Mechanically Robust Hybrid Gel Beads Loaded with “Naked” Palladium Nanoparticles as Efficient, Reusable, and Sustainable Catalysts for the Suzuki–Miyaura Reaction

The increase in demand for Pd and its low abundance pose a significant threat to its future availability, rendering research into more sustainable Pd-based technologies essential. Herein, we report Pd scavenging mechanically robust hybrid gel beads composed of agarose, a polymer gelator (PG), and an active low-molecular-weight gelator (LMWG) based on 1,3:2,4-dibenzylidenesorbitol (DBS), DBS-CONHNH2. The robustness of the PG and the ability of the LMWG to reduce Pd(II) in situ to generate naked Pd(0) nanoparticles (PdNPs) combine within these gel beads to give them potential as practical catalysts for Suzuki–Miyaura cross-coupling reactions. The optimized gel beads demonstrate good reusability, green metrics, and most importantly the ability to sustain stirring, improving reaction times and energy consumption compared to previous examples. In contrast to previous reports, the leaching of palladium from these next-generation beads is almost completely eliminated. Additionally, for the first time, a detailed investigation of these Pd-loaded gel beads explains precisely how the nanoparticles are formed in situ without a stabilizing ligand. Further, detailed catalytic investigations demonstrate that catalysis occurs within the gel beads. Hence, these beads can essentially be considered as robust “nonligated” heterogeneous PdNP catalysts. Given the challenges in developing ligand-free, naked Pd nanoparticles as stable catalysts, these gel beads may have future potential for the development of easily used systems to perform chemical reactions in “kit” form

Stabilizing silica nanoparticles in hydrogels: impact on storage and polydispersity

For successful nanomedicine, it is important that the unique, size-dependent physico-chemical properties of the nanomaterial remain predictably constant during both the storage and the manipulation of the material. Here a novel approach to preserve the colloidal stability and degradation of NPs is described. The concept is simple: (a) a solution of monodisperse particles is formulated into a responsive water- or PBS-based hydrogel; (b) the gel can be reversibly turned into a solution after long term storage by shaking it by hand; (c) the NP can be diluted and used in any desired application without the need for excessive manipulation. The differences between the physico-chemical properties of NPs stored in solution and in gel are compared. Two types of NPs were involved in this study: silica NPs of similar100 nm and Au-NPs of 30 and 80 nm in diameter. The key findings are: the fibrous matrix of the hydrogel limits the NP mobility{,} significantly reduces NP aggregation and conserves the NP morphology; both the hydrogelator and the NPs show negligible toxicity towards the model U937 human hematopoietic cell line; undesired leaching of cargo material loaded inside the particles is reduced{,} which could be an important feature for drug delivery systems

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Stabilizing silica nanoparticles in hydrogels: impact on storage and polydispersity

For successful nanomedicine, it is important that the unique, size-dependent physico-chemical properties of the nanomaterial remain predictably constant during both the storage and the manipulation of the material. Here a novel approach to preserve the colloidal stability and degradation of NPs is described. The concept is simple: (a) a solution of monodisperse particles is formulated into a responsive water- or PBS-based hydrogel; (b) the gel can be reversibly turned into a solution after long term storage by shaking it by hand; (c) the NP can be diluted and used in any desired application without the need for excessive manipulation. The differences between the physico-chemical properties of NPs stored in solution and in gel are compared. Two types of NPs were involved in this study: silica NPs of ∼100 nm and Au-NPs of 30 and 80 nm in diameter. The key findings are: the fibrous matrix of the hydrogel limits the NP mobility, significantly reduces NP aggregation and conserves the NP morphology; both the hydrogelator and the NPs show negligible toxicity towards the model U937 human hematopoietic cell line; undesired leaching of cargo material loaded inside the particles is reduced, which could be an important feature for drug delivery systems

Triggering a transient organo-gelation system in a chemically active solvent

A transient organo-gelation system with spatiotemporal dynamic properties is described. Here, the solvent actively controls a complex set of equilibria that underpin the dynamic assembly event. The observed metastability is due to the in situ formation of a secondary solvent, acting as an antagonist against the primary solvent of the organogel.peerReviewe