In most eukaryotes, the HISTONE 3 family comprises several variants distinguished by their amino acid sequence, localization, and correlation with transcriptional activity. Transgenerational inheritance of epigenetic information carried by histones is still unclear. In addition to covalent histone modifications, the mosaic distribution of H3 variants onto chromatin has been proposed to provide a new level of epigenetic information. To study the transmission of patterns of H3 variants through generations, we combined transcriptional profiling and live imaging of the 13 H3 variants encoded by the Arabidopsis plant genome. In comparison with somatic cells, only a restricted number of H3 variants are present in male and female gametes. Upon fertilization, H3 variants contributed by both gametes are actively removed from the zygote chromatin. The somatic H3 composition is restored in the embryo by de novo synthesis of H3 variants. A survey of Arabidopsis homologs of animal H3 chaperones suggests that removal of parental H3 from the zygote nucleus relies on a new mechanism. Our results suggest that reprogramming of parental genomes in the zygote limits the inheritance of epigenetic information carried by H3 variants across generations.

Background: Smokeless tobacco (ST) is consumed by more than 300 million people worldwide. The distribution, determinants and health risks of ST differ from that of smoking; hence, there is a need to highlight its distinct health impact. We present the latest estimates of the global burden of disease due to ST use. Methods: The ST-related disease burden was estimated for all countries reporting its use among adults. Using systematic searches, we first identified country-specific prevalence of ST use in men and women. We then revised our previously published disease risk estimates for oral, pharyngeal and oesophageal cancers and cardiovascular diseases by updating our systematic reviews and meta-analyses of observational studies. The updated countryspecific prevalence of ST and disease risk estimates, including data up to 2019, allowed us to revise the population attributable fraction (PAF) for ST for each country. Finally, we estimated the disease burden attributable to ST for each country as a proportion of the DALYs lost and deaths reported in the 2017 Global Burden of Disease study. Results: ST use in adults was reported in 127 countries; the highest rates of consumption were in South and Southeast Asia. The risk estimates for cancers were also highest in this region. In 2017, at least 2.5 million DALYs and 90,791 lives were lost across the globe due to oral, pharyngeal and oesophageal cancers that can be attributed to ST. Based on risk estimates obtained from the INTERHEART study, over 6 million DALYs and 258,006 lives were lost from ischaemic heart disease that can be attributed to ST. Three-quarters of the ST-related disease burden was among men. Geographically, > 85% of the ST-related burden was in South and Southeast Asia, India accounting for 70%, Pakistan for 7% and Bangladesh for 5% DALYs lost. Conclusions: ST is used across the globe and poses a major public health threat predominantly in South and Southeast Asia. While our disease risk estimates are based on a limited evidence of modest quality, the likely STrelated disease burden is substantial. In high-burden countries, ST use needs to be regulated through comprehensive implementation of the World Health Organization Framework Convention for Tobacco Control.

Background Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan.Methods We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1•5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete.

Background and aimsTuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. In general populations, behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost‐effectiveness of cytisine—a low‐cost plant‐derived nicotine substitute—for smoking cessation in TB patients compared with placebo, over and above brief behavioural support.DesignTwo‐arm, parallel, double‐blind, placebo‐controlled, multi‐centre (30 sites in Bangladesh and Pakistan), individually randomized trial.SettingTB treatment centres integrated into public health care systems in Bangladesh and Pakistan.ParticipantsNewly diagnosed (in the last 4 weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n = 2388).MeasurementsThe primary outcome measure is biochemically verified continuous abstinence from smoking at 6 months post‐randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events.CommentsThis is the first smoking cessation trial of cytisine in low‐ and middle‐income countries evaluating both cessation and TB outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke.