Novel Management of Ocular Surface Inflammation in Patients With Ocular Graft-Versus-Host Disease in the Setting of Cataract Surgery.

PURPOSE: To report the outcomes of cataract surgery in patients with ocular graft-versus-host disease (oGVHD) using a novel preoperative immunomodulatory regimen in a collaborative subspecialty care setting. METHODS: Retrospective case series of patients with oGVHD who underwent cataract surgery using a novel preoperative immunomodulatory regimen in a collaborative care setting. A preoperative regimen consisting of pooled human immune globulin 1%, autologous serum 50%, and methylprednisolone 1% eye drops was prescribed. Outcome measures included visual acuity (VA), ocular surface disease index (OSDI) score, lissamine green staining, and complications with a minimum of 2 years of follow-up. RESULTS: Thirty-five eyes from 20 patients with oGVHD were studied. The mean age was 59 years (range 30-70 years). A healthy comparison group included 35 eyes from 24 patients with a mean age of 63 years (range 44-74 years). At the 2-year follow-up, the mean corneal staining score was 2.3/15, the mean OSDI score was 37.5, and the mean VA was 20/30 (logarithm of the minimal angle of resolution 0.17). The global complication rate was 2.8% at the last follow-up with no difference versus a healthy comparison group. CONCLUSIONS: A collaborative care model improving ocular surface health before cataract surgery with dry eye and cataract subspecialists can optimize outcomes in patients with oGVHD.

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death.

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.

Dynamic Invasive Hemodynamic Congestion Profile Impacts Acute Myocardial Infarction Complicated by Cardiogenic Shock Outcomes: A Real-World Single-Center Study.

BACKGROUND: Cardiogenic shock (CS) commonly complicates the management of acute myocardial infarction (AMI), and it results in high mortality rates. Pulmonary artery catheter (PAC) monitoring can be valuable for personalizing critical-care interventions. We hypothesized that patients with AMI-CS experiencing persistent congestion measures during the first 24 hours of the PAC installment would exhibit worse in-hospital survival rates. METHODS AND RESULTS: We studied 295 patients with AMI-CS between January 2006 and December 2021. The first 24-hour PAC-derived hemodynamic measures were divided by the congestion profiling and the proposed 2022 Cardiovascular Angiography and Interventions (SCAI) classification. Biventricular congestion was the most common profile and was associated with the highest patient mortality rates at all time points (mean 56.6%). A persistent congestive profile was associated with increased mortality rates (hazard ratio [HR] = 1.85; P = 0.002) compared with patients who achieved decongestive profiles. Patients with SCAI stages D/E had higher levels of right atrial pressure (RAP): 14-15 mmHg) and pulmonary capillary wedge pressure (PCWP): 18-20 mmHg) compared with stage C (RAP, 10-11 mmHg, mean difference 3-5 mmHg; P < 0.001; PCWP 14-17 mmHg; mean difference 1.56-4 mmHg; P = 0.011). In SCAI stages D/E, the pulmonary artery pulsatility index (0.8-1.19) was lower than in those with grade C (1.29-1.63; mean difference 0.21-0.73; P < 0.001). CONCLUSIONS: Continuous congestion profiling using the SCAI classification matched the grade of hemodynamic severity and the increased risk of in-hospital death. Early decongestion appears to be an important prognostic and therapeutic goal in patients with AMI-CS and warrants further study.

Trypanosoma cruzi in Mexican Neotropical vectors and mammals: wildlife, livestock, pets, and human population.

OBJECTIVE: To provide primary evidence of Trypanosoma cruzi landscape genetics in the Mexican Neotropics. MATERIALS AND METHODS: Trypanosoma cruzi and discrete typing units (DTU) prevalence were analyzed in landscape communities of vectors, wildlife, livestock, pets, and sympatric human populations using endpoint PCR and sequencing of all relevant amplicons from mitochondrial (kDNA) and nuclear (ME, 18S, 24Sα) gene markers. RESULTS: Although 98% of the infected sample-set (N=2 963) contained single or mixed infections of DTUI (TcI, 96.2%) and TcVI (22.6%), TcIV and TcII were also identified. Sensitivity of individual markers varied and was dependent on host taxon; kDNA, ME and 18S combined identified 95% of infections. ME genotyped 90% of vector infections, but 60% of mammals (36% wildlife), while neither 18S nor 24Sα typed more than 20% of mammal infections. CONCLUSION: Available gene fragments to identify or genotype T. cruzi are not universally sensitive for all landscape parasite populations, highlighting important T. cruzi heteroge- neity among mammal reservoir taxa and triatomine species.

Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015-2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.

Silver and Copper Nitride Cooperate for CO Electroreduction to Propanol.

The need of carbon sources for the chemical industry, alternative to fossil sources, has pointed to CO2 as a possible feedstock. While CO2 electroreduction (CO2 R) allows production of interesting organic compounds, it suffers from large carbon losses, mainly due to carbonate formation. This is why, quite recently, tandem CO2 R, a two-step process, with first CO2 R to CO using a solid oxide electrolysis cell followed by CO electroreduction (COR), has been considered, since no carbon is lost as carbonate in either step. Here we report a novel copper-based catalyst, silver-doped copper nitride, with record selectivity for formation of propanol (Faradaic efficiency: 45 %), an industrially relevant compound, from CO electroreduction in gas-fed flow cells. Selective propanol formation occurs at metallic copper atoms derived from copper nitride and is promoted by silver doping as shown experimentally and computationally. In addition, the selectivity for C2+ liquid products (Faradaic efficiency: 80 %) is among the highest reported so far. These findings open new perspectives regarding the design of catalysts for production of C3 compounds from CO2 .

CO2 Electroreduction in Water with a Heterogenized C-Substituted Nickel Cyclam Catalyst.

Molecular catalysis for selective CO2 electroreduction into CO can be achieved with a variety of metal complexes. Their immobilization on cathodes is required for their practical implementation in electrolytic cells and can benefit from the advantages of a solid material such as easy separation of products and catalysts, efficient electron transfer to the catalyst, and high stability. However, this approach remains insufficiently explored up to now. Here, using an appropriate and original modification of the cyclam ligand, we report a novel [Ni(cyclam)]2+ complex which can be immobilized on carbon nanotubes. This material, once deposited on a gas diffusion layer, provides a novel electrode which is remarkably selective for CO2 electroreduction to CO, not only in organic solvents but also, more remarkably, in water, with faradic efficiencies for CO larger than 90% and current densities of 5-10 mA cm-2 during controlled potential electrolysis in H-cells.

Electrochemical CO2 reduction on Cu single atom catalyst and Cu nanoclusters: an ab initio approach.

The electrochemical CO2 reduction presents a sustainable route to the production of chemicals such as ethylene or ethanol, however the design of selective catalysts is still challenging. The use of single site copper nitrogen doped carbon materials with porphyrin-like Cu graphene structures have shown a significant improvement towards the production of multi carbon products, particularly ethanol. Nonetheless, during reaction the porphyrin like Cu sites transiently convert into metallic copper nanoclusters in a reversible process, making difficult to understand the actual role of each phase. Here, we present a computational study, where adequate structural models to describe the experimentally determined phases of the single atom catalyst (Cu-N-C material) have been constructed. Moreover, the electrochemical reduction of CO2 to ethanol and ethylene has been addressed via periodic DFT calculations on each of the systems. On the basis of the computed free energies of reaction, it was found that the Cu nanoclusters exhibit a superior performance for the CO reduction in comparison with the single site. Moreover, they possess a high activity towards the production of ethanol, suggesting them as the active phase responsible for the catalytic performance of the studied material.

Long-lasting brain fog is related with severity clusters of symptoms in COVID-19 patients.

BACKGROUND: COVID-19 patients may experience Long-lasting symptoms from weeks to even months. AIM: To evaluate long-term cognitive impairment based on the severity of symptoms of COVID-19 infection in a primary health system setting. MATERIAL AND METHODS: From a database of 363 patients, 83 cases aged 47 ± 15 years, (58% females) were selected from June to August 2020. In patients who survived the virus, 24 infection-related symptoms were collected to create three severity clusters (mild, moderate, and severe). The follow-up time was at least seven months. Comparing the first two clusters with the severe cluster, the existence of brain fog and risk factors (obesity, hypertension, diabetes, chronic lung disease, and hypothyroidism) were analyzed. RESULTS: Thirty-one patients (37%) had persistent symptoms lasting up to 240 days. Fifty-one patients (61%) experienced brain fog. Concentration was affected by symptom severity (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.26-10.46, p = 0.02). Short- or long-term memory loss was not affected. Moreover, symptom severity was related to brain fog (OR 3.16, 95% CI 1.05-9.51, p = 0.04). Patients with persistent symptoms had a concentration impairment associated with severity patterns (OR 24.3, 95% CI 1.73-340.11, p = 0.03). CONCLUSIONS: Brain fog is associated with symptom severity in COVID-19 survivors and lasts for more than eight months.

Molecular Inhibition for Selective CO2 Conversion.

Electrochemical CO2 reduction presents a sustainable route to the production of chemicals and fuels. Achieving a narrow product distribution with heterogeneous Cu catalysts is challenging and conventional material modifications offer limited control over selectivity. Here, we show that surface-immobilised molecular species can act as inhibitors for specific carbon products to provide rational control over product distributions. Combined experimental and computational results showed that anchoring of a thiol-functionalised pyridine on Cu destabilises a surface-bound reaction intermediate to energetically block a CO-producing pathway, thereby favouring formate production. The nitrogen atom was shown to be essential to the inhibition mechanism. The ability of molecules to control selectivity through inhibition of specific reaction pathways offers a unique approach to rationally modify heterogeneous catalysts.

Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors.

Controlled donation after circulatory death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). This is a retrospective analysis of all LTx performed between January 2013 and December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 h, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7% respectively; P = 0.42). Short- and mid-term outcomes are comparable between the three types of donors. These findings may encourage and reinforce all types of donation after circulatory death programmes as a valid and growing source of suitable organs for transplantation.

Distortion-Free Sensing of Neural Activity Using Graphene Transistors.

Graphene solution-gated field-effect transistors (g-SGFETs) are promising sensing devices to transduce electrochemical potential signals in an electrolyte bath. However, distortion mechanisms in g-SGFET, which can affect signals of large amplitude or high frequency, have not been evaluated. Here, a detailed characterization and modeling of the harmonic distortion and non-ideal frequency response in g-SGFETs is presented. This accurate description of the input-output relation of the g-SGFETs allows to define the voltage- and frequency-dependent transfer functions, which can be used to correct distortions in the transduced signals. The effect of signal distortion and its subsequent calibration are shown for different types of electrophysiological signals, spanning from large amplitude and low frequency cortical spreading depression events to low amplitude and high frequency action potentials. The thorough description of the distortion mechanisms presented in this article demonstrates that g-SGFETs can be used as distortion-free signal transducers not only for neural sensing, but also for a broader range of applications in which g-SGFET sensors are used.

A randomized controlled trial of lung ultrasound-guided therapy in heart failure (CLUSTER-HF study).

BACKGROUND: Lung ultrasound (LUS) has emerged as a new tool for the evaluation of congestion in heart failure (HF); incorporation of LUS during follow-up may detect congestion earlier and prompt interventions to prevent hospitalizations. The aim of this study was to test the hypothesis that the incorporation of LUS during follow-up of patients with HF may reduce the rate of adverse events compared with usual care. METHODS: In this single-blinded, randomized controlled trial, patients were randomized into an LUS-guided arm or control arm. Patients were followed in 4 prespecified visits during a 6-month period. LUS was performed in every patient visit in both groups; however, LUS results were available for the treating physician only in the LUS group. The primary outcome was the composite of urgent HF visits, rehospitalization for worsening HF, and death from any cause. RESULTS: One hundred twenty-six patients were randomized to either LUS (n = 63) or control (n = 63) (age 62.5 ±â€¯10 years, median left ventricular ejection fraction 31%). The primary end point occurred in 30 (47.6%) patients in the control group and 20 (31.7%) patients in the LUS group (P = .041). LUS-guided treatment was associated with a 45% risk reduction in the primary end point (hazard ratio 0.55, 95% CI 0.31-0.98, P = .044), mainly driven by a reduction in urgent HF visits (hazard ratio 0.28, 95% CI 0.13-0.62, P = .001). No significant differences in rehospitalizations for HF or death were found. CONCLUSIONS: Incorporation of LUS into clinical follow-up of patients with HF significantly reduced the risk of urgent visits for worsening HF.

High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors.

Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and pathological information. In this work, we use flexible epicortical and intracortical arrays of graphene solution-gated field-effect transistors (gSGFETs) to map cortical spreading depression in rats and demonstrate that gSGFETs are able to record, with high fidelity, infraslow signals together with signals in the typical local field potential bandwidth. The wide recording bandwidth results from the direct field-effect coupling of the active transistor, in contrast to standard passive electrodes, as well as from the electrochemical inertness of graphene. Taking advantage of such functionality, we envision broad applications of gSGFET technology for monitoring infraslow brain activity both in research and in the clinic.

Expanding the horizons: Uncontrolled donors after circulatory death for lung transplantation-First comparison with brain death donors.

Uncontrolled donation after cardiac death is an appealing source of organs for lung transplantation. We compare early and long-term outcomes of lung transplantation with these donors with a cohort of transplants from brain death donors at our institution. Retrospective analysis of all lung transplantations was performed from 2002 to 2012. We collected variables regarding recipients, donors, recover and transplant procedures, early and late complications, and survival. We included 292 lung transplants from brain death donors and 38 from uncontrolled donors after cardiac death. Both groups were comparable except for sex mismatch (male recipient-female donor was more frequent in the brain death cohort, 17.8% vs 0%, P 0.002), total ischemic time (longer for donors after cardiac death, 657 minutes for the first lung and 822 minutes for the second vs 309 and 425 minutes, P < 0.001), and ex vivo evaluation (more frequent in cardiac death donors, 21.1% vs 1.4%, P < 0.001). Early and late outcomes were not different (ICU stay [9 vs 10.5 days], hospital stay [33.5 vs 35 days], primary graft dysfunction G3 [24 vs 34.2%], and chronic graft dysfunction HR 1.19 [0.61-2.32]), but overall survival was significantly lower for patients transplanted from cardiac death donors [HR 1.67 (1.06-2.64)]. Lung transplantation after uncontrolled cardiac death offers poorer results in terms of survival compared to brain death donation. Refinement of current strategies for graft preservation and evaluation is essential to improve outcomes with this source of grafts.

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes.

1,3-Enynes are important building blocks in organic synthesis and also constitute the key motif in various bioactive natural products and functional materials. However, synthetic approaches to stereodefined substituted 1,3-enynes remain a challenge, as they are limited to Wittig and cross-coupling reactions. Herein, stereodefined 1,3-enynes, including tetrasubstituted ones, were straightforwardly synthesized from cis or trans-alkynylated oxiranes in good to excellent yields by a one-pot cascade process. The procedure relies on oxirane deprotonation, borylation and a stereospecific rearrangement of the so-formed alkynyloxiranyl borates. This stereospecific process overall transfers the cis or trans-stereochemistry of the starting alkynyloxiranes to the resulting 1,3-enynes.

Biofilm Formation on Bandage Contact Lenses Worn by Patients with the Boston Type 1 Keratoprosthesis: A Pilot Comparison Study of Prophylactic Topical Vancomycin 15 mg/mL and Linezolid 0.2.

OBJECTIVES: To determine the rate of biofilm formation on bandage contact lenses worn by patients with the Boston type 1 keratoprosthesis (K-Pro) while on prophylactic topical vancomycin versus linezolid. METHODS: Patients wearing a bandage contact lens (BCL) with a K-Pro were eligible for enrollment. After irrigation of the ocular surface with 5% povidone-iodine solution, each patient was placed on either topical vancomycin 15 mg/mL or linezolid 0.2% BID for one month. At the one-month visit, the BCL was collected and stored in fixative solution. Standard photographs were taken of each lens at high magnification using scanning electron microscopy (SEM), which were subsequently analyzed for evidence of biofilm. RESULTS: Nineteen contact lenses were obtained from 12 K-Pro patients at the Illinois Eye and Ear Infirmary. Zero of eight (0%; 95% CI=0 to 37%) contact lenses from patients treated with topical vancomycin, and 1 of 11 (9%; 95% CI=0 to 41%; P-value=1.00) contact lenses from patients treated with topical linezolid were found to have biofilm formation at one month as detected by SEM. None of the patients developed a clinically significant infection while on either prophylactic vancomycin or linezolid during the study period. CONCLUSIONS: Overall, the rate of biofilm formation as detected by SEM on the surface of bandage contact lenses was low. These results suggest that vancomycin and linezolid are both relatively effective in reducing biofilm-forming bacterial growth at one month. Accordingly, linezolid may be an effective alternative to vancomycin in patients with allergy or intolerance. However, further investigation is required to develop evidence-based antibiotic prophylaxis regimens.

Synthesis and Antioxidant Activity of Alkyl Nitroderivatives of Hydroxytyrosol.

A series of alkyl nitrohydroxytyrosyl ether derivatives has been synthesized from free hydroxytyrosol (HT), the natural olive oil phenol, in order to increase the assortment of compounds with potential neuroprotective activity in Parkinson's disease. In this work, the antioxidant activity of these novel compounds has been evaluated using Ferric Reducing Antioxidant Power (FRAP), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and Oxygen Radical Scavenging Capacity (ORAC) assays compared to that of nitrohydroxytyrosol (NO2HT) and free HT. New compounds showed variable antioxidant activity depending on the alkyl side chain length; compounds with short chains (2-4 carbon atoms) maintained or even improved the antioxidant activity compared to NO2HT and/or HT, whereas those with longer side chains (6-8 carbon atoms) showed lower activity than NO2HT but higher than HT.

17ß-estradiol induces hyperresponsiveness in guinea pig airway smooth muscle by inhibiting the plasma membrane Ca2+-ATPase.

High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17ß-estradiol (E2) has non-genomic effects via Ca2+ regulatory mechanisms; however, its effect on the plasma membrane Ca2+-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca2+ concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca2+-ATPases. In guinea pig ASM, Ca2+ microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca2+ ATPases. In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca2+ peak induced by caffeine to a Ca2+ plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca2+ plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca2+ entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17ß-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women.