The Dynamics of a Collapsing Polyelectrolyte Gel

We analyse the dynamics of different routes to collapse of a constrained polyelectrolyte gel in contact with an ionic bath. The evolution of the gel is described by a model that incorporates non-linear elasticity, Stefan-Maxwell diffusion and interfacial gradient free energy to account for phase separation of the gel. A bifurcation analysis of the homogeneous equilibrium states reveals three solution branches at low ion concentrations in the bath, giving way to only one above a critical ion concentration. We present numerical solutions that capture both the spatial heterogeneity and the multiple timescales involved in the process of collapse. These solutions are complemented by two analytical studies. Firstly, a phase-plane analysis that reveals the existence of a depletion front for the transition from the highly swollen to the new collapsed equilibrium state. This depletion front is initiated after the fast ionic diffusion has set the initial condition for this time regime. Secondly, we perform a linear stability analysis about the homogeneous states that show that for a range of ion concentrations in the bath, spinodal decomposition of the swollen state gives rise to localized solvent-rich(poor) and, due to the electroneutrality condition, ion-poor(rich) phases that coarsen on the route to collapse. This dynamics of a collapsing polyelectrolyte gel has not been described before

Night-time activity forecast by season and weather in a longitudinal design:natural light effects on three years' rest-activity cycles in nursing home residents with dementia

Backround: Night-time agitation is a frequent symptom of dementia. It often causes nursing home admission and has been linked to circadian rhythm disturbances. A positive influence of light interventions on night-time agitation was shown in several studies. The aim of our study was to investigate whether there is a long-term association between regional weather data (as indicator for daylight availability) and 24-hour variations of motor activity. Methods: Motor activity of 20 elderly nursing home residents living with dementia was analyzed using recordings of continuously worn wrist activity monitors over a three-year period. The average recording duration was 479 206 days per participant (mean SD). Regional cloud amount and day length data from the local weather station (latitude: 52 degrees 56N) were included in the analysis to investigate their effects on several activity variables. Results: Nocturnal rest, here defined as the five consecutive hours with the least motor activity during 24 hours (L5), was the most predictable activity variable per participant. There was a significant interaction of night-time activity with day length and cloud amount (F-1,F-1174 = 4.39; p = 0.036). Night-time activity was higher on cloudy short days than on clear short days (p = 0.007), and it was also higher on cloudy short days than on cloudy long days (p = 0.032). Conclusions: The need for sufficient zeitgeber (time cue) strength during winter time, especially when days are short and skies are cloudy, is crucial for elderly people living with dementia. Activity forecast by season and weather might be a valuable approach to anticipate adequately complementary use of electrical light and thereby foster lower night-time activity

Emulsion polymerizations for a sustainable preparation of efficient TEMPO‐based electrodes

Organic polymer‐based batteries represent a promising alternative to present‐day metal‐based systems and a valuable step toward printable and customizable energy storage devices. However, most scientific work is focussed on the development of new redox‐active organic materials, while straightforward manufacturing and sustainable materials and production will be a necessary key for the transformation to mass market applications. Here, a new synthetic approach for 2,2,6,6‐tetramethyl‐4‐piperinidyl‐ N ‐oxyl (TEMPO)‐based polymer particles by emulsion polymerization and their electrochemical investigation are reported. The developed emulsion polymerization protocol based on an aqueous reaction medium allowed the sustainable synthesis of a redox‐active electrode material, combined with simple variation of the polymer particle size, which enabled the preparation of nanoparticles from 35 to 138 nm. Their application in cell experiments revealed a significant effect of the size of the active‐polymer particles on the performance of poly(2,2,6,6‐tetramethyl‐4‐piperinidyl‐ N ‐oxyl methacrylate) (PTMA)‐based electrodes. In particular rate capabilities were found to be reduced with larger diameters. Nevertheless, all cells based on the different particles revealed the ability to recover from temporary capacity loss due to application of very high charge/discharge rates.Sustainable and efficient organic electrode : A new synthetic approach for polymers for organic batteries includes an emulsion polymerization with adjustable particle sizes in aqueous dispersions and allows the sustainable manufacturing of active materials and composite electrodes. The electrochemical investigation shows that the influence of particle sizes and the resulting morphologies of composite films on the cell performance is as important as the active material itself

Structured health care for subjects with diabetic foot ulcers results in a reduction of major amputation rates

OBJECTIVE: We tested the effects of structured health care for the diabetic foot in one region in Germany aiming to reduce the number of major amputations. RESEARCH DESIGN AND METHODS: In a prospective study we investigated patients with diabetic foot in a structured system of outpatient, in-patient and rehabilitative treatment. Subjects were recruited between January 1(st), 2000 and December 31, 2007. All participants underwent a two-year follow-up. The modified University of Texas Wound Classification System (UT) was the basis for documentation and data analysis. We evaluated numbers of major amputations, rates of ulcer healing and mortality. In order to compare the effect of the structured health care program with usual care in patients with diabetic foot we evaluated the same parameters at another regional hospital without interdisciplinary care of diabetic foot (controls). RESULTS: 684 patients with diabetic foot and 508 controls were investigated. At discharge from hospital 28.3% (structured health care program, SHC) vs. 23.0% (controls) of all ulcers had healed completely. 51.5% (SHC) vs. 49.8% (controls) were in UT grade 1. Major amputations were performed in 32 subjects of the structured health care program group (4.7%) vs. 110 (21.7%) in controls (p<0.0001). Mortality during hospitalization was 2.5% (SHC) vs. 9.4% in controls (p<0.001). CONCLUSIONS: With the structured health care program we achieved a significant reduction of major amputation rates by more than 75% as compared to standard care

Significant Improvement in Shoulder Function and Pain in Patients Following Biologic Augmentation of Revision Arthroscopic Rotator Cuff Repair Using an Autologous Fibrin Scaffold and Bone Marrow Aspirate Derived From the Proximal Humerus

Purpose To clinically evaluate patients who underwent a biologic augmentation technique in revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated stem cells isolated from bone marrow aspirate (BMA) obtained from the proximal humerus. Methods This is a retrospective review of prospectively collected data from patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and BMA obtained from the proximal humerus between 2014 and 2015. Minimum follow-up was 12 months. Outcome measures were collected preoperatively and postoperatively including range of motion as well as American Shoulder and Elbow Surgeons Shoulder Form, Simple Shoulder Test, single assessment numeric evaluation, and visual analog score. In addition, BMA samples of each patient were assessed for the number of nucleated cells and colony-forming units. Regression analysis was performed to investigate whether the number of nucleated cells and colony-forming units had an influence on outcome and failure. Results Ten patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated BMA obtained from the proximal humerus between 2014 and 2015 were included. The mean follow-up time was 30.7 (range: 12-49) months. Four patients were revised at final follow-up. Postoperative clinical scores improved significantly: American Shoulder and Elbow Surgeons (28.1 ± 5.4 to 60.9 ± 9.0; P < .01), single assessment numeric evaluation (6.6 ± 2.3 to 65.1 ± 10.9; P < .01), visual analog scale (7.2 ± 0.9 to 3.1 ± 0.9; P < .01), and Simple Shoulder Test (1.6 ± 0.5 to 10.3 ± 5.7; P < .01). Postoperative range of motion increased significantly with regard to flexion (97.0 ± 13.6 to 151.0 ± 12.2; P < .01) and abduction (88.0 ± 14.0 to 134.0 ± 15.1; P = .038) but not with external rotation (38.0 ± 5.7 to 50.5 ± 6.5; P = .16). Less pain was correlated to an increased number of nucleated cells (P = .026); however, there was no correlation between failure rate and number of nucleated cells (P = .430). Conclusions Patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated BMA demonstrated a significant improvement in shoulder function along with reduction of pain. However, the overall revision rate for this procedure was 40%. Level of Evidence Level IV, therapeutic case series

Electroless Nanoplating of Pd−Pt Alloy Nanotube Networks: Catalysts with Full Compositional Control for the Methanol Oxidation Reaction

Due to its simplicity, flexibility and conformity, electroless plating presents itself as an attractive route towards functional metal nanostructures. Despite the importance for creating multimetallic materials with enhanced properties, the complex interactions between the components in electroless plating baths make alloy formations a challenging objective. In this work, we outline an electroless plating strategy fabricating Pd−Pt alloy nanomaterials, which is based on arbitrarily miscible plating baths for the individual metals. To demonstrate the excellent nanoscale conformity and homogeneity of our plating system, we apply it to ion track‐etched polymer templates with large inner surfaces as ambitious substrates, resulting in the formation of 3D free‐standing PdₓPt₁₀₀₋ₓ‐nanotube‐networks (NTNWs). Based on the electro‐oxidation of methanol as a model reaction, we utilize the compositional freedom provided by our syntheses for optimizing the catalytic performance of our metal NTNWs, which heavily depends on the Pd−Pt ratio. Within our system, the highest surface normalized activity was found for the Pd₂₀Pt₈₀ NTNW, reaching more than a two‐fold increase of the peak current density in comparison to pure Pt. Overall, our reaction system provides a versatile toolkit for fabricating intricate Pd−Pt nanostructures of arbitrary elemental composition, and constitutes a starting point for designing new electroless alloy plating baths

A Neutralizing Monoclonal Antibody Targeting the Acid-Sensitive Region in Chikungunya Virus E2 Protects from Disease.

The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV

Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling

PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon DNA damage, it was unknown whether this signal plays an active role in the cell or is just a byproduct of poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies for sensitive and flexible detection of mono-ADP-ribosylation, including fluorescence-based sensors for live-cell imaging, we demonstrate that serine mono-ADP-ribosylation constitutes a second wave of PARP1 signaling shaped by the cellular HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone mono-ADP-ribosylation readers, including RNF114, a ubiquitin ligase recruited to DNA lesions through a zinc-finger domain, modulating the DNA damage response and telomere maintenance. Our work provides a technological framework for illuminating ADP-ribosylation in a wide range of applications and biological contexts and establishes mono-ADP-ribosylation by HPF1/PARP1 as an important information carrier for cell signaling. © 2023 The Author(s

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303