Rapid In Situ Deposition of Iron-Chelated Polydopamine Coating on the Polyacrylamide Hydrogel Dressings for Combined Photothermal and Chemodynamic Therapy of Skin Wound Infection.

Pathogenic bacterial infections of skin wounds have caused a significant threat to clinical treatment and human life safety. Here, we develop a bactericidal hydrogel dressing consisting of a polyacrylamide (PAM) hydrogel framework with in situ surface-deposition of iron-dopped polydopamine (FePDA). The prepared hydrogel dressing (FePDA-PAM) has a compact surface, good tensile strength, and excellent elastic recovery ability. The introduction of Fe3+ ions improve the photothermal therapy (PTT) efficiency of the PDA and endow the hydrogel dressing with chemodynamic therapy (CDT) properties. In vitro experiments show that the antibacterial effect of FePDA-PAM hydrogel on Staphylococcus aureus reach nearly 100% under the combined action of H2O2 and 808 nm near-infrared (NIR) laser, indicating an excellent combined antibacterial property of PTT and CDT. Furthermore, the FePDA-PAM + H2O2 + NIR treatment group in the in vivo antibacterial experiments displays lowest relative wound area and optimal wound healing within 5 days of treatment, thereby indicating the intensive skin wound disinfection. To summarize, the FePDA-PAM hydrogel has simple preparation and good biosafety. It may serve as a potential wound dressing for the combined PTT/CDT dual-mode antibacterial therapy.

Single projection driven real-time multi-contrast (SPIDERM) MR imaging using pre-learned spatial subspace and linear transformation.

Objective.To develop and test the feasibility of a novel Single ProjectIon DrivEn Real-time Multi-contrast (SPIDERM) MR imaging technique that can generate real-time 3D images on-the-fly with flexible contrast weightings and a low latency.Approach.In SPIDERM, a 'prep' scan is first performed, with sparse k-space sampling periodically interleaved with the central k-space line (navigator data), to learn a subject-specific model, incorporating a spatial subspace and a linear transformation between navigator data and subspace coordinates. A 'live' scan is then performed by repeatedly acquiring the central k-space line only to dynamically determine subspace coordinates. With the 'prep'-learned subspace and 'live' coordinates, real-time 3D images are generated on-the-fly with computationally efficient matrix multiplication. When implemented based on a multi-contrast pulse sequence, SPIDERM further allows for data-driven image contrast regeneration to convert real-time contrast-varying images into contrast-frozen images at user's discretion while maintaining motion states. Both digital phantom andin-vivoexperiments were performed to evaluate the technical feasibility of SPIDERM.Main results.The elapsed time from the input of the central k-space line to the generation of real-time contrast-frozen 3D images was approximately 45 ms, permitting a latency of 55 ms or less. Motion displacement measured from SPIDERM and reference images showed excellent correlation (R2≥0.983). Geometric variation from the ground truth in the digital phantom was acceptable as demonstrated by pancreas contour analysis (Dice ≥ 0.84, mean surface distance ≤ 0.95 mm). Quantitative image quality metrics showed good consistency between reference images and contrast-varying SPIDREM images inin-vivostudies (meanNMRSE=0.141,PSNR=30.12,SSIM=0.88).Significance.SPIDERM is capable of generating real-time multi-contrast 3D images with a low latency. An imaging framework based on SPIDERM has the potential to serve as a standalone package for MR-guided radiation therapy by offering adaptive simulation through a 'prep' scan and real-time image guidance through a 'live' scan.

Spatial Bridge Locking Fixator versus Traditional Locking Plates in Treating AO/OTA 32-A3.2 Fracture: Finite Element Analysis and Biomechanical Evaluation.

OBJECTIVE: To compare the biomechanical behaviors of the spatial bridge locking fixator (SBLF), single locking plate (SP), and double locking plate (DP) for AO/OTA 32-A3.2 fractures using finite element analysis and biomechanical tests. METHODS: Axial loading of 700 N was conducted on the AO/OTA 32-A3.2 model via finite element analysis. The von Mises stress and the interfragmentary movement (IFM) were comparatively analyzed in the three configurations above. On the mechanical tester, axial and torsional loading of 30 synthetic femurs (five specimens of each configuration for each test at random) was performed, and the interfragmentary movement, torsion angle, stiffness, and ultimate load were recorded and analyzed. RESULTS: The finite element analysis (FEA) results showed that the von Mises stress of the spatial bridge locking fixator (SBLF) was lower than that of the single locking plate (SP) and higher than that of the double locking plate (DP). At 700 N, the axial IFMs were 0.15-0.38 mm (SBLF), 0.03-0.84 mm (SP), and 0.02-0.07 mm (DP). The biomechanical experiment indicated that the axial interfragmentary movements (IFMs) were 0.44 ± 0.23 mm (SBLF), 1.02 ± 0.40 mm (SP), and 0.07 ± 0.07 mm (DP) (p < 0.001). The axial IFM of the SBLF group had the highest probability (79.26%) of falling within the ideal range (0.2-0.8 mm), and the SP and DP groups had probabilities of 27.10% and 3.14%, respectively. The axial stiffness in the SBLF group (1586 ± 130 N/mm) was significantly lower than that in the DP group (10,264 ± 2671 N/mm) (p < 0.001) but greater than that in the SP group (725 ± 178 N/mm) (p = 0.396). The range of axial loads to ultimate failure was 3385-4527 N (SBLF), 3377-4664 N (SP), and 3780-4804 N (DP). The shear motion of the fracture end was 0.35 ± 0.14 mm (SBLF), 0.16 ± 0.10 mm (SP), and 0.08 ± 0.04 mm (DP) (p < 0.001). The torsional stiffness was 1.68 ± 0.14 Nm/degree (SBLF), 2.32 ± 0.29 Nm/degree (SP) (SBLF&SP, p < 0.001), and 3.53 ± 0.73 Nm/degree (DP) (SBLF&DP, p < 0.001). CONCLUSIONS: The SBLF structure may exhibit a better biomechanical performance compared with the SP and DP in providing the best quantity and more symmetrical interfragmentary movement for AO/OTA 32-A3.2 fractures.

Sex Differences in Intracranial Atherosclerosis in Patients With Hypertension With Acute Ischemic Stroke.

Background Studies suggest the presence of sex differences in hypertension prevalence and its associated outcomes in atherosclerosis and stroke. We hypothesized a higher intracranial atherosclerosis burden among men with hypertension and acute ischemic stroke compared with women. Methods and Results A multicenter retrospective study was performed from a prospective database identifying patients with hypertension presenting with intracranial atherosclerosis-related acute ischemic stroke and imaged with intracranial vessel wall magnetic resonance imaging. Proximal and distal plaques on vessel wall magnetic resonance imaging were scored. Negative binomial models assessed the associations between plaque-count and sex and the interaction between sex and treatment. Covariates were selected by a least absolute shrinkage and selection operator procedure. Sixty-one patients (n=42 men) were included. There were no significant differences in demographic or cardiovascular risk factors except for smoking history (P=0.002). Adjusted total and proximal plaque counts for men were 1.6 (95% CI, 1.2-2.1; P<0.01) and 1.4 (95% CI, 1.0-1.9; P=0.03) times as high as women, respectively. Female sex was more protective for proximal plaque if treated for hypertension. The risk ratio of men versus women was 1.5 (95% CI, 1.0-2.1) for treated patients. The risk ratio of men versus women was 0.7 (95% CI, 0.4-1.3) for untreated patients. The relative difference between these 2 risk ratios was 2.0 (95% CI, 1.1-3.9), which was statistically significant from the interaction test, P=0.04. Conclusions Men with hypertension with acute ischemic stroke have significantly higher total and proximal plaque burdens than women. Women with hypertension on anti-hypertensive medication showed a greater reduction in proximal plaque burden than men. Further confirmation with a longitudinal cohort study is needed and may help evaluate whether different treatment guidelines for managing hypertension by sex can help reduce intracranial atherosclerosis burden and ultimately acute ischemic stroke risk.

An Ultrasmall Fe3 O4 -Decorated Polydopamine Hybrid Nanozyme Enables Continuous Conversion of Oxygen into Toxic Hydroxyl Radical via GSH-Depleted Cascade Redox Reactions for Intensive Wound Disinfection.

Nanozyme-based chemodynamic therapy (CDT) for fighting bacterial infections faces several major obstacles including low hydrogen peroxide (H2 O2 ) level, over-expressed glutathione (GSH) in infected sites, and inevitable damage to healthy tissue with abundant nonlocalized nanozymes. Herein, a smart ultrasmall Fe3 O4 -decorated polydopamine (PDA/Fe3 O4 ) hybrid nanozyme is demonstrated that continuously converts oxygen into highly toxic hydroxyl radical (•OH) via GSH-depleted cascade redox reactions for CDT-mediated bacterial elimination and intensive wound disinfection. In this system, photonic hyperthermia of PDA/Fe3 O4 nanozymes can not only directly damage bacteria, but also improve the horseradish peroxidase-like activity of Fe3 O4 decorated for CDT. Surprisingly, through photothermal-enhanced cascade catalytic reactions, PDA/Fe3 O4 nanozymes can consume endogenous GSH for disrupting cellular redox homeostasis and simultaneously provide abundant H2 O2 for improving •OH generation, ultimately enhancing the antibacterial performance of CDT. Such PDA/Fe3 O4 can bind with bacterial cells, and reveals excellent antibacterial property against both Staphylococcus aureus and Escherichia coli. Most interestingly, PDA/Fe3 O4 nanozymes can be strongly retained in infected sites by an external magnet for localized long-term in vivo CDT and show minimal toxicity to healthy tissues and organs. This work presents an effective strategy to magnetically retain the therapeutic nanozymes in infected sites for highly efficient CDT with good biosafety.

Fully automated multiorgan segmentation in abdominal magnetic resonance imaging with deep neural networks.

PURPOSE: Segmentation of multiple organs-at-risk (OARs) is essential for magnetic resonance (MR)-only radiation therapy treatment planning and MR-guided adaptive radiotherapy of abdominal cancers. Current practice requires manual delineation that is labor-intensive, time-consuming, and prone to intra- and interobserver variations. We developed a deep learning (DL) technique for fully automated segmentation of multiple OARs on clinical abdominal MR images with high accuracy, reliability, and efficiency. METHODS: We developed Automated deep Learning-based abdominal multiorgan segmentation (ALAMO) technique based on two-dimensional U-net and a densely connected network structure with tailored design in data augmentation and training procedures such as deep connection, auxiliary supervision, and multiview. The model takes in multislice MR images and generates the output of segmentation results. 3.0-Tesla T1 VIBE (Volumetric Interpolated Breath-hold Examination) images of 102 subjects were used in our study and split into 66 for training, 16 for validation, and 20 for testing. Ten OARs were studied, including the liver, spleen, pancreas, left/right kidneys, stomach, duodenum, small intestine, spinal cord, and vertebral bodies. An experienced radiologist manually labeled each OAR, followed by reediting, if necessary, by a senior radiologist, to create the ground-truth. The performance was measured using volume overlapping and surface distance. RESULTS: The ALAMO technique generated segmentation labels in good agreement with the manual results. Specifically, among the ten OARs, nine achieved high dice similarity coefficients (DSCs) in the range of 0.87-0.96, except for the duodenum with a DSC of 0.80. The inference completed within 1 min for a three-dimensional volume of 320 × 288 × 180. Overall, the ALAMO model matched the state-of-the-art techniques in performance. CONCLUSION: The proposed ALAMO technique allows for fully automated abdominal MR segmentation with high accuracy and practical memory and computation time demands.

pH-Sensitive Mixed Micelles Assembled from PDEAEMA-PPEGMA and PCL-PPEGMA for Doxorubicin Delivery: Experimental and DPD Simulations Study.

To decrease critical micelle concentration (CMC), improve stability, and keep high drug-loading capacity, three pH-sensitive mixed micelles applied for anticancer drug controlled delivery were prepared by the mixture of polymers poly (N,N-diethylaminoethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (PDEAEMA-PPEGMA) and polycaprolactone-b-poly (poly(ethylene glycol) methyl ether methacrylate) (PCL-PPEGMA), which were synthesized and confirmed by 1H NMR and gel permeation chromatographic (GPC). The critical micelle concentration (CMC) values of the prepared mixed micelles were low, and the micellar sizes and zeta potentials of the blank mixed micelles demonstrated good pH-responsive behavior. Combined experimental techniques with dissipative particle dynamics (DPD) simulation, the particle sizes, zeta potentials, drug loading content (LC), encapsulation efficiency (EE), aggregation morphologies, and doxorubicin (DOX) distribution of the mixed micelles were investigated, and the high DOX-loading capacity of the mixed micelles was found. Both in vitro DOX release profiles and DPD simulations of the DOX dynamics release process exhibited less leakage and good stability in neutral conditions and accelerated drug release behavior with a little initial burst in slightly acidic conditions. Cytotoxicity tests showed that the polymer PDEAEMA-PPEGMA and the blank mixed micelles had good biocompatibility, and DOX-loaded mixed micelles revealed certain cytotoxicity. These results suggest that the drug-loaded mixed micelles that consisted of the two polymers PDEAEMA-PPEGMA and PCL-PPEGMA can be new types of pH-responsive well-controlled release anticancer drug delivery mixed micelles.

Delivery of anticancer drug using pH-sensitive micelles from triblock copolymer MPEG-b-PBAE-b-PLA.

To improve the drug release rate in well-controlled manner, a new pH-sensitive triblock amphiphilic copolymer methyl poly(ethylene glycol) ether-b-poly(ß-amino esters)-b-poly lactic acid (MPEG-b-PBAE-b-PLA) and its self-assembled micelles were developed for anticancer drug delivery. The average molecular weight and molecular structure of MPEG-b-PBAE-b-PLA were confirmed by gel permeation chromatography (GPC) and 1H NMR. The formation of self-assembled micelles, the microstructures at different pH values, and the distribution of doxorubicin (DOX) were investigated by dissipative particle dynamics (DPD) simulation combined with experimental techniques. The copolymers formed stable core-shell-type micelles in water. The critical micelle concentration (CMC) values, particle sizes and zeta potentials of the blank micelles increased along with globule-extended conformational transitions when the pH values decreased from 7.4 to 5.0, due to the protonation of amine groups of PBAE. Obvious increases in the particle sizes and the drug loading content of micelles were observed with increasing DOX. The in vitro release behavior of DOX from the micelles was pH-dependent. The DOX release rate was improved obviously as pH decreased from pH7.4 to pH5.0, with over 96% of DOX was released within 48h. The drug release mechanism under different conditions was also analyzed using theoretical formulas. All the results suggest that the pH-sensitive MPEG-b-PBAE-b-PLA micelles might be a prospective candidate as anticancer drug delivery carrier with well-controlled release behavior.

Sex differences of steroid receptor coactivator-1 expression after spinal cord injury in mice.

OBJECTIVE: The neural functional recovery of female is often better than that of male after spinal cord injury (SCI). Evidences show that estrogen can attenuate inflammation and promote the neural survival and regeneration after SCI. SRC-1 is an essential initiation factor for the estrogen-regulated target gene transcription and plays a key role in regulating estrogen activity. However, it is not known whether and how SRC-1 mediates the neural regeneration promoted by estrogen after SCI. Study of the sex differences and changes of SRC-1 expression after SCI will be helpful to understand the above questions. METHODS: In this study, the sex differences of expressions of SRC-1 and cytoskeleton-associated protein Profilin-1 in normal and SCI mice were detected by immunohistochemistry at 1-, 3-, and 7 days after injury, respectively. RESULTS: Although the SRC-1 expression in female mice was lower than that in males under normal conditions, its expression in females was more dominant after SCI. The expression of Profilin-1 in both sexes increased first, and then decreased at 3 days after injury. However, there was a second increase in females at 7 days after injury. CONCLUSION: Our study suggests that the more SRC-1 expression in females after SCI may play a role in improving the efficiency of estrogen function and thus, promote regeneration better. SRC-1 may also participate in the regulation of Profilin-1 in spinal cord, which is important in the assembly and extension of the axonal cytoskeleton during regeneration after SCI.

A Novel Fast Mobile-Window Small Incision Technique for Hip Arthroplasty in the Elderly and Comparison with Conventional Incision.

BACKGROUND We deeloped a novel technique - fast mobile-window small incision (FMWSI) - a modification of minimally invasive surgery for total hip arthroplasty, which we believe is particularly suited to elderly patients with hip fractures. The present article aimed to introduce this technique and compare the clinical effects between the FMWSI technique and conventional incision (CI) for hip arthroplasty in elderly patients. MATERIAL AND METHODS This study included 240 consecutive patients who underwent hip arthroplasty. Half received total hip arthroplasty and half received hemi hip arthroplasty. The 120 patients in each group were further divided into FMWSI and CI groups. The following parameters were compared between the FMWSI and CI groups: length of incision, operation time, bleeding volume, drainage volume, postoperative ambulation time, and Harris score. RESULTS Compared with the CI group, the FMWSI group had a significantly shorter incision length, operation time, and postoperative ambulation time, as well as lower bleeding and drainage volumes, irrespective of whether the treatment was total or hemi hip arthroplasty (P<0.05). However, no significant difference was found in the Harris score between the FMWSI and CI groups (P>0.05). CONCLUSIONS The novel FMWSI technique introduced in this study is a useful method for hip arthroplasty, especially for elderly patients with poor constitutions or tolerance to surgery.