Astigmatism and Pseudoaccommodation in Pseudophakic Eyes

noAdvanced IOLs with circumferential zones of different power provide pseudoaccommodation. We investigated the potential for power variation with meridian, namely astigmatism, to provide pseudo-accommodation. With appropriate power and axis orientations, acceptable pseudo-accommodation can be achieved

A nature-inspired protocol to generate mature hiPSC-derived hepatocytes: Unveiling the role of human intestinal microbiome

The production of hepatocytes derived from human induced pluripotent stem cells (hiPSC-HLC) holds great promise for multiple cell therapies and tissue engineering applications. Nonetheless, the current protocols to generate HLC in vitro are not yet successfully established resulting in low yields of mainly immature cells when compared to the adult counterparts. The major hurdle in recapitulating in vitro the physiological liver maturation process is due to its complexity as it takes approximately 2 years after birth and involves a wide range of biological events (1). Recent findings have been suggesting that liver maturation, that naturally occur during the early postnatal period, can be strongly associated with human intestinal microbiome (2). For example, lithocholic acid and vitamin K2, two intestinal postbiotics, were shown to induce the expression of CYP450 enzymes in HLC and fetal hepatocytes (3). Additionally, studies on germ-free animals reported dissimilar xenobiotic enzyme profiles (4) and an impaired liver regeneration (5) compared to wild type animals. Considering these evidences, we developed a nature-inspired bioprocess to produce relevant numbers of highly functional and mature HLC for application in regenerative medicine. In this study, hiPSC-HLC were generated as 3D cell aggregates in stirred-tank bioreactors according to the integrated bioprocess developed previously by our group (6), and matured with a novel strategy based on human intestinal microbiota’s secretome. The maturation profile of hiPSC-HLC was evaluated at transcriptional and functional levels, and the composition of microbial secretome formulation was also characterized by UPLC-MS/MS, GC-MS and LC–MS/MS technologies. Our results showed an efficient hiPSC differentiation into hepatic lineage with a production of 2.8x106 HLC/mL (~370 million cells in a 200mL ST-BR), displaying a mixture of adult (~80%ALB+ cells) and fetal traits (~30%AFP+ cells and CYP3A7+ cells). Noteworthy, HLC treated with bacterial secretome showed higher ALB expression (87%ALB+ cells), ALB and A1AT secretion, urea synthesis, and basal and inducible CYP3A4 metabolism, when compared to untreated HLC that were cultured in standard hepatocyte maintenance medium. Detailed analytical characterization of the microbial secretome revealed some of the potential biologically active molecules, such as bile acids, short-chain fatty acids and vitamins that could be responsible for HLC in vitro maturation. In conclusion, the protocol developed herein presents high technological relevance due to its efficiency, scalability, and reproducibility, but also unveils the potential role of human intestinal microbiome in hepatic cell maturation. Noteworthy, we also demonstrated that the 3D aggregates of mature hiPSC-HLC were able to adhere and migrate in human hepatic extracellular matrix scaffolds, while maintained their viability and functional features, showing to hold great promise to be used as cell therapy products or as cell ingredients for liver bioengineering applications. This work was funded by Projects EHD16PI02 from CIBERehd and LMP226_18 funded by DGA (Spain) as well as by Fundação para a Ciência e Tecnologia (FCT)-funded projects ERAdicatPH (E-Rare3/0002/2015) and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344). J.I. A. and P.V. were supported by FCT fellowships SFRH/BD/116780/2016 and SFRH/BD/145767/2019, respectively. [1] Chen C, Soto-Gutierrez A, Baptista PM, Spee B. Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells. Gastroenterology. 2018;154(5):1258–72; [2] Almeida, Joana I., Miguel F. Tenreiro, Lucía Martinez-Santamaria, Aspizua, Sara Guerrero, Javier P. Gisbert, Paula M. Alves, Margarida Serra PMB. Hallmarks of the human intestinal microbiome on liver maturation and function. J Hepatol. 2021; [3] Avior Y, Levy G, Zimerman M, Kitsberg D, Schwartz R, Sadeh R, et al. Microbial-Derived Lithocholic Acid and Vitamin K2 Drive the Metabolic Maturation of Pluripotent Stem Cells-Derived and Fetal Hepatocytes. Hepatology. 2015;62(1):265–78; [4] Selwyn FP, Cheng SL, Bammler TK, Prasad B, Vrana M, Klaassen C, et al. Developmental regulation of drug-processing genes in livers of germ-free mice. Toxicol Sci. 2015;147(1):84–103; [5] Cornell RP, Liljequist BL, Bartizal KF. Depressed liver regeneration after partial hepatectomy of germ‐free, athymic and lipopolysaccharide‐resistant mice. Hepatology. 1990;11(6):916–22; [6] Isidro, I., Vicente, P., Pais, D., Almeida, Joana I., Domingues, M., Abecasis, B., Mertinez-Turrillas, R., Rodriguez-Madoz, Juan R., Aspegren, A., Alves, Paula M., Serra M. On-line monitoring of hiPSC expansion and hepatic differentiation process in a 3D culture system by dielectric spectroscopy. Biotechnol Bioeng

Analysis of a Non-Iterative Algorithm for the Amplitude and Phase Difference Estimation of Two Acquired Sinewaves

In this paper, a non-iterative algorithm for amplitude and phase difference estimation of two acquired sinewaves is presented and analyzed. The method is based on the least-squares fitting of ellipses where the common signal frequency is eliminated from the algorithm

Visual status in a Portuguese population with intellectual disability

Background: Neurosensory deprivation associated with vision is a well-known fact in people with intellectual disability (ID). This work aims to report the visual status of a population with ID in Portugal. Methods: A vision screening protocol was conducted during two Special Olympics events. The vision protocol included personal medical history, ocular health evaluation, and clinical measures, such as visual acuity (VA), binocular vision, colour vision, refractive error, and intraocular pressure. This protocol was administered to 134 subjects. Results: Half of the subjects reported that they had never attended or they did not remember having attended a previous eye exam. Additionally, 10% of them had not attended an eye exam in the immediate past three years. Half the subjects failed the VA test and 13% presented moderate Visual Impairment (VI) (VA worse than 0.5 logMAR in the best eye). Manifest ocular deviation was found in 25% of the subjects and the most common ocular health dysfunction conditions were conjunctiva hyperaemia, meibomian gland dysfunction, and lens anomalies. Refractive error correction allowed a reduction in the level of moderate VI to 3.7%. Conclusions: The population analysed showed a poor eye care attendance rate and vision-related conditions are in agreement with previous reports. The development of national strategies to promote the awareness for routine eye care in people with ID and improving accessibility to eye care services may mitigate many of the most prevalent conditions encountered.ISA -Instituto Superior de Agronomia(undefined

Interference between variants of peach latent mosaic viroid reveals novel features of its fitness landscape: implications for detection

[EN] Natural populations of peach latent mosaic viroid (PLMVd) are complex mixtures of variants. During routine testing, TaqMan rtRT-PCR and RNA gel-blot hybridization produced discordant results with some PLMVd isolates. Analysis of the corresponding populations showed that they were exclusively composed of variants (of class II) with a structural domain different from that of the reference and many other variants (of class I) targeted by the TaqMan rtRT-PCR probe. Bioassays in peach revealed that a representative PLMVd variant of class II replicated without symptoms, generated a progeny with low nucleotide diversity, and, intriguingly, outcompeted a representative symptomatic variant of class I when co-inoculated in equimolecular amounts. A number of informative positions associated with the higher fitness of variants of class II have been identified, and novel sets of primers and probes for universal or specific TaqMan rtRT-PCR detection of PLMVd variants have been designed and tested.We thank A. Ahuir for excellent technical assistance and Dr. Francesco Di Serio for suggestions. This work was supported by grant BFU2014-56812-P (to R.F.) from Ministerio de Economia y Competitividad (MINECO) of Spain. P.S. was the recipient of a postdoctoral contract from MINECO and E. Bertolini of an INIA-CCA2011-2016 contract also from MINECO.Serra Alfonso, P.; Bertolini, E.; Martinez, MC.; Cambra, M.; Flores Pedauye, R. (2017). Interference between variants of peach latent mosaic viroid reveals novel features of its fitness landscape: implications for detection. Scientific Reports. 7. https://doi.org/10.1038/srep42825S7Diener, T. O. Discovering viroids - a personal perspective. Nat. Rev. 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Posterior chamber phakic intraocular lenses for the correction of myopia: factors influencing the postoperative refraction

Posterior chamber phakic intraocular lens implantation is a refractive technique for the correction of myopia. This study aimed to identify those factors contributing to variability in postoperative refraction. Methods: This retrospective study evaluated 73 eyes (one eye per patient) implanted with myopic implantable collamer lenses (ICL). Eyes were divided into two groups, the low myopic group (LMG) (ICL > −9.5 DS) and the high myopic group (HMG) (ICL ≤ −9.5 DS), to compare the predictability, efficacy index, and postoperative refraction between groups. The association of postoperative refraction with anatomical, demographic, and optical features was assessed through correlation analysis and investigated using ray-tracing. Results: Postoperative refraction at 3 months for the whole group was close to emmetropia at −0.02 ± 0.37 DS, the LMG tended toward myopia and the HMG, toward hyperopia. The results showed that 65% and 54% of the eyes had postoperative refraction of within ±0.25 DS, respectively, in the LMG and HMG, and in both groups, 100% were within ±1.00 DS. ICL implantation had a higher efficacy index in the HMG (1.13 ± 0.15) than in the LMG (1.04 ± 0.15). Postoperative refraction was positively associated with the vault (R = 0.408) and negatively correlated with ICL power (R = −0.382). Conclusion: The predictability and effectiveness of ICL implantation is high in a wide range of myopias. Considering the expected vault and including accurate vertex measurements would contribute to improving the predictability of the results

Towards large-scale production of human-induced pluripotent stem cell-derived extracellular vesicles in stirred-tank bioreactors

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Biometric and ICL-related risk factors associated to sub-optimal vaults in eyes implanted with implantable collamer lenses

The data used in this study can be requested by contacting the corresponding author.Background: To identify biometric and implantable collamer lens (ICL)-related risk factors associated with sub-optimal postoperative vault in eyes implanted with phakic ICL. Methods: This study reports a retrospective case series of the first operated eye in 360 patients implanted with myopic spherical or toric ICL. Preoperatively, white-to-white (WTW), central keratometry (Kc) and central corneal thickness (CCT) were measured using the Pentacam. Anterior-segment optical coherence tomography (AS-OCT, Visante) was applied preoperatively for measuring the horizontal anterior-chamber angle-to-angle distance (ATA), internal anterior chamber depth (ACD), crystalline lens rise (CLR), anterior-chamber angle (ACA) and postoperatively the vault. Eyes were divided into three vault groups: low (LVG: ≤ 250 μm), optimal (OVG: > 250 and < 1000 μm) and high (HVG: ≥ 1000 μm). Multinomial logistic regression (MLR) was used to find the sub-optimal vault predictors. Results: MLR showed that CLR, ICL size minus the ATA (ICL size-ATA), age, ICL spherical equivalent (ICLSE) and ICL size as contributing factors for sub-optimal vaults (pseudo-R2 = 0.40). Increased CLR (OR: 1.01, CI: 1.00–1.01) and less myopic ICLSE (OR: 1.22, CI: 1.07–1.40) were risk factors for low vaults. Larger ICL size-ATA (OR: 41.29, CI: 10.57–161.22) and the 13.7 mm ICL (OR: 7.08, CI: 3.16–15.89) were risk factors for high vaults, whereas less myopic ICLSE (OR: 0.85, CI: 0.76–0.95) and older age (OR: 0.92, CI: 0.88–0.98) were protective factors. Conclusion: High CLR and low ICLSE were the major risk factors in eyes presenting low vaults. In the opposite direction, ICL size-ATA was the major contributor for high vaults. This relationship was more critical in higher myopic ICLSE, younger eyes and when 13.7 mm ICL were used. The findings show that factors influencing the vault have differentiated weight of influence depending on the type of vault (low, optimal or high)