Tobacco Imagery in Movies and Web Series Streaming in India and Their Compliance With the Recent Anti-tobacco Rules for Over-the-Top (OTT) Platforms.

INTRODUCTION: Internet access, smartphones, and televisions have significantly boosted over-the-top (OTT) movies and web series viewing in India, especially among youths. Despite restrictions, OTT platforms continue to promote tobacco products. India has recently enforced the revised OTT Rules 2023 effective September 1, 2023, to counter tobacco promotion in OTT shows. This study explores compliance with the OTT Rules 2023 in popular movies and web series on select OTT platforms in India. METHODS: About 29 movies and 31 web series from seven popular OTT platforms as of September 26, 2023, were analyzed in this study. The incidence of tobacco imagery and compliance with the OTT Rules 2023 were assessed using a standardized format with the help of seven trained coders. Descriptive statistics were used to describe instances of tobacco imagery and violations of the provisions of Indian law. RESULTS: The average incidence of tobacco imagery per included show was 3.95. None of the movies and web series fully complied with the provisions of health spots and audio-visual warnings. Only 35.7% of the shows (movies: 57.1%, web series: 14.3%) fully complied with the anti-tobacco static message provisions. The foreign-origin movies had zero compliance with static messages, though they had fewer tobacco images. Half of the shows for children up to 12 years old had tobacco imagery but fully complied with the static warning message provisions. CONCLUSION: The portrayal of tobacco imagery in OTT shows is prevalent, and their poor compliance with the OTT Rules 2023 is a concern. Therefore, monitoring and stricter enforcement of the OTT Rules should be given priority to protect viewers from tobacco promotion in OTT shows.

Azadiradione up-regulates the expression of parvalbumin and BDNF via Ube3a.

Azadiradione is a small bioactive limonoid found in the seed of Azadirachta Indica, an Indian medicinal plant commonly known as Neem. Recently, it has been shown to ameliorate the disease pathology in fly and mouse model of Huntington's disease by restoring impaired proteostasis. Here we report that the azadiradione could be involved in modulating the synaptic function through increased expression of Ube3a, a dual function protein having ubiquitin ligase and co-activator functions and associated with Angelman syndrome and autism. Treatment of azadiradione to HT22 hippocampal cell line and in adult mice induced the expression of Ube3a as well as two important synaptic function and plasticity regulating proteins, parvalbumin and brain-derived neurotropic factor (BDNF). Interestingly, another synaptic plasticity modulating protein Arc (activity-regulated cytoskeletal associated protein) was down-regulated by azadiradione. Partial knockdown of Ube3a in HT22 cell abrogated azadiradione induced expression of parvalbumin and BDNF. Ube3a-maternal deficient mice also exhibited significantly decreased expression of parvalbumin and BDNF in their brain and treatment of azadiradione in these animals did not rescue the altered expression of either parvalbumin or BDNF. These results indicate that azadiradione-induced expression of parvalbumin and BDNF in the brain is mediated through Ube3a and suggest that azadiradione could be implicated in restoring synaptic dysfunction in many neuropsychiatric/neurodegenerative disorders.

Knockdown Experiment Reveals an Essential GTPase CgtA's Involvement in Growth, Viability, Motility, Morphology, and Persister Phenotypes in Vibrio cholerae.

CgtA is an essential bacterial GTPase consisting of a highly conserved N-terminal Spo0B-associated GTP-binding protein (Obg) domain, a central GTPase domain, and a variable C-terminal domain (CTD). This study reports global changes in the proteome and transcriptome of wild-type (Wt) versus full-length CgtA-depleted Vibrio cholerae in minimal media. Comparative transcriptome sequencing (RNA-Seq), followed by comparative proteomic analyses, revealed that the knockdown of cgtA significantly altered expressions of 311 proteins involved in diverse cellular activities, many of which are associated with the survival of V. cholerae. Various intracellular functional roles of CgtA in growth, viability, motility, morphology, and persister phenotypes in V. cholerae are revealed based on subsequent confirmatory experiments. Furthermore, a more sustained mRNA expression pattern of cgtA in a minimal medium than in a rich medium was also observed for Wt V. cholerae, where the highest level of mRNA expression of cgtA was observed during the logarithmic growth phase. Thereby, we propose that minimal medium-associated reduced growth rate coupled with cgtA depletion aggravates the intracellular stress in V. cholerae, interrupting vital cellular processes. The functional role of the CTD in V. cholerae is not fully understood. Hence, to specifically investigate the intracellular role of the 57-amino-acid-long CTD of CgtAVC, the CTD-only portion of CgtA was deleted. Subsequent proteomics studies revealed an altered expression of 240 proteins in the CgtA(ΔCTD) mutant, having major overlap with the full-length cgtA-deleted condition. Overall, our study reveals an alternative facet of the survival mechanism of V. cholerae during nutritional downshift as per the concomitant consequences of cgtA depletion. IMPORTANCE It is very important that we must find new drug target proteins from multidrug-resistant human-pathogenic organisms like V. cholerae. CgtA is among such potential candidates, and here, we are reporting about some newly identified cellular roles of it that are important for the survival of V. cholerae. Briefly, we knocked down the full-length cgtA gene, as well as did a partial deletion of this gene from the V. cholerae genome followed by RNA-Seq and proteomics studies. Results from our study revealed up- and downregulation of several known and unknown genes and proteins as the effect of the cgtA knockdown experiment. Also, we have presented some interesting observations that are linked with cgtA for growth, viability, motility, morphology, and persister phenotypes in V. cholerae. Our study enhances the importance of CgtA and paves the way for further exploration based on our provided data.

Performance of the Heaviness of Smoking Index in Indian Settings.

Background and objective The heaviness of smoking index (HSI) is a popular tool to assess nicotine dependence in clinical and community settings. Low cigarette consumption and concurrent use of other tobacco products raise concerns about its validity in Indian settings. This study explores the performance of HSI in Indian settings. Methods This study analyzed daily manufactured cigarette smoker data from the cross-sectional Global Adult Tobacco Surveys (GATS) from its first (GAST-1, 2009) and second waves (GATS-2, 2016), both of which were available in the public domain. The HSI scores were calculated based on the number of cigarettes smoked per day (CPD) and time to first smoke (TTFS) after waking up among the current daily cigarette users. This study examined the utility of the HSI scale in Indian settings by estimating the predictability of low dependence on quit attempts and quit intentions using the likelihood ratio parameter. Results About nine in 10 cigarette users in India consumed less than 10 cigarettes per day, yielding a low score on the HSI scale for most of the daily cigarette users. The majority of daily cigarette smokers scored ≤ 1 (low dependence) on the HSI scale both in GATS-1 and GATS-2, irrespective of their exclusive cigarette use status. The absolute value and the 95% confidence limit of positive likelihood ratios (falling below and above one) suggest that the predictability of low dependence on quit attempts and quit intention in the Indian setting is limited. Conclusions The utility of the HSI scale in assessing nicotine dependence among cigarette users in India is limited. This may be attributed to low average cigarette consumption, concurrent use of various tobacco products, and the sociocultural milieu of Indian smokers. This highlights the need for a new rapid nicotine dependence scale tailored to the specific patterns of tobacco use behavior prevalent in the Indian context.

Effect of a single amino acid substitution G98D in a ribosome-associated essential GTPase, CgtA, on the growth and morphology of Vibrio cholerae.

CgtA, a highly conserved 50S ribosome-associated essential GTPase, acts as a repressor of the stringent stress response under nutrient-rich growth conditions to suppress basal levels of the alarmone ppGpp in V. cholerae. To further explore the in vivo functionality of CgtA, we introduced an amino acid substitution, i.e., Gly98Asp, in a conserved glycine residue in the N-terminal domain. The constructed V. cholerae mutant was designated CgtA(G98D). Comparison of cell sizes of the CgtA(G98D)mutant with its isogenic wild-type (Wt) strain N16961 under different phases of growth by Transmission Electron Microscopy (TEM) and statistical analysis suggests that CgtA may control the cell size of V. cholerae. The cell length is significantly reduced, corresponding to the delayed growth in the mid-logarithmic phase. The differences in the cell length of CgtA(G98D) and Wt are indistinguishable in the late logarithmic phase. During the stationary phase, marked by higher OD600, a sub-population of CgtA(G98D) cells outnumbered the Wt cells lengthwise. CgtA(G98D) cells appeared slenderer than Wt cells with significantly reduced cell width. However, the centerline curvature is preserved in CgtA(G98D) cells. We propose that in addition to its multitude of intracellular roles, CgtA may influence the cell size of V. cholerae.

Deletion analyses reveal insights into the domain specific activities of an essential GTPase CgtA in Vibrio cholerae.

CgtA is an essential bacterial GTPase protein involved in multiple cellular activities. In the presence of 50S ribosome, its GTPase activity increases significantly. Through sequential deletions of CgtA protein of Vibrio cholerae (CgtAvc) we found that its N terminal Obg domain is essential for ribosome binding and augmenting the ribosome mediated GTPase activity. Strategic deletions of the three glycine rich loops of Obg domain revealed that loop 1 of Obg domain is involved in anchoring the protein into the 50S, whereas, loop 2 & loop 3 are involved in conveying the effect of interaction of the Obg domain with the 50S to the GTPase domain through an interdomain linker, followed by GTP hydrolysis. On the other hand, the non-conserved C-terminal domain (CTD) is not directly involved in ribosome binding but shows negative impact on GTPase activity.

Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit against isoproterenol-induced myocardial infarction in rats.

Increases in the incidence of cardiovascular disease (CVD) have aroused strong interest in identifying antioxidants from natural sources for use in preventive medicine. Citrus macroptera (C. macroptera), commonly known as "Satkara", is an important herbal and medicinal plant reputed for its antioxidant, nutritious and therapeutic uses. The aim of the present study was to investigate the cardio-protective effects of ethanol extracts of C. macroptera peel and pulp against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats (n=36) were pre-treated with peel and pulp extracts (500mg/kg) for 45days. They received a challenge with ISO (85mg/kg) on the 44th and 45th days. Our findings indicated that subcutaneous injection of ISO induced severe myocardial injuries associated with oxidative stress, as confirmed by elevated lipid peroxidation (LPO) and decreased cellular reduced glutathione (GSH) and anti-peroxidative enzymes, including glutathione peroxidase, glutathione reductase and glutathione-S-transferase, compared with levels observed in control animals. Pre-treatment with C. macroptera peel and pulp extracts prior to ISO administration however, significantly improved many of the investigated biochemical parameters, i.e., cardiac troponin I, cardiac marker enzymes, lipid profile and oxidative stress markers. The fruit peel extract showed stronger cardio-protective effects than the pulp extract. The biochemical findings were further confirmed by histopathological examinations. Overall, the increased endogenous antioxidant enzyme activity against heightened oxidative stress in the myocardium is strongly suggestive of the cardio-protective potential of C. macroptera.

Satkara (Citrus macroptera) Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats.

Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

Electronically Tunable Differential Integrator: Linear Voltage Controlled Quadrature Oscillator.

A new electronically tunable differential integrator (ETDI) and its extension to voltage controlled quadrature oscillator (VCQO) design with linear tuning law are proposed; the active building block is a composite current feedback amplifier with recent multiplication mode current conveyor (MMCC) element. Recently utilization of two different kinds of active devices to form a composite building block is being considered since it yields a superior functional element suitable for improved quality circuit design. The integrator time constant (τ) and the oscillation frequency (ω o ) are tunable by the control voltage (V) of the MMCC block. Analysis indicates negligible phase error (θ e ) for the integrator and low active ω o -sensitivity relative to the device parasitic capacitances. Satisfactory experimental verifications on electronic tunability of some wave shaping applications by the integrator and a double-integrator feedback loop (DIFL) based sinusoid oscillator with linear f o variation range of 60 KHz~1.8 MHz at low THD of 2.1% are verified by both simulation and hardware tests.

Tobacco use and quit behaviour assessment in the Global Adult Tobacco Survey (GATS): invalid responses and implications.

BACKGROUND: Tobacco use and quit attempts are two key indicators of the Global Adult Tobacco Survey (GATS) that assess quit attempts among current as well as former tobacco users. The relevant data have inherent policy implications for tobacco cessation programme evaluation. This study aimed to review the concepts of quit attempt assessment and quantifying invalid responses considering GATS-India data. MATERIALS AND METHODS: GATS assessment of tobacco use and quit attempts were examined in the current literature. Two categories of invalid responses were identified by stratified analysis of the duration of last quit attempt among current users and duration of abstinence among former users. Category A included absolute invalid responses when time- frame of assessment of current tobacco use and less than former tobacco use were violated. Category B included responses that violated the unit of measurement of time. RESULTS: Current daily use, current less than daily use and former use in GATS were imprecisely defined with overlapping of time-frame of assessment. Overall responses of 3,102 current smokers, 4,036 current smokeless users, 1,904 former smokers and 1,343 former smokeless users were analyzed to quantify invalid responses. Analysis indicated overall 21.2% (category A: 7.32%; category B: 17.7%) and 22.7% (category A: 8.05%; category B: 18.1%) invalid responses among current smokers and smokeless users respectively regarding their duration of last quit attempt. Similarly overall 6.62% (category A: 4.7%; category B: 2.3%) and 10.6% (category A: 8.6%; category B: 3.5%) invalid responses were identified among former smokers and smokeless users respectively regarding their duration of abstinence. CONCLUSIONS: High invalid responses for a single assessment are due to the imprecise definition of current use, former use and quit attempt; and failure to utilize opportunity of direct data entry interface use during the survey to validate responses instantly. Redefining tobacco use and quit attempts considering an appropriate timeframe would reduce invalid responses.

Hardcore smoking in three South-East asian countries: results from the global adult tobacco survey.

BACKGROUND: Hardcore smoking is represented by a subset of daily smokers with high nicotine dependence, inability to quit and unwillingness to quit. Estimating the related burden could help us in identifying a high risk population prone to tobacco induced diseases and improve cessation planning for them. This study assessed the prevalence and associated factors of hardcore smoking in three South-East Asian countries and discussed its implication for smoking cessation intervention in this region. MATERIALS AND METHODS: Global Adult Tobacco Survey (GATS) data of India, Bangladesh and Thailand were analyzed to quantify the hardcore smoking prevalence in the region. On the basis of review, an operational definition of hardcore smoking was adopted that includes (1) current daily smoker, (2) no quit attempt in the past 12 months of survey or last quit attempt of less than 24 hours duration, (3) no intention to quit in next 12 months or not interested in quitting, (4) time to first smoke within 30 minutes of waking up, and (5) knowledge of smoking hazards. Logistic regression analysis was carried out using hardcore smoking status as response variable and gender, type of residence, occupation, education, wealth index and age-group as possible predictors. RESULTS: There were 31.3 million hardcore smokers in the three Asian countries. The adult prevalence of hardcore smoking in these countries ranges between 3.1% in India to 6% in Thailand. These hardcore smokers constitute 18.3-29.7% of daily smokers. The logistic regression model indicated that age, gender, occupation and wealth index are the major predictors of hardcore smoking with varied influence across countries. CONCLUSIONS: Presence of a higher number of hardcore smoking populations in Asia is a major public health challenge for tobacco control and cancer prevention. There is need of intensive cessation interventions with due consideration of contextual predictors.

Extending application of the 'hardcore' definition to smokeless tobacco use: estimates from a nationally representative population in India and its implications.

BACKGROUND: The term 'hardcore' has been applied to use of smoking tobacco and generally referred to as the inability or unwillingness of regular smokers to quit. The component constructs of hardcore except nicotine dependence are product neutral. With the use of 'time to first chew' as a measure of nicotine dependence, hardcore definition can be extended to characterize smokeless tobacco users. Hardcore users respond less to tobacco cessation interventions, and are prone to tobacco induced diseases including cancer. Thus identifying hardcore users would help in estimate the burden of high risk population for tobacco induced diseases. Smokeless tobacco use is predominant and accounts for more than 50% of oral cancer in India. Hence, hardcore chewing information could be used for planning of tobacco and cancer control interventions. The objective of this study was to assess the prevalence and associated factors of hardcore smokeless tobacco use in India. MATERIALS AND METHODS: Global Adult Tobacco Survey (GATS)-India 2010 data were analyzed to quantify hardcore smokeless tobacco use in India with following five criteria: (1) current daily smokeless tobacco use; (2) no quit attempt in the past 12 months of survey or last quit attempt of less than 24 hours duration; (3) no intention to quit in next 12 months or not interested in quitting; (4) time to first use of smokeless tobacco product within 30 minutes of waking up; and (5) knowledge of smokeless tobacco hazards. RESULTS: The number of hardcore smokeless tobacco users among adult Indians is estimated to be 5% (39.5 million). This group comprises 23.2% of daily smokeless tobacco users. The population prevalence varied from 1.4-9.1% across different national regions of India. Logistic regression modeling indicated age, education and employment status to be the major predictors of hardcore smokeless tobacco use in India. CONCLUSIONS: The presence of a huge number (39.5 million) of hardcore smokeless tobacco users is a challenge to tobacco control and cancer prevention in India. There is an unmet need for a universal tobacco cessation programme and intensification of anti-tobacco education in communities.