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Bacteria within the gut microbiota possess the ability to metabolize a wide array of human drugs, foods, and toxins, but the responsible enzymes for these chemical events remain largely uncharacterized due to the time-consuming nature of current experimental approaches. Attempts have been made in the past to computationally predict which bacterial species and enzymes are responsible for chemical transformations in the gut environment, but with low accuracy due to minimal chemical representation and sequence similarity search schemes. Here, we present an in silico approach that employs chemical and protein Similarity algorithms that Identify MicrobioMe Enzymatic Reactions (SIMMER). We show that SIMMER accurately predicts the responsible species and enzymes for a queried reaction, unlike previous methods. We demonstrate SIMMER use cases in the context of drug metabolism by predicting previously uncharacterized enzymes for 88 drug transformations known to occur in the human gut. We validate these predictions on external datasets and provide an in vitro validation of SIMMER’s predictions for metabolism of methotrexate, an anti-arthritic drug. After demonstrating its utility and accuracy, we made SIMMER available as both a command-line and web tool, with flexible input and output options for determining chemical transformations within the human gut. We present SIMMER as a computational addition to the microbiome researcher’s toolbox, enabling them to make informed hypotheses before embarking on the lengthy laboratory experiments required to characterize novel bacterial enzymes that can alter human ingested compounds.

BACKGROUND: Spinal anesthesia is the most popular regional anesthesia technique for lower abdominal surgeries. The failure of many spinal anesthesia techniques is more due to inadequate sedation and anxiolysis than technically faulty blocks. This study was designed to determine the appropriate dose of intravenous dexmedetomidine maintainance infusion to provide adequate sedation for spinal anesthesia. METHODS: A prospective, randomized, controlled double-blind study was carried out on 75 patients aged 18-60 years with ASA I and ASA II physical status who were scheduled for elective lower abdominal surgery under spinal anesthesia. Before the spinal anesthesia, all study participants were given an initial loading dose of 0.5 µg/kg dexmedetomidine infusion. Participants were randomly divided into three groups for maintenance drug infusion, Group A (to receive dexmedetomidine infusion at 0.2 µg/kg/hr), Group B (to receive dexmedetomidine infusion at 0.4 µg/kg/hr) and Group C to receive an intravenous infusion of normal saline during surgery. The Ramsay Sedation Scale (RSS) score, duration of analgesia, hemodynamic variables and occurrence of adverse events were monitored in all patients. RESULTS: Dexmedetomidine group had increased RSS score in intraoperative period and upto first 30 minutes in postoperative period compared to control group . Time to request for first analgesic was prolonged and incidence of shivering and PONV in postoperative period was less in group B than group A. The hemodynamic parameters, Respiratory parameters were not statistically significant among group A and group B. CONCLUSION: We conclude that intravenous administration of dexmedetomidine0.5 µg/kg loading dose followed by 0.4 µg/kg/hr as maintenance infusion is the optimum dose to produce sedation during spinal anesthesia with an additional advantage of increased duration of analgesia and reduced postoperative sideeffects .

Teratomas are bizarre neoplasms that most commonly occur in infancy and childhood. Since surgical therapy is the primary treatment modality for any type of teratoma, we as anesthesiologists encounter these cases when they come for surgical removal. Providing anesthesia services for these cases is challenging because of the age at presentation, the complexity of the surgical condition, the inherent anomalies associated with it, and also the existing literature gaps in anesthesia management for these cases. In order to close this knowledge gap and to support future anesthesia planning, this case series was framed.

Abstract Background Nanotechnology's rapid development has been in great demand, particularly for silver nanoparticles, which are useful in a variety of industries including medicine, textiles, and home appliances. Silver nanoparticles are extremely essential due to their unique physicochemical and antibacterial properties, which can be used in a variety of applications. Green synthesis is an environmentally friendly alternative to conventional synthesis because it uses fewer chemical reagents and lowers temperature and pressure. Aloe vera and Thuja orientalis have a wide medical use because it contains a large number of compounds derived and was decided to use for the synthesis of nanoparticles. Main text The combination of silver nanoparticles has a wide range of applications, which has encouraged researchers to focus on the methods for the synthesis of silver nanoparticles from Aloe vera and Thuja orientalis leaves extract, characterization techniques of synthesized silver nanoparticles, and evaluation of their antimicrobial and antifungal activities. The synthesized AgNPs can be characterized by using various analytical techniques including UV–visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), etc. The various types of silver nanoparticles, various strategies for silver nanoparticle synthesis, nano-based drug delivery systems, taxonomy and chemical constituents of Aloe vera and Thuja orientalis plants, the general mechanism of action of silver nanoparticles in bacteria, and various applications of silver nanoparticles have also been discussed. Conclusion This review covers a wide range of research on silver nanoparticles to gain a better understanding of their physicochemical feature characterization, production, mechanisms of action, and applications. Various AgNP factors, such as size, surfactant, and structural shape, influence the unique physicochemical properties of these nanoparticles. Even though there are a variety of ways to make AgNPs, green synthesis has a high yield and biocompatibility because it uses natural agents and harmless chemicals. In this paper, we describe the green manufacture of silver nanoparticles utilizing Aloe vera and Thuja orientalis leaf extracts, as well as the method to test their antimicrobial and antifungal activity.

Crop duration of the cultivated Pleurotus spp. is 45 to 50 days. P. djamor isolate woody-1 was collected as natural selection and was found to be short cropping duration variety with total cropping duration of 30 days but it is less palatable. It produced very thin, loose and non-rhizomorphic mycelia appearing light white color. Whereas, other commercial Pleurotus varieties such as P. florida and P. djamor MDU1 are long crop duration varieties and palatable producing thick, compact and rhizomorphic mycelia with bright white color. Co-segregation of non-rhizomorphic mycelial phenotype and short cropping duration trait of P. djamor woody- 1 in hybrid progenies was evaluated. Hybrid strains viz., H2W12 and H2W14 have thin, loose and non-rhizomorphic mycelium and they produced primordia in 9-10 days after spawning with total cropping duration of 29-32 days. Whereas, hybrid strain namely Pf1W2 has thick, compact and rhizomorphic mycelial phenotype and it produced primordia in 20 days after spawning with the total cropping duration of 47 days. This study indicated that genes governing short cropping duration and non-rhizomorphic mycelial pattern were tightly linked and co-segregated in the progenies. Thus, non-rhizomorphic mycelial phenotype of P. djamor woody1 can be used as a phenotypic marker for selection of hybrid cultivar having short cropping duration with other desired agronomic traits in future breeding strategy.

Summary: Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.

Background: Patients with Ebstein anomaly have impaired aerobic capacity, but the relationship between aerobic capacity and clinical outcomes are unknown. The purpose of this study was to determine the prognostic role of aerobic capacity and the hemodynamic mechanism underlying temporal deterioration in aerobic capacity in this population. Methods: Retrospective cohort study of adults with Ebstein anomaly that underwent exercise test (2000–2018). Primary objective was to determine the relationship between aerobic capacity (%-predicted peak oxygen consumption, VO2) and cardiovascular adverse events (death, heart transplant, aborted sudden death, and heart failure hospitalization). Secondary objective was to delineate the relationship between temporal change in hemodynamic indices and subsequent decline in peak VO2. Results: We studied 248 patients (peak VO2 22.4 ​± ​7.1 ​ml/kg/min; 64 ​± ​21 %-predicted), and these events occurred during follow-up (death n ​= ​12, transplant n ​= ​1, aborted sudden death n ​= ​7, and heart failure hospitalization n ​= ​11). Peak VO2 was an independent predictor of cardiovascular adverse events (hazard ratio 1.32; 95% confidence interval 1.18–1.59, p ​= ​0.002 per 5%-point decrease). Of 101 patients with ≥2 exercise tests, %-predicted peak VO2 decreased by 2.3%-points/year, and rate of decline correlated with change in right atrial (RA) strain and left heart hemodynamics. Hemodynamic deterioration started with RA dysfunction, followed by left heart hemodynamic impairment, and then decline in peak VO2. Conclusions: Peak VO2 is a predictor of cardiovascular adverse events in Ebstein anomaly. Temporal decline in peak VO2 was preceded by RA dysfunction and left heart hemodynamic impairment suggesting that impaired aerobic capacity represents a late stage in disease pathogenesis.

Cardiac hypertrophy is recognized as an independent risk factor for cardiac failure. Efficient management of hypertensive heart disease requires identification of factors that can possibly mediate the transition from hypertrophy to failure. Resident cardiac stem cells have a prominent role in the maintenance of cardiac tissue homeostasis. Decline in the proportion of healthy cardiac stem cells (CSCs) can affect tissue regeneration. In pathological conditions, apart from natural aging, an adverse microenvironment can lead to decrease in efficiency of CSCs. A systematic analysis of cardiac stem cell characteristics in pathological conditions has not been reported so far. Therefore, this study was designed with the objective of examining the age associated variation in stem cell attributes of Spontaneously hypertensive rat (SHR) in comparison with normotensive Wistar rat. Spontaneously hypertensive rat was used as the experimental model since the cardiac remodeling resembles the clinical course of hypertensive heart disease. CSCs were isolated from atrial explants. Stem cell attributes were assessed in 1-week, 6, 12 and 18-month-old male SHR, in comparison with age matched Wistar rats. In 1-week-old pups, stem cell attributes of SHR and Wistar were comparable. Migration potential, proliferative capacity, TERT expression, telomerase activity and the proportion of c-kit+ cells decreased with age, both in SHR and Wistar. DNA damage and the proportion of senescent CSCs increased with age both in SHR and Wistar rats. Age associated increase was observed in the oxidative stress of stem cells, possibly mediated by the enhanced oxidative stress in the microenvironment. The changes were more pronounced in SHR, and as early as six months of age, there was significant decrease in efficiency of CSCs of SHR compared to Wistar. The density of healthy CSCs determined as a fraction of the differentiated cells was remarkably low in 18-month-old SHR. Age associated decrease in functionally efficient CSCs was therefore accelerated in SHR. Considering the vital role of CSCs in the maintenance of a healthy myocardium, decrease in functionally efficient CSCs can be a precipitating factor in pathological cardiac remodeling. Elevated ROS levels in CSCs of SHR lends scope for speculation that decrease in efficiency of CSCs is mediated by oxidative stress; and that modulation of the microenvironment by therapeutic interventions can restore a healthy stem cell population and facilitate maintenance of cardiac homeostasis and prevent cardiac decompensation.

Bacteria within the gut microbiota possess the ability to metabolize a wide array of human drugs, foods, and toxins, but the responsible enzymes for these chemical events remain largely uncharacterized due to the time-consuming nature of current experimental approaches. Attempts have been made in the past to computationally predict which bacterial species and enzymes are responsible for chemical transformations in the gut environment, but with low accuracy due to minimal chemical representation and sequence similarity search schemes. Here, we present an in silico approach that employs chemical and protein Similarity algorithms that Identify MicrobioMe Enzymatic Reactions (SIMMER). We show that SIMMER accurately predicts the responsible species and enzymes for a queried reaction, unlike previous methods. We demonstrate SIMMER use cases in the context of drug metabolism by predicting previously uncharacterized enzymes for 88 drug transformations known to occur in the human gut. We validate these predictions on external datasets and provide an in vitro validation of SIMMER's predictions for metabolism of methotrexate, an anti-arthritic drug. After demonstrating its utility and accuracy, we made SIMMER available as both a command-line and web tool, with flexible input and output options for determining chemical transformations within the human gut. We present SIMMER as a computational addition to the microbiome researcher's toolbox, enabling them to make informed hypotheses before embarking on the lengthy laboratory experiments required to characterize novel bacterial enzymes that can alter human ingested compounds.

Expression levels of human genes vary extensively among individuals. This variation facilitates analyses of expression levels as quantitative phenotypes in genetic studies where the entire genome can be scanned for regulators without prior knowledge of the regulatory mechanisms, thus enabling the identification of unknown regulatory relationships. Here, we carried out such genetic analyses with a large sample size and identified cis- and trans-acting polymorphic regulators for about 1,000 human genes. We validated the cis-acting regulators by demonstrating differential allelic expression with sequencing of transcriptomes (RNA-Seq) and the trans-regulators by gene knockdown, metabolic assays, and chromosome conformation capture analysis. The majority of the regulators act in trans to the target (regulated) genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past.

Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity.

Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity.

Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.

Immunomodulatory drugs can inhibit bacterial growth, yet their mechanism of action, spectrum, and clinical relevance remain unknown. Methotrexate (MTX), a first-line rheumatoid arthritis (RA) treatment, inhibits mammalian dihydrofolate reductase (DHFR), but whether it directly impacts gut bacteria is unclear. We show that MTX broadly alters the human gut microbiota. Drug sensitivity varied across strains, but the mechanism of action against DHFR appears conserved between mammalian and bacterial cells. RA patient microbiotas were sensitive to MTX, and changes in gut bacterial taxa and gene family abundance were distinct between responders and non-responders. Transplantation of post-treatment samples into germ-free mice given an inflammatory trigger led to reduced immune activation relative to pre-treatment controls, enabling identification of MTX-modulated bacterial taxa associated with intestinal and splenic immune cells. Thus, conservation in cellular pathways across domains of life can result in broad off-target drug effects on the human gut microbiota with consequences for immune function.

A low temperature hydrothermal method is employed in this study to synthesize CdSe doped TiO2 nanocomposites. Further characterization and studies of the synthesized particles were carried out. As part of this study, the sample was examined by X-ray diffraction to determine its structure, crystallite size, strain, and crystallinity. Molecules were analyzed by energy dispersive X-ray spectroscopy to determine their chemical composition. By using fourier transform infrared spectroscopy spectroscopy, we were able to observe the presence of functional groups as well as the types of bonds. By analyzing the scanning electron microscopy spectra, we were able to determine the particle size while by analyzing the photoluminescence spectra, we could determine the bandgap energy. To determine the nature of materials and their effective photocatalytic behavior, optical bandgap energies were observed in the ultra-violet visible spectrum of synthesized particles. For determining the charge transfer mechanism and specific capacitance, electrochemical studies were conducted using electrochemical impedance spectroscopy and cyclic voltammetry analysis. The degradation of malachite green and Rhodamine-B dyes with CdSe doped TiO2 nanocomposites in the visible region was studied for photocatalytic activity, degradation efficiency, and rate constant. According to the results, doped nanoparticles increased the efficiency of RhB dye degradation by ~ 4% and MG dye degradation by ~ 20% over pure nanoparticles. [ABSTRACT FROM AUTHOR]

In this study, silver sulfide nanoparticles (Ag2SNP's) were successfully produced by using fruit extracts of Phyllanthus emblica. UV–vis, FTIR, XRD with SEM and EDX techniques were used for the synthesis process and for characterization of the resulting nanostructures. According to the findings, the fabricated nanostructure had a monoclinic crystal structure, measuring 44 nm in grain size, and its strain was 1.82 × 10−3. As revealed by SEM analysis, the synthesized nanostructure consists of irregular spherical and triangular shapes. The presence of silver (Ag) and sulfur (S) was also confirmed through EDX spectra. Furthermore, Ag2S nanoparticles were tested for their ability to effectively inhibit gram‐positive and gram‐negative bacterial growth. As a result of this study, it was clearly demonstrated that Ag2S nanoparticles possess powerful antibacterial properties, particularly when it came to inhibiting Escherichia coli growth. Ag2S nanoparticles had high total H2O2 and flavonoid concentrations and the greatest overall antioxidant activity, according to the evaluation of antioxidant activity of the samples. The results obtained from the P. emblica fruit extract were followed by those obtained from Ag2S nanoparticles were reported in detail. Research Highlights: Innovative Ag2SNP synthesis using Phyllanthus emblica fruit extract.SEM with EDX revealed a monoclinic crystal structure with a grain size of 44 nm and a strain of 1.82 × 10−3.Many of these applications are demonstrated by the potential of Ag2SNPs to treat and combat bacteria, particularly Escherichia coli.A peak at 653 cm−1 indicates the presence of primary sulfide aliphatic C‐S extension vibrations.The abundant H2O2 and NO2 found in P. emblica nanocomposites make them potent antioxidants. [ABSTRACT FROM AUTHOR]

Drugs intended to target mammalian cells can have broad off‐target effects on the human gut microbiota with potential downstream consequences for drug efficacy and side effect profiles. Yet, despite a rich literature on antibiotic resistance, we still know very little about the mechanisms through which commensal bacteria evade non‐antibiotic drugs. Here, we focus on statins, one of the most prescribed drug types in the world and an essential tool in the prevention and treatment of high circulating cholesterol levels. Prior work in humans, mice, and cell culture support an off‐target effect of statins on human gut bacteria; however, the genetic determinants of statin sensitivity remain unknown. We confirmed that simvastatin inhibits the growth of diverse human gut bacterial strains grown in communities and in pure cultures. Drug sensitivity varied between phyla and was dose‐dependent. We selected two representative simvastatin‐sensitive species for more in‐depth analysis: Eggerthella lenta (phylum: Actinobacteriota) and Bacteroides thetaiotaomicron (phylum: Bacteroidota). Transcriptomics revealed that both bacterial species upregulate genes in response to simvastatin that alter the cell membrane, including fatty acid biogenesis (E. lenta) and drug efflux systems (B. thetaiotaomicron). Transposon mutagenesis identified a key efflux system in B. thetaiotaomicron that enables growth in the presence of statins. Taken together, these results emphasize the importance of the bacterial cell membrane in countering the off‐target effects of host‐targeted drugs. Continued mechanistic dissection of the various mechanisms through which the human gut microbiota evades drugs will be essential to understand and predict the effects of drug administration in human cohorts and the potential downstream consequences for health and disease. [ABSTRACT FROM AUTHOR]

In this study, we report the synthesis of silver nanoparticles (AgNP's) by reducing silver ions from a solution of silver nitrate with an aqueous extract from Azadirachta indica. Using silver ions as the catalyst, nanoparticles were formed in 8 min without the use of toxic chemicals. As evidenced by UV-vis spectroscopy, a broad surface plasmon resonance spectrum at 225 nm was detected, which indicates the colloidal solution of silver nanoparticles is stable and produces silver nanoparticles. As revealed by the fourier transform-infrared spectrometer (FTIR) analysis, the flower extract contained a variety of biomolecules that acted as capping and reducing agents for the synthesis of AgNPs. As determined by X-ray diffraction (XRD), silver nanoparticles displayed a crystalline structure and ranged in size from 18 to 39 nm. In addition to these findings, transmission electron microscopy (TEM) images showed that the silver nanoparticles were spherical and rod-shaped, as confirmed by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDAX). A variety of pathogenic bacteria, such as Klebsiella pneumoniae, Escherichia coli, Bacillus subtilis and Staphylococcus aureus, were tested against AgNP's antibacterial properties. A significant inhibition zone was observed for Escherichia coli when AgNPs were applied at different concentrations. Silver nanoparticles were shown to have antidiabetic effects through a diphtheria assay with inhibition rates ranging from 31.09% to 83.33% for concentrations of 50–250 μ g/mL. As researchers seek natural sources of compounds with potential health benefits, silver nanoparticles were also investigated for their antioxidant properties. Silver nanoparticles (AgNPs) were synthesized, using an aqueous extract from Azadirachta indica, as a reducing agent. UV-vis spectroscopy, shown a broad surface plasmon resonance spectrum at 225 nm, where SEM and HRTEM analyses revealed that the AgNPs were spherical and rod-shaped with sizes ranging from 18 to 39 nm. The AgNPs demonstrated significant antimicrobial properties against various pathogens and exhibited potent antioxidant activity, suggesting their potential for therapeutic applications. [ABSTRACT FROM AUTHOR]

BackgroundClinicians have known for centuries that there is substantial variability between patients in their response to medications-some individuals exhibit a miraculous recovery while others fail to respond at all. Still others experience dangerous side effects. The hunt for the factors responsible for this variation has been aided by the ability to sequence the human genome, but this just provides part of the picture. Here, we discuss the emerging field of study focused on the human microbiome and how it may help to better predict drug response and improve the treatment of human disease.DiscussionVarious clinical disciplines characterize drug response using either continuous or categorical descriptors that are then correlated to environmental and genetic risk factors. However, these approaches typically ignore the microbiome, which can directly metabolize drugs into downstream metabolites with altered activity, clearance, and/or toxicity. Variations in the ability of each individual's microbiome to metabolize drugs may be an underappreciated source of differences in clinical response. Complementary studies in humans and animal models are necessary to elucidate the mechanisms responsible and to test the feasibility of identifying microbiome-based biomarkers of treatment outcomes. We propose that the predictive power of genetic testing could be improved by taking a more comprehensive view of human genetics that encompasses our human and microbial genomes. Furthermore, unlike the human genome, the microbiome is rapidly altered by diet, pharmaceuticals, and other interventions, providing the potential to improve patient care by re-shaping our associated microbial communities.

ObjectivePrevious studies have shown that differential DNA methylation is associated with SLE susceptibility. How DNA methylation affects the clinical heterogeneity of SLE has not been fully defined. We conducted this study to identify differentially methylated CpG sites associated with nephritis among women with SLE.MethodsThe methylation status of 428 229 CpG sites across the genome was characterised for peripheral blood cells from 322 women of European descent with SLE, 80 of whom had lupus nephritis, using the Illumina HumanMethylation450 BeadChip. Multivariable linear regression adjusting for population substructure and leucocyte cell proportions was used to identify differentially methylated sites associated with lupus nephritis. The influence of genetic variation on methylation status was investigated using data from a genome-wide association study of SLE. Pathway analyses were used to identify biological processes associated with lupus nephritis.ResultsWe identified differential methylation of 19 sites in 18 genomic regions that was associated with nephritis among patients with SLE (false discovery rate q