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Contact Lenses as Drug Delivery System for Glaucoma: A Review

Glaucoma is an optical neuropathy associated to a progressive degeneration of retinal ganglion cells with visual field loss and is the main cause of irreversible blindness in the world. The treatment has the aim to reduce intraocular pressure. The first therapy option is to instill drugs on the ocular surface. The main limitation of this is the reduced time of the drug staying on the cornea. This means that high doses are required to ensure its therapeutic effect. A drug-loaded contact lens can diffuse into the post lens tear film in a constant and prolonged flow, resulting in an increased retention of the drug on the surface of the cornea for up to 30 min and thus providing a higher drug bioavailability, increasing the therapeutic efficacy, reducing the amount of administered drug, and thereby provoking fewer adverse events. Several different systems of drug delivery have been studied in recent decades; ranging from more simple methods of impregnating the lenses, such as soaking, to more complex ones, such as molecular imprinting have been proposed. Moreover, different drugs, from those already commercially available to new substances such as melatonin have been studied to improve the glaucoma treatment efficacy. This review describes the role of contact lenses as an innovative drug delivery system to treat glaucoma

Efficacy of artificial tears based on an extract of artemia salina containing dinucleotides in a rabbit dry eye model

Background: Artemia salina is a brine shrimp containing high concentrations of dinu-cleotides, molecules with properties for dry eye treatment. For this reason, the purpose of the study was to evaluate the effect of the artificial tears based on an extract of Artemia salina in a rabbit dry eye model. Methods: A prospective and randomized study was carried out. Twenty rabbits were divided into 4 groups (n = 5, each group): healthy rabbits, dry eye rabbits, dry eye rabbits treated with hypromellose (HPMC), and dry eye rabbits treated with Artemia salina. Dry eye was induced by the topical instillation of 0.2% benzalkonium chloride. The measurements were performed before and after the treatment for 5 consecutive days. Results: The topical instillation of artificial tears containing Artemia salina showed beneficial effects on tear secretion, tear break-up time, corneal staining, the density of Goblet cells, heigh of mucin cloud secreted by these cells, and mRNA levels of IL-1β and MMP9 in conjunctival cells. Compared with the HPMC, there was a statistically significant improvement (p < 0.05) with the Artemia salina in all the variables under study, except for the conjunc-tival hyperemia, density of Goblet cells, and mRNA levels of IL-6. Conclusions: The potential of artificial tears based on Artemia salina as a secretagogue agent for dry eye treatment was confirmed, opening the door for future clinical trials and studies to extrapolate the findings for dry eye patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerlan

Síntesis de los fotocatalizadores binarios SnO2/TiO2y ternarios SnO2/TiO2/nanohojas de g-C3N4 para la degradación de naranja de metilo y ciprofloxacino en presencia de luz ultravioleta

When emergent pollutantsare in wastewater they need oxidation advanced processes for their degradation, such Heterogeneous Photocatalysis. Nowadays more efficient photocatalysts than titanium dioxide (TiO2) are being sought to degrade complex molecules. Nanoparticles and Quantum Dots (QDs) of Tin Oxide (SnO2) were synthesized by different methods, binary SnO2/TiO2and ternary SnO2/TiO2/g-C3N4nanosheets heterojunctions were synthetized by wet impregnation method to Methyl Orange (MO) as model pollutant and Ciprofloxacin (CIP) degradation. The most efficient photocatalysts for MO degradation were SnO2-SG300/P25 andP25. The SnO2-QDs/P25 junction showed a great MO adsorption capacity. The binary heterojunctions SnO2-npAldrich/P25 and SnO2-SG300/P25 showed higher degradation percentages than TiO2and P25.Los contaminantes emergentes,al encontrarse en aguas residuales, requieren procesos avanzados de oxidación para su degradación, como la fotocatálisis heterogénea. Actualmente se buscan fotocatalizadores más eficientes que el dióxido de titanio (TiO2) para degradar moléculas complejas. Se sintetizó dióxido de estaño (SnO2) nanométrico y puntos cuánticos (QDs) por distintos métodos;se sintetizaron juntas binarias de SnO2/TiO2y juntas ternarias de SnO2/TiO2/nanohojas de g-C3N4por impregnación húmeda, para la degradación de Naranja de Metilo (NM) como contaminante modelo y Ciprofloxacino (CIP). Los fotocatalizadores más eficientes para la degradación de NM fueron SnO2-SG300/P25 y P25. La junta SnO2-QDs/P25 mostró una gran capacidad de adsorción del NM. Para la degradación de CIP las juntas SnO2-npA/P25 y SnO2-SG300/P25 mostraron porcentajes de degradación superiores al TiO2y P2

Perfusion Decellularization of Extrahepatic Bile Duct Allows Tissue-Engineered Scaffold Generation by Preserving Matrix Architecture and Cytocompatibility

Reconstruction of bile ducts damaged remains a vexing medical problem. Surgeons have few options when it comes to a long segment reconstruction of the bile duct. Biological scaffolds of decellularized biliary origin may offer an approach to support the replace of bile ducts. Our objective was to obtain an extracellular matrix scaffold derived from porcine extrahepatic bile ducts (dECM-BD) and to analyze its biological and biochemical properties. The efficiency of the tailored perfusion decellularization process was assessed through histology stainings. Results from 4’-6-diamidino-2-phenylindole (DAPI), Hematoxylin and Eosin (H&E) stainings, and deoxyribonucleic acid (DNA) quantification showed proper extracellular matrix (ECM) decellularization with an effectiveness of 98%. Immunohistochemistry results indicate an effective decrease in immunogenic marker as human leukocyte antigens (HLA-A) and Cytokeratin 7 (CK7) proteins. The ECM of the bile duct was preserved according to Masson and Herovici stainings. Data derived from scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) showed the preservation of the dECM-BD hierarchical structures. Cytotoxicity of dECM-BD was null, with cells able to infiltrate the scaffold. In this work, we standardized a decellularization method that allows one to obtain a natural bile duct scaffold with hierarchical ultrastructure preservation and adequate cytocompatibility

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

Background: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. Methods: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero (2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. Findings: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16-0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26-0·57; p<0·0001, compared with the VIR-N1-Storm group). Interpretation: The presence of a so-called viral storm is associated with increased all-cause death in patients admitted to the intensive care unit with severe COVID-19. Preventing this viral storm could help to reduce poor outcomes. Viral storm could be an enrichment marker for treatment with antivirals or purification devices to remove viral components from the blood.This work was supported by grants from the Instituto de Salud Carlos III (FONDO-COVID19, COV20/00110, CIBERES, 06/06/0028; AT), Proyectos de Investigación en Salud (PI19/00590; JFB-M), Miguel Servet (CP20/00041; DdG-C), Sara Borrell (CD018/0123; APT), and Predoctorales de Formación en Investigación en Salud (FI20/00278; AdF). We also received funds from Programa de Donaciones Estar Preparados, UNESPA (Madrid, Spain), and from the Canadian Institutes of Health Research (CIHR OV2–170357; DJK and JFB-M), Research Nova Scotia, Li-Ka Shing Foundation (DJK), and finally by a Research Grant 2020 from ESCMID (APT). COV20/00110, PI19/00590, CP20/00041, CD018/0123, FI20/00278 were co-funded by European Regional Development Fund and European Social Fund (A way to make Europe, and Investing in your future). We thank the IRB-Lleida Biobank 119 (B.0000682) and Plataforma Biobancos PT17/0015/0027 in Lleida, the Hospital Clinic Barcelona (HCB)-IDIBAPS biobank in Barcelona, and the National DNA Bank and the Hospital Universitario de Salamanca biobank (both in Salamanca) for their logistical support with sample processing and storage. We are indebted to the Fundació Glòria Soler for its contribution and support to the COVIDBANK of HCBIDIBAPS Biobank. This work was not supported by any pharmaceutical company or other agency.S

Spanish Pediatric Inflammatory Bowel Disease Diagnostic Delay Registry: SPIDER Study From Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica

Background and Aims: Diagnostic delay (DD) is especially relevant in children with inflammatory bowel disease, leading to potential complications. We examined the intervals and factors for DD in the pediatric population of Spain. Methods: We conducted a multicentric prospective study, including 149 pediatric inflammatory bowel disease patients, obtaining clinical, anthropometric, and biochemical data. Time to diagnosis (TD) was divided into several intervals to identify those where the DD was longer and find the variables that prolonged those intervals. Missed opportunities for diagnosis (MODs) were also identified. Results: Overall TD was 4.4 months (interquartile range [IQR] 2.6–10.4), being significantly higher in Crohn’s disease (CD) than in ulcerative colitis (UC) (6.3 [IQR 3.3–12.3] vs. 3 [IQR 1.6–5.6] months, p = 0.0001). Time from the visit to the first physician until referral to a pediatric gastroenterologist was the main contributor to TD (2.4 months [IQR 1.03–7.17] in CD vs. 0.83 months [IQR 0.30–2.50] in UC, p = 0.0001). One hundred and ten patients (78.3%) visited more than one physician (29.9% to 4 or more), and 16.3% visited the same physician more than six times before being assessed by the pediatric gastroenterologist. The number of MODs was significantly higher in CD than that in UC patients: 4 MODs (IQR 2–7) vs. 2 MODs ([IQR 1–5], p = 0.003). Referral by pediatricians from hospital care allowed earlier IBD diagnosis (odds ratio 3.2 [95% confidence interval 1.1–8.9], p = 0.025). Conclusions: TD and DD were significantly higher in CD than those in UC. IBD patients (especially those with CD) undergo a large number of medical visits until the final diagnosis.Jiménez Treviño S, Pujol Muncunill G, Martín-Masot R, Rodríguez Martínez A, Segarra Cantón O, Peña Quintana L, Armas Ramos H, Eizaguirre Arocena FJ, Barrio Torres J, García Burriel JI, Ortigosa Castillo L, Donat Aliaga E, Crujeiras Martínez V, Barros García P, Botija Arcos G, Bartolomé Porro JM, Juste Ruiz M, Ochoa Sangrador C, García Casales Z, Galicia Poblet G, Oliver Goicolea P, Lorenzo Garrido H, García Romero R, La Orden Izquierdo E, Pérez Solis D, Navas-López VM, Díaz Martin JJ and Martín de Carpi J (2020) Spanish Pediatric Inflammatory Bowel Disease Diagnostic Delay Registry: SPIDER Study From Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica. Front. Pediatr. 8:584278. doi: 10.3389/fped.2020.58427

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul