BACKGROUND: An optimum restoration for reconstructing endodontically treated teeth should provide excellent marginal adaptation, high fracture resistance as well as maximum tooth structure conservation. The purpose of this study was to evaluate the marginal adaptation and fatigue resistance of different coronal restorations in endodontically treated premolars.
METHODS: Thirty sound maxillary first premolars were endodontically treated and received MOD cavities. Teeth were randomly allocated into three groups (n = 10) according to the type of coronal restoration: Group R: polyethylene fibers (ribbond), fibers-reinforced composite (everX posterior) and final layer of nano-hybrid composite. Group O: indirect lithium disilicate overlay and Group C: fiber-post, resin composite restoration, and lithium disilicate crown. Marginal gap assessment was performed before and after thermocycling (5000 cycles) using stereomicroscope. Samples were subjected to stepwise-stress loading starting at 200 N, and increased by 100 N in each step until failure occurred. Statistical analysis was done by One-way ANOVA followed Tukey`s Post Hoc test for multiple comparison. Paired t test was used to compare the marginal adaptation before and after thermocycling. Survival probability was evaluated by Life table survival analysis. Failure mode analysis was performed with Chi-square test.
RESULTS: Marginal gap was significantly the lowest in group R (37.49 ± 5.05) and (42.68 ± 2.38), while being the highest in group C (59.78 ± 5.67) and (71.52 ± 5.18) in before and after thermocycling respectively (P < 0.0001). Fatigue resistance was the highest for group O (1310.8 ± 196.7), and the lowest for group R (905.4 ± 170.51) with a significant difference between groups (P < 0.0001). Crown group had the highest percentage (80%) of catastrophic failure, while, overlay group exhibited the lowest (20%).
CONCLUSIONS: Direct restoration without cuspal coverage using ribbon fibers with short FRC provided better marginal adaptation than indirect overlays and crowns, but fatigue resistance wasn\'t significantly improved. Adhesive ceramic overlays showed the best fatigue performance and the least catastrophic failure rate compared to both direct fiber-reinforced composite and indirect ceramic full coverage restorations.
CONCLUSIONS: Indirect adhesive overlays are a suitable, more conservative restorative option for endodontically treated teeth than full coverage restorations, especially when tooth structure is severely compromised.

UNASSIGNED: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.
UNASSIGNED: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.
UNASSIGNED: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.
UNASSIGNED: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.

Membrane-based lateral flow immunoassays (LFAs) have been employed as early point-of-care (POC) testing tools in clinical settings. However, the varying membrane properties, uncontrollable sample transport in LFAs, visual readout, and required large sample volumes have been major limiting factors in realizing needed sensitivity and desirable precise quantification. Addressing these challenges, we designed a membrane-free system in which the desirable three-dimensional (3D) structure of the detection zone is imitated and used a small pump for fluid flow and fluorescence as readout, all the while maintaining a one-step assay protocol. A hydrogel-like protein-polyelectrolyte complex (PPC) within a polyelectrolyte multilayer (PEM) was developed as the test line by complexing polystreptavidin (pSA) with poly(diallyldimethylammonium chloride) (PDDA), which in turn was layered with poly(acrylic acid) (PAA) resulting in a superior 3D streptavidin-rich test line. Since the remainder of the microchannel remains material-free, good flow control is achieved, and with the total volume of 20 μL, 7.5-fold smaller sample volumes can be used in comparison to conventional LFAs. High sensitivity with desirable reproducibility and a 20 min total assay time were achieved for the detection of NT-proBNP in plasma with a dynamic range of 60-9000 pg·mL-1 and a limit of detection of 56 pg·mL-1 using probe antibody-modified fluorescence nanoparticles. While instrument-free visual detection is no longer possible, the developed lateral flow channel platform has the potential to dramatically expand the LFA applicability, as it overcomes the limitations of membrane-based immunoassays, ultimately improving the accuracy and reducing the sample volume so that finger-prick analyses can easily be done in a one-step assay for analytes present at very low concentrations.

OBJECTIVE: The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test.
METHODS: Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform.
RESULTS: After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P < 0.0001).
CONCLUSIONS: In conclusion, we modified the Shilla technique and designed a novel growth guidance system by changing the friction interface of sliding screw and rod, which may significantly reduce the metallic debris and promote spine growth. The fatigue test and sliding dislocation test demonstrated the better durability and glidability of the system. An in vivo animal experiment should be performed to further verify the system.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-β1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-β1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-β1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE.
METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-β1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics.
RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis.
CONCLUSIONS: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

Polycationic polymers are widely studied antiseptics, and their efficacy is usually quantified by the solution concentration required to kill a fraction of a population of cells (e.g., by Minimum Bactericidal Concentration (MBC)). Here we describe how the response to a polycationic antimicrobial varies greatly among members of even a monoclonal population of bacteria bathed in a single common antimicrobial concentration. We use fluorescence microscopy to measure the adsorption of a labeled cationic polymer, polydiallyldimethylammmonium chloride (PDADMAC, Mw ≈ 4 × 105 g mol-1) and the time course of cell response via a cell permeability indicator for each member of an ensemble of either Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa cells. This is a departure from traditional methods of evaluating synthetic antimicrobials, which typically measure the overall response of a collection of cells at a particular time and therefore do not assess the diversity within a population. Cells typically die after they reach a threshold adsorption of PDADMAC, but not always. There is a substantial time lag of about 5-10 min between adsorption and death, and the time to die of an individual cell is well correlated with the rate of adsorption. The amount adsorbed and the time-to-die differ among species but follow a trend of more adsorption on more negatively charged species, as expected for a cationic polymer. The study of individual cells via time-lapse microscopy reveals additional details that are lost when measuring ensemble properties at a particular time.

UNASSIGNED: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.
UNASSIGNED: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.
UNASSIGNED: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.
UNASSIGNED: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There are no effective therapies available for TBI patients. Vepoloxamer is an amphiphilic polyethylene-polypropylene-polyethylene tri-block copolymer that seals membranes and restores plasma membrane integrity in damaged cells. We previously demonstrated that treatment of TBI rats with Vepoloxamer improves functional recovery. However, additional studies are needed to potentially translate Vepoloxamer treatment from preclinical studies into clinical applications. We thus conducted a study to investigate dose-response and therapeutic window of Vepoloxamer on functional recovery of adult rats after TBI. To identify the most effective dose of Vepoloxamer, male Wistar adult rats with controlled cortical impact (CCI) injury were randomly treated with 0 (vehicle), 100, 300, or 600 mg/kg of Vepoloxamer, administered intravenously (IV) at 2 h after TBI. We then performed a therapeutic window study in which the rats were treated IV with the most effective single dose of Vepoloxamer at different time points of 2 h, 4 h, 1 day, or 3 days after TBI. A battery of cognitive and neurological tests was performed. Animals were killed 35 days after TBI for histopathological analysis. Dose-response experiments showed that Vepoloxamer at all three tested doses (100, 300, 600 mg/kg) administered 2 h post injury significantly improved cognitive functional recovery, whereas Vepoloxamer at doses of 300 and 600 mg/kg, but not the 100 mg/kg dose, significantly reduced lesion volume compared to saline treatment. However, Vepoloxamer at 300 mg/kg showed significantly improved neurological and cognitive outcomes than treatment with a dose of 600 mg/kg. In addition, our data demonstrated that the dose of 300 mg/kg of Vepoloxamer administered at 2 h, 4 h, 1 day, or 3 days post injury significantly improved neurological function compared with vehicle, whereas Vepoloxamer administered at 2 h or 4 h post injury significantly improved cognitive function compared with the 1-day and 3-day treatments, with the most robust effect administered at 2 h post injury. The present study demonstrated that Vepoloxamer improves functional recovery in a dose-and time-dependent manner, with therapeutic efficacy compared with vehicle evident even when the treatment is initiated 3 days post TBI in the rat.

The occurrence of periprosthetic joint infections (PJI) after total joint replacement constitutes a great burden for the patients and the healthcare system. Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is often used in temporary spacers during antibiotic treatment. PMMA is not a load-bearing solution and needs to be replaced by a functional implant. Elution from the ultrahigh molecular weight polyethylene (UHMWPE) bearing surface for drug delivery can combine functionality with the release of clinically relevant doses of antibiotics. In this study, the feasibility of incorporating a range of antibiotics into UHMWPE is investigated. Drug stability is assessed by thermo-gravimetric analysis and nuclear magnetic resonance spectroscopy. Drug-loaded UHMWPEs are prepared by compression molding, using eight antibiotics at different loading. The predicted intra-articular concentrations of drugs eluted from UHMWPE are above minimum inhibitory concentration for at least 3 weeks against Staphylococci, which are the major causative bacteria for PJI. The antibacterial efficacy is confirmed for samples covering 2% of a representative knee implant in vitro over 72 h, showing that a small fraction of the implant surface loaded with antibiotics may be sufficient against Staphylococci.

This study presents a new method for identifying radiation modifications in UHMWPE polymer samples. The method involves using a mathematical technique called fractional order differential transformation on IR spectra obtained through ATR-FTIR spectroscopy. This new method was compared to existing techniques such as FTIR, XRD, and DSC, and it was found to be more sensitive and accurate in detecting radiation-induced changes in the polymer. The study focused on identifying changes in weak IR bands in the UHMWPE samples caused by gamma sterilization while simulating IR spectra using different orders of fractional derivatives and compared them to experimental spectra. It was found that applying a lower order of differentiation was more suitable for identifying radiation-induced changes in the UHMWPE samples. Using this method, they were able to identify specific changes in the gamma irradiated structure, such as the splitting of a single absorption peak into a doublet, which was only present in the 50 kGy irradiated sample. The study also used correlation index analysis, principal component analysis, and hierarchy cluster analysis to analyze the simulated and experimental spectra. These techniques allowed to confirm the effectiveness of the fractional order differential transformation method and to identify the specific regions of the IR spectra that were affected by radiation-induced changes in the UHMWPE samples. Overall, this study presents a new method for identifying radiation-induced changes in UHMWPE polymer samples that is more sensitive and accurate than existing techniques. By identifying these changes, researchers can better understand the effects of gamma sterilization on medical equipment and potentially develop new methods for sterilization that do not damage the equipment.