CONTROLLED RELEASE OF OSTEOTROPIC MOLECULES STIMULATES IN VITRO CELLULAR ACTIVITY AND IN VIVO LOCAL BONE REGENERATION

Bone defects treatment and reconstructive surgery continues to increase at a significant rate. Current bone defect treatments are autotransplantation, allograft, and xenografts create many problems such as, inflammation, infection and chronic pain. Moreover, allografts and xenografts arouse immune rejection. These problems have led to development of controlled release system for use as alternatives to autografts, allografts and xenografts in bone repair. There have been many approaches for sustained drug delivery in local bone regeneration using biodegradable polymers and osteotropic biomolecules. This dissertation presents new approaches that apply intermittent drug delivery for local bone regeneration. In the first, the osteotropic molecules simvastatin (Sim) or parathyroid hormone (PTH) were released with intermittent profiles. In the second, alternating delivery of Sim and PTH as well as alternating release of the antimicrobial agent cecropin B (CB) with Sim or PTH. An association polymer system of cellulose acetate phthalate (CAP) and Pluronic F-127 (PF-127) was used for the delivery vehicle. Each device showed discrete peaks in release profiles and lasted more than 10 days. Release profiles could be controlled by altering surface area exposed to aqueous environment, number of layers, loading, and blending ratios. Cells were cultured with sustained or intermittent exposure to Sim or PTH at various concentrations, and alternating exposure to CB and Sim or PTH and to Sim and PTH at different concentrations. Low dose Sim and PTH treatments stimulated higher osteoblastic activity than observed in control cultures. Furthermore, intermittent delivery was more effective than sustained exposure. In vivo, newly formed bone was found in animals implanted with both blank Sim-loaded devices. However, a greater anabolic effect was seen for Sim release devices. Further, intermittent release devices stimulated the greatest woven bone thickness, total bone area, and lamellar bone area. These results suggest that intermittent release devices containing a single molecule, Sim or PTH, and alternating release devices containing multiple molecules, CB with Sim or PTH, possess promising potential as a treatment for local bone regeneration

Terahertz detector with aperture for enhanced performance and resolution by near-field microscopy technology

Department of Electrical Engineeringmaging technology in sub-THz frequency range (f= 0.1~1 THz) has various applications such as scanning the body in security and medical region. Recently, some research group have been reported on the multipixel THz detector for real-time and large-area THz imaging [1,2]. However, since sub-THz waves have relatively long wavelength (??= 0.3~3 mm), and it cause the limit of spatial resolution in THz imaging by its diffraction limit (??/2). In this work, we experimentally demonstrate the enhanced photoresponse and spatial resolution of THz detector with novel nano-scale aperture by near-field microscopy technology. The layout of FET with aperture width of 1 ??m and probe distance of 280 nm, which is designed in single copper layer for enhancing and focusing the electric field when THz wave is incoming. Through the raster scanning of key-shape structure at 0.5 THz, the photoresponse of detector with probe-type aperture is 7 times more enhanced than without aperture. Furthermore, the spatial resolution, which is minimum distinguishable distance between boundary of materials, of detector with aperture is 2 times higher than detector without aperture. Therefore, our probe-type aperture design on THz detector can provide the possibility of high performance and resolution THz imaging system.clos

Tailoring of processing parameters for sintering microsphere-based scaffolds with dense phase carbon dioxide

Jeon, J. H., Bhamidipati, M., Sridharan, B., Scurto, A. M., Berkland, C. J. and Detamore, M. S. (2013), Tailoring of processing parameters for sintering microsphere-based scaffolds with dense-phase carbon dioxide. J. Biomed. Mater. Res., 101B: 330–337. doi:10.1002/jbm.b.32843Microsphere-based polymeric tissue-engineered scaffolds offer the advantage of shape-specific constructs with excellent spatiotemporal control and interconnected porous structures. The use of these highly versatile scaffolds requires a method to sinter the discrete microspheres together into a cohesive network, typically with the use of heat or organic solvents. We previously introduced subcritical CO2 as a sintering method for microsphere-based scaffolds; here we further explored the effect of processing parameters. Gaseous or subcritical CO2 was used for making the scaffolds, and various pressures, ratios of lactic acid to glycolic acid in poly(lactic acid-co-glycolic acid), and amounts of NaCl particles were explored. By changing these parameters, scaffolds with different mechanical properties and morphologies were prepared. The preferred range of applied subcritical CO2 was 15–25 bar. Scaffolds prepared at 25 bar with lower lactic acid ratios and without NaCl particles had a higher stiffness, while the constructs made at 15 bar, lower glycolic acid content, and with salt granules had lower elastic moduli. Human umbilical cord mesenchymal stromal cells (hUCMSCs) seeded on the scaffolds demonstrated that cells penetrate the scaffolds and remain viable. Overall, the study demonstrated the dependence of the optimal CO2 sintering parameters on the polymer and conditions, and identified desirable CO2 processing parameters to employ in the sintering of microsphere-based scaffolds as a more benign alternative to heat-sintering or solvent-based sintering methods

Simultaneous determination of 13 mycotoxins in feedstuffs using QuEChERS extraction

Mycotoxins are secondary metabolites produced by various fungi and are known to have a significant negative impact on human and animal health. When feedstuffs are contaminated with mycotoxins, their toxicities may be caused a variety of diseases. In this study, the residual mycotoxins in feedstuffs were analyzed using LC-MS/MS incorporated with QuEChERS extraction. Analytical method validation was performed for LOD, LOQ, linearity, and recoveries with consideration of matrix effects prior to the residual analysis. They were all reached to the accepted range of validation level. Using 39 feedstuff samples (5 g) for mycotoxin analysis, nine samples were contaminated by four major mycotoxins such as fumonisin B1 (FB1), deoxynivalenol, fumonisin B2, and zearalenone. Among them, FB1 was detected at the highest concentration as 18.0943 mg/kg. The total sum of fumonisins in 39 samples did not exceed the maximum residual level (MRL) criterion set by Korean Food and Drug Administration. Altogether, intensive management of mycotoxins in Korean feedstuffs should be implemented with proper and routine monitoring, even their residual concentrations are not exceeded over the MRL levels because of high frequent detection found in this study

Design and Preclinical Evaluation of a Universal SARS-CoV-2 mRNA Vaccine

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated lipid nanoparticle (LNP) formulated mRNA vaccines that induce only T cell responses or both T cell and neutralizing antibody responses by using two mRNAs. One mRNA encodes SARS-CoV-2 Omicron Spike protein in prefusion conformation for induction of neutralizing antibodies. The other mRNA encodes over one hundred T cell epitopes (multi-T cell epitope or MTE) derived from non-Spike but conserved regions of the SARS-CoV-2. We show immunization with MTE mRNA alone protected mice from lethal challenge with the SARS-CoV-2 Delta variant or a mouse-adapted virus MA30. Immunization with both mRNAs induced the best protection with the lowest viral titer in the lung. These results demonstrate that induction of T cell responses, in the absence of preexisting antibodies, is sufficient to confer protection against severe disease, and that a vaccine containing mRNAs encoding both the Spike and MTE could be further developed as a universal SARS-CoV-2 vaccine

The Concept of Sasang Health Index and Constitution-Based Health Assessment: An Integrative Model with Computerized Four Diagnosis Methods

Sasang constitutional medicine (SCM) shares its philosophy with that of personalized medicine: it provides constitution-specific treatment and healthcare individualized for each patient. In this work, we propose the concept of the Sasang Health Index (SHI) as an attempt to assess the individualized health status in the framework of SCM. From the target population of females in their fifties and older, we recruited 298 subjects and collected their physiological data, including complexion, radial pulse, and voice, and their questionnaire responses. The health status of each subject was evaluated by two Korean medical doctors independently, and the SHI model was obtained by combining all the integrative features of the phenotype data using a regression technique. As a result, most subjects belonged to either the healthy, subhealthy, or slightly diseased group, and the intraclass correlation coefficient between the two doctors’ health scoring reached 0.95. We obtained an SHI model for each constitution type with adjusted R-squares of 0.50, 0.56, and 0.30, for the TE, SE, and SY constitution types, respectively. In the proposed SHI model, the significant characteristics used in the health assessment consisted of constitution-specific features in accordance with the classic literature and features common to all the constitution types

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Fully Transparent and Sensitivity-Programmable Amorphous Indium-Gallium-Zinc-Oxide Thin-Film Transistor-Based Biosensor Platforms with Resistive Switching Memories

This paper presents a fully transparent and sensitivity-programmable biosensor based on an amorphous-indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) with embedded resistive switching memories (ReRAMs). The sensor comprises a control gate (CG) and a sensing gate (SG), each with a resistive switching (RS) memory connected, and a floating gate (FG) that modulates the channel conductance of the a-IGZO TFT. The resistive coupling between the RS memories connected to the CG and SG produces sensitivity properties that considerably exceed the limit of conventional ion-sensitive field-effect transistor (ISFET)-based sensors. The resistances of the embedded RS memories were determined by applying a voltage to the CG–FG and SG–FG structures independently and adjusting the compliance current. Sensors constructed using RS memories with different resistance ratios yielded a pH sensitivity of 50.5 mV/pH (RCG:RSG = 1:1), 105.2 mV/pH (RCG:RSG = 2:1), and 161.9 mV/pH (RCG:RSG = 3:1). Moreover, when the RCG:RSG = 3:1, the hysteresis voltage width (VH) and drift rate were 54.4 mV and 32.9 mV/h, respectively. As the increases in VH and drift rate are lower than the amplified sensitivity, the sensor performs capably. The proposed device is viable as a versatile sensing device capable of detecting various substances, such as cells, antigens, DNA, and gases