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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.