Identification of G-quadruplex structures in MALAT1 lncRNA that interact with nucleolin and nucleophosmin.

Nuclear-retained long non-coding RNAs (lncRNAs) including MALAT1 have emerged as critical regulators of many molecular processes including transcription, alternative splicing and chromatin organization. Here, we report the presence of three conserved and thermodynamically stable RNA G-quadruplexes (rG4s) located in the 3' region of MALAT1. Using rG4 domain-specific RNA pull-down followed by mass spectrometry and RNA immunoprecipitation, we demonstrated that the MALAT1 rG4 structures are specifically bound by two nucleolar proteins, Nucleolin (NCL) and Nucleophosmin (NPM). Using imaging, we found that the MALAT1 rG4s facilitate the localization of both NCL and NPM to nuclear speckles, and specific G-to-A mutations that disrupt the rG4 structures compromised the localization of both NCL and NPM in speckles. In vitro biophysical studies established that a truncated version of NCL (ΔNCL) binds tightly to all three rG4s. Overall, our study revealed new rG4s within MALAT1, established that they are specifically recognized by NCL and NPM, and showed that disrupting the rG4s abolished localization of these proteins to nuclear speckles.

Alternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA.

MALAT1, an abundant lncRNA specifically localized to nuclear speckles, regulates alternative-splicing (AS). The molecular basis of its role in AS remains poorly understood. Here, we report three conserved, thermodynamically stable, parallel RNA-G-quadruplexes (rG4s) present in the 3' region of MALAT1 which regulates this function. Using rG4 domain-specific RNA-pull-down followed by mass-spectrometry, RNA-immuno-precipitation, and imaging, we demonstrate the rG4 dependent localization of Nucleolin (NCL) and Nucleophosmin (NPM) to nuclear speckles. Specific G-to-A mutations that abolish rG4 structures, result in the localization loss of both the proteins from speckles. Functionally, disruption of rG4 in MALAT1 phenocopies NCL knockdown resulting in altered pre-mRNA splicing of endogenous genes. These results reveal a central role of rG4s within the 3' region of MALAT1 orchestrating AS.

Impact of leachate and landfill gas on the ecosystem and health: Research trends and the way forward towards sustainability.

Globally, a whopping increase in solid waste (SW) generation and the risks posed by climate change are major concerns. A wide spread practice for disposal of municipal solid waste (MSW) is landfill, which swells with population and urbanization. Waste, if treated properly, can be used to produce renewable energy. The recent global event COP 27 mainly stressed on production of renewable energy to achieve the Net Zero target. The MSW landfill is the most significant anthropogenic source of methane (CH4) emission. On one side, CH4 is a greenhouse gas (GHG), and on the other it is a main component of biogas. Wastewater that collects due to rainwater percolation in landfills creates landfill leachate. There is a need to understand global landfill management practices thoroughly for implementation of better practices and policies related to this threat. This study critically reviews recent publications on leachate and landfill gas. The review discusses leachate treatment and landfill gas emissions, focusing on the possible reduction technology of CH4 emission and its impact on the environment. Mixed leachate will benefit from the combinational therapy method because of its intricate combination. Implementation of circular material management, entrepreneurship ideas, blockchain, machine learning, LCA usage in waste management, and economic benefits from CH4 production have been emphasized. Bibliometric analysis of 908 articles from the last 37 years revealed that industrialized nations dominate this research domain, with the United States having the highest number of citations.

Measurement invariance of the Mental Health Continuum-Short Form across US military veteran and civilian adults.

OBJECTIVE: Recent research has suggested that mental health is not only the absence of mental illness but includes aspects of well-being. One common psychological assessment used to assess dimensions of well-being is the Mental Health Continuum-Short Form (MHC-SF). The MHC-SF is a 14-item measure that assesses emotional, psychological, and social well-being. The purpose of this study was to assess measurement invariance of the MHC-SF across US military veterans and civilians. METHOD: First, we examined the factor structure of the MHC-SF separately for veterans (n = 418) and civilians (n = 411). We then conducted multiple group confirmatory factor analysis (MG-CFA) to assess measurement invariance for the two groups. RESULTS: Findings suggested there were three latent factors representing emotional, social, and psychological well-being. Results from MG-CFA suggested that the MHC-SF is invariant across veterans and civilians. CONCLUSION: Researchers and practitioners can administer the MHC-SF with both groups.

Hope, proactive personality, coping styles, and satisfaction with life among veterans during COVID-19.

Veterans of the U.S. Armed Forces are an at-risk population given their increased mental health concerns resulting from their military service. However, there has been limited research conducted with this population during the novel coronavirus (COVID-19) pandemic. The purpose of this exploratory study was to examine aspects of positive psychological functioning with 132 U.S. veterans during COVID-19 using Lazarus and Folkman's (1984) transactional model of stress and coping. Specifically, we examined the personal resources of hope and proactive personality, two coping styles, and satisfaction with life. We performed correlation analyses to determine how these constructs related to each other. We also conducted a regression analysis to examine if the two dimensions of hope, proactive personality, adaptive coping, and maladaptive coping predicted veterans' satisfaction with life. Lastly, we utilized a mediation analysis to investigate whether two coping styles mediated the relationships among personal resources and satisfaction with life. Findings from the regression analysis suggested hope pathways and proactive personality were significant predictors of satisfaction with life. Results from the mediation analysis suggested that adaptive and maladaptive coping did not mediate the relationships among personal resources and satisfaction with life.

Cardiovascular disease risk profile and management practices in 45 low-income and middle-income countries: A cross-sectional study of nationally representative individual-level survey data.

BACKGROUND: Global cardiovascular disease (CVD) burden is high and rising, especially in low-income and middle-income countries (LMICs). Focussing on 45 LMICs, we aimed to determine (1) the adult population's median 10-year predicted CVD risk, including its variation within countries by socio-demographic characteristics, and (2) the prevalence of self-reported blood pressure (BP) medication use among those with and without an indication for such medication as per World Health Organization (WHO) guidelines. METHODS AND FINDINGS: We conducted a cross-sectional analysis of nationally representative household surveys from 45 LMICs carried out between 2005 and 2017, with 32 surveys being WHO Stepwise Approach to Surveillance (STEPS) surveys. Country-specific median 10-year CVD risk was calculated using the 2019 WHO CVD Risk Chart Working Group non-laboratory-based equations. BP medication indications were based on the WHO Package of Essential Noncommunicable Disease Interventions guidelines. Regression models examined associations between CVD risk, BP medication use, and socio-demographic characteristics. Our complete case analysis included 600,484 adults from 45 countries. Median 10-year CVD risk (interquartile range [IQR]) for males and females was 2.7% (2.3%-4.2%) and 1.6% (1.3%-2.1%), respectively, with estimates indicating the lowest risk in sub-Saharan Africa and highest in Europe and the Eastern Mediterranean. Higher educational attainment and current employment were associated with lower CVD risk in most countries. Of those indicated for BP medication, the median (IQR) percentage taking medication was 24.2% (15.4%-37.2%) for males and 41.6% (23.9%-53.8%) for females. Conversely, a median (IQR) 47.1% (36.1%-58.6%) of all people taking a BP medication were not indicated for such based on CVD risk status. There was no association between BP medication use and socio-demographic characteristics in most of the 45 study countries. Study limitations include variation in country survey methods, most notably the sample age range and year of data collection, insufficient data to use the laboratory-based CVD risk equations, and an inability to determine past history of a CVD diagnosis. CONCLUSIONS: This study found underuse of guideline-indicated BP medication in people with elevated CVD risk and overuse by people with lower CVD risk. Country-specific targeted policies are needed to help improve the identification and management of those at highest CVD risk.

Serum catalytic iron and progression of chronic kidney disease: findings from the ICKD study.

BACKGROUND: The non-transferrin bound catalytic iron moiety catalyses production of toxic reactive oxygen species and is associated with adverse outcomes. We hypothesized that serum catalytic iron (SCI) is associated with progression of chronic kidney disease (CKD). METHODS: Baseline samples of the Indian Chronic Kidney Disease participants with at least one follow up visit were tested for total iron, iron binding capacity, transferrin saturation, SCI, ferritin and hepcidin. SCI was measured using the bleomycin-detectable iron assay that detects biologically active iron. Association with the incidence of major kidney endpoints, (MAKE, a composite of kidney death, kidney failure or > 40% loss of eGFR) was examined using Cox proportional hazards model adjusted for sex and age. RESULTS: 2002 subjects (49.9 ± 11.6 years, 68.1% males, baseline eGFR 41.01 ml/min/1.73m2) were enrolled. After a median follow up of 12.6 (12.2, 16.7) months, the composite MAKE occurred in 280 (14%). After adjusting for age and sex, increase from 25th to 75th percentile in SCI, transferrin saturation, ferritin and hepcidin were associated with 78% (43-122%), 34% (10-62%), 57% (24-100%) and 74% (35-124%) increase in hazard of MAKE, respectively. SCI was associated with MAKE and kidney failure after adjustment for occupational exposure, hypertension, diabetes, tobacco, alcohol use, history of AKI, baseline eGFR, uACR, and allowing baseline hazard to vary by centre. CONCLUSIONS: SCI is strongly and independently associated with composite MAKE in patients with mild to moderate CKD. Confirmation in other studies will allow consideration of SCI as a risk marker and treatment target.

Radiationless Decay Processes of an Unnatural DNA Base: Pyrrole 2-Carbaldehyde.

Pyrrole-2-carbaldehyde (Pa) forms one of the unnatural nucleic acid bases, and as a base pair with 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds), it has been known to be stable in DNA. The Ds-Pa pair is stabilized in DNA via van der Waals' interaction and shape fitting. There are some studies on the origin of its stability and reactivity in the ground state. However, for a successful unnatural base pair, it needs to be stable not only in the ground state but also upon irradiation with UV-visible light. To understand the photoinduced reactivity, we investigate the excited-state properties of the Pa base and understand the energetically feasible photoprocesses that can occur upon excitation in the UV region. Two distinct pathways are obtained. One of the pathways involves an out-of-plane mode and has some similarities with the deactivation channels in the natural pyrimidine bases. On the other hand, the second pathway involves an excited-state proton transfer.

Genetics of colour variation in wild versus cultured queen loach, Botia dario (Hamilton, 1822).

The Queen loach (Botia dario), an ornamental fish species having export potential, belongs to family Cobitidae of order Cypriniformes. The dull colouration in captive condition as compared to nature is a drawback in ornamental fisheries. We report the first comparative transcriptomic analysis of Cultured (CBD) and Natural (NBD) B. dario using bioinformatics tools. Total 26 and 7 key genes for melanin and carotenoid colouration were found, respectively. KEGG pathway annotations of the genes were carried out, to annotate and describe their relevance for pigmentation. The qPCR validation of genes confirmed their expression pattern in the skin and muscle. Differential expression of, slc7a11, asip1, mc1r, dct, tyrp1a, tyr, bcdo2, csf1r, plin2, gsta2, star3 and stard5 in the skin and muscle tissues revealed the reasons for wild versus cultured colour variation. The molecular data was further supported by low yellowness and redness values of CBD skin and muscle in a colorimeter.

Dynamic changes in generalized anxiety and depression during counseling.

Comorbidity of generalized anxiety and depression is common in clinical populations. Understanding how change in generalized anxiety and depression are related during counseling may help improve treatment. College student data (N = 51,922) from university and college counseling centers across the United States were used to examine relationships between change in generalized anxiety and depression across 12 counseling sessions using bivariate dual change score models. Results suggested greater improvement in depression was related to greater improvement in generalized anxiety across sessions, but greater improvement in generalized anxiety was related to less improvement in depression across sessions. This same pattern of results generalized to individuals who attended counseling with concerns in anxiety only, depression only, and both anxiety and depression. Although there were general improvements in generalized anxiety and depression across counseling sessions, greater improvement in depression at earlier sessions appeared to be a leading indicator of greater improvement in generalized anxiety at later sessions. Implications and future directions are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Is India's public health care system prepared for cervical cancer screening?: Evaluating facility readiness from the fourth round of the District Level Household and Facility Survey (DLHS-4).

India's cervical cancer screening program was launched in 2016. We evaluated baseline facility readiness using nationally representative data from the 2012-13 District Level Household and Facility Survey on 4 tiers of the public health care system - 18,367 sub-health centres (SHCs), 8540 primary health centres (PHCs), 4810 community health centres and 1540 district/sub-divisional hospitals. To evaluate facility readiness we used the Improving Data for Decision Making in Global Cervical Cancer Programmes toolkit on six domains - potential staffing, infrastructure, equipment and supplies, infection prevention, medicines and laboratory testing, and data management. Composite scores were created by summing responses within domains, standardizing scores across domains at each facility level, and averaging across districts/states. Overall, readiness scores were low for cervical cancer screening. At SHCs, the lowest scores were observed in 'infrastructure' (0.55) and 'infection prevention' (0.44), while PHCs had low 'potential staffing' scores (0.50) due to limited manpower to diagnose and treat (cryotherapy) potential cases. Scores were higher for tiers conducting diagnostic work-up and treatment/referral. The highest scores were in 'potential staffing' except for PHCs, while the lowest scores were in 'infection & prevention' and 'medicines and laboratory'. Goa and Maharashtra were consistently among the top 5 ranking states for readiness. Substantial heterogeneity in facility readiness for cervical cancer screening spans states and tiers of India's public healthcare system. Infrastructure and staffing are large barriers to screening at PHCs, which are crucial for referral of high-risk patients. Our results suggest focus areas in cervical cancer screening at the district level for policy makers.

Restoration of miRNA-149 Expression by TmPyP4 Induced Unfolding of Quadruplex within Its Precursor.

Noncoding RNAs are functional RNA molecules that get transcribed from DNA but are not translated into proteins; yet, they can regulate gene expression at transcriptional and post-transcriptional levels. Secondary structures present within these RNAs play a major role in determining their nature of function. In the case of miRNAs, the precursor miRNA have a hairpin stem loop structure which is required for Dicer recognition and further maturation. Alternately, it might assume a G-quadruplex structure. The transition from hairpin to G-quadruplex depends upon the nucleotide sequence as well as the cellular microenvironment, and this might affect the miRNA maturation and other downstream activity. Formation of the G-quadruplex within precursor miRNA-149 has been shown to inhibit Dicer processing activity followed by suppression of miRNA-149 maturation in cancer cells. In this report, we show that suppression of cell proliferation by the upregulated miRNA-149 could be rescued by unfolding the G-quadruplex present in pre-miRNA-149 by TmPyP4 (Porphyrin) treatment. Using UV-visible spectroscopy, circular dichroism, and isothermal titration calorimetry, we observed that TmPyP4 binds strongly to G-quadruplex and unfolds it, which was further verified by NMR spectroscopy. In cellulo, qRT-PCR measurements of miRNA-149 in MCF-7 breast cancer cells showed concentration dependent enhancement of mature miRNA-149 upon treatment of TmPyP4. As a consequence of enhanced miRNA-149 activity, we also observe the reduction in miRNA-149 target protein ZBTB2 that eventually leads to reduced cell proliferation.

Establishing Baseline Cervical Cancer Screening Coverage - India, 2015-2016.

Cervical cancer is the second leading cause of new cancer cases and cancer-related deaths among women in India, with an estimated 96,922 new cases and 60,078 deaths each year.* Despite the availability of effective low-cost screening options in India, limited access to screening and treatment services, diagnosis at a later stage, and low investment in health care infrastructure all contribute to the high number of deaths (1). In 2016 the Ministry of Health and Family Welfare of India recommended cervical cancer screening using visual inspection with acetic acid every 5 years for women aged 30-65 years (per World Health Organization [WHO] guidelines) (2,3). To establish a baseline for cervical cancer screening coverage, survey data were analyzed to estimate the percentage of women aged 30-49 years who had ever been screened for cervical cancer (defined as ever having had a cervix examination). Cervical cancer screening was estimated using data from the Fourth National Family Health Survey† (NFHS-4), a nationally representative survey conducted at the district level during 2015-2016, which included 699,686 Indian women aged 15-49 years. Lifetime cervical cancer screening prevalence was low (29.8%) and varied by geographic region, ranging from 10.0% in the Northeast Region to 45.2% in the Western Region. Prevalence of screening was higher among women with higher levels of education and household wealth, those who had ever been married, and urban residents. This screening prevalence can be used as a baseline indicator for cervical cancer screening in India in accordance with the WHO Noncommunicable Diseases Global Monitoring Framework during state-based programmatic rollout and program evaluation (4).

Vibronic Coupling in the First Five Electronic States of Dicyanodiacetylene Radical Cation.

We examine vibronic coupling in the first five electronic states (X̃2Πg-Ã2Πu-B̃2Σg+-C̃2Σu+-D̃2Πg-E2Πu) of dicyanodiacetylene radical cation (C6N2•+) in this article. Prompted by the prediction of its existence in the astrophysical environment, the vibronic band structure of these electronic states of C6N2•+ has been probed in spectroscopic measurements in laboratory by various groups. Inspired by numerous experimental data, we undertook the task of investigating topographical details of electronic potential energy surfaces, their coupling mechanism and nuclear dynamics on them. The degenerate Π electronic states of this radical are prone to Renner-Teller instability, and in addition symmetry allowed Σ-Π and Π-Π vibronic coupling is expected to play crucial role in the detailed vibronic structure of each of the above electronic states. A vibronic coupling model is developed here and first-principles nuclear dynamics study is carried out employing quantum mechanical methods. The vibronic band structure thus calculated is compared with experimental results and the progressions are identified and assigned. The nonradiative internal conversion dynamics among electronic states is also examined and discussed in relation to the various coupling of electronic states.

Photophysics of phenol and pentafluorophenol: The role of nonadiabaticity in the optical transition to the lowest bright 1ππ* state.

We report multimode vibronic coupling of the energetically low-lying electronic states of phenol and pentafluorophenol in this article. First principles nuclear dynamics calculations are carried out to elucidate the optical absorption spectrum of both of the molecules. This is motivated by the recent experimental measurements [S. Karmakar et al., J. Chem. Phys. 142, 184303 (2015)] on these systems. Diabatic vibronic coupling models are developed with the aid of adiabatic electronic energies calculated ab initio by the equation of motion coupled cluster quantum chemistry method. A nuclear dynamics study on the constructed electronic states is carried out by both the time-independent and time-dependent quantum mechanical methods. It is found that the nature of low-energy πσ* transition changes, and in pentafluorophenol the energy of the first two 1πσ* states, is lowered by about half an eV (vertically, relative to those in phenol), and they become energetically close to the optically bright first excited 1ππ* (S1) state. This results in strong vibronic coupling and multiple multi-state conical intersections among the ππ* and πσ* electronic states of pentafluorophenol. The impact of associated nonadiabatic effects on the vibronic structure and dynamics of the 1ππ* state is examined at length. The structured vibronic band of phenol becomes structureless in pentafluorophenol. The theoretical results are found to be in good accord with the experimental finding at both high energy resolution and low energy resolution.

Impact evaluation of a community engagement intervention in improving childhood immunization coverage: a cluster randomized controlled trial in Assam, India.

BACKGROUND: To improve immunization coverage, most interventions that are part of the national immunization program in India address supply-side challenges. But, there is growing evidence that addressing demand-side factors can potentially contribute to improvement in childhood vaccination coverage in low- and middle-income countries. Participatory engagement of communities can address demand-side barriers while also mobilizing the community to advocate for better service delivery. The objective of this study is to evaluate the impact of a novel community engagement approach in improving immunization coverage. In our proposed intervention, we go a step beyond merely engaging the community and strive towards increasing 'ownership' by the communities. METHODS/DESIGN: We adopt a cluster randomized design with two groups to evaluate the intervention in Assam, a state in the northeast region of India. To recruit villages and participants at baseline, we used a two-stage stratified random sampling method. We stratified villages; our unit of randomization, based on census data and randomly selected villages from each of the four strata. At the second-stage, we selected random sub-sample of eligible households (having children in the age group of 6-23 months) from each selected village. The study uses a repeated cross sectional design where we track the same sampled villages but draw independent random samples of households at baseline and endline. Total number of villages required for the study is 180 with 15 eligible HHs from each village. Post-baseline survey, we adopt a stratified randomization strategy to achieve better balance in intervention and control groups, leveraging information from the extensive baseline survey. DISCUSSION: The proposed intervention can help identify barriers to vaccination at the local level and potentially lead to more sustainable solutions over the long term. Our sampling design, sample size calculation, and randomization strategy address internal validity of our evaluation design. We believe that it would allow us to causally relate any observed changes in immunization coverage to the intervention. TRIAL REGISTRATION: The trial has been registered on 7th February, 2017 under the Clinical Trials Registry- India (CTRI), hosted at the ICMR's National Institute of Medical Statistics, having registration number CTRI/2017/02/007792 . This is the original study protocol.

Empirical influence of the multicultural guidelines: A brief report.

OBJECTIVE: In 2002, the American Psychological Association (APA) Council of Representatives approved the "Guidelines for Multicultural Education, Training, Research, Practice and Organizational Change for Psychologists." The Guidelines have been downloaded 64,153 times from the APA website from 2007 to 2013, and have been cited nearly 900 times. This suggests that the Guidelines have influenced education, training, research, and practice in psychology. However, it is unclear how the Guidelines have influenced these domains. We conducted a comprehensive literature review to examine how the Guidelines have influenced the field. Articles were coded for several criteria, including whether the Guidelines were cited, the type of research that was conducted, study findings, limitations, and future directions of research. METHOD: The data for this study consisted of 895 empirical articles published since the 2003 publication of the Guidelines. A literature review using the keywords APA and multicultural guidelines were searched in PsycINFO and ERIC databases. Articles were then coded by the research team. RESULTS: Findings from the literature review suggested that although there were a total of 895 articles and books that cited the Guidelines, only 34 met our coding criteria. CONCLUSIONS: Our findings suggest that most of the articles that cited the Guidelines used the citation as a way to document that culture is important to consider. In some cases, other professions cited the Guidelines to argue that their discipline should also attend to culture. However, very few articles focused on framing an investigation around a specific guideline. (PsycINFO Database Record

Response surface modeling of bioremediation of acid black 52 dye using Aspergillus flavus.

Bioremediation is an efficient process to remove metals and dyes from solutions using different micro-organisms. In the present study, the efficiency of growing Aspergillus flavus (isolated from the effluent of an electroplating industry) to treat a synthetic solution of acid black 52 dye (a trivalent chromium complex dye) was investigated. Maximum removal of dye and chromium was observed to be 390 and 17.22 mg/L, respectively, at an initial dye concentration of 750 mg/L and at pH 4.5 in 50 hours in a batch bioreactor. The biomass concentration was reduced from 4.1 to 0.4 g/L with increasing dye concentration from 100 to 2,000 mg/L. The response surface modeling for color removal was performed using the range of initial dye concentration 200-400 mg/L, pH 4-6 and time 35-50 hours. The optimum conditions for maximum color removal (76.52%) were observed at initial dye concentration: 200 mg/L, pH: 4.75 and time: 50 hours. The deviation (-0.02%) showed a close agreement between the experimental and predicted values of color removal. The scanning electron microscopic and energy dispersive X-ray analyses indicated bioremediation of the dye.

Vibronic Coupling in the X̃2Πg-Ã2Πu Band System of Diacetylene Radical Cation.

Vibronic interactions in the two energetically lowest electronic states (X̃2Πg-Ã2Πu) of the diacetylene radical cation (C4H2•+) are theoretically examined here. The spectroscopy of these two electronic states of C4H2•+ has been a subject of considerable interest and measured in the laboratory by various groups. Inspired by numerous experimental data, we attempt here a detailed investigation of vibronic interactions within and between the doubly degenerate Π electronic states and their impact on the vibronic structure of each state. A vibronic coupling model is constructed in a diabatic electronic basis and with the aid of ab initio quantum chemistry calculations. The vibronic structures of the electronic states are calculated by time-independent and time-dependent quantum mechanical methods. The progression of vibrational modes in the vibronic band is identified, assigned, and compared with the literature data. The nonradiative internal conversion dynamics is also examined and discussed.

Nitric oxide donors for cervical ripening and induction of labour.

BACKGROUND: Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol. OBJECTIVES: To determine the effects of NO donors (isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nitroglycerin and sodium nitroprusside) for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (15 August 2016) and the reference lists of trial reports. SELECTION CRITERIA: Clinical trials comparing NO donors for cervical ripening or labour induction with other methods listed above it on a predefined list of methods of labour induction. Interventions include NO donors (isosorbide mononitrate, isosorbide dinitrate, nitroglycerin and sodium nitroprusside) compared with other methods listed above it on a predefined list of methods of labour induction. DATA COLLECTION AND ANALYSIS: This review is part of a series of reviews focusing on methods of induction of labour, based on a generic protocol. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. In this update, the quality of the evidence for the main comparison was assessed using the GRADE approach. MAIN RESULTS: We included 23 trials (including a total of 4777 women). Included studies compared NO donors with placebo, vaginal prostaglandin E2 (PGE2), intracervical PGE2, vaginal misoprostol and intracervical Foley catheter. The majority of the included studies were assessed as being at low risk of bias. Nitric oxide versus placebo There was no evidence of a difference for any of the primary outcomes analysed: vaginal delivery not achieved in 24 hours (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.83 to 1.15; one trial, 238 women; low-quality evidence), uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.09, 95% CI 0.01 to 1.62; two trials, 300 women; low-quality evidence), caesarean section (RR 0.99, 95% CI 0.88 to 1.11; nine trials, 2624 women; moderate-quality evidence) or serious neonatal morbidity/perinatal death (average RR 1.61, 95% CI 0.08 to 33.26; two trials, 1712 women; low-quality evidence). There were no instances of serious maternal morbidity or death (one study reported this outcome).There was a reduction in an unfavourable cervix at 12 to 24 hours in women treated with NO donors (average RR 0.78, 95% CI 0.67 to 0.90; four trials, 762 women), and this difference was observed in both subgroups of standard release and slow release formulation. Women who received NO donors were less likely to experience uterine hyperstimulation without FHR rate changes (RR 0.05, 95% CI 0.00 to 0.80; one trial, 200 women), and more likely to experience side effects, including nausea, headache and vomiting. Nitric oxide donors versus vaginal prostaglandins There was no evidence of any difference between groups for uterine hyperstimulation with FHR changes or caesarean section (RR 0.97, 95% CI 0.78 to 1.21; three trials, 571 women). Serious neonatal morbidity and serious maternal morbidity were not reported. There were fewer women in the NO donor group who did not achieve a vaginal delivery within 24 hours (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 primiparae women). Nitric oxide donors versus intracervical prostaglandins One study reported a reduction in the number of women who had not achieved a vaginal delivery within 24 hours with NO donors (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 women). This result should be interpreted with caution as the information was extracted from an abstract only and a full report of the study is awaited. No differences were observed between groups for uterine hyperstimulation with FHR changes (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women) or serious neonatal morbidity/perinatal death (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women). Fewer women in the NO donor group underwent a caesarean section in comparison to women who received intracervical prostaglandins (RR 0.63, 95% CI 0.44 to 0.90; two trials, 442 women). No study reported on the outcome serious maternal morbidity or death. Nitric oxide donors versus vaginal misoprostol There was a reduction in the rate of uterine hyperstimulation with FHR changes with NO donors (RR 0.07, 95% CI 0.01 to 0.37; three trials, 281 women). There were no differences in caesarean section rates (RR 1.00, 95% CI 0.82 to 1.21; 761 women; six trials) and no cases of serious neonatal morbidity/perinatal death were reported. One study found that women in the NO donor group were more likely to not deliver within 24 hours (RR 5.33, 95% CI 1.62 to 17.55; one trial, 150 women). Serious maternal morbidity or death was not reported.In terms of secondary outcomes, there was an increase in cervix unchanged/unfavourable with NO (RR 3.43, 95% CI 2.07 to 5.66; two trials, 151 women) and an increase in the need for oxytocin augmentation with NO induction (RR 2.67, 95% CI 1.31 to 5.45; 7 trials; 767 women), although there was evidence of significant heterogeneity which could not be fully explained. Uterine hyperstimulation without FHR was lower in the NO group, as was meconium-stained liquor, Apgar score less than seven at five minutes and analgesia requirements. Nitric oxide donors versus intracervical catheter There was no evidence on any difference between the effects of NO and the use of a Foley catheter for induction of labour for caesarean section (RR 1.00, 95% CI 0.39 to 2.59; one trial, 80 women). No other primary outcomes were reported. One study of 75 participants did not contribute any data to the review.For all comparisons, women who received NO donors were more likely to experience side effects such as headache, nausea or vomiting. AUTHORS' CONCLUSIONS: Available data suggests that NO donors can be a useful tool in the process of induction of labour causing the cervix to be more favourable in comparison to placebo. However, additional data are needed to assess the true impact of NO donors on all important labour process and delivery outcomes.