Relationship between the main components of the crystalline lens and the anterior chamber depth after cataract formation

Producción CientíficaPurpose To assess the relationship between anterior chamber depth (ACD) and lens thickness (LT), as well as its three main components (anterior and posterior cortex and nucleus thickness), in cataractous and non-cataractous eyes, depending on the axial length (AxL). Methods Anterior and posterior cortex and nucleus thickness of the crystalline lens, ACD, and AxL were measured using optical low-coherence reflectometry in cataractous and non-cataractous eyes. They were also classified into hyperopia, emme- tropia, myopia, and high myopia, depending on AxL; thus, eight subgroups were created. A minimum sample size of 44 eyes (of 44 patients) for each group was recruited. Linear models were fitted for the whole sample and each AxL subgroup to assess if there were differences in the relationships between the crystalline lens variables and ACD, including age as a covariate. Results Three hundred seventy cataract patients (237 females, 133 males) and 250 non-cataract controls (180 females, 70 males), aged 70.5 ± 9.4 and 41.9 ± 15.5 years, respectively, were recruited. The mean AxL, ACD, and LT for the cataractous and non-cataractous eyes were 23.90 ± 2.05, 24.11 ± 2.11, 2.64 ± 0.45, and 2.91 ± 0.49, 4.51 ± 0.38, 3.93 ± 0.44 mm, respec- tively. The inverse relationship of LT, anterior and posterior cortex, and nucleus thickness with ACD was not significantly (p ≥ 0.26) different between cataractous and non-cataractous eyes. Further subclassification of the sample depending on AxL showed that the inverse relationship between the posterior cortex and ACD was no longer significant (p > 0.05) for any non-cataractous AxL group. LT, anterior and posterior cortex, and nucleus thickness was not significantly (p ≥ 0.43) different between cataractous and non-cataractous eyes for the whole sample, and all AxL groups after adjusting for age. Conclusions The presence of cataracts does not modify the inverse relationship of the LT, anterior and posterior cortex, and nucleus with ACD. And this relationship does not seem to depend importantly on AxL. Besides, the possible differences in LT, anterior and posterior cortex, and nucleus between cataractous and non-cataractous eyes may not be caused by lens opacification, but possibly by the progressive lens growth due to aging.Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) through Research Projects (RETICS RD16/008/0001)Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Can we measure mesopic pupil size with the cobalt blue light slit-lamp biomicroscopy method?

Producción CientíficaThe aim of this work is to assess a previously described slit-lamp biomicroscopy-based method (SLBM) for measuring pupil diameter and compare it to Colvard infrared pupillometry (CIP). METHODS: Two examiners performed three repeated measurements with each instrument in 40 healthy eyes. We determined the agreement of SLBM and CIP, intraobserver and interobserver repeatabilities, and interobserver concordance (kappa) and SLBM ability for detecting pupil sizes over 6.0 mm. RESULTS: The mean (±standard deviation [SD]) pupil diameter was 5.81 ± 0.70 mm with SLBM and 6.26 ± 0.68 mm with CIP (p = 0.01) averaging both examiner's results. Mean differences between the SLBM and CIP were -0.60 mm and -0.30 mm for each examiner using the average of the three readings (p = 0.02), and they were very similar using the first reading. Intraobserver reproducibility: the width of the 95% LoA ranged from 1.79 to 2.30 mm. The ICCs were 0.97 and 0.92 for SLBM, and 0.96 and 0.90 for CIP. Interobserver reproducibility: the width of the LoA ranged from 1.82 to 2.09 mm. Kappa statistics were 0.39 and 0.49 for the first and mean SLBM readings, respectively, and 0.45 for both the first and mean CIP readings. Sensitivity and specificity of SLBM for detection of pupils larger than 6 mm ranged from 55.56% to 73.68% and from 76.19% to 95.45%, respectively. The best trade-off between sensitivity and specificity ranged from 5.4 mm to 6.2 mm. CONCLUSIONS: Although the SLBM is quite repeatable, it underestimates mesopic pupil size and shows a too wide range of agreement with CIP. SLBM shows low sensitivity in detecting pupils larger than 6 mm, which may be misleading when planning anterior segment surgery. Previous grading-consensus training strategies may increase interrater reproducibility, and compensation for the systematic underestimation could improve accuracy of the SLBM

Epithelial cells removed in advanced surface ablation (ASA) surgery can be used as a source of corneal samples to perform in vitro studies

Producción CientíficaHuman corneal epithelial cells are needed to study corneal pathophysiology in vitro. Due to the limitations of cell lines, the use of primary cells is highly desirable, but the scarcity of human tissues, along with ethical issues, make it difficult to accomplish all required experiments. In advanced surface ablation (ASA), the central corneal epithelium is removed and discarded. We hypothesized that ASA samples could be used to perform in vitro assays. In this study, 29 samples from patients undergoing ASA were recovered in supplemented DMEM/F12 culture medium, RIPA buffer, or RLT lysis buffer. The first aim was to determine whether cells could be maintained in culture. Although with the explant technique, tissue pieces did not attach to the culture surface, after disaggregation, cells showed high viability (90.0 ± 6.0%), attached to plates, and remained viable for up to 14 days. The second aim was to elucidate if ASA samples could be used to study protein or gene expression. Cytokeratin-3, ZO-1, Ki67, and E-cadherin protein expression were confirmed by immunofluorescence. Total protein (485.8 ± 115.8 μg) was isolated from cells in RIPA buffer, and GAPDH was detected by Western blotting, indicating that samples are adequate for protein studies. RNA (9.0 ± 3.6 μg) was isolated from samples in RLT lysis buffer, and GAPDH gene expression was studied by PCR, confirming that samples were also suitable for gene expression studies. These results suggest that samples obtained from corneal surface ablation procedures may constitute a valuable source of human cells to accomplish in vitro studies.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project FEDER-CICYT MAT2013-47501-C02-R)Ministerio de Ciencia, Innovación y Universidades - Fondo Europeo de Desarrollo Regional (project RTI2018-094071-B-C21

Mesopic Disability Glare in Stage-Two Dysfunctional Lens Syndrome

To analyze visual function under different conditions and glare sources in stage-2 dysfunctional lens syndrome (DLS). Forty patients over 49 years of age with initial bilateral lens opacification (Lens Opacities Classification System III [LOCS-III] scores up to 3), best-corrected visual acuity of 20/25 or better, and no ocular disease were evaluated. Binocular photopic and mesopic contrast sensitivity (CS) with/without halogen and xenon increasing glare sources were analyzed. Mesopic disability glare (MDG) was calculated as the difference between mesopic CS with/without the glare source. The median logarithmic CS (logCS) values were lower under mesopic conditions (1.05) than under photopic illumination (1.65; P < 0.001). Halogen and xenon glare further decreased mesopic CS (both, median logCS 0.75, P < 0.001). The mean MDG was 0.31 ± 0.10 log units for halogen glare and 0.33 ± 0.09 log units for xenon glare. The mesopic CS and MDG were not associated with any photopic test. The mesopic CS with glare but not photopic CS or mesopic CS was correlated with the LOCS-III scores. The best association was provided by MDG, which showed a pooled correlation with LOCS-III nuclear opalescence (r = 0.411, P < 0.001) and cortical scores (r = 0.226, P = 0.04). The mesopic CS under a glare source is an independent early indicator of visual impairment in stage-2 DLS patients, and appears to be substantial. Furthermore, the MDG is more sensitive than photopic and mesopic CS for evaluating patients with initial phacosclerosis. Surgeons should consider this in the decision-making process of the correct timing for lens surgery.This work was supported in part by the Spanish Ministry of Interior (Directorate-General for Traffic) through call for Complementary R&D Projects and Grants in Traffic, Mobility and Road Safety INT/864/2014, Madrid, Spain. AH and EM-P were supported by Junta de Castilla y León and European Social Fund (EDU/556/2019 and EDU/1100/2017, respectively), Castilla y León, Spain. No funding or sponsorship was received for publication of this article

Moderating Effect of Changes in Perceived Social Support during Pregnancy on the Emotional Health of Mothers and Fathers and on Baby’s Anthropometric Parameters at Birth

(1) Background: this study is based on a model of how changes in protective factors may affect the emotional health of mothers and fathers and thus influence the development of the baby. Our research goal is to determine whether variations in perceived social support moderate levels of stress and depression during pregnancy and/or the effect of parents’ emotional health on the baby’s anthropometric parameters. (2) Methods: to achieve these aims, a longitudinal study was made of 132 couples and babies, who were evaluated at weeks 12 and 32 of gestation and at birth. Separate analyses were performed for the mothers and fathers, focused on the role of social support in moderating their levels of depression and stress during pregnancy, and the consequent impact on the baby. (3) Results: the results obtained show the moderating effects of changes in social support on maternal and paternal stress and depression. Reduced social support during pregnancy is associated with higher levels of stress and depression in both parents and with a high cephalisation index in their babies. (4) Conclusions: special attention should be paid to social support, which can have a strong impact on the evolution of emotional health during pregnancy and concomitantly on the development of the baby.University of Granada (Spain)Andalusian Public Foundation for Biosanitary Research Eastern Andalusia (Spain)Regional Ministry of Health within Junta de Andalucia (Spain) PC-0526-2016-052

Evaluating the cancer therapeutic potential of cardiac glycosides

Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na(+)/K(+)-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studie

Diabetes Mellitus and Amyloid Beta Protein Pathology in Dementia

Amyloidosis is a pathological condition which consists on the accumulation of fibrillar proteins. This disease is characterized by extracellular amyloid deposits with a clinical variability depending on the affected tissue. Histopathological evidence indicates that diabetes mellitus type 2 (DM2) induces dementia development, specifically Alzheimer’s disease (AD). It has been demonstrated in animal subjects that there is a possibility that aberrant signaling of insulin is a key factor in the induction of the pathology of AD. Recently, there has been newly emerged evidence regarding the relationship between the pathogenesis of Parkinson’s disease (PD) and insulin resistance. On another note, the importance of the amyloid deposits in the patients’ pancreas with DM2 was evidenced by the discovery of islets of amyloid polypeptide. This has generated interest in the search of the etiopathogenic role of DM2 in the carbohydrates’ metabolism. Finally, it is important to consider DM2 as a risk factor essential for the formation of deposits of amyloid-β in patients’ brains with dementia

Safety, biocompatibility, and potential functionality of a new accommodative intraocular lens: An experimental study in rabbits

Producción CientíficaThis study aims to evaluate the safety, biocompatibility, and functionality of a new accommodative intraocular lens (IOL) (LUZ, patent PCT/ES2016/070,813) after implantation in rabbit eyes. LUZ (Study) and EyeCee® plus a capsular ring (Control) were implanted in rabbits (n = 8 each) after phacoemulsification. Intraoperative follow-up, long-term clinical follow-up, and functional IOL studies were carried out periodically for up to 180 days. A macroscopic examination of the eyeballs to reveal abnormalities and determine the implant centering and a microscopic examination to semi-quantify cell and tissue response were performed. Statistical analysis of the collected data was finally achieved. During follow-up, no significant changes in the general condition nor the clinical evaluation were observed between both groups. However, Study IOL remained centered throughout the study and did not present severe complications as observed in the Control group. Functional studies did not reveal significant differences between both materials. Study showed better centering, fewer adhesions, and maintenance of an opening capsular bag compared to the Control. Local biological effects caused by Study implantation are minimal and comparable to the Control. Therefore, LUZ showed no clinical signs or histological response of adverse reaction to the implanted material, according to UNE-EN ISO 11979-5 and 10993-6. Functionality must be confirmed in another animal species with greater lens accommodation capacity than the rabbit. LUZ keeps the capsular bag open, favoring its centering and avoiding fibrosis and adherence to the bag; this allows potential accommodation of this IOL and theoretically enables the patient to focus dynamically.Ministerio de Ciencia e Innovación (Neotec Project EXP-00104711/SNEO-20171172

Impact of contact lens wear on epithelial alterations in keratoconus

Purpose The purpose of this study was to characterize the central epithelial thickness (CET) of penetrating keratoplasty corneal specimens obtained from patients with keratoconus (KC) and correlate the histological patterns with their clinical history.Methods Ex vivo histological imaging was performed to measure CET and total corneal thickness (TCT) in 56 patients with KC. Microscopic slides from penetrating keratoplasty corneal specimens, stained with hematoxylin and eosin were evaluated using bright field microscopy. CET and TCT were measured, and morphological features were studied. Clinical history regarding duration of KC prior to surgery and length of and tolerance to contact lens wear were compared and analyzed. Results The microscopic slides of all patients available for follow up (n = 48) were analyzed and CET and TCT were measured. The histological evaluation revealed 3 distinctive epithelial patterns. Pattern 1 with central hypertrophic and hydropic changes (n = 19) measured 70.89 ± 25.88 μm in CET and 308.63 ± 100.74 μm in TCT; Pattern 2 (n = 14) had not changed, similar to normal epithelium CET and TCT measuring 36.5 ± 7.02 μm and 260.14 ± 87.93 μm respectively. Pattern 3 (n = 15) demonstrated thinner central epithelium characterized by atrophy and focal hydropic changes measuring 19.93 ± 4.60 μm and 268.00 ± 79.39 μm in CET and TCT respectively (all p < 0.0001). The presence of Pattern 2 characterized by similar to normal CET was correlated with the duration of the condition (R = 0.600, p = 0.030). There was a significant difference in the length of CL wear comparing those with patterns 1 and 2 versus 3 (least no. of CL years) (p = 0.05 and p = 0.33 respectivelly). Conclusions Patients with advanced disease have various central corneal epithelial changes detected with histology. Although each central epithelial pattern type was distinctive comparing the 3 patterns, there was no correlation with years of CL wear but only with the duration of the condition.Office of Research of the University of Waterlo

Validation and functional characterization of GWAS-identified variants for chronic lymphocytic leukemia: a CRuCIAL study

This work was partially supported by the European Union's Horizon 2020 research and innovation program (grant No 856620); grants from the Instituto de Salud Carlos III (Madrid, Spain; PI17/02256 and PI20/01845); Consejeria de Economia, Conocimiento, Empresas y Universidad (Granada, Spain; A-CTS-448-UGR18); Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (Sevilla, Spain; PY20/01282); Generalitat de Catalunya (17SGR437); Gilead Sciences Fellowship (GLD17/00282); the "Xarxa de Bancs de tumors" sponsored by Pla Director d'Oncologia de Catalunya (XBTC); the Associazione Italiana per la Ricerca sul Cancro and Fondazione Cariplo (TRIDEO 16923 and AIRC IG21436); the Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE; and the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), action Genrisk. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.In conclusion, this study confirmed the association of 31 GWASidentified SNPs with CLL risk and shed some light on the function of some of these biomarkers in the modulation of TReg, B, and T cell differentiation and proliferation, blood concentrations of B cell-related proteins, cell survival, and the expression of immuneand non-immune-related loci. Though outside the scope of the current study, it is important to mention that additional functional studies using blood samples from CLL patients are still required to validate our findings and to decipher the exact biological mechanisms behind the observed associations. A potential limitation of this work was the relatively small population size of the CRuCIAL cohort that hampered the validation of the SNPs showing modest associations.European Union's Horizon 2020 research and innovation program 856620Instituto de Salud Carlos III PI17/02256 PI20/01845Consejeria de Economia, Conocimiento, Empresas y Universidad (Granada, Spain) A-CTS-448-UGR18 Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (Sevilla, Spain) PY20/01282Generalitat de CatalunyaGeneral Electric 17SGR437Gilead Sciences GLD17/00282"Xarxa de Bancs de tumors" - Pla Director d'Oncologia de Catalunya (XBTC)Fondazione AIRC per la ricerca sul cancro Fondazione Cariplo TRIDEO 16923 AIRC IG21436Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MOREConsortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), action Genris