Targeted Nanocarriers for Systemic Delivery of IRAK4 Inhibitors to Inflamed Tissues.

Persistent and uncontrolled inflammation is the root cause of various debilitating diseases. Given that interleukin-1 receptor-associated kinase 4 (IRAK4) is a critical modulator of inflammation, inhibition of its activity with selective drug molecules (IRAK4 inhibitors) represents a promising therapeutic strategy for inflammatory disorders. To exploit the full potential of this treatment approach, drug carriers for efficient delivery of IRAK4 inhibitors to inflamed tissues are essential. Herein, the first nanoparticle-based platform for the targeted systemic delivery of a clinically tested IRAK4 inhibitor, PF-06650833, with limited aqueous solubility (57 µg mL-1 ) is presented. The developed nanocarriers increase the intrinsic aqueous dispersibility of this IRAK4 inhibitor by 40 times. A targeting peptide on the surface of nanocarriers significantly enhances their accumulation after intravenous injection in inflamed tissues of mice with induced paw edema and ulcerative colitis when compared to non-targeted counterparts. The delivered IRAK4 inhibitor markedly abates inflammation and dramatically suppresses paw edema, mitigates colitis symptoms, and reduces proinflammatory cytokine levels in the affected tissues. Importantly, repeated injections of IRAK4 inhibitor-loaded nanocarriers have no acute toxic effect on major organs of mice. Therefore, the developed nanocarriers have the potential to significantly improve the therapeutic efficacy of IRAK4 inhibitors for different inflammatory diseases.

Targeted nanoparticles for imaging and therapy of endometriosis†.

In this brief review, we discuss our efforts to validate nanoplatforms for imaging and treatment of endometriosis. We specifically highlight our use of nonhuman primates and primate tissues in this effort. Endometriosis is a painful disorder of women and nonhuman primates where endometrium-like tissue exists outside of the uterus. There are no reliable, specific, and noninvasive diagnostic tests for endometriosis. Laparoscopic imaging remains the gold standard for identifying small endometriotic lesions in both women and monkeys. Visualizing and surgically removing microscopic lesions remains a clinical challenge. To address this challenge, we have created nanoparticle reagents that, when administered intravenously, enter endometriotic lesions both passively and by targeting endometriotic cells. The particles can carry payloads, including near-infrared fluorescent dyes and magnetic nanoparticles. These agents can be used for imaging and thermal ablation of diseased tissues. We evaluated this approach on macaque endometriotic cells, human and macaque endometrium engrafted into immunodeficient mice, in endometrium subcutaneously autografted in macaques, and in rhesus monkeys with spontaneous endometriosis. Employing these models, we report that nanoplatform-based reagents can improve imaging and provide thermal ablation of endometriotic tissues.

The Rise of Structurally Anisotropic Plasmonic Janus Gold Nanostars.

Nanostructures intrinsically possessing two different structural or functional features, often called Janus nanoparticles, are emerging as a potential material for sensing, catalysis, and biomedical applications. Herein, we report the synthesis of plasmonic gold Janus nanostars (NSs) possessing a smooth concave pentagonal morphology with sharp tips and edges on one side and, contrastingly, a crumbled morphology on the other. The methodology reported herein for their synthesis - a single-step growth reaction - is different from any other Janus nanoparticle preparation involving either template-assisted growth or a masking technique. Interestingly, the coexistence of lower- and higher-index facets was found in these Janus NSs. The general paradigm for synthesizing gold Janus NSs was investigated by understanding the kinetic control mechanism with the combinatorial effect of all the reagents responsible for the structure. The optical properties of the Janus NSs were realized by corelating their extinction spectra with the simulated data. The size-dependent surface-enhanced Raman scattering (SERS) activity of these Janus NSs was studied with 1,4-BDT as the model analyte. Finite-difference time-domain simulations for differently sized particles revealed the distribution of electromagnetic hot-spots over the particles resulting in enhancement of the SERS signal in a size-dependent manner.

Recent advancement in functional properties and toxicity assessment of plant-derived bioactive peptides using bioinformatic approaches.

Nowadays, biopeptides have gained considerable interest by the food industries, given their potent biological effect on health. BPs, when released from the sequence of their precursors by proteolytic enzymes, improved the various physiological functions of the body. Diabetic and hypertension are the two most common life-threatening diseases linked to dietary patterns. Angiotensin-converting enzyme (ACE) (hypertension-responsible glycoprotein) and dipeptidyl peptidase IV (DPP-IV) (proline-specific dimeric aminopeptidase) have been widely used as molecular target sites of action of bioactive compounds possessing antihypertensive and antidiabetic effects. Although, BPs possess considerable biological properties (antioxidant, antimicrobial, antiviral, immunomodulating, antiproliferative, antidiabetic, and antihypertensive effects), most of them possess inherent lacunae such as toxicity, allergenicity, bitterness, and lack of detailed mechanistic investigation, limiting their commercial application. The present review provides an overview on various sources of bioactive peptides, conventional and modern methods of extraction, and challenges that need to be addressed before its commercial application. In addition, bioinformatics' role in exploring the functional properties of biopeptides (ACE and DPP-IV inhibitory effects) toxicity, the target site of action with special reference to plant-based peptides, and recent burgeoning proficiencies in biopeptide research have been discussed.

Superior Peroxidase-Like Activity of Gold Nanorattles in Ultrasensitive H2 O2 Sensing and Antioxidant Screening.

Nanozymes are artificial enzyme systems which are easy to produce, highly stable and cost-effective in comparison to natural enzymes. Herein, we evaluated the peroxidase-like activity of gold nanorattles (Au NRTs) having a solid gold octahedron core and thin, porous cubic gold shell. We also prepared solid gold nanocubes and nanospheres of similar sizes and surface charge as that of Au NRTs and compared their activity with standard horse radish peroxidase (HRP). All the prepared nanostructures followed Michaelis-Menten kinetics as observed from their substrate concentration vs. initial reaction velocity plot using 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate. The kinetic parameters and the catalytic efficiency for the peroxidase-like activity of the nanostructures and HRP were calculated, and it was observed that Au NRTs possess the best nanozymatic activity with lowest KM and highest catalytic efficiency (kcat /KM ). The better activity of Au NRTs compared with other nanostructures and HRP could be attributed to the hollow porous structure with a solid core where different surfaces are available for reaction. Au NRTs, being the best amongst the tested nanozymes were further used for the sensing of hydrogen peroxide (H2 O2 ) and were found to sense H2 O2 down to 0.5 µM. Further, two naturally occurring antioxidants, tannic acid and ascorbic acid showed inhibitory effect on the peroxidase-like activity of Au NRTs in a concentration dependent manner which can be further used for screening of antioxidants or for determining the antioxidant potential.

Poly(aspartic acid)-Based Polymeric Nanoparticle for Local and Systemic mRNA Delivery.

Recently, therapeutics based on mRNA (mRNA) have attracted significant interest for vaccines, cancer immunotherapy, and gene editing. However, the lack of biocompatible vehicles capable of delivering mRNA to the target tissue and efficiently expressing the encoded proteins impedes the development of mRNA-based therapies for a variety of diseases. Herein, we report mRNA-loaded polymeric nanoparticles based on diethylenetriamine-substituted poly(aspartic acid) that induce protein expression in the lungs and muscles following intravenous and intramuscular injections, respectively. Animal studies revealed that the amount of polyethylene glycol (PEG) on the nanoparticle surface affects the translation of the delivered mRNA into the encoded protein in the target tissue. After systemic administration, only mRNA-loaded nanoparticles modified with PEG at a molar ratio of 1:1 (PEG/polymer) induce protein expression in the lungs. In contrast, protein expression was detected only following intramuscular injection of mRNA-loaded nanoparticles with a PEG/polymer ratio of 10:1. These findings suggest that the PEG density on the surface of poly(aspartic acid)-based nanoparticles should be optimized for different delivery routes depending on the purpose of the mRNA treatment.

Assessing the efficacy of chitosan nanomatrix incorporated with Cymbopogon citratus (DC.) Stapf essential oil against the food-borne molds and aflatoxin B1 production in food system.

The chitosan nanomatrix incorporated with Cymbopogon citratus essential oil (Ne-CcEO) possess enhanced efficacy against the food-borne molds and aflatoxin B1 production compared to free essential oil. The CcEO was encapsulated inside the chitosan nanomatrix with an average size 147.41 ± 16.18 nm and characterized by Scanning electron microscopy, Fourier transforms infrared spectroscopy, and X-ray diffraction assay. The encapsulation efficiency and loading capacity were ranged between (41.68-76.78%) and (5.3-8.80%). The biochemical and in-silico analysis results revealed the interference in functioning of membrane integrity, mitochondrial membrane potential, antioxidant defense, carbon source metabolism, methylglyoxal, and laeA gene in response to treatment of Ne-CcEO (0.5 µl/ml). In addition, Ne-CcEO significantly protects the deterioration of Pennisetum glaucum (L.) R. Br. seed samples by A. flavus, aflatoxin B1 contamination, and lipid peroxidation. The Ne-CcEO could be considered as promising antifungal additives for the control of food-borne molds and aflatoxin B1 contamination in the food system.

Visualization of Plasmonic Couplings Using Ultrafast Electron Microscopy.

Hybrids of graphene and metal plasmonic nanostructures are promising building blocks for applications in optoelectronics, surface-enhanced scattering, biosensing, and quantum information. An understanding of the coupling mechanism in these hybrid systems is of vital importance to its applications. Previous efforts in this field mainly focused on spectroscopic studies of strong coupling within the hybrids with no spatial resolution. Here we report direct imaging of the local plasmonic coupling between single Au nanocapsules and graphene step edges at the nanometer scale by photon-induced near-field electron microscopy in an ultrafast electron microscope for the first time. The proximity of a step in the graphene to the nanocapsule causes asymmetric surface charge density at the ends of the nanocapsules. Computational electromagnetic simulations confirm the experimental observations. The results reported here indicate that this hybrid system could be used to manipulate the localized electromagnetic field on the nanoscale, enabling promising future plasmonic devices.

Morpho-physiological and demographic responses of three threatened Ilex species to changing climate aligned with species distribution models in future climate scenarios.

The success of a species in future climate change scenarios depends on its morphological, physiological, and demographic adaptive responses to changing climate. The existence of threatened species against climate adversaries is constrained due to their small population size, narrow genetic base, and narrow niche breadth. We examined if ecological niche model (ENM)-based distribution predictions of species align with their morpho-physiological and demographic responses to future climate change scenarios. We studied three threatened Ilex species, viz., Ilex khasiana Purkay., I. venulosa Hook. f., and I. embelioides Hook. F, with restricted distribution in Indo-Burma biodiversity hotspot. Demographic analysis of the natural populations of each species in Meghalaya, India revealed an upright pyramid suggesting a stable population under the present climate scenario. I. khasiana was confined to higher elevations only while I. venulosa and I. embelioides had wider altitudinal distribution ranges. The bio-climatic niche of I. khasiana was narrow, while the other two species had relatively broader niches. The ENM-predicted potential distribution areas under the current (2022) and future (2050) climatic scenarios (General Circulation Models (GCMs): IPSL-CM5A-LR and NIMR-HADGEM2-AO) revealed that the distribution of highly suitable areas for the most climate-sensitive I. khasiana got drastically reduced. In I. venulosa and I. embelioides, there was an increase in highly suitable areas under the future scenarios. The eco-physiological studies showed marked variation among the species, sites, and treatments (p < 0.05), indicating the differential responses of the three species to varied climate scenarios, but followed a similar trend in species performance aligning with the model predictions.

VO2 Nanostructures for Batteries and Supercapacitors: A Review.

Vanadium dioxide (VO2 ) received tremendous interest lately due to its unique structural, electronic, and optoelectronic properties. VO2 has been extensively used in electrochromic displays and memristors and its VO2 (B) polymorph is extensively utilized as electrode material in energy storage applications. More studies are focused on VO2 (B) nanostructures which displayed different energy storage behavior than the bulk VO2 . The present review provides a systematic overview of the progress in VO2 nanostructures syntheses and its application in energy storage devices. Herein, a general introduction, discussion about crystal structure, and syntheses of a variety of nanostructures such as nanowires, nanorods, nanobelts, nanotubes, carambola shaped, etc. are summarized. The energy storage application of VO2 nanostructure and its composites are also described in detail and categorically, e.g. Li-ion battery, Na-ion battery, and supercapacitors. The current status and challenges associated with VO2 nanostructures are reported. Finally, light has been shed for the overall performance improvement of VO2 nanostructure as potential electrode material for future application.

Pesticidal efficacy, mode of action and safety limits profile of essential oils based nanoformulation against Callosobruchus chinensis and Aspergillus flavus.

The study explores the pesticidal efficacy, mode of action, and safety limit profile of essential oils-based formulation using the combination of Myristica fragrans (M), Bunium persicum (B), and Zanthoxylum alatum (Z) (1:1:1 v/v/v) and their nanoformulation (Ne-MBZ) against the Callosobruchus chinensis, Aspergillus flavus and aflatoxin B1 production. Linalool, γ-terpinene, and cuminaldehyde were identified as the major compounds of the formulation (MBZ) by Gas chromatography-mass spectrometry (GC-MS). Nanoencapsulation of developed formulation (Ne-MBZ) was prepared using chitosan and characterized by scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), and Fourier transform infrared spectroscopy (FTIR). The pesticidal efficacy of nanoformulation (Ne-MBZ) against C. chinensis IC50 (0.14 µl/ml), A. flavus (0.8 µl/ml) and AFB1 (0.8 µl/ml) was significantly higher in both in-vitro and in-situ conditions than the sum of their individual revealing a notable synergistic effect. Besides, the detailed mode of pesticidal action and safety limit profile were explored using biochemical, in-silico and ADMET (absorption, distribution, metabolism, excretion, and toxicity) approaches.

Study of Association of Metabolic Syndrome and Risk Factors of Nephrolithiasis.

BACKGROUND AND AIM: The increasing incidence of nephrolithiasis in recent decades is coinciding with rising epidemic of obesity, metabolic syndrome, and type 2 diabetes. This temporal concordance suggests that a link might exist between these metabolic abnormalities and urinary stone disease. Therefore, the present study was aimed to investigate the association between presence of risk factors of nephrolithiasis and metabolic syndrome. METHODS: In a hospital-based, case control study, hundred patients of metabolic syndrome diagnosed according to IDF criteria and hundred age and matched controls were studied for presence of risk factors of nephrolithiasis. RESULTS: Patients with metabolic syndrome had significantly higher uricosuri a,hypercalciuria,oxaluria and hypocitraturia. The prevalence of risk factors of nephrolithiasis was also higher in patients with metabolic syndrome. The most prevalent was low urinary pH in 40% patients with mean pH of 5.8±1.6. Amongst other factors, 33% had hyperuricemia, 29% had hypercalciuria, 15% had oxaluria 13% had hypocitraturia and 10% had hyperuricosuria. Significant correlation was observed between risk factors of nephrolithiasis and components of metabolic syndrome. CONCLUSION: The present study provides an evidence of association between risk factors of nephrolithiasis and metabolic syndrome and suggests that nephrolithiasis may be a systemic disorder representing the interaction of multiple metabolic derangements. Determining common modifiable risk factors for the development of kidney stones might uncover new preventive strategies.

2D MoS2 -Based Nanomaterials for Therapeutic, Bioimaging, and Biosensing Applications.

Molybdenum disulfide (MoS2 ), a typical layered 2D transition metal dichalcogenide, has received colossal interest in the past few years due to its unique structural, physicochemical, optical, and biological properties. While MoS2 is mostly applied in traditional industries such as dry lubricants, intercalation agents, and negative electrode material in lithium-ion batteries, its 2D and 0D forms have led to diverse applications in sensing, catalysis, therapy, and imaging. Herein, a systematic overview of the progress that is made in the field of MoS2 research with an emphasis on its different biomedical applications is presented. This article provides a general discussion on the basic structure and property of MoS2 and gives a detailed description of its different morphologies that are synthesized so far, namely, nanosheets, nanotubes, and quantum dots along with synthesis strategies. The biomedical applications of MoS2 -based nanocomposites are also described in detail and categorically, such as in varied therapeutic and diagnostic modalities like drug delivery, gene delivery, phototherapy, combined therapy, bioimaging, theranostics, and biosensing. Finally, a brief commentary on the current challenges and limitations being faced is provided, along with a discussion of some future perspectives for the overall improvement of MoS2 -based nanocomposites as a potential nanomedicine.

Ecological niche modeling as a cumulative environmental impact assessment tool for biodiversity assessment and conservation planning: A case study of critically endangered plant Lagerstroemia minuticarpa in the Indian Eastern Himalaya.

Cumulative environmental impact assessment (CEIA) at river basin level for hydroelectric projects is an evolving concept and has proved to be a useful tool to assess the cumulative impact of developmental projects on the natural ecosystems. However, the generality of CEIA studies is often contested because of methodological limitations, especially in the domain of biodiversity conservation and conservation planning. Ecological niche modeling (ENM) can be a useful tool in CEIA studies for conservation planning of threatened plants in hydroelectric project (HEP) areas. We elucidate this hypothesis taking the example of Lagerstroemia minuticarpa Debberm. ex P.C. Kanjilal, a critically endangered tree species in the Indian Eastern Himalaya. Standard ecological methods were employed to document occurrence records, estimate population size, and characterize habitats. ENM was used to estimate the species potential environmental niche and distribution areas. The possible impacts of HEPs on the potential habitats were predicted by overlaying the HEPs on the potential area map as well as using the conceptual network diagram. The study revealed that the species occupies an environmental niche characterized by humid to per-humid conditions, and is distributed mostly in the Lohit and Teesta basins. Potential areas of the species with high environmental suitability coincide with 19 HEPs, which point to a potential threat to the survival of the species. Network diagram indicated that project activities might deteriorate the habitats thereby affecting the population and regeneration of the species. Our study provides a framework for developing appropriate measures for species conservation and reintroduction at basin level using ENM.

Association of Genetic Non-alcoholic Fatty Liver Disease with Insulin Resistance-Are we Different?

INTRODUCTION: Metabolic risk factors such as obesity, insulin resistance, type 2 diabetes mellitus and dyslipidemia are associated with non-alcoholic fatty liver disease (NAFLD). In the development and progression of NAFLD genetic mutations also play a significant role. NAFLD associated with the rs 738409 polymorphism of patatin-like phospholipase domain containing 3 gene (PNPLA3) G allele does not feature the typical metabolic abnormalities of NAFLD, including insulin resistance. In the light of rising epidemic of metaobesity in our population this study aimed to evaluate the relation of PNPLA3 polymorphism with insulin resistance. METHODS: In this case control hospital based study, 100 patients of NAFLD were recruited based on ultrasound findings of hepatic steatosis. Healthy subjects age and gender matched(n = 100) from the institute who volunteered to be part of the study were recruited as controls based on the sole criteria of the absence of fatty liver on ultrasonography and normal alanine and aspartate transaminases (ALT and AST) levels. Anthropometry, biochemical profiles and insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) were assessed. RESULTS: A higher frequency of CG and GG genotypes of rs738409 polymorphism of PNPLA3 was observed in patients with NAFLD than controls. These patients with G allele had increased ALT, dyslipidemia and insulin resistance. The polymorphism had positive correlation with severity of hepatic steatosis. CONCLUSION: The presence of the PNPLA3 G allele is associated with a risk of NAFLD. Our study shows that subjects with variant PNPLA3 are not only at increased risk for the development and progression of NAFLD, but also have increased insulin resistance.

Distribution of cyanobacteria and their interactions with pesticides in paddy field: A comprehensive review.

Cyanobacteria, also known as blue green algae are one of the important ubiquitous oxygen evolving photosynthetic prokaryotes and ultimate source of nitrogen for paddy fields since decades. In past two decades, indiscriminated use of pesticides led to biomagnification that intensively harm the structure and soil functions of soil microbes including cyanobacteria. Cyanobacterial abundance biomass, short generation, water holding capacity, mineralizing capacity and more importantly nitrogen fixing have enormous potential to abate the negative effects of pesticides. Therefore, investigation of the ecotoxicological effects of pesticides on the structure and function of the tropical paddy field associated cyanobacteria is urgent and need to estimate the fate of interaction of pesticides over nitrogen fixations and other attributes. In this regard, comprehensive survey over cyanobacterial distribution patterns and their interaction with pesticides in Indian context has been deeply reviewed. In addition, the present paper also deals the molecular docking pattern of pesticides with the nitrogen fixing proteins, which helps in revealing the functional interpretation over nitrogen fixation process.

Legacy of Polio-Use of India's Social Mobilization Network for Strengthening of the Universal Immunization Program in India.

The Social Mobilization Network (SMNet) has been lauded as one of the most successsful community engagement strategies in public health for its role in polio elimination in India. The UNICEF-managed SMNet was created as a strategy to eradicate polio by engaging >7000 frontline social mobilizers to advocate for vaccination in some of the most underserved, marginalized, and at-risk communities in India. This network focused initially on generating demand for polio vaccination but later expanded its messaging to promote routine immunization and other health and sanitation interventions related to maternal and children's health. As an impact of the network's interventions, in collaboration with other eradication efforts, these high-risk pockets witnessed an increase in full routine immunization coverage. The experience of the SMNet offers lessons for health-system strengthening for social mobilization and promoting positive health behaviors for other priority health programs like the Universal Immunization Program.

Is robot-assisted radical cystectomy superior to standard open radical cystectomy? An Indian perspective.

INTRODUCTION: Open radical cystectomy (ORC) has been the standard treatment for muscle-invasive bladder cancer, but this is associated with significant morbidity and mortality. Robot-assisted radical cystectomy (RARC) has been proposed as minimally invasive alternative with improved morbidity and acceptable oncological outcomes, but a large series featuring RARC and their comparison with ORC is still lacking in India despite more than a decade of its inception. We have conducted this study with an objective to see the feasibility of RARC in the Indian context and compare it with contemporary standard. METHODS: This is a prospective cohort study conducted at two tertiary cancer institutes. We have evaluated the patients pertaining to operative and early post-operative factors from January 2014 to December 2015. Necessary statistical tests applied to see comparability of the arms and their outcomes. RESULTS: A total of 170 patients underwent surgery for carcinoma bladder (45 ORC while 125 RARC). Intraoperative blood loss (RARC and ORC: 228 and 529 ml) and average transfusion rate were lower with RARC. A trend towards benefit was noted in favour of robotic arm in terms of mean complication rate (RARC and ORC: 54 and 39%). CONCLUSIONS: The present study has shown comparable surgical and early post-operative outcomes with clear advantage of robotic approach in terms of intraoperative blood transfusion and lymph node yield. Although the study was non-randomised in nature, it should provide substantial evidence on safety and feasibility of RARC in the Indian context and a reference point of evidence to look ahead.

Intranasal exposure to silica nanoparticles induces alterations in pro-inflammatory environment of rat brain.

Silica nanoparticles (SiNPs) are being used increasingly in biomedical and industrial fields; however, their adverse effects on human health have not been fully investigated. In this study, we focused on some of the toxicological aspects of SiNPs by studying oxidative stress and pro-inflammatory responses in the frontal cortex, corpus striatum and hippocampus regions of rat brain. Wistar rats were exposed to SiNPs of size 80 nm and 10 nm at a dose of 150 µg/50 µL phosphate-buffered saline/rat for 30 days. The results indicated a significant increase of lipid peroxide levels and hydrogen peroxide content in various regions of the treated rat brain. Moreover, these changes were accompanied with a significant decrease in the activities of manganese superoxide dismutase, glutathione reductase, catalase and reduced glutathione in different brain regions, suggesting impaired antioxidant defence system. Furthermore, SiNPs exposure not only increased messenger RNA (mRNA) and protein expression of nuclear factor-κB (NF-κB) but also significantly increased the mRNA and protein levels of tumour necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and monocyte chemoattractant protein 1 (MCP-1) in different regions of rat brain. Cumulatively, these data suggest that SiNPs induced the activation of NF-κB and increased the expression of TNF-α, IL-1ß and MCP-1 in rat brain, possibly via redox-sensitive cellular signalling pathways.

An in-depth assessment of India's Mother and Child Tracking System (MCTS) in Rajasthan and Uttar Pradesh.

BACKGROUND: India's Mother and Child Tracking System (MCTS)(1) is an information system for tracking maternal and child health beneficiaries in India's public health system, and improving service delivery planning and outcomes. This ambitious project was launched in 2009 and currently covers all states in India, but no in-depth assessment of the system has been conducted. This study by the Public Health Foundation of India (PHFI) evaluated the performance of MCTS and identified implementation challenges in areas in Rajasthan and Uttar Pradesh (UP) in December 2012. METHODS: Two assessment methods were employed: a Data Quality Assessment (DQA) to evaluate data quality and an assessment survey to identify implementation challenges. The survey comprised semi-structured questionnaires for health staff in the sampled districts, observation checklists and survey investigator notes. Purposive sampling was used for selecting two districts in each state and two blocks in each district. For the DQA, 45 mothers who became pregnant and 84 children born within the stipulated timeframes were randomly sampled. RESULTS: DQA overall performance numbers were 34% for pregnant women and 33% for children in the Rajasthan study areas, while UP's performance numbers were 18% for pregnant women and 25% for children. Weaknesses in the MCTS' data completeness accounted for much of this performance shortfall. The beneficiary profiles for Rajasthan were largely incomplete, and the MCTS in UP struggled to register beneficiaries. Shared challenges in both states were the absence of clear processes and guidelines governing data processes, and the lack of systematic monitoring and supervision frameworks for MCTS implementation. As a result, Front Line Health Workers (FHWs) were overburdened with data documentation work, and there were long delays in data capturing. FHWs and block level health officials were not adequately trained in using the MCTS. UP staff reported unreliable internet and electricity availability, lack of dedicated data entry personnel, and a shortage of consumables such as MCTS registers. CONCLUSIONS: There is an urgent need to create data processes and supervision guidelines that complement existing workflows and service delivery priorities. Health staff should be trained to implement these guidelines. MCTS outputs, such as service delivery planning tools, should replace existing tools once data quality improves.