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RE Ang,1,2 GA Martinez,2,3 EM Cruz,1 AA Tiongson,1 AG Dela Cruz1 1Asian Eye Institute, Makati City, Philippines; 2Cardinal Santos Medical Center, San Juan City, Philippines; 3Pasig City General Hospital, Pasig City, Philippines Purpose: To compare the visual acuity and quality of vision achieved with three widely-used intraocular lenses (IOLs) in subjects with bilateral cataracts. Patients and methods: This three-arm, parallel, prospective, partially masked, single-surgeon study randomized 78 subjects to receive bilateral Crystalens® Advanced Optics (AO) accommodating IOLs, AcrySof® IQ ReSTOR® +3.0 multifocal IOLs, or TECNIS® Multifocal IOLs. Examinations were assessed through days 120 to 180. Results: The Crystalens AO group had statistically significantly better monocular and binocular, high-contrast (HC) and low-contrast (LC) uncorrected intermediate visual acuity, HC and LC distance-corrected intermediate visual acuity, and significantly fewer monocular and binocular halos and starbursts than did the ReSTOR and TECNIS groups. Monocular and binocular, HC and LC uncorrected near visual acuity exhibited no significant differences among the three lenses. For monocular and binocular HC distance-corrected near visual acuity, the Crystalens AO performed significantly better than the TECNIS and was not significantly different from the ReSTOR. For monocular and binocular LC distance-corrected near visual acuity, the Crystalens AO performed significantly better than both the ReSTOR and the TECNIS. Contrast sensitivity was clinically similar between groups. The Crystalens AO produced statistically fewer halos and starbursts. Conclusion: All three IOLs had excellent uncorrected acuity results at all distances and had good safety, confirming the established safety and effectiveness of these IOLs. Distance and near vision were similar between all three IOLs, and the Crystalens AO provided statistically significantly better intermediate vision. Keywords: Crystalens, accommodating, AcrySof, TECNIS, multifocal

Background: This study aimed at describing the demographic and clinical characteristics, treatment patterns and overall survival of patients with MM in Brazil to identify gaps in the disease diagnosis and treatment., Methods: MMyBRAve (NCT03506386) was a multicenter, observational study of patients diagnosed with MM in Brazil between January 2008 and December 2016, with data collection between August 2018 and September 2019 at 17 participating centers., Results: Of 943 patients included, 914 had complete data for overall survival (OS) analysis. The most used frontline regimens were cyclophosphamide, thalidomide and dexamethasone; bortezomib, cyclophosphamide and dexamethasone; and thalidomide and dexamethasone. After a median follow-up of 63 months, the median OS from diagnosis was 70 months. These results indicate continuous improvements in comparison with previous observational studies from Brazil. The median OS in transplantation-ineligible (N = 491) and eligible (N = 452) patients were 49 and 93 months, respectively (hazard ratio [HR] = 0.52; 95% confidence interval [CI], 0.43 to 0.63; P < .001). The median OS also differed between patients with and without known prognostic factors., Conclusion: Despite the improvements, our results suggest that access to novel agents and transplantation continue to hinder further progress in patient outcomes in Brazil and countries with similar health-care constraints., Competing Interests: Disclosure V. HUNGRIA and D.L.C. FARIAS received honoraria as speaker from Takeda. V. HUNGRIA and R. BITTENCOURT received honoraria for advisory committee from Takeda. G. MARTINEZ, J.A. SANTOS, D.R. ALMEIDA, V.L.P. FIGUEIREDO, K.R. ZANELLA, L.B. MUNIZ and E.R. MATTOS don´t have any disclosure. J.T. SENRA and R.M. ABREU are Takeda Pharmaceuticals, Brazil-São Paulo-SP employees., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Epigenetic regulations, such as DNA methylation and microRNAs, play an important role in renal fibrosis. Here, we report the regulation of microRNA219a-2 by DNA methylation in fibrotic kidneys, unveiling the crosstalk between these epigenetic mechanisms. Through genome-wide DNA methylation analysis and pyrosequencing, we detected the hypermethylation of microRNA219a-2 in renal fibrosis induced by unilateral ureteral obstruction (UUO) or renal ischemia/reperfusion, which was accompanied by a significant decrease in microRNA-219a-5p expression. Functionally, overexpression of microRNA219a-2 enhanced fibronectin induction during hypoxia or TGF-β1 treatment of cultured renal cells. In mice, inhibition of microRNA-219a-5p suppressed fibronectin accumulation in UUO and ischemic/reperfused kidneys. Aldehyde dehydrogenase 1 family member L2 (ALDH1L2) was identified to be the direct target gene of microRNA-219a-5p in renal fibrotic models. MicroRNA-219a-5p suppressed ALDH1L2 expression in cultured renal cells, while inhibition of microRNA-219a-5p prevented the decrease of ALDH1L2 in injured kidneys. Knockdown of ALDH1L2 enhanced plasminogen activator inhibitor-1 (PAI-1) induction during TGF-β1 treatment of renal cells, which was associated with fibronectin expression. In conclusion, the hypermethylation of microRNA219a-2 in response to fibrotic stress may attenuate microRNA-219a-5p expression and induce the upregulation of its target gene ALDH1L2, which reduces fibronectin deposition by suppressing PAI-1., (Published by Elsevier Inc.)

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis ( Calr +/- ), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS., Competing Interests: AP, CR, JM, AS, CZ, CV, KR, GG, PD, BH, CU, AW, DB, MC, LA, PE, MS, IK, CG, RF, FR No competing interests declared, (© 2023, Philp et al.)

Glaucoma is considered a neurodegenerative disease characterized by progressive visual field defects that may lead to blindness. Although controlling intraocular pressure (IOP) is the mainstay of glaucoma treatment, some glaucoma patients have unmet needs due to unclear pathogenic mechanisms. Recently, there has been growing evidence that neuroinflammation is a potential target for the development of novel antiglaucoma agents. In this study, we investigated the protective effects and cellular mechanisms of H7E, a novel small molecule inhibits HDAC8, using in vitro and in vivo glaucoma-like models. Importantly, H7E mitigated extracellular MMP-9 activity and MCP-1 levels in glutamate- or S100B-stimulated reactive Müller glia. In addition, H7E inhibited the upregulation of inflammation- and proliferation-related signaling pathways, particularly the ERK and JNK MAPK pathways. Under conditions of oxidative damage, H7E prevents retinal cell death and reduces extracellular glutamate released from stressed Müller glia. In a mouse model of NMDA-induced retinal degeneration, H7E alleviated functional and structural defects within the inner retina as assessed by electroretinography and optical coherence tomography. Our results demonstrated that the newly identified compound H7E protects against glaucoma damage by specifically targeting HDAC8 activity in the retina. This protective effect is attributed to the inhibition of Müller glial activation and the prevention of retinal cell death caused by oxidative stress., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Dermatology is one of the medical fields outside the radiology service that uses image acquisition and analysis in its daily medical practice, mostly through digital dermoscopy imaging modality. The acquisition, transfer, and storage of dermatology images has become an important issue to resolve. We aimed to describe our experience in integrating dermoscopic images into PACS using DICOM as a guide for the health informatics and dermatology community. During 2022 we integrated the video dermoscopy equipment through a strategic plan with an 8-step procedure. We used the DICOM standard with Modality Worklist and Storage commitment. Three systems were involved (video dermoscopy software, the EHR, and PACS). We identified critical steps and faced many challenges, such as the lack of a final model of DICOM standard for dermatology images.

Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. Inflammatory injury and aberrant repair processes contribute to the development of kidney fibrosis. Myeloid cells, particularly monocytes/macrophages, play a crucial role in kidney fibrosis by releasing their proinflammatory cytokines and extracellular matrix components such as collagen and fibronectin into the microenvironment of the injured kidney. Numerous signaling pathways have been identified in relation to these activities. However, the involvement of metabolic pathways in myeloid cell functions during the development of renal fibrosis remains understudied. In our study, we initially reanalyzed single-cell RNA sequencing data of renal myeloid cells from Dr. Denby's group and observed an increased gene expression in glycolytic pathway in myeloid cells that are critical for renal inflammation and fibrosis. To investigate the role of myeloid glycolysis in renal fibrosis, we utilized a model of unilateral ureteral obstruction in mice deficient of Pfkfb3 , an activator of glycolysis, in myeloid cells (Pfkfb3 ΔMϕ ) and their wild type littermates ( Pfkfb3 WT ). We observed a significant reduction in fibrosis in the obstructive kidneys of Pfkfb3 ΔMϕ mice compared to Pfkfb3 WT mice. This was accompanied by a substantial decrease in macrophage infiltration, as well as a decrease of M1 and M2 macrophages and a suppression of macrophage to obtain myofibroblast phenotype in the obstructive kidneys of Pfkfb3 ΔMϕ mice. Mechanistic studies indicate that glycolytic metabolites stabilize HIF1α, leading to alterations in macrophage phenotype that contribute to renal fibrosis. In conclusion, our study implicates that targeting myeloid glycolysis represents a novel approach to inhibit renal fibrosis., 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 Yang, Huo, Cai, Zhang, Dong, Asara, Shi and Wei.)

This study investigated the relationship between nutrient levels, source of fecal contamination, and pathogenic Leptospira in Puerto Rico's northern coast and San Juan Bay Estuary (SJBE) aquatic ecosystems. Microbial source tracking (MST) was also used to investigate the connections between sources of feces contamination and the presence of Leptospira. Eighty-seven water samples were collected during the June (n=44) and August (n=43) in 2020. To quantify phosphorus and nitrogen concentrations, standard USEPA protocols were utilized, specifically Methods 365.4 for total and dissolved phosphorus, 351.2 for total Kjeldahl nitrogen and ammonium, and 353.2 for nitrate. Lipl32 gene-specific quantitative polymerase chain reaction (qPCR) was used to detect the presence of Leptospira. Human (HF183), canine (BacCan-UCD), and equine (HoF597) MST assays were utilized to trace the origins of fecal contamination. Forty one percent of the locations exceeded Puerto Rico's authorized total phosphorus limit of 160 g L -1 , while 34% exceeded the total nitrogen limit of 1700 g L -1 . Nearly half of the streams examined are affected by eutrophication. The MST analysis identified human and canine feces as the most prevalent contaminants, affecting approximately 50% of the sites. In addition, Leptospira was detected in 32% of the June samples. There was a significant correlation (r = 0.79) between the incidence of pathogenic Leptospira and the human bacterial marker (HF183). This study illuminates the central role of anthropogenic inputs in nutrient enrichment and pathogen proliferation in Puerto Rico's aquatic ecosystems., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)