Assessment of Plant Growth Promotion Potential of Endophytic Bacterium B. subtilis KU21 Isolated from Rosmarinus officinalis.

The current study aimed to evaluate the plant growth-promoting (PGP) potential of endophytic strain Bacillus subtilis KU21 isolated from the roots of Rosmarinus officinalis. The strain exhibited multiple traits of plant growth promotion viz., phosphate (P) solubilization, nitrogen fixation, indole-3-acetic acid (IAA), siderophore, hydrogen cyanide (HCN), lytic enzymes production, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. The isolate also exhibited antagonistic activity against phytopathogenic fungi, i.e., Fusarium oxysporum, Fusarium graminiarum, and Rhizoctonia solani. The P-solubilization activity of B. subtilis KU21 was further elucidated via detection of glucose dehydrogenase (gdh) gene involved in the production of gluconic acid which is responsible for P-solubilization. Further, B. subtilis KU21 was evaluated for in vivo growth promotion studies of tomato (test crop) under net house conditions. A remarkable increase in seed germination, plant growth parameters, nutrient acquisition, and soil quality parameters (NPK) was observed in B. subtilis KU21-treated plants over untreated control. Hence, the proposed module could be recommended for sustainable tomato production in the Northwest Himalayan region without compromising soil health and fertility.

Advances in xanthine biosensors and sensors: A review.

Xanthine is derived from hypoxanthine by xanthine oxidase (XOD), a flavoprotein containing molybdenum and non-haem iron, sulfur and from guanine by guanine deaminase enzyme. Xanthine is oxidized into uric acid by XOD. Xanthine is used as an indicator of fish freshness, based on the reactions in which ATP is degraded into xanthine and its quantity increases with time of fish death. Fresh fish meat is required in food industry for making high quality items. The determination of xanthine in biological fluids is also used in diagnosing and curing many diseases like renal failure, gout, xanthinuria, hyperuricemia. Various methods are available for detection of xanthine but most of them are complicated, time consuming less sensitive & specific and require expensive instrumental setup and trained person to operate. Enzyme based biosensors and non enzymic sensors overcome these disadvantages, as these are simple, rapid, specific, sensitive and easy to operate. Present review describes xanthine biosensors, which work optimally between pH 3.5-9.0, temperature 25 °C-65 °C, xanthine concentration ranging from 0.001-50 × 104 µM. These biosensors have also been used to measure xanthine concentration in beverages, urine and serum samples. Various modified electrodes have been discussed for the detection of xanthine using both enzymatic and non-enzymatic approaches in the present review.

An impedimetric immunosensor based on chitosan-Au nanoparticles-reduced graphene oxide nanosheet composite modified PG electrode for detection of brain natriuretic peptide.

An ultrasensitive impedimetric immunosensor was developed to detect brain natriuretic peptide (BNP) for early diagnosis of heart failure. To construct this immunosensor, anti-BNP antibodies were immobilized covalently onto nanocomposite of chitosan-Au nanoparticles and reduced graphene oxide nanosheets (CHIT-Au@rGONs) electrodeposited onto pencil graphite electrode. This approach impedes charge transfer resistance (Rct) value proportionally to the BNP captured by antigen-antibody interactions. The observed Rct values by this immunosensor, were correlated with linear concentrations of BNP in the range, 1 × 10-2 to 1 × 103 pg/mL, with a limit of detection of 12 pg/mL and limit of quantification of 36.3 pg/mL. The immunosensor detected BNP in spiked human sera. The analytic recovery of added BNP in human sera was 97.04%. The present method was fairly consistent with commercial approach. The working electrode was stored for 2 months in cold. BSA-IgG had no interference in the electrode activity showing its high specificity for BNP. This novel approach provided a new POC-diagnostics, as direct sample measurements are easier and more efficient by this immunosensor compared to existing immunosensors. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03704-x.

Association of cancer information seeking behavior with cigarette smoking and E-cigarette use among U.S. adults by education attainment level: A multi-year cross-sectional analysis from a nationally representative sample in 2017-2020.

Little is known about the association of cancer information seeking behavior with cigarette smoking and e-cigarette use. A multi-year cross-sectional analysis using a pooled data of the Health Information National Trends Survey 5, Cycles 1-4 (2017-2020) was conducted. To examine the association of cancer information seeking behavior with current cigarette smoking (currently smoke every day/some days among individuals who smoked 100+ cigarettes in lifetime) and e-cigarette use (currently use every day/some days among lifetime users) in nationally representative U.S. adults, we conducted weighted multiple logistic regression analysis, adjusting for sex, race/ethnicity, age, obese status, depressed mood, cancer diagnosis history, metropolitan status, and survey year. The regression models were stratified by education level (

An Amperometric Acetylcholine Biosensor Based on Co-Immobilization of Enzyme Nanoparticles onto Nanocomposite.

An electrochemical biosensor was fabricated using nanoparticles of acetylcholinesterase (AChE) and choline oxidase (ChO)/Pt nanoparticles (PtNPs)/porous graphene oxide nanosheet (GONS) composite. A pencil graphite electrode (PGE) was used for the electrodeposition of nanocomposite and the determination of acetylcholine (ACh), a neurotransmitter. Various techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectra and cyclic voltammetry (CV) were used for characterization. This biosensor (AChENPs-ChONPs/GONS/PtNPs/PGE) indicated a very short response time (3 s), a lower limit of detection (0.001 µM), good linearity (0.001-200 µM), longer storage stability (6 months) and better reproducibility. The percent analytical recoveries of added acetylcholine in serum (5.0 and 10 µM) were found to be 97.6 ± 0.7 and 96.5 ± 0.3 for the present biosensor. The coefficients of variation were obtained to be 8% and 3.25%, correspondingly. The biosensor was applied to measure the ACh amount in the serum of healthy individuals and patients with Alzheimer's disease. The number of interferents had no effect on the biosensor at their physiological concentrations.

Pfprex from Plasmodium falciparum can bypass oxidative stress-induced DNA lesions.

Apicomplexans such as the malaria parasite Plasmodium falciparum possess a unique organelle known as the apicoplast that has its own circular genome. The apicoplast genome is AT rich and is subjected to oxidative stress from the byproducts of the normal biochemical pathways that operate in the apicoplast. It is expected that oxidative stress will lead to the appearance of DNA lesions such as 2-hydroxydeoxyadenine, thymine glycol, and 8-oxodeoxyguanine in the apicoplast genome. The apicoplast genome is replicated by the DNA polymerase activity present in the Pfprex enzyme. We have named the polymerase module of Pfprex as PfpPol and the enzyme belongs to the A family of DNA polymerases. Similar to other members of this family, PfpPol also exhibits high fidelity of DNA synthesis. We show that this enzyme is also capable of carrying out translesion DNA synthesis past common DNA lesions that arise due to oxidative stress. The residues N505 and Y509 from the fingers sub-domain, which are unique to PfpPol, play an important role in the ability of PfpPol to bypass the three lesions. The observed lesion-bypass ability of the Pfprex enzyme will minimize the adverse effects of oxidative stress on the apicoplast genome of the malaria parasite. These findings also have implications regarding the evolution of the machinery responsible for replication of organellar genomes.

Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells.

Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effects in vitro as well as in vivo. TMA-induced oxidative stress causes DNA damage, and compromised cell membrane integrity leading to the release of LDH outside the cells which ultimately leads to cell death. Besides, TMA also exhibited pronounced increase in cell cycle arrest at G2/M phase in both HCT116 and HT29 cell lines. TMA was found to be genotoxic and cytotoxic as the TMA concentration increased from 0.15 mM. A decreased ATP intracellular content was observed after 24 h, 48 h, and 72 h treatment in a time and dose-dependent manner. For in vivo research, TMA (100 mM, i.p. and intra-rectal) once a week for 12 weeks caused significant changes in cellular morphology of colon and rectum epithelium as assessed by H & E staining. TMA also significantly increased the infiltration of inflammatory cells in the colon and rectal epithelium indicating the severity of inflammation. In addition, TMA caused extensive mucosal damage and distortion in the epithelium, decrease in length of small intestine compared to control mice. In conclusion, these results highlight the detrimental effects of TMA in the colon and rectal epithelium.

Promotion of Early Childhood Development Using mHealth: Learnings From an Implementation Experience in Haryana.

Pregnancy and the early years of life (0-3 years) are of crucial importance for a child's survival, health, growth and development. Improving care for young children is now considered fundamental to achieving the Sustainable Development Goals by 2030. With support from WHO and Intervida (an international non-governmental organization), implementation on care for early childhood development was carried out by Survival for Women and Children Foundation in 100 villages in Haryana, India. In addition to the implementation of evidence-based interventions, mHealth (phone message (SMS) and phone call) was used as a complementary strategy. The intention was to promote self-care, increase coverage, and improve inter-sectoral collaboration. One message per day was developed (915 messages) and 1564630 SMS were sent to all beneficiaries and providers to facilitate interaction. Based on learnings, the consolidation of this approach into 46 core themes helped to refine interactions. Lot Quality Assurance Sampling was used for evaluation. SMS was received, read and practiced by the caregivers and the care providers in the intervention block, being substantially higher than in the control blocks. There was a remarkable improvement in under-nutrition and wasting; however, the reduction in stunting was modest in the intervention area as compared with two control blocks. This is attributed to implementation of all strategies in the project including the complementary approach of use of mHealth. The application of SMS and phone communication continues to have relevance, since people most in need are poor and require integrated package of services maximally during this crucial period for improving equity and coverage.

Recent advancements in urea biosensors for biomedical applications.

The quick progress in health care technology as a recurrent measurement of biochemical factors such as blood components leads to advance development and growth in biosensor technology necessary for effectual patient concern. The review wok of authors present a concise information and brief discussion on the development made in the progress of potentiometric, field effect transistor, graphene, electrochemical, optical, polymeric, nanoparticles and nanocomposites based urea biosensors in the past two decades. The work of authors is also centred on different procedures/methods for detection of urea by using amperometric, potentiometric, conductometric and optical processes, where graphene, polymer etc. are utilised as an immobilised material for the fabrication of biosensors. Further, a comparative revision has been accomplished on various procedures of urea analysis using different materials-based biosensors, and it discloses that electrochemical and potentiometric biosensor is the most promise one among all, in terms of rapid response time, extensive shelf life and resourceful design.

Emerging role of trimethylamine-N-oxide (TMAO) in colorectal cancer.

Among gut microbiota-derived metabolites, trimethylamine-N-oxide (TMAO) is receiving increased attention due to its possible role in the carcinogenesis of colorectal cancer (CRC). In spite of numerous reports implicating TMAO with CRC, there is a lack of empirical mechanistic evidences to concretize the involvement of TMAO in the carcinogenesis of CRC. Possible mechanisms such as inflammation, oxidative stress, DNA damage, and protein misfolding by TMAO have been discussed in this review in the light of the latest advancements in the field. This review is an attempt to discuss the probable correlation between TMAO and CRC but this linkage can be concretized only once we get sufficient empirical evidences from the mechanistic studies. We believe, this review will augment the understanding of linking TMAO with CRC and will motivate researchers to move towards mechanistic study for reinforcing the idea of implicating TMAO with CRC causation. KEY POINTS: • TMAO is a gut bacterial metabolite which has been implicated in CRC in recent years. • The valid mechanistic approach of CRC causation by TMAO is unknown. • The article summarizes the possible mechanisms which need to be explored for validation.

Bioprospecting beneficial endophytic bacterial communities associated with Rosmarinus officinalis for sustaining plant health and productivity.

The present study aimed to isolate and identify root endophytic bacteria with multifunctional plant growth promoting (PGP) traits from medicinal plant Rosmarinus officinalis grown in the North-Western Himalayas. A total of 42 strains were isolated, exhibiting variable degrees of PGP traits, including phosphate solubilization (10-375 µg/mL), indole-3-acetic acid (6-66 µg/mL), siderophore (32.37%-301.48% SU) production and antifungal activity in terms of percent growth inhibition (% GI) against Fusarium oxysporum (44.44%-77.77% GI), Fusarium graminearum (48.88%-71.42% GI) and Rhizoctonia solani (44.44%-77.7% GI). The 16S rDNA sequencing results showed lineage of these strains to 15 genera viz., Aneurinibacillus, Bacillus, Beijerinckia, Cedecea, Ensifer, Enterobacter, Kosakonia, Lactobacillus, Lysobacter, Oxynema, Pseudomonas, Pantoea, Paenibacillus, Pseudoxanthomonas and Serratia. Out of 42 strains, 11 potential strains were selected for in vivo growth studies of R. officinalis. The results showed that the inoculation of Bacillus subtilis KU21, Pseudomonas aeruginosa SI12, and Cedecea lapagei KU14 significantly increased the physical growth parameters of plant over uninoculated control viz., number of lateral of branches (43.95%-46.39%), stem height (29.04%-38.57%), root length (32.31%-37.14%), shoot (34.76%-40.91%) and root biomass (62.89%-70.70%). Physiological characteristics such as total chlorophyll (30.41%-30.96%), phenol (14.43%-24.55%) and carotenoids (34.26%-39.87%) content, also showed a relative increase as compared to uninoculated control; furthermore, the macronutrients (NPK) contents of the plant as well as soil also showed an increase. The developed module may be recommended for sustainable production of R. officinalis in the North-Western Himalayan region without hampering the soil health and fertility.

Gut microbiota-derived metabolites in CRC progression and causation.

BACKGROUND: Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may result into the carcinogenesis of colorectal cancer. Recent advancement also highlights the involvement of bacteria and their secreted metabolites in the cancer causation. Gut microbial metabolites are functional output of the host-microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities. PURPOSE: In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently cancer development. CONCLUSION: Recent studies suggest that gut microbiota-derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy.

Comparative accuracy of 1,3 beta-D glucan and galactomannan for diagnosis of invasive fungal infections in pediatric patients: a systematic review with meta-analysis.

Invasive fungal infections (IFI) cause considerable morbidity and mortality in pediatric patients. Serum biomarkers such as 1,3-beta-D glucan (BDG) and galactomannan (GM) have been evaluated for the IFI diagnosis. However, most evidence regarding their utility is derived from studies in adult oncology patients. This systematic review aimed to compare the diagnostic accuracy of BDG and GM individually or in combination for diagnosing IFI in pediatric patients. PubMed, CINAHL, Embase, and Cochrane Library were searched until March 2019 for diagnostic studies evaluating both serum GM and BDG for diagnosing pediatric IFI. The pooled diagnostic odds ratio (DOR), specificity and sensitivity were computed. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were used for summarizing overall assay performance. Six studies were included in the meta-analysis. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the GM assay for proven or probable IFI were 0.74, 0.76, 13.25, and 0.845. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the BDG assay were 0.70, 0.69, 4.3, and 0.722. The combined predictive ability of both tests was reported in two studies (sensitivity: 0.67, specificity: 0.877). Four studies were performed in hematology-oncology patients, while two were retrospective studies from pediatric intensive care units (ICUs). In the subgroup of hematology-oncology patients, DOR of BDG remained similar at 4.25 but increased to 40.28 for GM. We conclude that GM and BDG have a modest performance for identifying IFI in pediatric patients. GM has a better accuracy over BDG. Combining both improves the specificity at the cost of sensitivity.

Omics technologies for improved diagnosis and treatment of colorectal cancer: Technical advancement and major perspectives.

Colorectal cancer (CRC) ranks third among the most commonly occurring cancers worldwide, and it causes half a million deaths annually. Alongside mechanistic study for CRC detection and treatment by conventional techniques, new technologies have been developed to study CRC. These technologies include genomics, transcriptomics, proteomics, and metabolomics which elucidate DNA markers, RNA transcripts, protein and, metabolites produced inside the colon and rectum part of the gut. All these approaches form the omics arena, which presents a remarkable opportunity for the discovery of novel prognostic, diagnostic and therapeutic biomarkers and also delineate the underlying mechanism of CRC causation, which may further help in devising treatment strategies. This review also mentions the latest developments in metagenomics and culturomics as emerging evidence suggests that metagenomics of gut microbiota has profound implications in the causation, prognosis, and treatment of CRC. A majority of bacteria cannot be studied as they remain unculturable, so culturomics has also been strengthened to develop culture conditions suitable for the growth of unculturable bacteria and identify unknown bacteria. The overall purpose of this review is to succinctly evaluate the application of omics technologies in colorectal cancer research for improving the diagnosis and treatment strategies.

Electrochemical sensing of cytochrome c using Graphene Oxide nanoparticles as platform.

An improved cytochrome c (Cyt c) biosensor based on immobilization of cytochrome c oxidase (COx) on the surface of graphene oxide nanoparticles (GONPs) electrodeposited onto pencil graphite (PG) electrode. Characterization of graphene oxide nanoparticle was done by Transmission electron microscopy (TEM), Fourier transform infra-red spectroscopy (FTIR) and X-ray diffraction study (XRD). The working electrode (COx/GONPs/PG) was characterized at its different stages of fabrication by scanning electron microscopy (SEM) and FTIR. Fabrication of Cyt c biosensor was done by connecting COx/GONPs/PG as working electrode, Ag/AgCl as reference electrode and Pt as auxiliary electrode to potentiostat. The mechanism of detection of present biosensor was based on oxidation of Cyt c (reduced) to Cyt c (oxidized) by COx resulting in flow of electrons through GONPs to the PG electrode, hence current generated is proportional to the concentration of Cyt c. Present biosensor exhibited optimum potential at 0.49 V with optimum pH 7.5 and optimum temperature 35°C. Biosensor showed linearity within 40-180 ng/ml having 40 ng/ml limit of detection. The precision i.e. within and between-batch coefficients of variation (CVs) were found <0.04% and <0.21% respectively. The enzyme electrode lost 50% of its initial activity when operated for more than 6 months on weekly basis. It was applied for detection of Cyt c level in in apparently healthy and diseased human sera. The present biosensing method was co-related with standard colorimetric method and co-relation coefficient was found 0.99.

Strategies and perspectives to develop SARS-CoV-2 detection methods and diagnostics.

To develop diagnostics and detection methods, current research is focussed on targeting the detection of coronavirus based on its RNA. Besides the RNA target, research reports are coming to develop diagnostics by targeting structure and other parts of coronavirus. PCR based detection system is widely used and various improvements in the PCR based detection system can be seen in the recent research reports. This review will discuss multiple detection methods for coronavirus for developing appropriate, reliable, and fast alternative techniques. Considering the current scenario of COVID-19 diagnostics around the world and an urgent need for the development of reliable and cheap diagnostic, various techniques based on CRISPR technology, antibody, MIP, LAMP, microarray, etc. should be discussed and tried.

The proofreading activity of Pfprex from Plasmodium falciparum can prevent mutagenesis of the apicoplast genome by oxidized nucleotides.

The DNA polymerase module of the Pfprex enzyme (PfpPol) is responsible for duplication of the genome of the apicoplast organelle in the malaria parasite. We show that PfpPol can misincorporate oxidized nucleotides such as 8oxodGTP opposite dA. This event gives rise to transversion mutations that are known to lead to adverse physiological outcomes. The apicoplast genome is particularly vulnerable to the harmful effects of 8oxodGTP due to very high AT content (~ 87%). We show that the proofreading activity of PfpPol has the unique ability to remove the oxidized nucleotide from the primer terminus. Due to this property, the proofreading domain of PfpPol is able to prevent mutagenesis of the AT-rich apicoplast genome and neutralize the deleterious genotoxic effects of ROS generated in the apicoplast due to normal metabolic processes. The proofreading activity of the Pfprex enzyme may, therefore, represent an attractive target for therapeutic intervention. Also, a survey of DNA repair pathways shows that the observed property of Pfprex constitutes a novel form of dynamic error correction wherein the repair of promutagenic damaged nucleotides is concomitant with DNA replication.

Novel electrochemical sensing of galactose using GalOxNPs/CHIT modified pencil graphite electrode.

For the construction of galactose biosensor, chitosan was electropolymerised onto the pencil graphite electrode. This chitosan modified pencil graphite electrode acts as good matrix for immobilization of enzyme nanoparticles of galactose oxidase. Development of this nanocomposite was further confirmed by Fourier transform infrared spectroscopy and scanning electron microscopy. The presence of chitosan makes the present galactose biosensor more efficient, reproducible and stable. The sensitivity was reported 7 × 10-3 mA/mM/cm2 with linear range from 0.05 to 25 mM and better detection limit of 0.05 mM. When the solution of galactose was spiked with 0.5 mM and 1 mM, the analytical recoveries were found 98.6% and 97.6%. A better storage stability was achieved (90days) when compared to earlier reported biosensors.

Cholesterol biosensors: A review.

Cholesterol is the most important sterol synthesized by most of the human cells majorly in the liver. It is a necessary constituent of cell membranes, it acts as a precursor for the synthesis of steroid hormones, vitamin D, and bile acids. Cholesterol is transported in plasma primarily in the form of low-density lipoproteins (LDL), the principal route for its removal from tissues to the liver is in high-density lipoproteins (HDL), followed by excretion in the bile. Cholesterol level is less than 200 mg/dL in healthy persons. 200 and 239 mg/dL is considered borderline high and 240 mg/dL and above is considered a biomarker for cardiovascular diseases, heart attack, strokes, peripheral arterial disease, type 2 diabetes and high blood pressure. Several methods are available for detection of cholesterol, among them, most are burdensome, time-consuming, require sample pre-treatment, high-cost instrumental set-up, and experienced personnel to operate. Biosensing approach overcomes these disadvantages, as these are highly specific, fast, easy, cost-effective, and highly sensitive. The review describes the various cholesterol biosensors. Cholesterol biosensors work ideally within 1 to 300 s, in pH range, 7.0-8.6, temperature 25-37 °C and cholesterol concentration range, 0.000025-700 mM, the detection limits being in the range, 0.000002-4 mM, with working potential -0.05 to 0.65 V. These biosensors measured cholesterol level in fruit juices, beverages, sera and urine samples and reused up to 200 times over a period of 15 to 50 days, while stored dry at 4 °C (Table 1). Future perspective for further improvement and commercialization of cholesterol biosensors are discussed.

Improving quality of care during childbirth in primary health centres: a stepped-wedge cluster-randomised trial in India.

BACKGROUND: Low/middle-income countries need a large-scale improvement in the quality of care (QoC) around the time of childbirth in order to reduce high maternal, fetal and neonatal mortality. However, there is a paucity of scalable models. METHODS: We conducted a stepped-wedge cluster-randomised trial in 15 primary health centres (PHC) of the state of Haryana in India to test the effectiveness of a multipronged quality management strategy comprising capacity building of providers, periodic assessments of the PHCs to identify quality gaps and undertaking improvement activities for closure of the gaps. The 21-month duration of the study was divided into seven periods (steps) of 3 months each. Starting from the second period, a set of randomly selected three PHCs (cluster) crossed over to the intervention arm for rest of the period of the study. The primary outcomes included the number of women approaching the PHCs for childbirth and 12 directly observed essential practices related to the childbirth. Outcomes were adjusted with random effect for cluster (PHC) and fixed effect for 'months of intervention'. RESULTS: The intervention strategy led to increase in the number of women approaching PHCs for childbirth (26 vs 21 women per PHC-month, adjusted incidence rate ratio: 1.22; 95% CI 1.17 to 1.28). Of the 12 practices, 6 improved modestly, 2 remained near universal during both intervention and control periods, 3 did not change and 1 worsened. There was no evidence of change in mortality with a majority of deaths occurring either during referral transport or at the referral facilities. CONCLUSION: A multipronged quality management strategy enhanced utilisation of services and modestly improved key practices around the time of childbirth in PHCs in India. TRIAL REGISTRATION NUMBER: CTRI/2016/05/006963.