Hydration-induced Void-containing Hydrogels for Encapsulation and Sustained Release of Small Hydrophilic Molecules.

Efficient encapsulation and sustained release of small hydrophilic molecules from traditional hydrogel systems have been challenging due to the large mesh size of 3D networks and high water content. Furthermore, the encapsulated molecules are prone to early release from the hydrogel prior to use, resulting in a short shelf life of the formulation. Here, we present a hydration-induced void-containing hydrogel (HVH) based on hyperbranched polyglycerol-poly(propylene oxide)-hyperbranched polyglycerol (HPG-PPG-HPG) as a robust and efficient delivery system for small hydrophilic molecules. Specifically, after the HPG-PPG-HPG is incubated overnight at 4 °C in the drug solution, it is hydrated into a hydrogel containing micron-sized voids, which could encapsulate hydrophilic drugs and achieve 100% drug encapsulation efficiency. In addition, the voids are surrounded by a densely packed polymer matrix, which restricts drug transport to achieve sustained drug release. The hydrogel/drug formulation can be stored for several months without changing the drug encapsulation and release properties. HVH hydrogels are injectable due to shear thinning properties. In rats, a single injection of the HPG-PPG-HPG hydrogel containing 8 µg of tetrodotoxin (TTX) produced sciatic nerve block lasting up to 10 hours without any TTX-related systemic toxicity nor local toxicity to nerves and muscles.

Homogeneity of liquid metal polymer composites: impact on mechanical, electrical, and sensing behavior.

Liquid metal polymer composites (LMPCs) are formed by dispersing eutectic gallium-indium-tin (galinstan) droplets within a soft polymer matrix, such as polydimethylsiloxane (PDMS), resulting in an insulating composite that is suitable for dielectric applications, including wearable sensors and actuators. LMPCs offer a unique combination of robust mechanical performance and desirable electrical properties. While much research has focused on the effects of rigid fillers in polymer composites, the behavior of liquid metal fillers, particularly the impact of homogeneity, has received limited attention. The density disparity between galinstan and the polymer matrix (6.44 g cm-3 compared to 0.97 g cm-3) results in the settling of galinstan droplets before curing, especially in matrices with low viscosity, leading to an inhomogeneous composition that may affect material performance. To address this, an innovative approach was introduced that enabled a spatially uniform (homogeneous) dispersion of galinstan droplets in PDMS while preserving the non-conductive nature of the composites. Work described herein evaluates the influence of homogeneity on electrical and mechanical properties as well as performance of LMPCs as pressure sensors. It was found that homogeneity has minimal effect on permittivity and dielectric loss but exhibits a complex behavior with respect to other parameters, including dielectric strength, which is often exacerbated at higher concentrations (≥50 vol%). These findings provide valuable insight that contributes to improved control over the material properties of LMPCs and expands their potential applications in soft robotics and stretchable electronics.

Risk of osteopaenia, osteoporosis and osteoporotic fractures in patients with chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND & AIMS: Chronic pancreatitis results in irreversible pancreatic dysfunction and malnutrition which, alongside excess alcohol intake, can increase the risk of low bone density. Osteoporosis increases the risk of fractures and chronic bone pain, reduces quality of life, and poses considerable costs to healthcare. Despite this, there remains a paucity of literature evaluating bone health in this patient population. This systematic review and meta-analysis evaluated the prevalences of osteopaenia, osteoporosis and fractures in patients with chronic pancreatitis. METHODS: A comprehensive search of Medline, Embase, ClinicalTrials.gov, and CENTRAL databases was undertaken to identify eligible studies from January 2000 to May 2022. The prevalences of osteopenia, osteoporosis and fragility fractures were extracted from the included studies. Where available, a subgroup analysis was performed to compare the likelihood of developing osteoporosis in patients with chronic pancreatitis compared with control. RESULTS: Nineteen studies reporting on 2,027,764 participants (20,460 with chronic pancreatitis and 2,007,304 controls) were included. The pooled prevalence of osteoporosis was 19% (95% CI 13 to 26%; I2 = 94%). Patients with chronic pancreatitis were more likely to have osteoporosis when compared with those in the control group (OR 2.80, 95% CI 1.86 to 4.21; I2 = 21%). The prevalences of osteopaenia and fractures in patients with chronic pancreatitis were 37% (95% CI 31 to 44%; I2 = 81%) and 14% (95% CI 7 to 22%; I2 = 99%) respectively. CONCLUSION: The prevalences of osteopenia and osteoporosis are significant in patients with chronic pancreatitis and can increase the risk of developing fractures. Further population-based studies are required to evaluate the disease burden of osteoporotic fractures and associated morbidity and mortality in chronic pancreatitis.

Study of n-Alkanethiol Self-Assembly Behavior on Iron Particles: Effect of Alkyl Chain Length and Adsorption Solvent on Resulting Iron-Based Magnetorheological Fluids.

Self-assembled monolayers (SAMs) of organic molecules on metal surfaces are a type of inexpensive surface coating often used to improve metal substrate properties for sensors, electrochemistry, and nanofabrication applications. Iron, specifically, is one of the most commonly used metals, both as a pure metal and as an alloy due to its high conductivity, strong ferromagnetism, and low cost. However, magnetorheological fluids, which have shown impressive energy dampening in fields from civil infrastructure to biomedical devices utilizing iron dispersions, have suffered from low reliability and efficiency due to iron particle oxidation, corrosion, and settling. To understand the effect of self-assembled monolayers on iron and both the adsorbed particle's resistance against aggregation and performance impact, this work performs an in-depth study on alkanethiol-based self-assembled monolayers on iron particles. Adsorption of alkanethiols and the generation of SAMs on micron-sized iron particles were evaluated as a function of adsorption solvent polarity and alkanethiol chain length. Maximum alkanethiol loading, determined from appropriate isotherms, was found to strongly be a function of both parameters. Alkanethiol adsorption increased with increasing alkyl chain length and increasing solvent log P values in polar solvents. With respect to magnetorheologically relevant parameters, alkanethiol adsorption did not show any significant effect on both the magnetic properties of iron (as particles) and fluid on-state yield stress. The colloidal stability of n-alkanethiol adsorbed iron-based magnetorheological fluids (MRFs) was a function of both n-alkanethiol chain length and the iron particle adsorption solvent. MRFs composed of hexadecanethiol adsorbed iron prepared in polar solvents like methanol and ethanol showed excellent sedimentation stability compared to all other MRFs prepared in this study.

Multimodal Deformation of Liquid Metal Multimaterial Composites as Stretchable, Dielectric Materials for Capacitive Pressure Sensing.

Traditional electronic devices are composed of rigid materials and components that tend to be unsuitable for soft robotic and stretchable electronic applications, such as wearable or continuous pressure sensing. However, deformable materials have the potential to improve upon traditional devices through enhanced sensitivity and responsiveness, better conformability and biocompatibility at the human-machine interface, and greater durability. This work presents deformable composite materials composed of the gallium-indium-tin alloy galinstan (GaInSn) that combines the conductivity of a metal and the intrinsic deformability of a liquid. Dispersing galinstan in an elastomer allows for the formation of deformable dielectric materials that have tunable mechanical and electrical behavior, for example, modulus and relative permittivity. Galinstan composites have been shown previously to have a minimal modulus impact on the elastomer but concurrently achieve impressive dielectric performance. However, galinstan dispersions can be costly and face challenges of mechanical and electrical reliability. Thereby, this work investigates multimaterial composites composed of galinstan and a rigid filler, either iron or barium titanate, with respect to morphology, mechanical behavior, dielectric behavior, and pressure sensing performance for the purpose of achieving a balance between a low modulus and superior electrical performance. By combining galinstan and rigid fillers, it was found that the mechanical and electrical properties, such as modulus, permittivity, loss behavior, sensitivity, and linearity of the multimaterial composites can be improved by tuning filler formulation. This suggests that these dielectric materials can be used for sensing applications that can be precisely calibrated to specific material properties and the needs of the user. These deformable multimaterial composites, found to be stretchable and highly responsive in sensing applications, will expand the current mechanical abilities of deformable dielectric materials to improve soft robotic and stretchable electronic devices.

Colchicine for symptomatic coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI), the preferred coronary reperfusion strategy, induces endothelial trauma which may mount an inflammatory response. This has been shown to increase the likelihood of further major adverse cardiovascular events (MACE). Colchicine, a cheap and widely used anti-inflammatory has shown promise in improving cardiovascular outcomes. We aimed to perform a systematic review and meta-analysis to study the effects of colchicine in patients with symptomatic coronary artery disease (CAD) who have undergone PCI. METHOD: We systematically reviewed and meta-analysed 7 randomised controlled trials including a total of 6660 patients (colchicine group: 3347, control group: 3313; mean age=60.9±10). Six studies included participants who had a ≤13.5-day history of acute coronary syndrome (ACS). One study included patients with both ACS and chronic coronary syndrome. The follow-up of studies ranged from 3 days to 22.6 months. RESULTS: The use of colchicine in patients who underwent PCI significantly reduced MACE outcomes (risk ratio 0.73 (95% CI 0.61 to 0.87); p=0.0003) with minimal heterogeneity across the analysis (I2=6%; P for Cochran Q=0.38). These results were driven mainly by the reduction in repeat vessel revascularisation, stroke and stent thrombosis. The number needed to treat to prevent one occurrence of MACE was 41. CONCLUSION: Colchicine significantly reduced the risk of MACE in patients with CAD who underwent PCI, mostly in the reduction of repeat vessel revascularisation, stroke and stent thrombosis. The efficacy of colchicine should be further studied by distinguishing its use alongside different stent types and dosing regimens. PROSPERO REGISTRATION NUMBER: CRD42021245699.

Safety and Efficacy of Tranexamic Acid to Minimise Perioperative Bleeding in Hepatic Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: Perioperative bleeding poses a major risk during liver surgery, which can result in increased transfusion requirements, morbidity, and mortality. Tranexamic acid (TXA) effectively reduces perioperative bleeding and transfusion requirements in trauma patients. However, there remains a lack of evidence of its use in liver surgery. This meta-analysis of randomised controlled trials evaluated the efficacy and safety of TXA in liver resection and transplantation. METHOD: A comprehensive search of Medline, Embase, CENTRAL and Clinicaltrials.gov databases was undertaken to identify studies from January 1947 to September 2021. The outcomes of the need for blood transfusion, thromboembolic events and mortality were extracted from the included studies. Quantitative pooling of data was based on the random effects model. RESULTS: Six studies reporting on 429 patients were included. TXA reduced the need for perioperative blood transfusion in liver resection and transplantation (OR 0.09; 95% CI 0.01 to 0.72). More importantly, TXA did not increase the incidence of thromboembolic events (OR 2.22; 95% CI 0.47 to 10.43) and mortality (OR 0.60; 95% CI 0.13 to 2.76). CONCLUSION: TXA safely reduces the need for blood transfusion in patients undergoing liver resection and transplantation.

Digital health promotion: promise and peril.

The World Health Organization defines health promotion as process of enabling people to increase control over their health and its determinants, and thereby improve their health. As the world transitions into the information age, incorporating digital technologies into health promotion is becoming commonplace. This article discusses current applications of digital health promotion (DHP) and addresses its potential benefits, challenges, as well as how differences in cultures, governance models and digital readiness across the globe will shape the implementation of DHP differently in each society. The benefits include expanding access to health information and health promoting services, lowering scaling up costs, personalizing health advice and real-time 'nudging' toward healthier options. Key challenges would involve privacy control, appropriate use of data including secondary usage beyond the original intention, defining the limits of 'nudging' and the right of free choice, and ensuring widespread accessibility and affordability to minimize the exacerbation of social inequities. Finally, we discuss the enabling factors for successful DHP implementation, suggesting measures that should be taken at both individual and system levels. At the individual level, we explore the factors necessary to access and benefit from DHP meaningfully; at the system level, we examine the infrastructure required to provide wide access, establish trust among users and enable sustainability of behavioral changes.

Publication Rates, Ethnic and Sex Disparities in UK and Ireland Surgical Research Prize Presentations: An Analysis of Data From the Moynihan and Patey Prizes From 2000 to 2020.

BACKGROUND: Presentation at academic conferences is an important marker of research productivity. However, not all accepted abstracts progress to full publication, and there is anecdotal evidence suggesting an imbalance in sex and ethnicity amongst presenters. There is a lack of data evaluating the outcome of prize presentation sessions at academic surgical conferences in the UK. This study aimed to analyse the outcomes and demographics from presentations at prize sessions at two prestigious UK surgical conferences. METHODS: This retrospective observational study compared data on all Moynihan (Association of Surgeons of Great Britain and Ireland) and Patey (Surgical Research Society) prize presentations from 2000 to 2020. The primary outcome was rate of publication. Secondary outcomes included demographic differences in sex and ethnicity, publication according to prize outcome, academic affiliation, time to publication, and journal impact factor. RESULTS: Some 442 accepted abstracts were identified over the 21-year period, with 71.0% from the Moynihan sessions and 79.3% from the Patey sessions leading to full publications, with a median time to publication of 448 days (IQR 179-859) in journals with relatively high impact factors (median 5.00; IQR 3.15-6.36). Of the 442 prize presenters, 85 (19.2%) were female. The majority of the presenters were White males (211, 47.7%), followed by Asian males (112, 25.3%). However, there was a continuously increasing overall trend of female presenters from 2000 to 2020 (P = 0.019). CONCLUSION: Publication rates from the two prize sessions were high, with presenters publishing in journals with high impact factors. There, however, was a disparity in sex and ethnicity amongst presenters.

Therapeutic Role of Water-Soluble Contrast Media in Adhesive Small Bowel Obstruction: a Systematic Review and Meta-Analysis.

BACKGROUND: Adhesive small bowel obstruction (ASBO) is a common post-operative cause of hospitalisation. Water-soluble contrast media (WSCM) has become a popular non-surgical approach to treatment. However, previous reviews have concluded with conflicting results. This meta-analysis of randomised controlled trials (RCTs) re-evaluated the therapeutic value of WSCM in the management of ASBO. METHODS: A comprehensive search of PubMed, Embase, and Cochrane databases was undertaken to identify RCTs from January 2000 to November 2018. The primary outcomes of length of stay and secondary outcomes of time to resolution, need for surgery, and mortality were extracted from the included studies. Quantitative pooling of the data was based on the random effects model. RESULTS: Eight hundred and seventy-nine patients from the nine studies were included in the analysis. The administration of oral WSCM reduced the length of hospital stay (weighted mean difference - 0.15 days, P < 0.0001). However, WSCM does not reduce the need for surgery (relative risk 0.84, P < 0.009) and makes no difference to mortality rate (RR 0.99, P < 1.000). The definition of time to resolution of ASBO differed between the studies, ranging from time to passing flatus, to cessation of abdominal pain, and time to initiating oral intake. The significant differences in definition precluded meaningful quantitative pooling of this outcome. CONCLUSIONS: This meta-analysis evaluating the therapeutic value of WSCM has shown that it does not reduce the need for operative management in ASBO or impact mortality rates. It shortens hospital stay by 0.15 days (3.6 h) which is not clinically significant.

Statin therapy does not influence the outcome of patients undergoing surgery for pancreatic cancer.

BACKGROUND: Recently, statins have been associated with improved survival in certain cancers. The aim of this study was to evaluate the impact of statins on the outcome of patients undergoing surgery for pancreatic cancer. In addition, the effect of statins on the histopathological characteristics of the disease was assessed. METHODS: A retrospective review of the prospectively maintained hepato-pancreatico-biliary database was performed and patients with pancreatic cancer who underwent surgery between January 2014 and December 2017 were included. Statistical analysis was performed to assess the impact of statins on histopathological characteristics and survival outcome. RESULTS: A total of 151 patients were included, of whom 71 underwent pancreatic resections and 80 underwent trial dissection and bypass procedures. In the operated group, 20 patients were on statin therapy preoperatively. With respect to disease-free survival, tumour size (P = 0.023) and lymphatic invasion (P = 0.015) were significant variables on univariate analysis. Gender (P = 0.022), adjuvant chemotherapy (P < 0.001), lymphatic invasion (P = 0.021) and tumour size (P = 0.041) were significant variables on univariate analysis with respect to overall survival. Multivariate analysis identified adjuvant chemotherapy as the only independent predictor of overall survival (P < 0.001). No correlations between the use of statins and the histopathological characteristics were identified. CONCLUSION: Adjuvant chemotherapy is an independent predictor of overall survival in patients undergoing surgery for pancreatic cancer. Statin therapy does not influence survival outcomes and histopathological characteristics following surgery for pancreatic cancer.

Correction to: Therapeutic Role of Water-Soluble Contrast Media in Adhesive Small Bowel Obstruction: a Systematic Review and Meta-Analysis.

This published article omitted a reference to the paper.

Fundamental Characterization of the Micellar Self-Assembly of Sophorolipid Esters.

Surfactants are ubiquitous constituents of commercial and biological systems that function based on complex structure-dependent interactions. Sophorolipid (SL) n-alkyl esters (SL-esters) comprise a group of modified naturally derived glycolipids from Candida bombicola. Herein, micellar self-assembly behavior as a function of SL-ester chain length was studied. Surface tensions as low as 31.2 mN/m and critical micelle concentrations (CMCs) as low as 1.1 µM were attained for diacetylated SL-decyl ester (dASL-DE) and SL-octyl ester, respectively. For deacetylated SL-esters, CMC values reach a lower limit at SL-ester chains above n-butyl (SL-BE, 1-3 µM). This behavior of SL-esters with increasing hydrophobic tail length is unlike other known surfactants. Diffusion-ordered spectroscopy (DOSY) and T1 relaxation NMR experiments indicate this behavior is due to a change in intramolecular interactions, which impedes the self-assembly of SL-esters with chain lengths above SL-BE. This hypothesis is supported by micellar thermodynamics where a disruption in trends occurs at n-alkyl ester chain lengths above those of SL-BE and SL-hexyl ester (SL-HE). Diacetylated (dA) SL-esters exhibit an even more unusual trend in that CMC increases from 1.75 to 815 µM for SL-ester chain lengths of dASL-BE and dASL-DE, respectively. Foaming studies, performed to reveal the macroscopic implications of SL-ester micellar behavior, show that the observed instability in foams formed using SL-esters are due to coalescence, which highlights the importance of understanding intermicellar interactions. This work reveals that SL-esters are an important new family of green high-performing surfactants with unique structure-property relationships that can be tuned to optimize micellar characteristics.

Pathological consequences of MICU1 mutations on mitochondrial calcium signalling and bioenergetics.

Loss of function mutations of the protein MICU1, a regulator of mitochondrial Ca2+ uptake, cause a neuronal and muscular disorder characterised by impaired cognition, muscle weakness and an extrapyramidal motor disorder. We have shown previously that MICU1 mutations cause increased resting mitochondrial Ca2+ concentration ([Ca2+]m). We now explore the functional consequences of MICU1 mutations in patient derived fibroblasts in order to clarify the underlying pathophysiology of this disorder. We propose that deregulation of mitochondrial Ca2+ uptake through loss of MICU1 raises resting [Ca2+]m, initiating a futile Ca2+ cycle, whereby continuous mitochondrial Ca2+ influx is balanced by Ca2+ efflux through the sodium calcium exchanger (NLCXm). Thus, inhibition of NCLXm by CGP-37157 caused rapid mitochondrial Ca2+ accumulation in patient but not control cells. We suggest that increased NCLX activity will increase sodium/proton exchange, potentially undermining oxidative phosphorylation, although this is balanced by dephosphorylation and activation of pyruvate dehydrogenase (PDH) in response to the increased [Ca2+]m. Consistent with this model, while ATP content in patient derived or control fibroblasts was not different, ATP increased significantly in response to CGP-37157 in the patient but not the control cells. In addition, EMRE expression levels were altered in MICU1 patient cells compared to the controls. The MICU1 mutations were associated with mitochondrial fragmentation which we show is related to altered DRP1 phosphorylation. Thus, MICU1 serves as a signal-noise discriminator in mitochondrial calcium signalling, limiting the energetic costs of mitochondrial Ca2+ signalling which may undermine oxidative phosphorylation, especially in tissues with highly dynamic energetic demands. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.

Effect of Sophorolipid n-Alkyl Ester Chain Length on Its Interfacial Properties at the Almond Oil-Water Interface.

Sophorolipids (SLs), produced by Candida bombicola, are of interest as potential replacements for hazardous commercial surfactants. For the first time, a series of molecularly edited SLs with ethyl (EE), n-hexyl (HE), and n-decyl (DE) esters were evaluated at an oil (almond oil)-water interface for their ability to reduce interfacial tension (IFT) and generate stable emulsions. An increase in the n-alkyl ester chain length from ethyl to hexyl resulted in a maximum % decrease in the IFT from 86.1 to 95.3, respectively. Furthermore, the critical aggregation concentrations (CACs) decreased from 0.035 to 0.011 and 0.006 mg/mL as the ester chain length was increased from ethyl to n-hexyl and n-decyl, respectively. In contrast, the CAC of natural SL, composed of 50/50 acidic and LSL, is 0.142 mg/mL. Dynamic IFT analysis showed significant differences in diffusion coefficients for all SLs studied. Almond oil emulsions with up to 200:1 (by weight) oil/SL-DE were stable against oil separation for up to 1 week with average droplet sizes below 5 µm. Emulsions of almond oil with natural SLs showed consistent oil separation 24 h after emulsification. A unique connection between IFT and emulsification was found as SL-DE has both the lowest CAC and the best emulsification performance of all natural and modified SLs studied herein. This connection between CAC and emulsification may be generally applicable, providing a tool for the prediction of optimal surfactants in other oil-water interfacial applications.

Surface modification of a polyethylene film for anticoagulant and anti-microbial catheter.

A functional anticoagulant and anti-bacterial coating for polyethylene (PE) films is described. The stepwise preparation of this nanocomposite surface coating involves O2 plasma etching of PE film, carbodiimide coupling of cysteamine to the etched PE film, binding of Ag to sulfhydryl groups of cysteamine, and assembly of heparin capped AgNPs on the PE film. The nanocomposite film and its components were characterized by 1H-nuclear magnetic resonance spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and field emission-scanning electron microscopy. The resulting PE films demonstrate anticoagulant activity using a hemoglobin whole blood clotting assay, and anti-bacterial activity against Bacillus cereus 3551 (Gram-positive) and Escherichia coli BL21 (Gram-negative) bacteria. The hydrophilicity of the heparin coated PE was determined by contact angle measurements; and the stability of the nanocomposite film, with respect to Ag leaching, was assessed by atomic absorption spectroscopy.