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José I Belda,1,2 Javier Placeres,1,2 Juan C Elvira,3 Xavier Puig,4 Caridad Pérez-Vives,5 Ming Zou,6 Jing Yu,6 Shaohui Sun,6 Derek O’Boyle7 1Department of Ophthalmology, Hospital Universitario de Torrevieja, Alicante, Spain; 2Visionker Eye Clinic, Alicante, Spain; 3Department of Ophthalmology, Hospital Universitario del Vinalopó, Alicante, Spain; 4Alcon Healthcare SA, Barcelona, Spain; 5Alcon Management SA, Cointrin, Switzerland; 6IQVIA Real World Solutions, Basel, Switzerland; 7Alcon Laboratories Ireland Ltd, Cork, IrelandCorrespondence: Derek O’Boyle, Alcon Laboratories Ireland Ltd., Cork, Ireland, Tel +353879080235, Email derek.oboyle@alcon.comPurpose: To estimate the incidence of neodymium-doped yttrium aluminum garnet laser (Nd:YAG) capsulotomy up to five years after cataract surgery with different single-piece acrylic monofocal IOLs in a Spanish cohort.Patients and Methods: Data were extracted from electronic medical records. Eligible participants were aged ≥ 65, had cataract surgery with one of five different acrylic monofocal IOLs (Alcon AcrySof, AJL LLASY60, Medicontur Bi-flex, IOL Tech Stabibag and Zeiss Asphina), and more than six months baseline data. Participants were followed up to five years from surgery and up to six months from Nd:YAG. The incidence of Nd:YAG was compared between the IOLs and multivariate analyses were conducted to identify predictors of Nd:YAG incidence at five-years after cataract surgery.Results: The initial cohort included 9545 patients with 14,519 eyes (53% female, average age 75 years). Of those, 3955 eyes were available for analysis five years after cataract surgery. Throughout the five years post-surgery, Nd:YAG incidence was consistently lower with Alcon Acrysof IOLs than the other IOLs. At five years the Nd:YAG incidence rate for Alcon Acrysof was 8.8%. In comparison, the incidence was 47.4% for AJL LLASY60 (OR = 9.54, 95% CI [6.57, 13.84]), 44.3% for Zeiss Asphina (OR = 8.35, 95% CI [5.85, 11.94]) and 44.0% for IOL Tech Stabibag (OR = 8.02, 95% CI [4.60, 13.84]).Conclusion: Alcon AcrySof IOLs have a consistently lower risk of Nd:YAG incidence over a long follow-up period after cataract surgery, highlighting the importance of IOL choice for patients’ long-term outcomes.Keywords: Nd:YAG, long-term outcome, monofocal IOLs, real-world evidence

José I Belda,1 Javier Placeres,1 Juan Carlos Elvira,2 Xavier Puig,3 Caridad Pérez-Vives,4 Ming Zou,5 Shaohui Sun,5 Jing Yu,5 Derek O’Boyle6 1Hospital Universitario de Torrevieja, Torrevieja, Alicante, Spain; 2Hospital Universitario del Vinalopó, Elche, Alicante, Spain; 3Alcon Healthcare, S.A, Barcelona, Spain; 4Alcon Management SA, Cointrin, Switzerland; 5IQVIA Real World Solutions, Basel, Switzerland; 6Alcon Laboratories Ireland Ltd., Cork, IrelandCorrespondence: Derek O’Boyle, Alcon Laboratories Ireland Ltd., Cork, Ireland, Email derek.oboyle@Alcon.comPurpose: To estimate the economic impact of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy and its related complications for five different intraocular lenses (IOLs) from the payer and hospital perspectives in Spain.Materials and Methods: The three-year incidence rates of Nd:YAG laser capsulotomy after cataract surgery with five different single-piece acrylic monofocal IOLs (AcrySof IOLs, AJL LLASY60, IOL Tech Stabibag, Medicontur Bi-flex, Zeiss Asphina) for 8293 patients were derived from odds ratios of multivariate analysis adjusted for age, gender, and diabetic retinopathy. A cost-consequence model for a hypothetical cohort of 2000 eyes was then developed to quantify the potential impact of Nd:YAG capsulotomy in terms of costs and time for each of the included IOLs, from the payer and hospital perspectives.Results: The adjusted three-year Nd:YAG laser capsulotomy incidence was 5.0% (95% CI 3.9 to 6.1) for AcrySof and ranged from 26.0% to 44.0% for the other four IOLs. The average costs of Nd:YAG treatment and related complications were € 261.90 for payers and € 19.99 for hospitals. The average time needed for Nd:YAG treatment and related complications was 32.82 minutes. Model estimates based on 2000 hypothetical cataract surgeries showed that AcrySof IOLs could lead to cost savings between € 110,259.90 and € 205,591.50 for payers. For hospitals, time, and cost savings with AcrySof ranged from 230.29 hours and € 8415.79 compared to Zeiss Asphina to 429.40 hours and € 15,692.15 compared to AJL LLASY60 IOLs.Conclusion: Post cataract surgery, AcrySof IOLs were associated with a significantly lower incidence of Nd:YAG treatment and its subsequent complications compared to other IOLs. Our analysis shows that IOL choice is an important factor that can reduce the burden for patients, payers, and hospitals.Keywords: cost, resources, Nd:YAG capsulotomy, cataract, PCO, IOL

In this study, we developed a process combining dilute alkali (NaOH or NaHCO 3 ) and physical (disk milling and/or ball milling) treatments to improve the functionality and fermentability of corn fiber. The results showed that combining chemical with physical processes greatly improved the functionality and fermentability of corn fiber. Corn fiber treated with NaOH followed by disk milling (NaOH-DM-CF) had the highest water retention (19.5 g/g), water swelling (38.8 mL/g), and oil holding (15.5 g/g) capacities. Moreover, NaOH-DM-CF produced the largest amount (42.9 mM) of short-chain fatty acid (SCFA) during the 24-hr in vitro fermentation using porcine fecal inoculum. In addition, in vitro fermentation of NaOH-DM-CF led to a targeted microbial shifting to Prevotella (genus level), aligning with a higher fraction of propionic acid. The outstanding functionality and fermentability of NaOH-DM-CF were attributed to its thin and loose structure, decreased ester linkages and acetyl groups, and enriched structural carbohydrate exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aryl hydrocarbon receptor (AhR) responds to endogenous and exogenous ligands as a cytosolic receptor, transcription factor, and E3 ubiquitin ligase. Several studies support an anti-inflammatory effect of AhR activation. However, exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early stages of development results in an autoimmune phenotype and exacerbates lupus. The effects of TCDD on lupus in adults with pre-existing autoimmunity have not been described. We present novel evidence that AhR stimulation by TCDD alters T cell responses but fails to impact lupus-like disease using an adult mouse model. Interestingly, AhR antagonist CH223191 also changed T cell balance in our model. We next developed a conceptual framework for identifying cellular and molecular factors that contribute to physiological outcomes in lupus and created models that describe cytokine dynamics that were fed into a system of differential equations to predict the kinetics of T follicular helper (Tfh) and regulatory T (Treg) cell populations. The model predicted that Tfh cells expanded to larger values following TCDD exposure compared with vehicle and CH223191. Following the initial elevation, both Tfh and Treg cell populations continuously decayed over time. A function based on the ratio of predicted Treg/Tfh cells showed that Treg cells exceed Tfh cells in all groups, with TCDD and CH223191 showing lower Treg/Tfh cell ratios than the vehicle and that the ratio is relatively constant over time. We conclude that AhR ligands did not induce an anti-inflammatory response to attenuate autoimmunity in adult lupus mice. This study challenges the dogma that TCDD supports an immunosuppressive phenotype., (Copyright © 2024 The Authors.)

The analysis of time series studies linking daily counts of a health indicator with environmental variables (e.g., mortality or hospital admissions with air pollution concentrations or temperature; or motor vehicle crashes with temperature) is usually conducted with Poisson regression models controlling for long-term and seasonal trends using temporal strata. When the study includes multiple zones, analysts usually apply a two-stage approach: first, each zone is analyzed separately, and the resulting zone-specific estimates are then combined using meta-analysis. This approach allows zone-specific control for trends. A one-stage approach uses spatio-temporal strata and could be seen as a particular case of the case-time series framework recently proposed. However, the number of strata can escalate very rapidly in a long time series with many zones. A computationally efficient alternative is to fit a conditional Poisson regression model, avoiding the estimation of the nuisance strata. To allow for zone-specific effects, we propose a conditional Poisson regression model with a random slope, although available frequentist software does not implement this model. Here, we implement our approach in the Bayesian paradigm, which also facilitates the inclusion of spatial patterns in the effect of interest. We also provide a possible extension to deal with overdispersed data. We first introduce the equations of the framework and then illustrate their application to data from a previously published study on the effects of temperature on the risk of motor vehicle crashes. We provide R code and a semi-synthetic dataset to reproduce all analyses presented., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

There is need for novel fast acting treatment options in affective disorders. 3α-reduced neurosteroids such as allopregnanolone are powerful positive allosteric modulators of GABA A receptors and target also extrasynaptic receptors. Their synthesis is mediated by the translocator protein 18 kDa (TSPO). TSPO ligands not only promote endogenous neurosteroidogenesis, but also exert a broad spectrum of functions involving modulation of mitochondrial activity and acting as anti-inflammatory and neuroregenerative agents. Besides affective symptoms, in depression cognitive impairment can be frequently observed, which may be ameliorated through targeting of extrasynaptic GABA A receptors either via TSPO ligands or exogenously administered 3α-reduced neurosteroids. Interestingly, recent findings indicate an enhanced activation of the complement system, e.g., enhanced expression of C1q, both in depression and dementia. It is of note that benzodiazepines have been shown to reduce long-term potentiation and to cause cognitive decline. Intriguingly, TSPO may be crucial in mediating the effects of benzodiazepines on synaptic pruning. Here, we discuss how benzodiazepines and TSPO may interfere with synaptic pruning. Moreover, we highlight recent developments of TSPO ligands and 3α-reduced neurosteroids as therapeutic agents. Etifoxine is the only clinically available TSPO ligand so far and has been studied in anxiety disorders. Regarding 3α-reduced neurosteroids, brexanolone, an intravenous formulation of allopregnanolone, has been approved for the treatment of postpartum depression and zuranolone, an orally available 3α-reduced neurosteroid, is currently being studied in major depressive disorder and postpartum depression. As such, 3α-reduced neurosteroids and TSPO ligands may constitute promising treatment approaches for affective disorders., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

One of the challenges in the field of human activity recognition in smart homes based on IoT sensors is the variability in the recorded data. This variability arises from differences in home configurations, sensor network setups, and the number and habits of inhabitants, resulting in a lack of data that accurately represent the application environment. Although simulators have been proposed in the literature to generate data, they fail to bridge the gap between training and field data or produce diverse datasets. In this article, we propose a solution to address this issue by leveraging the concept of digital twins to reduce the disparity between training and real-world data and generate more varied datasets. We introduce the Virtual Smart Home, a simulator specifically designed for modeling daily life activities in smart homes, which is adapted from the Virtual Home simulator. To assess its realism, we compare a set of activity data recorded in a real-life smart apartment with its replication in the VirtualSmartHome simulator. Additionally, we demonstrate that an activity recognition algorithm trained on the data generated by the VirtualSmartHome simulator can be successfully validated using real-life field data.

Objective: Patients with systemic lupus erythematosus (SLE) often develop multi-organ damages including heart and kidney complications. We sought to better define the underlying mechanisms with a focus on the chemokine receptor CX 3 CR1., Methods: We generated Cx3cr1-deficient MRL/lpr lupus-prone mice through backcrossing. We then employed heterozygous intercross to generate MRL/lpr littermates that were either sufficient or deficient of CX 3 CR1. The mice were also treated with either Lactobacillus spp. or a high-fat diet (HFD) followed by assessments of the kidney and heart, respectively., Results: Cx3cr1 -/- MRL/lpr mice exhibited a distinct phenotype of exacerbated glomerulonephritis compared to Cx3cr1 +/+ littermates, which was associated with a decrease of spleen tolerogenic marginal zone macrophages and an increase of double-negative T cells. Interestingly, upon correction of the gut microbiota with Lactobacillus administration, the phenotype of exacerbated glomerulonephritis was reversed, suggesting that CX 3 CR1 controls glomerulonephritis in MRL/lpr mice through a gut microbiota-dependent mechanism. Upon treatment with HFD, Cx3cr1 -/- MRL/lpr mice developed significantly more atherosclerotic plaques that were promoted by Ly6C + monocytes. Activated monocytes expressed ICOS-L that interacted with ICOS-expressing follicular T-helper cells, which in turn facilitated a germinal center reaction to produce more autoantibodies. Through a positive feedback mechanism, the increased circulatory autoantibodies further promoted the activation of Ly6C + monocytes and their display of ICOS-L., Conclusions: We uncovered novel, Cx3cr1 deficiency-mediated pathogenic mechanisms contributing to SLE-associated glomerulonephritis and cardiovascular disease., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

NLRP12 has dual roles in shaping inflammation. We hypothesized that NLRP12 would modulate myeloid cells and T cell function to control systemic autoimmunity. Contrary to our hypothesis, the deficiency of Nlrp12 in autoimmune-prone B6. Fas lpr/lpr mice ameliorated autoimmunity in males but not females. Nlrp12 deficiency dampened B cell terminal differentiation, germinal center reaction, and survival of autoreactive B cells leading to decreased production of autoantibodies and reduced renal deposition of IgG and complement C3. In parallel, Nlrp12 deficiency reduced the expansion of potentially pathogenic T cells, including double-negative T cells and T follicular helper cells. Furthermore, reduced pro-inflammatory innate immunity was observed, where the gene deletion decreased in-vivo expansion of splenic macrophages and mitigated ex-vivo responses of bone marrow-derived macrophages and dendritic cells to LPS stimulation. Interestingly, Nlrp12 deficiency altered the diversity and composition of fecal microbiota in both male and female B6/ lpr mice. Notably, however, Nlrp12 deficiency significantly modulated small intestinal microbiota only in male mice, suggesting that the sex differences in disease phenotype might be gut microbiota-dependent. Together, these results suggest a potential pathogenic role of NLRP12 in promoting systemic autoimmunity in males. Future studies will investigate sex-based mechanisms through which NLRP12 differentially modulates autoimmune outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abdelhamid, Mao, Cabana-Puig, Zhu, Swartwout, Edwards, Testerman, Michaelis, Allen, Ahmed and Luo.)

Vitamin A (VA) deficiency (VAD) is observed in both humans and mice with lupus nephritis. However, whether VAD is a driving factor for accelerated progression of lupus nephritis is unclear. In this study, we investigated the effect of VAD on the progression of lupus nephritis in a lupus-prone mouse model, MRL/lpr. We initiated VAD either during gestation or after weaning to reveal a potential time-dependent effect. We found exacerbated lupus nephritis at ∼15 wk of age with both types of VAD that provoked tubulointerstitial nephritis leading to renal failure. This was concomitant with significantly higher mortality in all VAD mice. Importantly, restoration of VA levels after weaning reversed VAD-induced mortality. These results suggest VAD-driven acceleration of tubulointerstitial lupus nephritis. Mechanistically, at the earlier time point of 7 wk of age and before the onset of clinical lupus nephritis, continued VAD (from gestation until postweaning) enhanced plasma cell activation and augmented their autoantibody production, while also increasing the expansion of T lymphocytes that could promote plasma cell autoreactivity. Moreover, continued VAD increased the renal infiltration of plasmacytoid dendritic cells. VAD initiated after weaning, in contrast, showed modest effects on autoantibodies and renal plasmacytoid dendritic cells that were not statistically significant. Remarkably, analysis of gene expression in human kidney revealed that the retinoic acid pathway was decreased in the tubulointerstitial region of lupus nephritis, supporting our findings in MRL/lpr mice. Future studies will elucidate the underlying mechanisms of how VAD modulates cellular functions to exacerbate tubulointerstitial lupus nephritis., (Copyright © 2023 The Authors.)

Objectives: To investigate the associations between different single-piece monofocal intraocular lenses (IOLs) and neodymium-doped yttrium aluminum garnet laser (Nd:YAG) capsulotomy incidence 3 years after cataract surgery in a Spanish cohort., Methods: This is a longitudinal retrospective cohort study. Data were extracted from the electronic medical records of two large regional hospitals in Spain. Patients aged ≥65 years receiving cataract surgery with placement of five different IOLs and with ≥6 months of baseline data were included. We report the Nd:YAG capsulotomy incidence 3 years post cataract surgery, and the survival plot over the 3 years of follow-up time. The associated adjusted (age, gender, and diabetic retinopathy) multivariate analysis with odds ratios (ORs) and 95% CIs is also presented., Results: The cohort (53% female, mean age 75 ± 5.9 years) included 14,519 eyes (Alcon AcrySof = 2968, AJL LLASY60 = 1776, Medicontur Bi-flex = 5176, Zeiss Asphina = 4478, and IOL Tech Stabibag = 121). Of these, 8293 were retained until 3-year follow-up. At 3 years after cataract surgery, the Nd:YAG capsulotomy incidence was 5% for Alcon AcrySof, while it ranged from 21.2% to 31.1% for the other IOLs (p < 0.0001 for each comparison). The odds for Nd:YAG capsulotomy were significantly higher (p < 0.0001) for other IOLs compared with those of Alcon AcrySof (ORs = 8.85, 5.86, 5.74, 5.21 for AJL LLASY60, Medicontur Bi-flex, IOL Tech Stabibag, and Zeiss Asphina, respectively)., Conclusions: The lower Nd:YAG capsulotomy rates for Alcon AcrySof IOLs compared to the other IOLs support the importance of lens choice in reducing patient burden and treatment costs., (© 2021. The Author(s).)

Objective: To assess whether alcohol intake is associated with the onset of migraine attacks up to 2 days after consumption in individuals with episodic migraine (EM)., Background: Although alcohol has long been suspected to be a common migraine trigger, studies have been inconclusive in proving this association., Methods: This was an observational prospective cohort study among individuals with migraine who registered to use a digital health platform for headache. Eligible individuals were aged ≥18 years with EM who consumed alcohol and had tracked their headache symptoms and alcohol intake for ≥90 days. People who did not drink any alcohol were excluded. The association of alcohol intake ("Yes/No") and of the number of alcoholic beverages in the 2 days preceding a migraine attack was assessed accounting for the presence of migraine on day-2 and its interaction with alcohol intake on day-2, and further adjusted for sex, age, and average weekly alcohol intake., Results: Data on 487 individuals reporting 5913 migraine attacks and a total of 40,165 diary days were included in the analysis. Presence of migraine on day-2 and its interaction with alcohol intake on day-2 were not significant and removed from the model. At the population level, alcohol intake on day-2 was associated with a lower probability of migraine attack (OR [95% CI] = 0.75 [0.68, 0.82]; event rate 1006/4679, 21.5%), while the effect of alcohol intake on day-1 was not significant (OR [95% CI] = 1.01 [0.91, 1.11]; event rate 1163/4679, 24.9%) after adjusting for sex, age, and average weekly alcohol intake. Similar results were obtained with the number of beverages as exposure., Conclusions: In this English-speaking cohort of individuals with EM who identified themselves as mostly low-dose alcohol consumers, there was no significant effect on the probability of a migraine attack in the 24 h following consumption, and a slightly lower likelihood of a migraine attack from 24 to 48 h following use., (© 2022 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Commensal bacteria and the immune system have a close and strong relationship that maintains a balance to control inflammation. Alterations of the microbiota, known as dysbiosis, can direct reactivity to self-antigens not only in the intestinal mucosa but also at the systemic level. Our laboratory previously reported gut dysbiosis, particularly lower abundance of bacteria in the family Lactobacillaceae , in lupus-prone MRL/ lpr mice, a model of systemic autoimmunity. Restoring the microbiota with a mix of 5 different Lactobacillus species (spp.), L. reuteri, L. oris, L. johnsonii, L. gasseri and L. rhamnosus , attenuated lupus-liked clinical signs, including splenomegaly and lymphadenopathy. However, our understanding of the mechanism was limited. In this study, we first investigated the effects of individual species. Surprisingly, none of the species individually recapitulated the benefits of the mix. Instead, Lactobacillus spp. acted synergistically to attenuate splenomegaly and renal lymphadenopathy through secreted factors and a CX 3 CR1-dependent mechanism. Interestingly, oral administration of MRS broth exerted the same benefits likely through increasing the relative abundance of endogenous Lactobacillus spp. Mechanistically, we found increased percentages of FOXP3-negative type 1 regulatory T cells with administration of the mix in both spleen and mesenteric lymph nodes. In addition, oral gavage of Lactobacillus spp. decreased the percentage of central memory T cells while increasing that of effector memory T cells in the lymphoid organs. Furthermore, a decreased percentage of double negative T cells was observed in the spleen with the mix. These results suggest that Lactobacillus spp. might act on T cells to attenuate splenomegaly and lymphadenopathy. Together, this study advances our understanding of how Lactobacillus spp. attenuate lupus in MRL/ lpr mice. The synergistic action of these bacteria suggests that multiple probiotic bacteria in combination may dampen systemic autoimmunity and benefit lupus patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cabana-Puig, Mu, Lu, Swartwout, Abdelhamid, Zhu, Prakash, Cecere, Wang, Callaway, Sun, Reilly, Ahmed and Luo.)

Systemic lupus erythematosus (SLE) is an autoimmune disorder with no known cure and is characterized by persistent inflammation in many organs, including the kidneys. Under such circumstances, the kidney loses its ability to clean waste from the blood and regulate salt and fluid concentrations, eventually leading to renal failure. Women, particularly those of childbearing age, are diagnosed nine times more often than men. Kidney disease is the leading cause of mortality in SLE patients. The present protocol describes a quick and simple method to measure excreted protein levels in collected urine, tracking lupus progression over time. In addition, an approach to isolate kidney mononuclear cells is provided based on size and density selection to investigate renal infiltration of leukocytes. Furthermore, an immunohistochemical method has been developed to characterize protein deposition in the glomeruli and leukocyte infiltration in the tubulointerstitial space. Together, these methods can help investigate the progression of chronic inflammation associated with the kidneys of lupus-prone MRL/lpr mice.

Gut microbiota has an important role in educating the immune system. This relationship is extremely important for understanding autoimmune diseases that are not only driven by genetic factors, but also environmental factors that can trigger the onset and/or worsen the disease course. A previously published study on the dynamics of the gut microbiota in lupus-prone MRL/lpr female mice showed how changes of the gut microbiota can alter disease progression. Here, a protocol is described for extracting representative samples from the gut microbiota for studies of autoimmunity. Microbiota samples are collected from the anus and processed, from which the DNA is extracted using a phenol-chloroform method and purified by alcohol precipitation. After PCR is performed, purified amplicons are sequenced using a Next Generation Sequencing platform at Argonne National Laboratory. Finally, the 16S ribosomal RNA gene sequencing data is analyzed. As an example, data obtained from gut microbiota comparisons of MRL/lpr mice with or without CX3CR1 are shown. Results showed significant differences in genera containing pathogenic bacteria such as those in the phylum Proteobacteria, as well as the genus Bifidobacterium, which is considered part of the healthy commensal microbiota. In summary, this simple, cost-effective DNA isolation method is reliable and can help the investigation of gut microbiota changes associated with autoimmune diseases.

MRL/lpr mice have been extensively used as a murine model of lupus. Disease progression in MRL/lpr mice can differ among animal facilities, suggesting a role for environmental factors. We noted a phenotypic drift of our in-house colony, which was the progeny of mice obtained from The Jackson Laboratory (JAX; stocking number 000485), that involved attenuated glomerulonephritis, increased splenomegaly, and reduced lymphadenopathy. To validate our in-house mice as a model of lupus, we compared these mice with those newly obtained from JAX, which were confirmed to be genetically identical to our in-house mice. Surprisingly, the new JAX mice exhibited a similar phenotypic drift, most notably the attenuation of glomerulonephritis. Interestingly, our in-house colony differed from JAX mice in body weight and kidney size (both sexes), as well as in splenic size, germinal center formation, and level of anti-dsDNA auto-IgG in the circulation (male only). In addition, we noted differential expression of microRNA (miR)-21 and miR-183 that might explain the splenic differences in males. Furthermore, the composition of gut microbiota was different between in-house and new JAX mice at early time points, which might explain some of the renal differences (e.g., kidney size). However, we could not identify the reason for attenuated glomerulonephritis, a shared phenotypic drift between the two colonies. It is likely that this was due to certain changes of environmental factors present in both JAX and our facilities. Taken together, these results suggest a significant phenotypic drift in MRL/lpr mice in both colonies that may require strain recovery from cryopreservation., (Copyright © 2022 The Authors.)