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Protein therapeutics, particularly antibodies, depend on maintaining their native structures for optimal function. Hydrophobic interfaces, such as the air-water interface, can trigger protein aggregation and denaturation. While completely avoiding such interfacial exposures during manufacturing and storage is impractical, minimizing them is crucial for enhancing protein drug stability and extending shelf life. In the biologics industry, surfactants like polysorbates are commonly used as additives (excipients) to mitigate these undesirable interfacial exposures. However, polysorbates, the most prevalent choice, have recognized limitations in terms of polydispersity, purity, and stability, prompting the exploration of alternative excipients. The present study identifies poly(N-isopropylacrylamide)-poly(ethylene glycol) (PNIPAM-PEG) block copolymers as a promising alternative to polysorbates. Due to its stronger affinity for the air-water interface, PNIPAM-PEG significantly outperforms polysorbates in enhancing protein stability. This claim is supported by results from multiple tests. Accelerated dynamic light scattering (DLS) experiments demonstrate PNIPAM-PEG's exceptional efficacy in preserving IgG stability against surface-induced aggregation, surpassing conventional polysorbate excipients (Tween 80 and Tween 20) under high-temperature conditions. Additionally, circular dichroism (CD) spectroscopy results reveal conformational alterations associated with aggregation, with PNIPAM-PEG consistently demonstrates a greater protective effect by mitigating negative shifts at λ ≅ 220 nm, indicative of changes in secondary structure. Overall, this study positions PNIPAM-PEG as a promising excipient for antibody therapeutics, facilitating the development of more stable and effective biopharmaceuticals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [A provisional patent application has been filed for the subject matter disclosed in this article and is currently undergoing evaluation.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrogels are promising materials for biomedical applications, particularly in drug delivery and tissue engineering. This study highlights thermoresponsive hydrogels, specifically poly(lactic- co -glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA triblock copolymers, and introduces a feed rate-controlled polymerization (FRCP) method. By utilizing an organic catalyst and regulating the monomer feed rate, the sequence distribution of PLGA within the triblock copolymer is controlled. Various analyses, including 13 C NMR and rheological measurements, were conducted to investigate the impact of sequence distribution. Results show that altering sequence distribution significantly influences the sol-gel transition, hydrophobicity-hydrophilicity balance, and drug release profile. Increased sequence uniformity lowers the glass transition temperature, raises the sol-gel transition temperature due to enhanced hydrophilicity, and promotes a more uniform drug (curcumin) distribution within the PLGA domain, resulting in a slower release rate. This study emphasizes the importance of PLGA sequence distribution in biomedical applications and the potential of FRCP to tailor thermoresponsive hydrogels for biomedical advancements.

Hypothesis Conventional solvent exchange formulation methods face limitations when trying to control the final non-equilibrium size properties of block copolymer micelles containing a strongly hydrophobicity and a rigid block because the solvent conditions are not well controlled during micelle formation. Therefore, using an alternative formulation method, named Equilibration-Nanoprecipitation (ENP), in which micelles are formed under uniform solvent conditions, will significantly reduce the final dispersity compared a conventional solvent exchange method. EXPERIMENTAL: Size properties of the final aqueous micelle dispersions formed from the ENP method and a conventional solvent exchange are measured using DLS. Also, a parallel modelling study is completed to predict the final size distributions using both methods. Findings The experimental results demonstrate the ENP method is effective producing non-equilibrium micelles with low dispersity below the monodisperse polydispersity index (PDI) cutoff for DLS while the conventional solvent exchange method leads to significantly greater dispersity. Also the experimental results highlight ENP can be used to tune the final size properties which cannot be done using methods which do not properly control the micelle formation conditions. Additionally, the modelling study supports the utility of the ENP approach for producing monodisperse dispersions of nonequilibrium polymer micelles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: There have been insufficient data regarding the long-term results of unrestricted kinematically aligned total knee arthroplasty (unKATKA) in Asian patients. We investigated mid- to long-term clinical and radiological follow-up data of Korean patients after caliper-verified unKATKA of minimum 7.4-10 years including categorised data of postoperative tibial component, limb and knee alignment. Additionally, we analysed the preoperative distribution and postoperative restoration of coronal plane alignment of knee (CPAK) phenotypes., Methods: This study is a retrospective analysis of 63 patients: 96 osteoarthritic underwent consecutive caliper-verified unKATKA between October 2013 and May 2016 by a single surgeon. Implant survivorship was investigated for revision for any reason. Each knee was categorised into an in-range or outlier group by three postoperative alignment parameters: tibial component, knee and limb alignment. Statistical analyses were done for any significant differences in clinical scores and implant survival rates between groups. Finally, all knees were classified into CPAK classification postoperatively and postoperatively. The CPAK restoration rate was calculated., Results: Among 85 knees in the clinically confirmed group, implant survival was 98.8%. There was one case of revision due to periprosthetic fracture. The percentage postoperatively aligned in the varus (valgus) outlier range was 100% (0%) for tibial component, 16.7% (24.8%) for the knee alignment and 51% (0%) for the limb alignment. All three categories did not affect implant survival or clinical scores. Eighty one out of 96 knees (84.4%) were restored to their CPAK phenotype postoperatively., Conclusion: With the limitation of a case series having a small number of patients and gender deviation, our study suggests that caliper-verified unKATKA could be a good option regardless of geographical variation of constitutional alignment in patients with osteoarthritis (OA)., Level of Evidence: Level IV, therapeutic study., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: To assess current practice in the treatment of osteoporosis in patients who underwent treatment for hip fracture in South Korea., Materials and Methods: A survey of 97 members of the Korean Hip Society, orthopedic hip surgeons who administer treatment for hip fractures in South Korea, was conducted. The survey was conducted for assessment of demographic data and perceptions regarding the management of osteoporosis in patients who have undergone treatment for hip fracture. Analysis of the data was performed using descriptive statistical methods., Results: The majority of participants were between the age of 41 and 50 years, and 74% were practicing in tertiary hospitals. Testing for serum vitamin D levels (82%) was the most commonly performed laboratory test. Calcium and vitamin D were prescribed for more than 80% of patients by 47% and 52% of participants, respectively. Denosumab was the most commonly used first-line treatment option for osteoporosis in hip fracture patients. Bisphosphonate was most often perceived as the cause of atypical femoral fractures, and the most appropriate time for reoperation was postoperative 12 months. Teriparatide was most preferred after cessation of bisphosphonate and only prescribing calcium and vitamin D was most common in high-risk patients for prevention of atypical femoral fracture., Conclusion: The results of this study that surveyed orthopedic hip surgeons showed that most participants followed the current strategy for management of osteoporosis. Because the end result of osteoporosis is a bone fracture, active involvement of orthopedic surgeons is important in treating this condition.

Rare but consistent reports of abscopal remission in patients challenge the notion that radiotherapy (RT) is a local treatment; radiation-induced cancer cell death can trigger activation and recruitment of dendritic cells to the primary tumor site, which subsequently initiates systemic immune responses against metastatic lesions. Although this abscopal effect was initially considered an anomaly, combining RT with immune checkpoint inhibitor therapies has been shown to greatly improve the incidence of abscopal responses via modulation of the immunosuppressive tumor microenvironment. Preclinical studies have demonstrated that nanomaterials can further improve the reliability and potency of the abscopal effect for various different types of cancer by (1) altering the cell death process to be more immunogenic, (2) facilitating the capture and transfer of tumor antigens from the site of cancer cell death to antigen-presenting cells, and (3) co-delivering immune checkpoint inhibitors along with radio-enhancing agents. Several unanswered questions remain concerning the exact mechanisms of action for nanomaterial-enhanced RT and for its combination with immune checkpoint inhibition and other immunostimulatory treatments in clinically relevant settings. The purpose of this article is to summarize key recent developments in this field and also highlight knowledge gaps that exist in this field. An improved mechanistic understanding will be critical for clinical translation of nanomaterials for advanced radio-immunotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2023 Wiley Periodicals LLC.)

In the pursuit of the development of a first-in-kind polymer lung surfactant (PLS) therapeutic whose effects are biophysical in nature, a comprehensive understanding of the factors affecting the air-water surface mechanical behavior of water-spread block copolymer micelles is desired. To this end, we explore the effect of temperature on the surface mechanical behavior of two different micelle core chemistries, poly(styrene) (PS) and poly( tert -butyl methacrylate) (PtBMA), each having poly(ethylene glycol) (PEG) as the hydrophilic block. The behavior is characterized using surface pressure-area isotherms and quantitative Brewster angle microscopy. The results indicate that the temperature has a significant effect on the micelle structure at the interface and this effect is related to the core T g as well as the core interfacial tension properties. When temperature is higher than the core T g for PS-PEG, the spherical micelle core rearranges to form an oblate-like structure which increases its interfacial area. The structural rearrangement changes the mechanism by which the film produces high surface pressure. For PtBMA-PEG, which has a lower interfacial tension with water and air compared to PS, the core domains spread at the interface when the mobility is sufficiently high such that a PtBMA film is formed under high compression. The implications of these changes on PLS efficacy are discussed highlighting the importance of core T g characterization for polymer nanoparticle applications.

Polymer lung surfactant (PLS) is a polyethylene glycol (PEG)-brushed block copolymer micelle designed for pulmonary surfactant replacement therapy. Saccharides (e.g., sucrose and (2-hydroxypropyl)-β-cyclodextrin) and water-soluble polymers (e.g., PEG), common excipients for lyophilization, were found to severely impair the surface activity of lyophilized PLS. To investigate the feasibility of excipient-free lyophilization of PLS, we studied the effects of both PLS material parameters and lyophilization operating parameters on the redispersibility and surface availability of reconstituted PLS, all without relying on excipients. We found that the redispersibility was improved by three factors; a faster cooling rate during the freezing stage reduced freezing stress; a higher PEG grafting density enhanced dissipating effects; and the absence of hydrophobic endgroups in the PEG block further prevented micelle aggregation. Consequently, the surface availability of PLS increased, enabling the micelle monolayer at the air/water interface to achieve a surface tension below 10 mN/m, which is a key pharmaceutical function of PLS. Moreover, the lyophilized micelles in powder form could be easily dispersed on water surfaces without the need for reconstitution, which opens up the possibility of inhalation delivery, a more patient-friendly administration method compared to instillation. The successful excipient-free lyophilization unlocks the potential of PLS for addressing acute respiratory distress syndrome (ARDS) and other pulmonary dysfunctions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Amphiphilic block copolymer micelles can mimic the ability of natural lung surfactant to reduce the air-water interfacial tension close to zero and prevent the Laplace pressure-induced alveolar collapse. In this work, we investigated the air-water interfacial behaviors of polymer micelles derived from eight different poly(ethylene glycol) (PEG)-based block copolymers having different hydrophobic block chemistries to elucidate the effect of the core block chemistry on the surface mechanics of the block copolymer micelles. Aqueous micelles of about 30 nm in hydrodynamic diameter were prepared from the PEG-based block copolymers via equilibration-nanoprecipitation (ENP) and spread on the water surface using water as the spreading medium. Surface pressure-area isotherm and quantitative Brewster angle microscopy (QBAM) measurements were performed to investigate how the micelle/monolayer structures change during lateral compression of the monolayer; widely varying structural behaviors were observed, including the wrinkling/collapse of micelle monolayers and deformation and/or the desorption of individual micelles. By bivariate correlation regression analysis of surface pressure-area isotherm data, it was found that the rigidity and hydrophobicity of the hydrophobic core domain, which are quantified by glass-transition temperature ( T g ) and water contact angle (θ) measurements, respectively, are coupled factors that need to be taken into account concurrently in order to control the surface mechanical properties of polymer micelle monolayers; micelles having rigid and strongly hydrophobic cores exhibited high surface pressure and a high compressibility modulus under high compression. High surface pressure and a high compressibility modulus were also found to be correlated with the formation of wrinkles in the micelle monolayer (visualized by Brewster angle microscopy (BAM)). From this study, we conclude that polymer micelles based on hydrophobic block materials having higher T g and θ are more suitable for surfactant replacement therapy applications that require the therapeutic surfactant to produce a high surface pressure and modulus at the alveolar air-water interface.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) prodrug is a clinically tried and proven treatment modality for surface-level lesions. However, its use for deep-seated tumors has been limited due to the poor penetration depth of visible light needed to activate the photosensitizer protoporphyrin IX (PPIX), which is produced from ALA metabolism. Herein, we report the usage of poly(ethylene glycol- b -lactic acid) (PEG-PLA)-encapsulated calcium tungstate (CaWO 4 , CWO for short) nanoparticles (PEG-PLA/CWO NPs) as energy transducers for X-ray-activated PDT using ALA. Owing to the spectral overlap between radioluminescence afforded by the CWO core and the absorbance of PPIX, these NPs can serve as an in situ visible light activation source during radiotherapy (RT), thereby mitigating the limitation of penetration depth. We demonstrate that this effect is observed across different cell lines with varying radio-sensitivity. Importantly, both PPIX and PEG-PLA/CWO NPs exhibit no significant toxicities at therapeutic doses in the absence of radiation. To assess the efficacy of this approach, we conducted a study using a syngeneic mouse model subcutaneously implanted with inherently radio-resistant 4T1 tumors. The results show a significantly improved prognosis compared to conventional RT, even with as few as 2 fractions of 4 Gy X-rays. Taken together, these results suggest that PEG-PLA/CWO NPs are promising agents for application of ALA-PDT in deep-seated tumors, thereby significantly expanding the utility of the already established treatment strategy.

Purpose: The aim of this study was to assess the current status of venous thromboembolism (VTE) prevention in Korean patients with hip fractures., Materials and Methods: A survey using a questionnaire on the experiences and protocols of VTE prevention was conducted among 570 members of the Korean Hip Society., Results: A total of 97 surgeons responded, with a response rate of 17.0%. Of the 97 participants, 61.9% answered that they had encountered one or more cases of symptomatic VTE in the past year. Mechanical prophylaxis was applied most often (30.9%) until the point of ambulation in standard-risk patients and most often (34.0%) extended until discharge in high-risk patients. Chemical prophylaxis was most often prescribed for a particular period of time rather than for recovery of walking ability (24.7% in standard-risk patients and 26.8% in high-risk patients). Dual prophylaxis was administered in the standard-risk group by 58.8% of the participants and in the high-risk group by 83.5%. Among the participants, 73.2% answered that they had been attentive to wound complications during chemical prophylaxis. More than half of the participants (59.8%) reported that they did not perform routine screening for VTE after surgery., Conclusion: The results of our survey provided information regarding the current status of VTE prevention for patients undergoing surgery for treatment of hip fractures in Korea as well as a baseline for establishment of educational programs and guidelines in the future., Competing Interests: CONFLICT OF INTEREST: Young-Kyun Lee has been an editorial board member since January 2023, but had no role in the decision to publish this article. No other potential conflict of interest relevant to this article was reported., (Copyright © 2023 by Korean Hip Society.)

Purpose: This study examined the methods for treatment of femoral neck fracture (FNF) preferred by members of the Korean Hip Society (KHS) and identified factors that influence decisions regarding the surgical intervention of choice., Materials and Methods: A total of 97 members of the KHS responded to the 16-question survey which included questions about the mean number of surgeries performed each month for treatment of femoral neck fractures, the cut-off age for deciding between internal fixation and arthroplasty, the implant used most often, usage of cement, and factors influencing each decision., Results: The mean cut-off age used when deciding between internal fixation and arthroplasty was 64 years old. Hemiarthroplasty (HA) (70%) was the most preferred option for treatment of displaced FNFs in cases where arthroplasty was indicated (total hip arthroplasty [THA] 19% and dual mobility THA 11%). The main reasons for selection of arthroplasty over reduction with internal fixation were age and pre-fracture ambulatory status. Pre-trauma ambulatory status and/or sports activity were the main factors in selection of HA over THA. Cement was used by 33% of responders. Poor bone quality and a broad femoral canal were factors that influenced the usage of cement., Conclusion: Management of FNFs in the elderly is a major health problem worldwide; thus, remaining alert to current trends in treatment is essential for surgeons. The mean cut-off age used in deciding between internal fixation and arthroplasty was 64 years old. HA is the preferred method for treatment of displaced FNFs for members of the KHS., Competing Interests: CONFLICT OF INTEREST: Young-Kyun Lee has been an editorial board member since January 2023, but had no role in the decision to publish this article. No other potential conflict of interest relevant to this article was reported., (Copyright © 2023 by Korean Hip Society.)

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10 -7 (odds ratio = 1.72) and 1.1 × 10 -7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling., (© 2023. The Author(s).)

If not properly managed, acute lung injuries, either through direct or indirect causes, have the potential to present serious risk for many patients worldwide. One of the mechanisms for the transition from acute lung injury (ALI) to the more serious acute respiratory distress syndrome (ARDS) is the deactivation of the native lung surfactant by injury-induced infiltrates to the alveolar space. Currently, there are no surfactant replacement therapies that are used to treat ALI and subsequent ARDS. In this paper, we present an indepth efficacy study of using a novel polymer lung surfactant (PLS, composed of poly(styrene- block -ethylene glycol) (PS-PEG) block copolymer micelles), which has unique properties compared to other tested surfactant replacements, in two different mouse models of lung injury. The results demonstrate that pharyngeal administration of PLS after the instillation of either acid (HCl) or lipopolysaccharide (LPS) can decrease the severity of lung injury as measured by multiple injury markers.

Glioblastoma (GBM) is one of the most aggressive and lethal solid tumors in human. While efficacious therapeutics, such as emerging chimeric antigen receptor (CAR)-T cells and chemotherapeutics, have been developed to treat various cancers, their effectiveness in GBM treatment has been hindered largely by the blood-brain barrier and blood-brain-tumor barriers. Human neutrophils effectively cross physiological barriers and display effector immunity against pathogens but the short lifespan and resistance to genome editing of primary neutrophils have limited their broad application in immunotherapy. Here we genetically engineer human pluripotent stem cells with CRISPR/Cas9-mediated gene knock-in to express various anti-GBM CAR constructs with T-specific CD3ζ or neutrophil-specific γ-signaling domains. CAR-neutrophils with the best anti-tumor activity are produced to specifically and noninvasively deliver and release tumor microenvironment-responsive nanodrugs to target GBM without the need to induce additional inflammation at the tumor sites. This combinatory chemo-immunotherapy exhibits superior and specific anti-GBM activities, reduces off-target drug delivery and prolongs lifespan in female tumor-bearing mice. Together, this biomimetic CAR-neutrophil drug delivery system is a safe, potent and versatile platform for treating GBM and possibly other devastating diseases., (© 2023. The Author(s).)

A new technique to reduce flicker noise generated in light-fidelity (Li-Fi) transmission links based on the white light-emitting diode (LED) is proposed. Here, flicker noise with a frequency of 120 Hz, which is twice the frequency of AC power (60 Hz), is generated. The proposed technique is implemented in the receiver of the Li-Fi link. It can reduce flicker noise regardless of various digital modulation formats. In addition, there is no need to change the structure of the electrical circuit driving the LED to reduce the flicker noise. As a result, the non-return to-zero-on-off-keying (NRZ-OOK) signal waveform is tilted according to the flicker noise waveform. We implement the derivative equalization with a pseudo-flicker weight function to reduce the flicker noise. The derivative value of the NRZ-OOK signal mixed with flicker noise becomes larger than that without the flicker noise. In the proposed technique, the derivative value between adjacent sampling points is suppressed below the preset thresholds when it is greater than the preset threshold. Furthermore, a pseudo-flicker weight function is applied to accelerate the flicker noise reduction. As a result, using the proposed technique, a 2 dB signal-to-noise ratio (SNR) gain is obtained based on the bit error rate (BER) threshold (3.5 × 10 -5 ) corresponding to 10% flicker modulation, which is known to have no serious effect on human health. This means that it is possible to implement a Li-Fi transmission link based on an illumination environment with a flicker modulation reduced from 10% to 7%.

Radiotherapy (RT) is the primary standard of care for many locally advanced cancers. Often times, however, the efficacy of RT is limited due to radio-resistance that cancer cells develop. Photodynamic therapy (PDT) has gained importance as an alternative local therapy. Because its mechanism involves minimal acquired resistance, PDT is a useful adjunct to RT. This review discusses recent advances in combining RT with PDT for cancer treatment. In the first part of this review, we will discuss clinical trials on RT + PDT combination therapies. All these approaches suffer from the same inherent limitations as any current PDT methods; (i) visible light has a short penetration depth in human tissue (<∼10 mm), and (ii) it is difficult to illuminate the entire tumor homogeneously by external/interstitial laser irradiation. To address these limitations, scintillating nanoparticle-mediated RT-PDT approaches have been explored in which nanoparticles convert X-rays (RT) into visible light (PDT); high-energy X-rays can reach deep into the body to irradiate cancers uniformly and precisely. The second part of this review will discuss recent efforts in developing and applying nanoparticles for RT-PDT applications.

For many locally advanced tumors, the chemotherapy-radiotherapy (CT-RT) combination ("chemoradiation") is currently the standard of care. Intratumoral (IT) CT-based chemoradiation has the potential to overcome the limitations of conventional systemic CT-RT (side effects). For maximizing the benefits of IT CT-RT, our laboratory has previously developed a radiation-controlled drug release formulation, in which anticancer drug paclitaxel (PTX) and radioluminescent CaWO 4 (CWO) nanoparticles (NPs) are co-encapsulated with poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) block copolymers ("PEG-PLA/CWO/PTX NPs"). These PEG-PLA/CWO/PTX NPs enable radiation-controlled release of PTX and are capable of producing sustained therapeutic effects lasting for at least one month following a single IT injection. The present article focuses on discussing our recent finding about the effect of the stereochemical structure of PTX on the efficacy of this PEG-PLA/CWO/PTX NP formulation. Stereochemical differences in two different PTX compounds ("PTX-S" from Samyang Biopharmaceuticals and "PTX-B" from Biotang) were characterized by 2D heteronuclear/homonuclear NMR, Raman spectroscopy, and circular dichroism measurements. The difference in PTX stereochemistry was found to significantly influence their water solubility (WS); PTX-S (WS ≈ 4.69 μg/mL) is about 19 times more water soluble than PTX-B (WS ≈ 0.25 μg/mL). The two PTX compounds showed similar cancer cell-killing performances in vitro when used as free drugs. However, the subtle stereochemical difference significantly influenced their X-ray-triggered release kinetics from the PEG-PLA/CWO/PTX NPs; the more water-soluble PTX-S was released faster than the less water-soluble PTX-B. This difference was manifested in the IT pharmacokinetics and eventually in the survival percentages of test animals (mice) treated with PEG-PLA/CWO/PTX NPs + X-rays in an in vivo human tumor xenograft study; at short times (<1 month), concurrent PEG-PLA/CWO/PTX-S NPs produced a greater tumor-suppression effect, whereas PEG-PLA/CWO/PTX-B NPs had a longer-lasting radio-sensitizing effect. This study demonstrates the importance of the stereochemistry of a drug in a therapy based on a controlled release formulation.

Hypothesis: The surface mechanical properties of poly(styrene)-poly(ethylene glycol) (PS-PEG) micelles are influenced by the PEG corona structure. Changes in micelle aggregation number as well as changes in the PEG end group and linking group chemistry of the PS-PEG block copolymer are expected to alter PEG corona characteristics and therefore affect surface mechanical properties of the resulting micelle film., Experiments: Different sized micelles comprised of PS-PEG block copolymer chains were formulated by equilibrating micelles in different ratios of acetone/water mixtures and subsequently removing acetone using dialysis. Additionally, micelles of a similar size and PS-PEG molecular weight but slightly different chemistry were formulated. The micelles were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), 1 H NMR, surface pressure-area isotherms and Brewster angle microscopy (BAM)., Findings: The reduction in micelle aggregation number results in the subsequent monolayer having higher compressibility moduli and bending stiffnesses and collapsing at lower surface pressures. Micelle hydrophobicity was shown to improve readsorption of micelles to interface after collapse. Analysis of Brewster angle microscopy images of out-of-plane wrinkle structures which formed upon monolayer collapse indicates the presence of continuous 1 nm thick PEG layer which allows micelle monolayers to bend under high compression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We have recently discovered that pulmonary administration of nanoparticles (micelles) formed by amphiphilic poly(styrene- block -ethylene glycol) (PS-PEG) block copolymers has the potential to treat a lung disorder involving lung surfactant (LS) dysfunction (called acute respiratory distress syndrome (ARDS)), as PS-PEG nanoparticles are capable of reducing the surface tension of alveolar fluid, while they are resistant to deactivation caused by plasma proteins/inflammation products unlike natural LS. Herein, we report studies of the clearance pathways and kinetics of PS-PEG nanoparticles from the lung, which are essential for designing further preclinical IND-enabling studies. Using fluorescently labeled PS-PEG nanoparticles, we found that, following pharyngeal aspiration in mice, the retention of these nanoparticles in the lungs extends over 2 weeks, while their transport into other (secondary) organs is relatively insignificant. An analysis based on a multicompartmental pharmacokinetic model suggests a biphasic mechanism involving a fast mucociliary escalator process through the conducting airways and much slower alveolar clearance processes by the action of macrophages and also via direct translocation into the circulation. An excessive dose of PS-PEG nanoparticles led to prolonged retention in the lungs due to saturation of the alveolar clearance capacity.

Background: Kinematically aligned total knee arthroplasty (KA-TKA) may lead to a different pattern of osteotomy from mechanically aligned total knee arthroplasty (MA-TKA). This paper aims to analyze the effects of KA and MA on the morphology of the distal femoral osteotomy surface. Methods: Computed tomography scans of 80 TKA candidates were reconstructed into 3D models. The measurement of bone morphology was performed after the distal femur cut according to two different alignment techniques. The aspect ratio, trapezoidicity ratio, and asymmetry ratio of the distal femur were assessed. Results: The aspect ratio and the asymmetry ratio in the KA group was significantly lower than that in the MA group in the general population (p < 0.001). The trapezoidicity ratio in the KA group was significantly higher than that in the MA group in the general population (p < 0.001). Conclusions: It was found that KA-TKA and MA-TKA presented different morphologies of the distal femoral osteotomy surface, and this difference was also influenced by gender. The surgery pattern of KA-TKA and MA-TKA and gender should be considered when surgeons choose femoral prostheses.

Objectives: This study aims to analyze the changes in epidemiology and the postoperative outcomes in patients with hip fractures during the COVID-19 pandemic compared to non-pandemic period., Methods: According to the date of declaration of "mandatory social distance", we separated patients into 2 groups over a 1-year period: Period A and period B. We assessed the overall time to surgery, delay in surgery (> 24 hours, > 36 hours, and > 48 hours), reason of delay, length of hospital stay, type of surgery, and postoperative complications., Results: The number of operated hip fractures and other trauma decreased in period B compared with period A by 17%, and 23%, respectively. The number of patients with delay in surgery by > 24 hours and > 36 hours was significantly higher in period B compared to that in period A (P = 0.035, P = 0.012, respectively). However, no significant difference in the number of delay in surgery > 48 hours and mean overall time to surgery between the 2 groups was observed (P = 0.856, P = 0.399, respectively). There was no difference in the duration of hospital stay, type of surgery, and postoperative complications between periods A and B., Conclusions: During the COVID-19 pandemic, the decrease in hip fractures was relatively fewer compared to the decrease in orthopedic trauma. Although hip fracture surgeries were delayed for over 24 hours and 36 hours, there was no increase in delay for over 48 hours and postoperative complications., Competing Interests: The authors declare no competing interests., (© 2022 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.)

Extensive studies have been conducted to elucidate the effects of such parameters as molecular weight, polydispersity, and composition on the controlled release properties of poly(d,l-lactic- co -glycolic acid) (PLGA). However, studies dealing with the effect of monomer sequence distribution have been sparse mainly because of the difficulty of precisely controlling the monomer sequence in PLGA. Herein, we present a semibatch copolymerization strategy that enables the production of statistically sequence-controlled "uniform PLGA" polymers through control of the rate of comonomer addition. Using this method, a series of PEG-PLGA samples having a comparable molecular weight and composition but different sequence distributions (uniform vs gradient) were prepared. The properties of these materials (PEG crystallization/melting, hygroscopicity, aqueous sol-gel transition, drug release kinetics) were found to significantly vary, demonstrating that sequence control only at the statistical level still significantly influences the properties of PLGA. Most notably, uniform PLGA exhibited the more sustained drug release behavior compared to gradient PLGA.

The integral imaging system has received considerable research attention because it can be applied to real-time three-dimensional image displays with a continuous view angle without supplementary devices. Most previous approaches place a physical micro-lens array in front of the image, where each lens looks different depending on the viewing angle. A computational integral imaging system with a virtual micro-lens arrays has been proposed in order to provide flexibility for users to change micro-lens arrays and focal length while reducing distortions due to physical mismatches with the lens arrays. However, computational integral imaging methods only represent part of the whole image because the size of virtual lens arrays is much smaller than the given large-scale images when dealing with large-scale images. As a result, the previous approaches produce sub-aperture images with a small field of view and need additional devices for depth information to apply to integral imaging pickup systems. In this paper, we present a single image-based computational RGB-D integral imaging pickup system for a large field of view in real time. The proposed system comprises three steps: deep learning-based automatic depth map estimation from an RGB input image without the help of an additional device, a hierarchical integral imaging system for a large field of view in real time, and post-processing for optimized visualization of the failed pickup area using an inpainting method. Quantitative and qualitative experimental results verify the proposed approach's robustness.

Teriparatide (TPTD) is a bone-forming agent used to treat postmenopausal osteoporosis. Since hip fractures are related to higher morbidity and mortality rates than other fractures, efficacious osteoporosis drugs for the hip are critical. We reviewed research articles reporting the efficacy of TPTD in terms of bone mineral density (BMD), fractures prevention, changes in the outer diameter, cortical thickness and porosity, post-operative periprosthetic BMD loss, and healing of typical and atypical fractures of the hip. Data meta-analyses indicated that TPTD not only increased the BMD of the proximal femur but also decreased the risk of hip fractures. Even though TPTD increases the cortical bone porosity of the proximal femur, the bone strength does not decrease as the majority of the porosity is located at the endocortex; further, it increases the outer diameter and thickens the cortical bone. TPTD stimulates bone remodeling and facilitates callus maturity and fracture healing. There have been many reports on improving the effect of TPTD on the healing of atypical fractures; therefore it is advisable to use TPTD considering the increase benefit compared to the risk., Competing Interests: CONFLICT OF INTEREST: The authors declare that there is no potential conflict of interest relevant to this article., (Copyright © 2021 by Korean Hip Society.)

For Li-Fi wireless links based on a white light emitting diode, an adaptive differential equalization (ADE) technique that reduces various noises such as interference noise and shot one generated from ambient light sources is pro-posed. The ADE technique reduces noise by taking advantage of the fact that the derivative between adjacent sampling points of signal with digital waveform is very different from that of noise with the random analog waveform. Furthermore, a weighting function that reflects the Poisson characteristics of shot noise is applied to the ADE technique in order to maximize the reduction efficiency of ambient noise. The signal-to-noise ratio of input non-return-to-zero-on-off keying (NRZ-OOK) signal is improved by 7.5 dB at the first-generation forward error correction (FEC) threshold (the bit error rate (BER) of 8 × 10 -5 ) using the optical wireless experimental link. In addition, it is confirmed that it is possible to maintain the transmission performance corresponding to the BER of 1 × 10 -5 by using the proposed ADE technique, even when the intensity of the ambient light source increases by 6 dB.

Poly(lactic- co -glycolic acid) (PLGA) is the most prevalent polymer drug delivery vehicle in use today. There are about 20 commercialized drug products in which PLGA is used as an excipient. In more than half of these formulations, PLGA is used in the form of microparticles (with sizes in the range between 60 nm and 100 μm). The primary role of PLGA is to control the kinetics of drug release toward achieving sustained release of the drug. Unfortunately, most drug-loaded PLGA microparticles exhibit a common drawback: an initial uncontrolled burst of the drug. After 30 years of utilization of PLGA in controlled drug delivery systems, this initial burst drug release still remains an unresolved challenge. In this Review, we present a summary of the proposed mechanisms responsible for this phenomenon and the known factors affecting the burst release process. Also, we discuss examples of recent efforts made to reduce the initial burst release of the drug from PLGA particles.

Photodynamic therapy (PDT) has shown potential as a cancer treatment modality, but its clinical application is limited due to its visible-light activation since visible wavelengths of light cannot penetrate tissues well. Additionally, combination therapies utilizing PDT and radiotherapy have shown clinical promise in several cancers but are limited again by light penetration and the need for selective photosensitization of the treatment area. Herein, we report the development of bilirubin-photodynamic nanoparticles (PEGylated bilirubin-encapsulated CaWO 4 nanoparticles or "PEG-BR/CWO NPs"). PEG-BR/CWO NPs are a formulation of PEGylated bilirubin micelles encapsulating CaWO 4 nanoparticles. These particles are capable of activating PDT via X-ray irradiation within deep tissues due to the radioluminescence properties of their CaWO 4 nanoparticle cores. PEG-BR/CWO NPs facilitate a combination of photodynamic and radiation therapy and represent a previously unexplored application of PEG-bilirubin conjugates as photosensitizing agents. When irradiated by X-rays, PEG-BR/CWO NPs emit UV-A and visible light from their CaWO 4 cores, which excites bilirubin and leads to the production of singlet oxygen. PEG-BR/CWO NPs exhibit improvements over X-ray therapy alone in vitro and in murine xenograft models of head and neck cancer. The data presented in this study indicate that PEG-BR/CWO NPs are promising agents for facilitating combined radio-photodynamic therapy in deep tissue tumors.

Aim: To examine a hypothetical model of physical activity and health outcomes (cardiovascular risk and quality of life) based on the information-motivation-behavioural skills model in adults., Design: A cross-sectional survey., Methods: A total of 165 adults with osteoarthritis at risk for metabolic syndrome were recruited between October 2016 and September 2017 from the outpatient clinic in South Korea. Data were collected on the model constructs such as cognitive function, social support, depressive symptoms, barriers to self-efficacy, physical activity and quality of life. A hypothetical model was tested using the AMOS 25.0 program., Results: Cognitive function and barriers to self-efficacy had a direct effect on physical activity. Physical activity had a direct effect on cardiovascular risk, while social support and depressive symptoms had a direct effect on quality of life., Conclusions: The information-motivation-behavioural skills model can predict physical activity and, in turn, cardiovascular risk and quality of life in adults with osteoarthritis at risk for metabolic syndrome., Competing Interests: No conflict of interest has been declared by the authors., (© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Hypothesis: This paper investigates the self-assembly behavior of a new amphiphilic block copolymer, PPEGMA-PPC-PPEGMA, in dilute aqueous solution and at the air-water interface. In PPEGMA-PPC-PPEGMA, the hydrophilic PEG moieties exist as side chains attached to the PMA backbone. Because of this unique non-linear architecture, the morphological and conformational properties of self-assembled PPEGMA-PPC-PPEGMA polymers are expected to be different from those of conventional linear PEG-based polymer surfactants., Experiments: For this study, three PPEGMA-PPC-PPEGMA samples having an identical PPC molecular weight (5.6 kDa) and different PPEGMA molecular weights (7.2, 2.8 and 2.1 kDa on either side) (named "G7C6G7", "G3C5G3", and "G2C6G2", respectively) were synthesized. The micellar self-assembly behaviors of these materials were investigated by cryo-TEM, rheology, DLS, and visual observation. Langmuir monolayers of these materials were characterized by surface mechanical testing., Findings: PPEGMA-PPC-PPEGMA micelles were found to have a spherical geometry, irrespective of copolymer composition. Interestingly, G2C6G2 and G3C6G3 micelles formed weakly-bound clusters, whereas G7C6G7 micelles predominantly existed as isolated micelles. Detailed analysis suggests that this unexpected trend in micelle morphology originates from the fact that the PPEGMA blocks are only partially hydrated at aqueous interfaces. Detailed features of the surface pressure-area isotherms obtained from Langmuir PPEG-PPC-PPEGMA monolayers further supported this notion., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Kinematically aligned total knee arthroplasty (TKA) is a new alignment technique. Kinematic alignment corrects arthritic deformity to the patient's constitutional alignment in order to position the femoral and tibial components, as well as to restore the knee's natural tibial-femoral articular surface, alignment, and natural laxity. Kinematic knee motion moves around a single flexion-extension axis of the distal femur, passing through the center of cylindrically shaped posterior femoral condyles. Since it can be difficult to locate cylindrical axis with conventional instrument, patient-specific instrument (PSI) is used to align the kinematic axes. PSI was recently introduced as a new technology with the goal of improving the accuracy of operative technique, avoiding practical issues related to the complexity of navigation and robotic system, such as the costs and higher number of personnel required. There are several limitations to implement the kinematically aligned TKA with the implant for mechanical alignment. Therefore, it is important to design an implant with the optimal shape for restoring natural knee kinematics that might improve patient-reported satisfaction and function., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

The efficacy of once-weekly risedronate with and without cholecalciferol in bone mineral density (BMD) in Korean patients with osteoporosis was compared. After 12 months, both spine and hip BMD increased significantly in both groups, but there was no significant difference between two groups., Introduction: This study investigated the efficacy and safety of once-weekly risedronate with and without cholecalciferol in BMD in Korean patients with osteoporosis., Methods: This was a prospective, 12-month, randomized, open-labeled, actively controlled trial involving 41 hospitals. A total of 841 subjects with osteoporosis were randomized to once-weekly risedronate (35 mg) and cholecalciferol (5600 IU) in a single pill (RSD+, n = 642) or once-weekly risedronate (35 mg) alone (RSD, n = 199). BMD was measured via dual-energy X-ray absorptiometry at the lumbar spine and hip, and the serum levels of 25-hydroxy vitamin D (25(OH) D), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were assayed at baseline and after 12 months of treatment., Results: After 12 months, the lumbar spine, femoral neck, and total hip BMD increased significantly in both groups; there was no significant difference between two groups. Women in the RSD+ group exhibited significantly increased lumbar spine BMD, and subjects with previous fracture history in the RSD+ group had significantly increased total hip BMD compared with the RSD group. The serum 25(OH) D level increased significantly in the RSD+ group. The serum PTH level decreased in the RSD+ group but increased in the RSD group. The serum ALP level significantly decreased in both groups; there was no significant difference between two groups., Conclusions: A once-weekly pill containing risedronate and cholecalciferol had the equivalent antiresorptive efficacy on BMD compared with risedronate alone and improved 25(OH) D serum levels after 12 months of treatment without significant adverse events in Korean patients with osteoporosis.

Background/objective: The choice of implant is one of the most easily controllable factors affecting the outcome of intertrochanteric fractures. While most of the caput-collum-diaphysis (CCD) angles of the femur are within the range of 125° and 130°, there is a shortage of data on whether 125° or 130° implants are preferable. Thus, the present finite element analysis (FEA) aimed to compare the biomechanical effects on the fracture surface when using implants with different CCD angles where the anatomical CCD angle of the femur was between 125° and 130°., Methods: After establishing a finite element model of an unstable intertrochanteric fracture from the femur with a native CCD angle of 127.3°, proximal femoral nail antirotation (PFNA) models with CCD angles of 125° and 130° were virtually implanted to have the same position of screw tip, respectively., Results: In the one-leg stance during walking, when the implant with 130º CCD angle was used, the magnitude of compressive stress (1.61 and 2.12 MPa in the 130° and 125° model, respectively) was lower and the area of the fracture surface under tensile stress (55% and 5% in 130° and 125° model, respectively), the interfragmentary movements (40.9% more movement in 130° model), and the magnitude of bone deformation (23.5% more deformation in 130° model) were more than those of the 125° model., Conclusion: The intertrochanteric fracture fixed with PFNA with a 125º CCD angle revealed less interfragmentary movement on the fracture surface when the native CCD was an in-between angle in the FEA., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Mechanically aligned total knee arthroplasty (MATKA) aims to make alignment of the hip, knee, and ankle straight unexceptionally. However, emerging evidence suggests that unexceptional straightening the mechanical axis of the lower limb may lead to clinical and radiological problems of the ankle joint. By contrast, kinematically aligned total knee arthroplasty (KATKA) strives to restore the articular surface of the prearthritic knee. In this study, we examined results from KATKA and MATKA to determine which surgery restores the ankle joint orientation closer to the native ankle joint in bipedal stance and hypothesized that KATKA, rather than MATKA, would be more effective. Data from long-leg standing radiographs of 60 healthy adults (control group, n  = 120 knees), patients who underwent MATKA ( n  = 90 knees), and patients who underwent KATKA ( n  = 90 knees) were retrospectively reviewed. The hip-knee-ankle angle, orientation of the tibial plafond and the talar dome relative to the ground (G-plafond and G-talus, respectively), and orientation of the plafond relative to the mechanical axis of the limb (M-plafond and M-talus, respectively) were measured and analyzed for comparison. Results show that bipedal stance alignment in patients who underwent KATKA (G-plafond: -0.65 ± 3.03 and G-talus: -1.72 ± 4.02) were not significantly different to native ankle joint alignment indicated by the control group. Compared with the native ankle joint measured in the control group (G-plafond: -0.76 ± 2.69 and G-talus: -1.30 ± 3.25), the tibial plafond and talar dome significantly tilted laterally relative to the ground in ankle joints after MATKA (G-plafond: -2.32 ± 3.30 and G-talus: -2.97 ± 3.98, p  = 0.001 and p  = 0.004, respectively). Thus, postoperative ankle joint line orientation after KATKA was horizontal to the floor and closer to that of native ankle joints than those after MATKA. The level of evidence is Level III., Competing Interests: This work was supported by the faculty research fund of Ajou University School of Medicine., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Radiation therapy is a primary treatment modality for many forms of cancer. Normally, the highest tolerable dose of ionizing radiation is used to treat tumors, but limitations imposed by normal tissue complications present challenges for local tumor control. In light of this, a class of compounds called radio-sensitizers have been developed to enhance the effectiveness of radiation. Many of these are small molecule drugs found to interact favorably with radiation therapy, but recent advances have been made using nanoparticles as radio-sensitizers. Herein, we report the utilization of radio-luminescent calcium tungstate nanoparticles that emit photoelectrons, UV-A, and visible light during X-ray irradiation, acting as effective radio-sensitizers ("Radio Luminescence Therapy"). In addition, a folic acid-functionalized form of these nanoparticles was shown to enhance radio-sensitization in vitro and in murine models of head and neck cancer. Folic acid-functionalized particles were found to decrease UV-A-induced clonogenic cell survival relative to nonfunctionalized particles. Several possible mechanisms were explored, and the folic acid-functionalized particles were found to mediate this increase in efficacy likely by activating pro-proliferative signaling through folate's innate mitogenic activity, leading to decreased repair of UV-A-induced DNA lesions. Finally, a clinical case study of a canine sarcoma patient demonstrated the initial safety and feasibility of translating these folic acid-functionalized particles into the clinic as radio-sensitizers in the treatment of spontaneous tumors.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

We argue that for situations involving spatially varying linear transport coefficients (diffusivities, thermal conductivities, and viscosities), the original Fick's, Fourier's, and Newton's law equations should be modified to place the diffusivity, thermal conductivity, and viscosity inside the derivative operator, that is, in one-dimensional rectilinear situations, , , and . We present simple derivations of these formulas in which diffusive mass transfer, conductive heat transfer, and molecular momentum transfer processes are described using lattice random walk models. We also present simple examples demonstrating how these modifications affect calculations., Competing Interests: The authors declare no competing financial interest.

The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO 4 (CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30-40 fractions of 2-3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle ("PEG-PLA/CWO/PTX") formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1 month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1 month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO 4 , or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Animal-derived lung surfactants annually save 40 000 infants with neonatal respiratory distress syndrome (NRDS) in the United States. Lung surfactants have further potential for treating about 190 000 adult patients with acute respiratory distress syndrome (ARDS) each year. To this end, the properties of current therapeutics need to be modified. Although the limitations of current therapeutics have been recognized since the 1990s, there has been little improvement. To address this gap, our laboratory has been exploring a radically different approach in which, instead of lipids, proteins, or peptides, synthetic polymers are used as the active ingredient. This endeavor has led to an identification of a promising polymer-based lung surfactant candidate, poly(styrene- b -ethylene glycol) (PS-PEG) polymer nanomicelles. PS-PEG micelles produce extremely low surface tension under high compression because PS-PEG micelles have a strong affinity to the air-water interface. NMR measurements support that PS-PEG micelles are less hydrated than ordinary polymer micelles. Studies using mouse models of acid aspiration confirm that PS-PEG lung surfactant is safe and efficacious., Competing Interests: The authors declare the following competing financial interest(s): A company, Spirrow Therapeutics, is currently attempting to commercialize the technology discussed in this manuscript. H.K.K., D.Q.A., and Y.Y.W. have an ownership interest in this company.

Poly(propylene carbonate) (PPC) decomposes at high temperature to release CO 2 . This CO 2 -generation temperature of PPC can be reduced down to less than 80 °C with the aid of a photoacid generator (PAG). In the present work, we demonstrate that using an additional helper component, surface plasmonic gold nanorods (GNRs), the PPC degradation reaction can also be initiated by infrared (IR) irradiation. For this purpose, a PPC-containing nanoparticle formulation was developed in which PPC-based amphiphilic block copolymers (BCPs), poly(poly(ethylene glycol) methacrylate- b-propylene carbonate- b-poly(ethylene glycol) methacrylate) (PPEGMA-PPC-PPEGMA), were self-assembled with GNRs and PAG molecules via solvent exchange. Under IR irradiation, GNRs produce heat that can cause PPC to decompose into CO 2 , and PAG (after UV pretreatment) catalyzes this PPC degradation process. Two PPEGMA-PPC-PPEGMA materials were used for this study: PPEGMA 7.3K -PPC 5.6K -PPEGMA 7.3K ("G7C6G7") and PPEGMA 2.1K -PPC 5.6K -PPEGMA 2.1K ("G2C6G2"). Addition of CTAB-coated GNRs dispersed in water to a G2C6G2 solution in DMF produced individually G2C6G2-encapsulated GNRs, whereas the same solvent exchange procedure resulted in the formation of polymer-coated GNR clusters when G7C6G7 was used as the encapsulating material. GNR/G2C6G2 NPs exhibited a surface plasmon resonance peak at 697 nm. The clustered morphology of G7C6G7-encapsulated GNRs caused a blue shift of the absorbance maximum to 511 nm. As a consequence, GNR/G2C6G2 NPs showed a greater absorbance/heat generation rate under IR irradiation than did GNR/G7C6G7 NPs. The IR-induced CO 2 generation rate was about 4.2 times higher with the GNR/G2C6G2+PAG sample than that with the GNR/G7C6G7+PAG sample. Both GNR/G7C6G7+PAG and GNR/G2C6G2+PAG systems produced ultrasound contrast enhancement effects under continuous exposure to IR light for >20 min; contrast enhancement was more spatially uniform for the GNR/G2C6G2+PAG sample. These results support the potential utility of PPC as a CO 2 -generating contrast agent in ultrasound imaging applications.

Backgrounds: Impingement is a risk factor for instability and prosthetic failure following total hip arthroplasty (THA). If the periacetabular osteophytes are not removed at surgery, impingement could occur between the osteophytes and the femoral stem following THA. However, excessive removal of the osteophytes could lead to bleeding from the bone. The aim of our study, therefore, was to locate the site of the impingement and to determine the width of tolerable osteophytes, which does not induce impingement during activities of daily living (ADL), using a three-dimensional simulation., Methods: On 35 hip models, virtual THA was performed. The acetabular cups were positioned at 45° abduction and 20° anteversion, and the anteversion of femoral stems was 15°. Circular osteophytes with a 30-mm rim were built around the acetabular cup. Fourteen ADL motions were simulated, and the osteophytes were removed until there was no impingement. A clock face was used to map the location and the width of tolerable osteophytes., Results: The impingement mainly occurred in antero-superior and posterior portions around the acetabular cup. Only 4.2-6.2-mm osteophytes were tolerable at the antero-superior portion (12-3 o'clock) and 6.3-7.2-mm osteophytes at the posterior portion (8-10 o'clock) following a total hip arthroplasty. In antero-inferior and postero-superior portions, over-20-mm osteophytes did not induce any impingement., Conclusion: Osteophytes in the antero-superior and posterior portion of the acetabulum should be excised during a THA to avoid impingement of the femur-stem construct on the acetabular osteophytes during ADLs.

Background: "Grand-piano sign" has been used as a popular benchmark to facilitate correct rotational alignment during total knee arthroplasty (TKA). The purpose was to quantitatively determine morphological patterns on anterior femoral resection in mechanically aligned (MA) and kinematically aligned (KA) TKA., Methods: Computed tomography scans of 60 TKA candidates were reconstructed into 3D models. Femurs were virtually cut with a 3D imaging program using various anterior flange flexion angles (AFFAs) of 3°, 5°, and 7°. The anterior femoral resection was performed parallel to the surgical epicondylar axis, at an external rotation and internal rotation of 3° relative to surgical epicondylar axis for MA-TKA, and parallel to the cylindrical axis, at an external rotation and internal rotation of 3° to cylindrical axis for KA-TKA. The ratio of vertical distance from the anterior margin of distal femoral resection to the most proximal peak of each medial and lateral condyle of anterior femoral resection was defined as AC/BC ratio., Results: The mean ratios of AC/BC were 0.57, 0.60, and 0.63 respectively, according to 3°, 5°, and 7° of AFFA with standard MA-TKA method and were 0.73, 0.74, and 0.76, respectively, according to 3°, 5°, and 7° of AFFA with standard KA-TKA method. The AC/BC ratios of malrotated planes were significantly different from those of both standard MA- and KA-TKAs (P-values < .01)., Conclusion: Surgeons can accessorily use the quantifying method for anterior femoral resection intraoperatively to ensure correct rotational alignment of femoral resection in both mechanically and kinematically aligned TKA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Discovery of lung surfactant deficiency as a main cause of neonatal respiratory distress syndrome (NRDS) has influenced a steep increase in lung surfactant research. Although this has yielded impactful scientific discoveries, much of the basic research on lung surfactants has failed to translate into clinical practices. This is attributed to insufficient information covering the entire lung surfactant ecosystem, from the basic science to economics surrounding the development and clinical practices. In this manuscript, developments related to improving therapeutic lung surfactant as well as the degree of unmet need are analyzed from both technical and economic perspectives. Two potential opportunities are emphasized: (1) aerosolized lung surfactants to treat NRDS infants, and (2) synthetic lung surfactants for acute respiratory distress syndrome (ARDS) patients. Each has a modestly projected US market size of $120 million and $4 billion, well enough to make up for the high development costs associated with investigational drug development. Both opportunities have been pursued in the past, but to date these attempts have met with no success mainly due to technical limitations. With the recent advancements in both fields, technology improvements have created opportunities to solve both decades-old problems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Polymers at fluid interfaces are used for a number of applications that include coatings, electronics, separation, energy, cosmetics, and medicines. Here, we present a study on an amphiphilic block copolymer, poly((d,l-lactic acid- co-glycolic acid)- block-ethylene glycol) (PLGA-PEG), at the air-water interface. PLGA-PEG at the air-water interface prepared by using an organic spreading solvent exhibits an extremely high surface pressure without the occurrence of desorption, making it an attractive candidate for a variety of uses in the areas mentioned above. The origin of this high surface pressure increase was shown to be due to the glass transition of the PLGA segments. The temperature at which this glass transition occurs for the PLGA segments of PLGA-PEG at the air-water interface was measured to be about 290 K by thermodynamic analysis based on the two-dimensional Maxwell relations. However, from an applications standpoint, spreading by an organic solvent greatly limits its scope of feasible uses. To explore the possibility of maintaining the excellent surface mechanical properties of the PLGA-PEG at the air-water interface while not using an organic solvent, we investigated the air-water interfacial properties of water-spread PLGA-PEG. When spread with water, it was shown that the initial micelles that form in the aqueous spreading solution remain intact even after being spread onto the air-water interface. Due to this different morphology, the surface pressure and monolayer stability were greatly reduced for the water-spread PLGA-PEG at the air-water interface. We used the Daoud and Cotton's blob scaling model to describe the desorption process of the water-spread PLGA-PEG at the air-water interface. From the scaling concept, it was shown that with higher PEG molecular weight and larger micelle size, the adsorption energy of the water-spread PLGA-PEG to the air-water interface was increased.

Currently, there is great interest in the development of ways to achieve the benefits of radiation treatments with reduced negative effects. The present study demonstrates the utilization of radio-luminescent particles (RLPs) as a means to achieve radio-sensitization and enhancement and their ability to affect head- and neck-cancer-cell cultures (in vitro) and xenografts (in vivo). Our approach utilizes a naturally abundant radio-luminescent mineral, calcium tungstate (CaWO 4 ), in its micro or nanoparticulate form for generating secondary UV-A light by γ ray or X-ray photons. In vitro tests demonstrate that unoptimized RLP materials (uncoated CaWO 4 (CWO) microparticles (MPs) and PEG-PLA-coated CWO nanoparticles (NPs)) induce a significant enhancement of the tumor-suppressive effect of X-rays and γ rays in both radio-sensitive- and radio-resistant-cancer models; uncoated CWO MPs and PEG-PLA-coated CWO NPs demonstrate comparable radio-sensitization efficacies in vitro. Mechanistic studies reveal that concomitant CaWO 4 causes increased mitotic death in radio-resistant cells treated with radiation, whereas CaWO 4 sensitizes radio-sensitive cells to X-ray-induced apoptosis and necrosis. The radio-sensitization efficacy of intratumorally injected CaWO 4 particles (uncoated CWO MPs and PEG-PLA-coated CWO NPs) is also evaluated in vivo in mouse head- and neck-cancer xenografts. Uncoated CWO MPs suppress tumor growth more effectively than PEG-PLA-coated CWO NPs. On the basis of theoretical considerations, an argument is proposed that uncoated CWO MPs release subtoxic levels of tungstate ions, which cause increased photoelectric-electron-emission effects. The effect of folic acid functionalization on the in vitro radio-sensitization behavior produced by PEG-PLA-coated CWO NPs is studied. Surface folic acid results in a significant improvement in the radio-sensitization efficiency of CaWO 4 .

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.