size of the Canadian menthol ban on quitting (percentage of increased quitting among menthol smokers) by the number of menthol smokers overall and among African Americans, from the 2019 National Survey on Drug Use and Health. RESULTS: After the menthol cigarette ban, menthol smokers were more likely than non-menthol smokers to have quit smoking among daily smokers (difference=8.0%; 95% CI: 2.4% to 13.7%,p=0.005) and all (daily+non-daily) smokers (difference=7.3%; 95% CI: 2.1% to 12.5%,p=0.006). The projected number of smokers who would quit after a US menthol ban would be 789 724 daily smokers (including 199 732 African Americans) and 1 337 988 daily+non-daily smokers (including 381 272 African Americans). CONCLUSIONS: This pooled analysis of Canada's menthol cigarette ban provides the foundation for estimating the impact of menthol bans in the USA and other countries. Projections suggest that a US menthol cigarette ban would have a substantial impact on increasing quitting.

The skin is no barrier to mixtures: Air pollutant mixtures and reported psoriasis or eczema in the Personalized Environment and Genes Study (PEGS).

BACKGROUND: Autoimmune (AI) diseases appear to be a product of genetic predisposition and environmental triggers. Disruption of the skin barrier causes exacerbation of psoriasis/eczema. Oxidative stress is a mechanistic pathway for pathogenesis of the disease and is also a primary mechanism for the detrimental effects of air pollution. METHODS: We evaluated the association between autoimmune skin diseases (psoriasis or eczema) and air pollutant mixtures in 9060 subjects from the Personalized Environment and Genes Study (PEGS) cohort. Pollutant exposure data on six criteria air pollutants are publicly available from the Center for Air, Climate, and Energy Solutions and the Atmospheric Composition Analysis Group. For increased spatial resolution, we included spatially cumulative exposure to volatile organic compounds from sites in the United States Environmental Protection Agency Toxic Release Inventory and the density of major roads within a 5 km radius of a participant's address from the United States Geological Survey. We applied logistic regression with quantile g-computation, adjusting for age, sex, diagnosis with an autoimmune disease in family or self, and smoking history to evaluate the relationship between self-reported diagnosis of an AI skin condition and air pollution mixtures. RESULTS: Only one air pollution variable, sulfate, was significant individually (OR = 1.06, p = 3.99E-2); however, the conditional odds ratio for the combined mixture components of PM2.5 (black carbon, sulfate, sea salt, and soil), CO, SO2, benzene, toluene, and ethylbenzene is 1.10 (p-value = 5.4E-3). SIGNIFICANCE: While the etiology of autoimmune skin disorders is not clear, this study provides evidence that air pollutants are associated with an increased prevalence of these disorders. The results provide further evidence of potential health impacts of air pollution exposures on life-altering diseases. SIGNIFICANCE AND IMPACT STATEMENT: The impact of air pollution on non-pulmonary and cardiovascular diseases is understudied and under-reported. We find that air pollution significantly increased the odds of psoriasis or eczema in our cohort and the magnitude is comparable to the risk associated with smoking exposure. Autoimmune diseases like psoriasis and eczema are likely impacted by air pollution, particularly complex mixtures and our study underscores the importance of quantifying air pollution-associated risks in autoimmune disease.

Impact of the European Union's menthol cigarette ban on smoking cessation outcomes: longitudinal findings from the 2020-2021 ITC Netherlands Surveys.

INTRODUCTION: To reduce the appeal of tobacco, the European Union (EU) banned menthol as a characterising flavour in cigarettes in May 2020. This pre/post-study evaluated the impact of the menthol ban on smoking cessation outcomes among a representative cohort of Dutch smokers. METHODS: Adult (18+ years) smokers were recruited at wave 1 (pre-ban) of the International Tobacco Control Netherlands Surveys (February-March 2020) and followed post-ban at wave 2 (September-November 2020) and wave 3 (June-July 2021) (N=1326 participated in all three waves). Weighted bivariate, logistic regression and generalised estimating equation model analyses were conducted. RESULTS: Usual menthol use decreased from pre-ban (7.8%) to post-ban (4.0% at wave 2 and 4.4% at wave 3) (p<0.001). Pre-ban menthol smokers had greater odds of making a post-ban quit attempt than non-menthol smokers (66.9% vs 49.6%, adjusted OR (aOR)=1.89, 95% CI: 1.13 to 3.16). Compared with pre-ban non-menthol smokers, a higher proportion of menthol smokers quit by wave 2 (17.8% vs 10.2%, p=0.025) and by wave 3 (26.1% vs 14.1%, p=0.002), although this was not significant after adjusting for other factors. Female pre-ban menthol smokers had greater odds of quitting by wave 3 than female non-menthol smokers (aOR=2.23, 95% CI: 1.10 to 4.51). Most pre-ban menthol smokers (n=99) switched to non-menthol cigarettes (40.0%) or reported that they continued to smoke menthol cigarettes (33.0%) at wave 3. CONCLUSIONS: The EU menthol ban was effective in reducing menthol use and in increasing quit attempts and quitting among pre-ban menthol smokers. Impact could be maximised by closing gaps that allow post-ban menthol cigarette use.

Determination of Half-lives of Circulating FSH and LH Glycoforms in Women During GnRH Receptor Blockade.

CONTEXT: Both FSH and LH circulate as 2 glycoforms, differing in number of glycans: low-N-glycosylated glycoforms, FSHtri and LHdi, and fully N-glycosylated glycoforms, FSHtetra and LHtri. OBJECTIVES: To determine the half-lives of endogenous circulating gonadotropin glycoforms in women during GnRH receptor blockade. DESIGN/PARTICIPANTS: Serum samples were collected in 8 healthy women before and up to 20 hours after administration of the NAL-GLU GnRH antagonist. Three women were in early follicular phase, 2 at mid-cycle phase, and 3 were postmenopausal. MAIN OUTCOME MEASURES: The half-life of each glycoform was estimated by monoexponential decay for FSH (n = 8) and LH (n = 5). Data were analyzed using paired t tests. RESULTS: Half-lives in the circulation of low-N-glycosylated glycoforms of both FSH and LH were shorter than those of the fully N-glycosylated glycoforms (mean; range, FSHtri 343; 116-686 minutes vs FSHtetra 757; 436-1038, minutes, P = 0.0003; LHdi 125, 84-198 minutes vs LHtri 164, 107-235 minutes, P = 0.004). The half-lives of low-and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH glycoforms, P = 0.0008. CONCLUSIONS: For both FSH and LH, low-N-glycosylated glycoforms disappeared from the circulation faster than the fully N-glycosylated. The half-lives of low and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH. The estimated values for half-life in the circulation of total FSH and total LH will depend on the relative amounts of the 2 glycoforms of each hormone and their individual disappearance rates in circulation.

Poly(ADP-Ribose) Polymerase Inhibition as a Promising Approach for Hepatocellular Carcinoma Therapy.

Primary liver cancer is the sixth most common cancer in men and seventh in women, with hepatocellular carcinoma (HCC) being the most common form (75-85% of primary liver cancer cases) and the most frequent etiology being viral infections (HBV and HCV). In 2020, mortality represented 92% of the incidence-830,180 deaths for 905,677 new cases. Few treatment options exist for advanced or terminal-stage HCC, which will receive systemic therapy or palliative care. Although radiotherapy is used in the treatment of many cancers, it is currently not the treatment of choice for HCC, except in the palliative setting. However, as radiosensitizing drugs, such as inhibitors of DNA repair enzymes, could potentiate the effects of RT in HCC by exploiting the modulation of DNA repair processes found in this tumour type, RT and such drugs could provide a treatment option for HCC. In this review, we provide an overview of PARP1 involvement in DNA damage repair pathway and discuss its potential implication in HCC. In addition, the use of PARP inhibitors and PARP decoys is described for the treatment of HCC and, in particular, in HBV-related HCC.