Generation of Induced-Primary Retinal Pigment Epithelium from Human Retinal Organoids.

Retinal pigment epithelium (RPE) cells derived from induced pluripotent stem cells (iPSCs) serve multiple roles, including among others, modeling RPE development in normal and pathological conditions, investigating mechanisms of RPE physiology, modeling retinal diseases involving the RPE, and developing strategies for regenerative therapies. We have developed a simple and efficient protocol to generate RPE tissue from human iPSCs-derived retinal organoids. The RPE tissue present in the retinal organoids is analogous to the native human RPE in differentiation timeline, histological organization, and key features of functional maturation. Building upon this system, we established a method to generate functionally mature, polarized RPE monolayers comparable to human primary RPE. This comprehensive protocol outlines the steps for isolating and culturing RPE tissue using retinal organoids. The outcome is a pure population of cells expressing mature RPE signatures and organized in a characteristic cobblestone monolayer featuring robust ultrastructural polarization. These RPE monolayers also exhibit the functional hallmarks of bona fide mature RPE cells, providing a suitable system to mimic the biology and function of the native human RPE.

Preoperative coagulation tests: A narrative review of current guidelines.

INTRODUCTION: Hemostasis tests are traditionally requested for all patients requiring any surgical act or invasive diagnostic-therapeutic procedure to prevent hemorrhagic complications. The aim of this study is to assess the necessity of requesting standard pre-procedure hemostasis tests. METHODOLOGY: A narrative literature review was conducted using the PubMed data-base. Search terms included «Hemostasis¼ or «Blood coagulation¼ in combination with «Preoperative care¼, «Preoperative period¼, or «Preoperative procedure¼. Additionally, a targeted search was performed to find recommendations from international societies related to the topic. RESULTS: A total of 233 articles were found, 17 were pre-selected, and after full-text evaluation, 14 relevant articles were identified. The targeted search yielded an additional 12 articles. The request for tests should be individualized according to the clinical history. Standardized screening questionnaires for hemostasis disorders are useful and complement the aforementioned approach. Factors such as age, ASA classification, bleeding potential-complexity of the procedure, and anesthetic technique may influence their request. DISCUSSION: The incidence of hemostasis disorders in the general population is very low, and these can mostly be detected through clinical history. Thus, it is the clinical history that should guide the need for laboratory test requests. CONCLUSIONS: Preoperative hemostasis tests should not be indiscriminately requested for all patients needing an intervention or invasive diagnostic-therapeutic procedure, but rather when there are doubts about their hemostatic competence or as advised by the nature of the procedure they are undergoing.

Effects of dietary free fatty acid content and degree of fat saturation on tibia bone properties of laying hens.

Acid oils and fatty acid distillates are fat by-products of the refining process of edible oils and are characterized by their high proportion of free fatty acids (FFA). While lipids are essential in poultry diets, their chemical structure may interfere with calcium absorption. Therefore, this study investigated the effects of dietary FFA content and the degree of fat saturation on bone metabolism in commercial layers. For 15-wk, a total of 144 laying hens (19-wk-old) were randomly assigned to 8 treatments (6 replicates with 3 birds each), which were obtained by gradually replacing crude soybean oil (rich in unsaturated fatty acids [UFA]) with soybean acid oil (rich in UFA and FFA), or crude palm oil (rich in saturated fatty acids [SFA]) with palm fatty acid distillate (rich in SFA and FFA). Following a 2 × 4 factorial design, 4 UFA-rich and 4 SFA-rich diets were created with varying FFA content: 10, 20, 30, and 45%. Tibiae (6 birds/treatment) were collected at the end of the trial for the assessment of mineral composition, morphological properties, and mechanical characteristics. The data were analyzed using a 2-way ANOVA with the GLM procedure. Orthogonal polynomial contrasts were employed to determine the linear effect of increasing %FFA, with statistical significance set at P < 0.05. The degree of saturation was found to negatively impact on calcium and phosphorus bone content, with higher levels found in soybean-based diets (P < 0.001). A significant interaction was observed for medullary bone mineral content, showing a linear decrease as the dietary %FFA increased (P < 0.05) in palm diets. In contrast, morphological and mechanical bone traits, total ash content, and cortical bone mineral composition remained unaffected (P > 0.05). These results suggest that the degree of fat saturation exerts a greater impact than FFA content on bone mineral metabolism, supporting the commercial use of fat by-products rich in FFA in laying hen diets, at least during the early stages of the laying cycle.

Characterization of hospitalized patients with acute kidney injury associated with COVID-19 in Spain: renal replacement therapy and mortality. FRA-COVID SEN Registry Data.

BACKGROUND: Acute kidney injury (AKI) is common among hospitalized patients with COVID-19 and associated with worse prognosis. The Spanish Society of Nephrology created the AKI- COVID Registry to characterize the population admitted for COVID-19 that developed AKI in Spanish hospitals. The need of renal replacement therapy (RRT) therapeutic modalities, and mortality in these patients were assessed MATERIAL AND METHOD: In a retrospective study, we analyzed data from the AKI-COVID Registry, which included patients hospitalized in 30 Spanish hospitals from May 2020 to November 2021. Clinical and demographic variables, factors related to the severity of COVID-19 and AKI, and survival data were recorded. A multivariate regression analysis was performed to study factors related to RRT and mortality. RESULTS: Data from 730 patients were recorded. A total of 71.9% were men, with a mean age of 70 years (60-78), 70.1% were hypertensive, 32.9% diabetic, 33.3% with cardiovascular disease and 23.9% had some degree of chronic kidney disease (CKD). Pneumonia was diagnosed in 94.6%, requiring ventilatory support in 54.2% and admission to the ICU in 44.1% of cases. The median time from the onset of COVID-19 symptoms to the appearance of AKI (37.1% KDIGO I, 18.3% KDIGO II, 44.6% KDIGO III) was 6 days (4-10). A total of 235 (33.9%) patients required RRT: 155 patients with continuous renal replacement therapy, 89 alternate-day dialysis, 36 daily dialysis, 24 extended hemodialysis and 17 patients with hemodiafiltration. Smoking habit (OR 3.41), ventilatory support (OR 20.2), maximum creatinine value (OR 2.41), and time to AKI onset (OR 1.13) were predictors of the need for RRT; age was a protective factor (0.95). The group without RRT was characterized by older age, less severe AKI, and shorter kidney injury onset and recovery time (p < 0.05). 38.6% of patients died during hospitalization; serious AKI and RRT were more frequent in the death group. In the multivariate analysis, age (OR 1.03), previous chronic kidney disease (OR 2.21), development of pneumonia (OR 2.89), ventilatory support (OR 3.34) and RRT (OR 2.28) were predictors of mortality while chronic treatment with ARBs was identified as a protective factor (OR 0.55). CONCLUSIONS: Patients with AKI during hospitalization for COVID-19 had a high mean age, comorbidities and severe infection. We defined two different clinical patterns: an AKI of early onset, in older patients that resolves in a few days without the need for RRT; and another more severe pattern, with greater need for RRT, and late onset, which was related to greater severity of the infectious disease. The severity of the infection, age and the presence of CKD prior to admission were identified as a risk factors for mortality in these patients. In addition chronic treatment with ARBs was identified as a protective factor for mortality.

To evaluate the detection rate of local and whole-body recurrence by integrated [18F]F-PSMA-1007 PET/MR assessment of prostate cancer patients treated with prostatectomy with very low biochemical recurrence (<0.5ng/ml). Therapeutic implications.

OBJECTIVE: To analyse the efficacy of integrated assessment of [18F]F-PSMA-1007 PET/MRI on the early detection of local recurrence (LR) for prostate cancer patients with PSA levels <0.5ng/ml after radical prostatectomy. To assess the location of recurrence so that therapy may be tailored to patient. METHODS: Prospective study including 35 patients with prostate cancer (PCa), who were referred for a [18F]F-PSMA-1007 PET/MR after prostatectomy with a very initial PSA value increase (PSA<0,5ng/ml). Simultaneous acquisition in a PET/MRI hybrid equipment (SIGNA-GE), 1h after administration of 370%±10% MBq of [18F]F-PSMA-1007: Prostate selective imaging (20min): multiparametric PET+MRI (MRImp): DIXON, T1, T2, diffusion sequences post-gadolinium administration. Whole body image (30min): PET+MRI: DIXON, T1, T2, diffusion, STIR sequences. A nuclear physician and a radiologist jointly reviewed the studies: In order to assess LR, the "Prostate Imaging for Recurrence Reporting" system was used on MRI, as well as the Likert scale on the PET prostate imaging. The remaining lesions were classified as N1 and M1a. RESULTS: PET/MRI was positive in 25 patients (71,4%) and negative in 10 patients (28,6%). RL was detected in 15 patients (42.9%): in 2 (5.7%) MRI was superior; in 3 (8.6%) PET was superior; integrated PET/MRI showed improved results in 5 patients (14.3%) for the detection of LR. Location of recurrences: LR in 11 patients (44.0%); N1 in 10 (40.0%); LR+N1 (8.0%) in 2; LR+N1+M1a in 2 (8.0%). In 20 patients (80%) the PET/MRI findings allowed radioguided radiotherapy implementation (11 on LR, and 9 on N1), whereas hormonal treatment was decided in 5 patients (20%) due to multimetastases/spread disease. CONCLUSION: [18F]F-PSMA-1007 PET/MRI has a 71.4% recurrence detection rate after prostatectomy with PSA<0.5ng/ml. Its combined PET and MRI study increases the detection of LR by 14.3%, with a high N1+M1a detection rate (56%), allowing radioguided radiotherapy in 80% of patients.

[Two new cases of X-linked intellectual developmental disorder-105 linked to a previously unreported pathogenic variant in the USP27X gene]. / Dos nuevos casos de discapacidad intelectual ligada al cromosoma X tipo 105 por variante patógena en el gen USP27X no descrita previamente.

INTRODUCTION: X-linked intellectual developmental disorder is clinically and genetically heterogeneous. The ubiquitin specific peptidase 27 X-linked gene (USP27X) has been associated with X-linked intellectual developmental disorder, and only 17 affected males have been described in the literature to date. CASE REPORT: A 6-year-old boy was assessed due to intellectual developmental disability, language delay, behavioural disorder, microcephaly and particular features. His mother had learning difficulties and a facial phenotypic overlap. A maternal uncle had an intellectual developmental disorder. Physical examination revealed an unusual phenotype (triangular facies, long palpebral fissures and eyelashes, medially eyebrow loss, prominent auricles), mild brachydactylia and hypoplasia in the distal phalanges. The clinical exome identified the probably pathogenic variant NM_001145073.3: c.692delT in the USP27X gene. The results of the family segregation analysis were positive: the mother and maternal uncle were harbourers, while healthy maternal aunt was not. CONCLUSIONS: We present two new cases of X-linked intellectual developmental disorder due to a previously unreported variant in the USP27X gene. Both patients presented neurological symptoms without any significant involvement at other levels, according to the literature. One of the cases presented microcephaly, particular features and digital anomalies, which broadens the phenotypic spectrum of this disease.

TITLE: Dos nuevos casos de discapacidad intelectual ligada al cromosoma X tipo 105 por variante patógena en el gen USP27X no descrita previamente.Introducción. La discapacidad intelectual ligada al cromosoma X es un trastorno clínica y genéticamente heterogéneo. El gen de la proteasa 27 específica de la ubiquitina ligada al cromosoma X (USP27X) se ha asociado a discapacidad intelectual ligada al cromosoma X, y en la actualidad sólo se ha descrito a 17 varones afectos en la bibliografía. Caso clínico. Niño de 6 años valorado por discapacidad intelectual, retraso del lenguaje, trastorno de la conducta, microcefalia y rasgos particulares. Madre con dificultades de aprendizaje y fenotipo facial solapante. Un tío materno con discapacidad intelectual aislada. En la exploración física destaca un fenotipo peculiar (facies triangular, fisuras palpebrales y pestañas largas, cejas menos pobladas medialmente, pabellones auriculares prominentes), leve braquidactilia e hipoplasia de falanges distales. El exoma clínico identificó la variante probablemente patógena NM_001145073.3: c.692delT en el gen USP27X. El estudio de segregación familiar fue positivo: madre y tío materno portadores, tía materna sana no portadora. Conclusiones. Describimos dos nuevos casos con discapacidad intelectual ligada al cromosoma X por variante no descrita previamente en el gen USP27X. Ambos pacientes presentan clínica neurológica sin afectación significativa a otros niveles de acuerdo con la bibliografía. Uno de los casos asocia microcefalia, rasgos particulares y anomalías digitales, lo que permite ampliar el espectro fenotípico de esta enfermedad.

Presence of Epstein-Barr virus (EBV) antigens detected by sensitive methods has no influence on local immune environment in diffuse large B cell lymphoma.

EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL. In 48 DLBCL cases, the expression of immune response genes and the presence of molecules that induce tolerance, such as TIM3, LAG3 and PDL1 by immunohistochemistry (IHC), were studied. To broaden the study of the microenvironment, tumor-associated macrophages (TMAs) were also explored. No significant differences were observed in the expression of immune response genes in the EBV+ DLBCL and those cases that were EBV- DLBCL but that exhibited viral traces, assessed by ViewRNA assay. Only the EBV+ DLBCL cases displayed a significantly higher increase in the expression of CD8 and cytotoxic T cells detected by gene expression analysis, and of PDL1 in tumor cells and in the expression of CD68 in the tumor microenvironment detected by IHC, not observed in those cases with viral traces. The increase in CD8 and cytotoxic T cells, PDL1 and CD68 markers only in EBV+ DLBCL may indicate that traces of viral infection might not have influence in immune response markers.

Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases. / Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Expression of two major isoforms of MYO7A in the retina: Considerations for gene therapy of Usher syndrome type 1B.

Usher syndrome type 1B (USH1B) is a deaf-blindness disorder, caused by mutations in the MYO7A gene, which encodes the heavy chain of an unconventional actin-based motor protein. Here, we examined the two retinal isoforms of MYO7A, IF1 and IF2. We compared 3D models of the two isoforms and noted that the 38-amino acid region that is present in IF1 but absent from IF2 affects the C lobe of the FERM1 domain and the opening of a cleft in this potentially important protein binding domain. Expression of each of the two isoforms of human MYO7A and pig and mouse Myo7a was detected in the RPE and neural retina. Quantification by qPCR showed that the expression of IF2 was typically âˆ¼ 7-fold greater than that of IF1. We discuss the implications of these findings for any USH1B gene therapy strategy. Given the current incomplete knowledge of the functions of each isoform, both isoforms should be considered for targeting both the RPE and the neural retina in gene augmentation therapies.

Cost-effectiveness analysis of dyevert™ Power XT in patients with chronic kidney disease undergoing percutaneous coronary intervention procedures in Spain.

OBJECTIVE: To assess the efficiency of Dyevert™ Power XT compared to the standard clinical practice when used for percutaneous coronary interventions (PCI). METHODS: A Markov model was developed to estimate, over 3-month cycles and a lifetime time horizon, the cumulative costs and health outcomes (life years gained [LYG] and quality-adjusted life years [QALY]) in a hypothetical cohort of 1,000 patients with chronic kidney disease (CKD) 3b-4 and an average age of 72 years. The incidence of contrast-induced acute kidney injury for these patients is 18.89% in routine practice and 7.78% with Dyevert. QALYs were estimated by applying utilities by health state. Transitions between states and utilities were obtained from the literature. Overall all-cause and state-specific mortality were considered. The total cost (€2,022) estimated with the National Health System perspective included cost of the procedure and of CKD management. The parameters were validated by a panel of experts. A discount rate (3% per year) was applied to costs and outcomes. RESULTS: The use of Dyevert yielded more health benefits (34.60 LYG and 5.69 QALYs) compared to the current standard practice (33.11 LYG and 5.38 QALYs). Lifetime cost accumulated at the end of the simulation resulted €30,211/patient with Dyevert and €33,895/patient with current standard clinical practice. CONCLUSIONS: The use of Dyevert™ Power XT resulted dominant option, due to its higher effectiveness and lower cost as compared to standard clinical practice and, therefore, a preferred option in patients with CKD stages 3b-4 undergoing PCI in Spain.

Randomized clinical trial on the usefulness of 3D printing in intra-articular fractures of the distal radius. / Ensayo clínico aleatorizado sobre la utilidad de la impresión 3D en las fracturas intraarticulares de radio distal.

OBJECTIVES: We evaluated the utility of 3D printing technology for preoperative planning in the treatment of intra-articular fractures of the distal radius in relation to the improvement of surgical technique, radiological and clinical results. MATERIAL AND METHODS: A total of 30 patients with 2B and C fractures of the AO classification were operated on by a single surgeon with a volar plate, randomly divided into two groups, 15 of them with conventional planning (Rx and CT) and 15 adding a 3D model of the fracture and the previous simulation of the intervention. Simulation time, surgical time in minutes, radioscopy time in minutes, loss of material expressed in lost screws were recorded. Clinical evaluation based PRWE questionnaire and full radiographic analysis was done for all patients with a mean follow-up of 6 months by an independent, blinded observed. RESULTS: No statistically significant differences were observed in the PRWE questionnaire (p=0.22), nor were we observed differences in the radiological values, except in relation to the articular step (p=0.028), which represents statistical significance, but in both groups the median was of 0.0 (0.0-0.0). We also did not see statistically significant differences in surgical times (p=0.745), radioscopy (p=0.819) or in the loss of synthesis material (p=0.779). CONCLUSIONS: 3D printing has not improved the parameters studied in relation to routinely operated patients.

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by HIF-1 and -2 remain elevated in the eyes of people with diabetes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs, we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease. Accumulation of HIFs and HIF-regulated vasoactive mediators in hyperglycemic animals was observed in the absence of tissue hypoxia, suggesting that targeting HIFs may be an effective early treatment for diabetic retinopathy. However, while the HIF inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients. Conversely, 32-134D, a recently developed HIF inhibitor structurally unrelated to acriflavine, was not toxic to the retina, yet effectively inhibited HIF accumulation and normalized HIF-regulated gene expression in mice and in human retinal organoids. Intraocular administration of 32-134D prevented retinal neovascularization and vascular hyperpermeability in mice. These results provide the foundation for clinical studies assessing 32-134D for the treatment of patients with diabetic eye disease.

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases.

Brain system segregation and pain catastrophizing in chronic pain progression.

Pain processing involves emotional and cognitive factors that can modify pain perception. Increasing evidence suggests that pain catastrophizing (PC) is implicated, through pain-related self-thoughts, in the maladaptive plastic changes related to the maintenance of chronic pain (CP). Functional magnetic resonance imaging (fMRI) studies have shown an association between CP and two main networks: default mode (DMN) and dorsoattentional (DAN). Brain system segregation degree (SyS), an fMRI framework used to quantify the extent to which functional networks are segregated from each other, is associated with cognitive abilities in both healthy individuals and neurological patients. We hypothesized that individuals suffering from CP would show worst health-related status compared to healthy individuals and that, within CP individuals, longitudinal changes in pain experience (pain intensity and affective interference), could be predicted by SyS and PC subdomains (rumination, magnification, and helplessness). To assess the longitudinal progression of CP, two pain surveys were taken before and after an in-person assessment (physical evaluation and fMRI). We first compared the sociodemographic, health-related, and SyS data in the whole sample (no pain and pain groups). Secondly, we ran linear regression and a moderation model only in the pain group, to see the predictive and moderator values of PC and SyS in pain progression. From our sample of 347 individuals (mean age = 53.84, 55.2% women), 133 responded to having CP, and 214 denied having CP. When comparing groups, results showed significant differences in health-related questionnaires, but no differences in SyS. Within the pain group, helplessness (ß = 0.325; p = 0.003), higher DMN (ß = 0.193; p = 0.037), and lower DAN segregation (ß = 0.215; p = 0.014) were strongly associated with a worsening in pain experience over time. Moreover, helplessness moderated the association between DMN segregation and pain experience progression (p = 0.003). Our findings indicate that the efficient functioning of these networks and catastrophizing could be used as predictors of pain progression, bringing new light to the influence of the interplay between psychological aspects and brain networks. Consequently, approaches focusing on these factors could minimize the impact on daily life activities.

Perioperative colloids: From theory to practice.

INTRODUCTION: Fluid administration is the cornerstone in hypovolemic patient's reanimation. Clinical guidelines restrict colloid administration favouring crystalloids. Currently, we don't know exactly which is the daily clinical practice during the perioperative period. The objective of this study is to describe perioperative use of colloids analysing possible reasons aiming to use them. MATERIAL AND METHODS: Prospective, cross-section, national, multicentre observational study. Fluid Day sub-study. We enrolled all patient's older than 18 years old who underwent surgery during the 24 h of the 2-days study (February, 2019, 18th and 20th). We registered demographic data, comorbidities, anaesthetic and surgical procedure data, fluids administered, perioperative bleeding and monitoring type used during the perioperative period. RESULTS: A total of 5928 cases were analysed and 542 patients (9.1%) received any type of colloids, being hydroxiethyl-starch the most frequently used (5.1%). Patients receiving colloids suffered more longing surgery (150 [90-255] vs. 75 [45-120] min), were urgently operated (13.7 vs. 7.5%) and were more frequent classified as high risk (22 vs. 4.8%). Their recovery was mostly in critical care units (45.1 vs.15.8%). Patients with bleeding less than 500 ml received colloids in a percentage of 5.9 versus 45.9% when this figure was overcome. Patients who received colloids were anaemic more frequently: 29.4 vs. 16.3%. Colloids administration had a higher risk for transfusion (OR 15.7). Advanced monitoring also increased the risk for receiving colloids (OR 9.43). CONCLUSIONS: In our environment with routine clinical practice, colloids administration is limited and close linked to perioperative bleeding.

Influence of free fatty acid content and degree of fat saturation in laying hen diets on egg quality, yolk fatty acid profile, and cholesterol content.

The aim of the present study was to evaluate the effect of dietary free fatty acid (FFA) content and the degree of saturation on egg quality, yolk fatty acid (FA) profile, and yolk cholesterol content. For a 15-wk period, a total of 144 laying hens (19-wk-old) were randomly assigned to 8 treatments arranged in a 2 × 4 factorial design, with 2 sources of crude oil (soybean oil and palm oil) and 4 levels of FFA (10, 20, 30, and 45%). The dietary treatments were achieved by progressively substituting the original oils with equivalent amounts of their corresponding acid oils (soybean acid oil and palm fatty acid distillate, respectively). No differences in ADFI or egg mass were found. However, dietary FFA reduced egg production (linear, P < 0.05) and increased the feed conversion ratio (linear, P < 0.05). Higher levels of FFA in soybean diets resulted in higher egg weight with higher albumen and yolk weights (linear, P < 0.01). Palm diets presented higher yolk:albumen ratio than soybean diets (P < 0.001), but the effect of FFA did not follow a linear trend. Hens fed soybean diets laid eggs with higher Haugh units (HU) than palm diets (P < 0.001), although increasing the dietary FFA% reduced the HU values in both (linear, P < 0.001). Palm diets enhanced shell quality with greater resistance to breakage, and higher dry matter and ash content than soybean diets (P < 0.05). No differences in egg chemical composition and yolk cholesterol content were found (P > 0.05). The saturation degree had a significant effect on all the analyzed yolk FA (P < 0.001) except for arachidonic acid (C20:4 n-6), whereas increasing the FFA content did not affect to a great extent. These results show that varying dietary FFA level did not affect egg quality and yolk composition as much as the dietary fat source did, supporting the use of acid oils and fatty acid distillates as fat ingredients for feed.