Effect of Structural Elements of Heparin-Mimicking Polymers on Vascular Cell Distribution and Functions: Chemically Homogeneous or Heterogeneous?

Heparin-mimicking polymers (HMPs) are artificially synthesized alternatives to heparin with comparable regulatory effects on protein adsorption and cell behavior. By introducing two major structural elements of HMPs (sulfonate- and glyco-containing units) to different areas of material surfaces, heterogeneous surfaces patterned with different HMPs and homogeneous surfaces patterned with the same HMPs can be obtained. In this work, heterogeneous HMP-patterned poly(dimethylsiloxane) (PDMS) surfaces with sulfonate-containing polySS (pS) and glyco-containing polyMAG (pM) distributed in circular patterns (with a diameter of 300 µm) were prepared (S-M and M-S). Specifically, pS and pM were distributed inside and outside the circles on S-M, respectively, and exchanged their distribution on M-S. Homogeneous HMP-patterned silicone surfaces (SM-SM) where sulfonate- and glyco-containing poly(SS-co-MAG) (pSM) were distributed uniformly were prepared. Vascular cells showed interestingly different behaviors between chemically homogeneous and heterogeneous surfaces. They tended to grow in the sulfonate-modified area on S-M and M-S and were distributed uniformly on SM-SM. Compared with M-S, S-M showed a better promoting effect on the growth of vascular cells. Among all the samples, SM-SM exhibited the highest proliferation density and an optimum spreading state of vascular cells, as well as the highest human umbilical vein endothelial cell (HUVEC) viability (∼99%) and relatively low human umbilical vein smooth muscle cell (HUVSMC) viability (∼72%). By heterogeneous or homogeneous patterning with different structural elements of HMPs, the modified silicone surfaces spatially guided vascular cell distribution and functions. This strategy provides a new surface engineering approach to the study of cell-HMP interactions.

Comparing the efficacy of antimicrobial pocket-irrigation protocols in an in vivo breast implant infection model.

BACKGROUND: Breast implant infection and biofilm formation are major concerns in reconstructive and esthetic breast surgery, with significant medical and economic consequences. Staphylococcus is the common pathogen, with rapidly increasing rates of methicillin-resistant Staphylococcus aureus (MRSA). There is no consensus on prevention practices. This study compares the effect of several pocket irrigation and antibiotic prophylaxis regimens on implant colonization and biofilm formation in an established rat model of MRSA-infected silicone breast implants. METHODS: Silicone discs were inserted in a sub-pectoral pocket in 57 rats (114 implants). Implant infection was induced by injection of free planktonic MRSA into the surgical pocket. Rats were allocated to study groups treated by different antimicrobial protocols: pocket irrigation with vancomycin, povidone-iodine, or saline. Each group was divided into subgroups treated with or without additional peri-operative systemic vancomycin. Implant colonization or overt infection was assessed at post-operative day 14 both clinically and by cultures. RESULTS: Pocket irrigation with vancomycin prevented contamination in 87% of implants. Irrigation and systemic vancomycin prevented contamination in 100% of implants with no difference between a single preoperative dose and a 48-h regimen. Systemic vancomycin alone or irrigation with povidone-iodine alone resulted in 100% contamination rates. CONCLUSIONS: In this in vivo model, combination of systemic vancomycin with vancomycin pocket irrigation was the most effective regimen, preventing contamination in 100% of implants. Continuation of post-operative antibiotic treatment showed no added advantage.

Domestic LED bulb induced photodynamic effect of Toluidine Blue O-embedded silicone catheters against urinary tract infection.

BACKGROUND: Novel combination of Toluidine Blue O (TBO) embedded silicone catheter with domestic/household LED bulb has a potential in clinical infection such as prevention of multi drug resistant catheter-associated urinary tract infections (CAUTIs) through photodynamic therapy. MATERIAL AND METHODS: Preliminarily, TBO was entrapped into silicone catheter by swell-encapsulation-shrink method. Further, in vitro study was carried out to check the antimicrobial photodynamic efficacy of TBO with domestic/household LED light. Antibiofilm activity was evaluated by scanning electron microscopy. RESULTS: The results showed that these modified TBO embedded silicone catheters showed significant antimicrobial and antibiofilm activity against vancomycin resistant Staphylococcus aureus VRSA. Small piece (1 cm) of TBO-embedded silicone catheter (700 µM) showed 6 log10 reduction in the viable count when exposed for only 5 min of domestic/household LED bulb, while 1 cm piece of 500 µM and 700 µM concentration of TBO-embedded catheter eradicated all bacterial load when exposed to 15 min of light. Segment of medical grade TBO-embedded silicone catheters were used to carry out investigation of reactive oxygen species generation mainly singlet oxygen that contributes to type II phototoxicity. CONCLUSION: These modified catheter provides cost effective, easy to manage and less time consuming therapy to eliminate CAUTIs.

Effect of the Presence of Silicone Oil in the Anterior Chamber After Complicated Retinal Detachment Surgery on Corneal Morphology by In Vivo Confocal Microscopy.

PURPOSE: This study evaluated the corneal endothelium, stromal keratocytes, subbasal nerve number and density in patients with silicone oil transferred to the anterior camera after pseudophakic complicated retinal detachment surgery by in vivo laser scanning confocal microscopy (IVLSCM). METHODS: Sequential measurements were made by IVLSCM between 3-6 months after surgery in two groups of patients: a) with silicon oil migration (Group 1) and without silicone oil migration (Group 2). RESULTS: A total of 63 cases (Group 1: 32 and Group 2: 31) were examined. The mean ages of patients were 65 ± 12 and 61 ± 11 and M/F ratio was 18/14 and 17/14, respectively. Mean intraocular pressures were 16.60 ± 4.60 and 15.75 ± 5.70 mm Hg, respectively. Changes were detected by IVLSCM mostly on the superior part of the cornea. A significant decrease in endothelial cell density and the number was detected in group 1 (2072 ± 116.2 cells/mm2 vs 2752 ± 512.3 cells/mm2; p < 0.001). Significant increases in posterior keratocyte density and stromal hyperreflective deposits were observed in group 1 (887 ± 45.8 cells/mm2 vs 725 ± 65.8 cells/mm2; p < 0.001). A significant negative correlation was observed between the size of stromal deposits and endothelial cell density (r=-0.758; p < 0.001). The number and density of corneal subbasal nerves were significantly lower in group 1 (1.8 ± 0.8 and 4.8 ± 1.2 vs 420 ± 101 and 701 ± 112 µm/square; p < 0.001). CONCLUSION: IVLSCM is a useful tool for the early detection of corneal abnormalities caused by silicone oil injection. This study verified silicone oil's detrimental effect on the corneal endothelium and revealed stromal changes in the anterior chamber, which we believe can be also been associated with the presence of silicone oil.

A Gelatin Hydrogel Nonwoven Fabric Enhances Subcutaneous Islet Engraftment in Rats.

Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (p < 0.01). The cure rate was significantly higher in the GHNF group (p < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (p < 0.01), and lectin angiography showed the same tendency (p < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (p < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices.

Silicone Foley catheters impregnated with microbial indole derivatives inhibit crystalline biofilm formation by Proteus mirabilis.

Proteus mirabilis is a common causative agent for catheter-associated urinary tract infections (CAUTI). The crystalline biofilm formation by P. mirabilis causes catheter encrustation and blockage leading to antibiotic treatment resistance. Thus, biofilm formation inhibition on catheters becomes a promising alternative for conventional antimicrobial-based treatment that is associated with rapid resistance development. Our previous work has demonstrated the in vitro antibiofilm activity of microbial indole derivatives against clinical isolates of P. mirabilis. Accordingly, we aim to evaluate the capacity of silicone Foley catheters (SFC) impregnated with these indole derivatives to resist biofilm formation by P. mirabilis both phenotypically and on the gene expression level. Silicon Foley catheter was impregnated with indole extract recovered from the supernatant of the rhizobacterium Enterobacter sp. Zch127 and the antibiofilm activity was determined against P. mirabilis (ATCC 12435) and clinical isolate P8 cultured in artificial urine. The indole extract at sub-minimum inhibitory concentration (sub-MIC=0.5X MIC) caused a reduction in biofilm formation as exhibited by a 60-70% reduction in biomass and three log10 in adhered bacteria. Results were confirmed by visualization by scanning electron microscope. Moreover, changes in the relative gene expression of the virulence genes confirmed the antibiofilm activity of the indole extract against P. mirabilis. Differential gene expression analysis showed that extract Zch127 at its sub-MIC concentration significantly down-regulated genes associated with swarming activity: umoC, flhC, flhD, flhDC, and mrpA (p< 0.001). In addition, Zch127 extract significantly down-regulated genes associated with polyamine synthesis: speB and glnA (p< 0.001), as well as the luxS gene associated with quorum sensing. Regulatory genes for capsular polysaccharide formation; rcsB and rcsD were not significantly affected by the presence of the indole derivatives. Furthermore, the impregnated catheters and the indole extract showed minimal or no cytotoxic effect against human fibroblast cell lines indicating the safety of this intervention. Thus, the indole-impregnated catheter is proposed to act as a suitable and safe strategy for reducing P. mirabilis CAUTIs.

Harpagophytum procumbens Inhibits Iron Overload-Induced Oxidative Stress through Activation of Nrf2 Signaling in a Rat Model of Lumbar Spinal Stenosis.

Lumbar spinal stenosis (LSS) is a common degenerative spinal condition in older individuals that causes impaired walking and other disabilities due to severe lower back and leg pain. Ligamentum flavum hypertrophy is a major LSS cause that may result from oxidative stress caused by degenerative cascades, including imbalanced iron homeostasis that leads to excessive reactive oxygen species production. We investigated the effects of Harpagophytum procumbens (HP) on iron-induced oxidative stress associated with LSS pathophysiology. Primary spinal cord neuron cultures were incubated in FeSO4-containing medium, followed by addition of 50, 100, or 200 µg/mL HP. Cell viability was assessed by CCK-8 and live/dead cell assays and by propidium iodide-live imaging. In an in vivo rat model of LSS, HP were administered at 100, 200, and 400 mg/kg, and disease progression was monitored for up to 3 weeks. We investigated the in vitro and in vivo effects of HP on iron-induced neurotoxicity by immunochemistry, real-time PCR, and flow cytometry. HP exerted neuroprotective effects and enhanced neurite outgrowths of iron-injured rat primary spinal cord neurons in vitro. HP treatment significantly reduced necrotic cell death and improved cells' antioxidative capacity via the NRF2 signaling pathway in iron-treated neurons. At 1 week after HP administration in LSS rats, the inflammatory response and oxidative stress markers were substantially reduced through regulation of excess iron accumulation. Iron that accumulated in the spinal cord underneath the implanted silicone was also regulated by HP administration via NRF2 signaling pathway activation. HP-treated LSS rats showed gradually reduced mechanical allodynia and amelioration of impaired behavior for 3 weeks. We demonstrated that HP administration can maintain iron homeostasis within neurons via activation of NRF2 signaling and can consequently facilitate functional recovery by regulating iron-induced oxidative stress. This fundamentally new strategy holds promise for LSS treatment.

A PEDOT nano-composite for hyperthermia and elimination of urological bacteria.

Novel modalities for overcoming recurrent urinary tract infections associated with indwelling urinary catheters are needed, and rapidly induced hyperthermia is one potential solution. PEDOT nanotubes are a class of photothermal particles that can easily be incorporated into silicone to produce thin, uniform coating on medical grade silicone catheters; subsequent laser stimulation therein imparts temperature elevations that can eliminate bacteria and biofilms. PEDOT silicone coatings are stable following thermal sterilization and repeated heating and cooling cycles. Laser stimulation can induce temperature increases of up to 55 °C in 300 s, but only 45 s was needed for ablation of UTI inducing E. coli biofilms in vitro. This work also demonstrates that mild hyperthermia of 50 °C, applied for only 31 s in the presence of antibiotics could eliminate E. coli biofilm as effectively as high temperatures. This work culminates in the evaluation of the PEDOT NTs for photothermal elimination of E. coli in an in vivo model to demonstrate the safety and effectiveness of a photothermal nanocomposite (16 s treatment time) for rapid clearance of E. coli.

Effect of Breast Silicone Implant Topography on Bacterial Attachment and Growth: An In Vitro Study.

BACKGROUND/AIM: The mechanisms underlying capsular contracture remain unclear. Emerging evidence supports the inflammation hypothesis, according to which bacteria from an adherent biofilm cause chronic inflammation and collagen deposition on the implant and trigger capsular contracture. Our goal was to evaluate the effect of different types of breast implants on the growth of Staphylococcus aureus, S. epidermidis, and Pseudomonas aeruginosa, which are commonly found in biofilms in infection. MATERIALS AND METHODS: Bacteria were grown in tryptic soy broth at 37°C for 2, 6, and 24 h and subsequently incubated for 24 h on 12 shell sections of smooth, nano-, and macrotextured breast implants. After incubation, the solutions were ultrasonicated and bacterial numbers were determined by serial dilution. S. aureus were fixed, washed with phosphate-buffered saline, dehydrated in ethanol, and coated with a platinum film to visualize the presence of biofilms by scanning electron microscopy. RESULTS: The numbers of S. aureus and S. epidermidis attached to the smooth and nanotextured surface implants were significantly lower than those on the macrotextured surface for all incubation times, whereas the number of P. aeruginosa was non-significantly lowest on the nanotextured surface after 24h incubation. Biofilms on smooth and nanotextured implant surfaces showed patchy patterns on scanning electron microscopy in contrast to the continuous pattern detected on macrotextured implants. CONCLUSION: Nanotextured breast implants may limit bacterial growth and thus prevent capsular contracture.

Quercetin-loaded chitosan nanoparticles as an alternative for controlling bacterial adhesion to urethral catheter.

OBJECTIVES: The present study aimed to assess the antimicrobial and antiadhesion behavior of quercetin-loaded chitosan nanoparticles in Escherichia coli and Staphylococcus aureus multidrug-resistant isolates. METHODS: The ionic gelation method was used to prepare chitosan nanoparticles loaded with quercetin. The antimicrobial and antibiofilm effects were observed by minimum inhibitory concentration (MIC), plate count, crystal violet assay, and the matrix exopolysaccharide dosages. The nanoparticles coated in silicone urethral catheters were evaluated by crystal violet assay and plating count method. RESULTS: MIC ranged from 6.25 to 12.5 mg/ml. A reduction of at least 3.6 log CFU/ml and 6.2 log CFU/ml for, respectively, E. coli and S. aureus isolates was observed (p < 0.05). Under subinhibitory concentration (3.1 mg/ml) it was found a reduction of microbial adhesion and exopolysaccharide dosages in respectively 83.3% and 75% of the bacterial samples. The coated silicone urethral catheters showed a reduction of adhered cells in 25% of the isolates and biomass decreasing in 91.6% of them (p < 0.05). CONCLUSIONS: The quercetin nanoparticles provided antimicrobial and antiadhesion effects in multidrug-resistant isolates.

Novel axially symmetric and unsymmetric silicon(IV) phthalocyanines having anti-inflammatory groups: synthesis, characterization and their biological properties.

New asymmetric Si(IV)Pc (1), monomeloxicammonotriethyleneglycolmonomethylether (phthalocyaninano)silicone, axially ligated with meloxicam as a non-steroidal anti-inflammatory drug (NSAID), or triethylene glycol monomethyl ether and symmetric Si(IV)Pc (2), diclofenac(phthalocyaninano)silicone, axially ligated with two diclofenac as NSAID, were synthesized and characterized as antioxidant and antimicrobial agents together with polyoxo-SiPc (3), ditriethyleneglycolmonomethylether(phthalocyaninano)silicone, and SiPc(OH)2 (4), dihydroxy(phthalocyaninano)silicone. The photophysical and photochemical properties of these compounds were investigated. Then, antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferrous ion chelating activities, were performed for these Si(IV) phthalocyanine derivatives (1, 2, 3 and 4). The highest DPPH scavenging activity of 73.48% was achieved with compound 2 and the highest ferrous chelating ability of 66.42% was obtained with compound 3. The results of the antioxidant assays indicated that Pc derivatives 1, 2 and 3 have remarkable superoxide radical scavenging activities, and moderate 2,2-diphenyl-1-picrylhydrazyl activities and metal chelating activities. The antimicrobial effects of the Si(IV) phthalocyanine compounds were studied against six pathogenic bacteria and two pathogenic microfungi. The results for the antimicrobial activity of these compounds indicated that Enterococcus faecalis (ATCC 29212) was the most sensitive microorganism and Pseudomonas aeruginosa (ATCC 27853) and Legionella pneumophila subsp. pneumophila (ATCC 33152) were the most resistant microorganisms against the tested compounds. The DNA cleavage ability and microbial cell viability of these compounds were studied. The studied compounds demonstrated excellent DNA nuclease activity and exhibited 100% cell viability inhibition at 500 mg L-1. Also, the antimicrobial photodynamic therapy of the compounds was tested against Escherichia coli (ATCC 25922) and significant photodynamic antimicrobial activity was observed. In addition, the effect of phthalocyanines on biofilm inhibition produced by Staphylococcus aureus (ATCC 25923) was also tested and 3 showed excellent biofilm inhibition of 82.14%.

Strategies for the evaluation of the eye irritation potential of different types of surfactants and silicones used in cosmetic products.

The ocular irritation potential of products that may come into contact with the eyes should be assessed by the combination of different in vitro alternative methods to determine different mechanisms of toxicity previously evaluated by the Draize in vivo assay. Thus, this study proposed to apply two strategies for the prediction of the eye irritation potential of different concentrations of surfactants and silicones, the first one involving evaluation Hen's Egg Test - Chorioallantoic Membrane (HET-CAM), and the other one using Bovine Corneal Opacity and Permeability (BCOP) followed by histopathological. HET-CAM was considered important in assessing the ocular irritation potential and, despite classifying almost all surfactants as "severe irritants", it could discriminate moderate and slight irritant SLES concentrations as well as Cocoamidopropyl Betaine as a severe irritant, when the coagulation score was taken into consideration. The BCOP assay alone also did not offer a good prediction of the irritant potential of surfactants, since almost all of them were classified as "no prediction can be made". However, the histopathological evaluation of the BCOP corneas was very important for establishing the degree and depth of damage related to reversibility. The present study also showed those strategies are sensitive to small variations in the studied anionic, cationic amphoteric surfactant concentrations and can be used for predicting their toxicity in the final product and can be used depending on the focus of the analysis.

Comparison of the effect of removing bandage contact lens on the days 3 and 5 following photorefractive keratectomy.

AIM: To compare the outcomes of removing bandage contact lens (BCL) on days 3 and 5 after photorefractive keratectomy (PRK). METHODS: One hundred patients who underwent PRK (a total of 200 eyes) were enrolled in the present study. The subjects were assigned to two groups. Group 1 consisted of the right eyes of subjects and bandage contact lenses removal were on the 3rd day; Group 2 consisted of the fellow eyes of same subjects and removed bandage contact lenses on the 5th day after PRK. Then, data obtained from both groups were compared. To evaluate complications, the subjects underwent a slit-lamp examination in all visits. RESULTS: Filamentary keratitis was observed in one eye in both groups. The frequency of haze was higher in group 1; however, it was not significant between the two groups. Using mixed model analysis, significant differences were observed in the rate of complications as well as pain and eye discomfort scores between the groups (P < 0.05). No major complication was reported. CONCLUSION: Majority of post-PRK corneal epithelial defect is healed on day 3. However, keeping BCL for 5 days postoperatively instead of the three days produces a slightly lower rate of total complication.

Biofilm inhibition and antifouling evaluation of sol-gel coated silicone implants with prolonged release of eugenol against Pseudomonas aeruginosa.

The incidence of biofilm-linked catheter-associated urinary tract infections (CAUTIs) is increasing across the world. However, there is no clinical evidence to support the modifications of biomaterials, such as antimicrobial agent-coated catheters, that are known to reduce the risk of bacterial colonization and resistance development. The present study developed and tested silicone segments coated with an antivirulence agent, eugenol. The parameters for sol-gel preparation and coating were tailored to achieve a prolonged release of eugenol (for >35 days) at predefined antivirulence doses from dip-coated thin films. The eugenol-coated segments could prevent biofilm formation by Pseudomonas aeruginosa PAO1 as well as bacterial adhesion. Significant repression in the expression of virulence and biofilm-associated genes were recorded, confirming the antivirulence and biofilm inhibition properties of silicone segments coated with eugenol. The drug release profiles, efficacy analysis, neutrophil-response studies, and in vitro toxicity profiling further supported the contention that the activity of the eugenol-coated sections was effective and safe.

Impact of Different Mixing Methods on the Performance of Suspension-Based Transdermal Delivery Systems.

Suspension-based matrix transdermal delivery systems (TDSs) are specialized systems that maintain a continuous driving force for drug delivery over prolonged wear. The pressure-sensitive adhesive (PSA) is the most critical constituent of such systems. Our study aimed to determine the effect of different mixing methods on the performance of silicone PSA-based suspension TDSs. Lidocaine suspension TDSs were prepared using conventional slow rotary mixing, high-speed homogenization, bead-mill homogenization, vortex shaking, and by an unguator. Resultant TDSs were tested for tack, shear, and peel properties and correlated to coat weight, content uniformity, microstructure, and in vitro permeation across dermatomed human skin. Every mixing method tested caused a significant reduction in peel. However, bead-mill homogenization resulted in significant loss of all adhesive properties tested, while unguator-mixed TDSs retained most properties. Good linear correlation (R2 = 1.000) between the shear properties of the TDSs with the average cumulative amount of lidocaine permeated after 24 h was observed, with no significant difference between percutaneous delivery from slow rotary-mixed systems (1334 ± 59.21 µg/cm2) and unguator-mixed systems (1147 ± 108.3 µg/cm2). However, significantly lower delivery from bead-mill homogenized systems (821.1 ± 28.00 µg/cm2) was noted. While many factors affect TDS performance, careful consideration must also be given to the processing parameters during development as they have been shown to affect the resultant system's therapeutic efficacy. Extensive mixing with bead-mill homogenization demonstrated crystallization of drug, loss in adhesive properties, coat weight, and film thickness, with reduced transdermal delivery of lidocaine from the prepared system.

Cervical ripening in prolonged pregnancies by silicone double balloon catheter versus vaginal dinoprostone slow release system: The MAGPOP randomised controlled trial.

BACKGROUND: Prolonged pregnancies are a frequent indication for induction of labour. When the cervix is unfavourable, cervical ripening before oxytocin administration is recommended to increase the likelihood of vaginal delivery, but no particular method is currently recommended for cervical ripening of prolonged pregnancies. This trial evaluates whether the use of mechanical cervical ripening with a silicone double balloon catheter for induction of labour in prolonged pregnancies reduces the cesarean section rate for nonreassuring fetal status compared with pharmacological cervical ripening by a vaginal pessary for the slow release of dinoprostone (prostaglandin E2). METHODS AND FINDINGS: This is a multicentre, superiority, open-label, parallel-group, randomised controlled trial conducted in 15 French maternity units. Women with singleton pregnancies, a vertex presentation, ≥41+0 and ≤42+0 weeks' gestation, a Bishop score <6, intact membranes, and no history of cesarean delivery for whom induction of labour was decided were randomised to either mechanical cervical ripening with a Cook Cervical Ripening Balloon or pharmacological cervical ripening by a Propess vaginal pessary serving as a prostaglandin E2 slow-release system. The primary outcome was the rate of cesarean for nonreassuring fetal status, with an independent endpoint adjudication committee determining whether the fetal heart rate was nonreassuring. Secondary outcomes included delivery (time from cervical ripening to delivery, number of patients requiring analgesics), maternal and neonatal outcomes. Between January 2017 and December 2018, 1,220 women were randomised in a 1:1 ratio, 610 allocated to a silicone double balloon catheter, and 610 to the Propess vaginal pessary for the slow release of dinoprostone. The mean age of women was 31 years old, and 80% of them were of white ethnicity. The cesarean rates for nonreassuring fetal status were 5.8% (35/607) in the mechanical ripening group and 5.3% (32/609) in the pharmacological ripening group (proportion difference: 0.5%; 95% confidence interval (CI) -2.1% to 3.1%, p = 0.70). Time from cervical ripening to delivery was shorter in the pharmacological ripening group (23 hours versus 32 hours, median difference 6.5 95% CI 5.0 to 7.9, p < 0.001), and fewer women required analgesics in the mechanical ripening group (27.5% versus 35.4%, difference in proportion -7.9%, 95% CI -13.2% to -2.7%, p = 0.003). There were no statistically significant differences between the 2 groups for other delivery, maternal, and neonatal outcomes. A limitation was a low observed rate of cesarean section. CONCLUSIONS: In this study, we observed no difference in the rates of cesarean deliveries for nonreassuring fetal status between mechanical ripening with a silicone double balloon catheter and pharmacological cervical ripening with a pessary for the slow release of dinoprostone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02907060.

Mepitel Film is superior to Biafine cream in managing acute radiation-induced skin reactions in head and neck cancer patients: a randomised intra-patient controlled clinical trial.

INTRODUCTION: We previously showed that Mepitel Film decreased the severity of acute radiation-induced skin reactions in head and neck cancer patients. In the current study, we compared the effect of Mepitel Film and Biafine cream on skin reaction severity in a larger cohort of head and neck cancer patients. METHODS: A total of 44 head and neck cancer patients were recruited with 39 patients contributing full data sets for analysis. Patients received a dose of 50 Gy in 25 fractions to the bilateral lymph nodes in the neck. Left and right lymph node areas were randomised to either Mepitel Film or Biafine cream, applied prophylactically. Skin reaction severity was measured using Radiation-Induced Skin Reaction Assessment Scale (RISRAS) and expanded Radiation Oncology group (RTOG) grades. Skin dose was measured using gafchromic Film. RESULTS: Skin reaction severity (combined RISRAS score) underneath Mepitel Film was decreased by 30% (P < 0.001) and moist desquamation rates by 41% (P < 0.001). Skin dose underneath Mepitel Film and Biafine cream was similar (P = 0.925) and unlikely to have affected skin reaction severity. The vast majority (80%) of patients preferred Mepitel Film over Biafine cream. Negative aspects of Mepitel Film included poor adherence (11/39) and discomfort (16/39) during hot weather and showering and itchy skin underneath Mepitel Film (12/39). CONCLUSIONS: Mepitel Film was superior to Biafine cream in reducing the severity of acute radiation-induced skin reactions and moist desquamation incidence in our head and neck patient cohort.

A novel silicone derivative of natural osalmid (DCZ0858) induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma via the JAK2/STAT3 pathway.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor characterized by diffuse growth. DCZ0858 is a novel small molecule with excellent antitumor effects in DLBCL. This study explored in depth the inhibitory effect of DCZ0858 on DLBCL cell lines. Cell Counting Kit-8 (CCK-8) and plate colony formation assays were used to evaluate cell proliferation levels. Flow cytometry was employed to analyze apoptosis and the cell cycle, and western blotting was used to quantify the expression of cell cycle regulators. The results indicated that DCZ0858 inhibited cell growth in a concentration-dependent and time-dependent manner while inducing no significant toxicity in normal cells. Moreover, DCZ0858 initiated cell apoptosis via both internal and external apoptotic pathways. DCZ0858 also induced cell cycle arrest in the G0/G1 phase, thereby controlling cell proliferation. Further investigation of the molecular mechanism showed that the JAK2/STAT3 pathway was involved in the DCZ0858-mediated antitumor effects and that JAK2 was the key target for DCZ0858 treatment. Knockdown of JAK2 partly weakened the DCZ0858-mediated antitumor effect in DLBCL cells, while JAK2 overexpression strengthened the effect of DCZ0858 in DLBCL cells. Moreover, a similar antitumor effect was observed for DCZ0858 and the JAK2 inhibitor ruxolitinib, and combining the two could significantly enhance cancer-suppressive signaling. Tumor xenograft models showed that DCZ0858 inhibited tumor growth in vivo and had low toxicity in important organs, findings that were consistent with the in vitro data. In summary, DCZ0858 is a promising drug for the treatment of DLBCL.

Elastic net of polyurethane strands for sustained delivery of triamcinolone around silicone implants of various sizes.

We propose an elastic net made of a biocompatible polymer to wrap silicone implants of various sizes, which also allows for the sustained release of an anti-inflammatory drug, triamcinolone, to prevent fibrosis. For this, we first prepared a strand composed of a mixture of polyurethane and triamcinolone via electrospinning, which was then assembled to prepare the elastic drug-delivery net (DDN). The DDN was prepared to just fit for wrapping the small silicone implant sample herein, but was also able to wrap a sample 7 times as large at 72% strain due to the elastic property of polyurethane. The DDN exhibited sustained drug release for 4 weeks, the profile of which was not very different between the intact and strained DDNs. When implanted in a subcutaneous pocket in living rats, the DDN-wrapped silicone implant samples showed an obvious antifibrotic effect due to the sustained release of triamcinolone. Importantly, this effect was similar for the small and large silicone samples, both wrapped with the same DDN. Therefore, we conclude that this drug-loaded net made of an elastic, biocompatible polymer has high potential for sustained drug delivery around silicone implants manufactured in various sizes.

Development of a Gaussian Process - feature selection model to characterise (poly)dimethylsiloxane (Silastic® ) membrane permeation.

OBJECTIVES: The current study aims to determine the effect of physicochemical descriptor selection on models of polydimethylsiloxane permeation. METHODS: A total of 2942 descriptors were calculated for a data set of 77 chemicals. Data were processed to remove redundancy, single values, imbalanced and highly correlated data, yielding 1363 relevant descriptors. For four independent test sets, feature selection methods were applied and modelled via a variety of Machine Learning methods. KEY FINDINGS: Two sets of molecular descriptors which can provide improved predictions, compared to existing models, have been identified. Best permeation predictions were found with Gaussian Process methods. The molecular descriptors describe lipophilicity, partial charge and hydrogen bonding as key determinants of PDMS permeation. CONCLUSIONS: This study highlights important considerations in the development of relevant models and in the construction and use of the data sets used in such studies, particularly that highly correlated descriptors should be removed from data sets. Predictive models are improved by the methodology adopted in this study, notably the systematic evaluation of descriptors, rather than simply using any and all available descriptors, often based empirically on in vitro experiments. Such findings also have clear relevance to a number of other fields.