Safety and efficacy of acupuncture for mild cognitive impairment: a study protocol for clinical study.

Background: Mild cognitive impairment (MCI) is an intermediary condition between typical cognitive decline that occurs owing to aging and dementia. It is necessary to implement an intervention to slow the progression from MCI to Alzheimer's disease. This manuscript reports the protocol for a clinical trial on the effect of acupuncture in patients with MCI. Methods: The trial will be a randomized, prospective, parallel-arm, active-controlled trial. Sixty-four patients with MCI will be randomized to the Rehacom or acupuncture group (n = 32 each). The participants in the acupuncture group will receive electroacupuncture at GV24 (Shenting) and GV20 (Baihui) and acupuncture at EX-HN1 (Sishencong) once (30 min) a day, twice per week for 12 weeks. The patients in the Rehacom group will receive computerized cognitive rehabilitation using RehaCom software once (30 min) daily, twice weekly for 12 weeks. The primary outcome measure is the change in the Montreal Cognitive Assessment Scale score. The secondary outcome measures are the Geriatric Depression Scale, Alzheimer's Disease Assessment Scale-Korean version-cognitive subscale-3 scores, and European Quality of Life Five Dimensions Five Level Scale. The safety outcomes will include the incidence of adverse events, blood pressure, blood chemistry parameters, and pulse rate. The efficacy outcome will be assessed at baseline and at six weeks, 13 weeks, and 24 weeks after baseline. Discussion: The findings of this protocol will provide information regarding the effects of acupuncture on MCI. Clinical trial registration: https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=25579&status=5&seq_group=25579, KCT0008861.

Variations of oxidative potential of PM2.5 in a medium-sized residential city in South Korea measured using three different chemical assays.

Although it is evident that PM2.5 has serious adverse health effects, there is no consensus on what the biologically effective dose is. In this study, the intrinsic oxidative potential (OPm) and the extrinsic oxidative potential (OPv) of PM2.5 were measured using three chemical assays including dithiothreitol (DTT), ascorbic acid (AA), and reduced glutathione (GSH), along with chemical compositions of PM2.5 in South Korea. Among the three chemical assays, only OPmAA showed a statistically significant correlation with PM2.5 while OPmGSH and OPmDTT were not correlated with PM2.5 mass concentration. When the samples were categorized by PM2.5 mass concentrations, the variations in the proportion of Ni, As, Mn, Cd, Pb, and Se to PM2.5 mass closely coincided with changes in OPm across all three assays, suggesting a potential association between these elements and PM2.5 OP. Multiple linear regression analysis identified the significant PM components affecting the variability in extrinsic OPv. OPvAA was determined to be significantly influenced by EC, K+, and Ba while OC and Al were common significant factors for OPvGSH and OPvDTT. It was also found that primary OC was an important variable for OPvDTT while secondary OC significantly affected the variability of OPvGSH.

Just noticeable difference for simulation accuracy between full and reduced order models (L).

Model order reduction techniques significantly reduce the computational time when performing accurate room acoustic simulations with numerical methods that inherently include all the wave phenomena. There is a clear trade-off between physical accuracy and acceleration, but how humans perceive these errors is unknown. This study aims to investigate physical error limit that does not induce perceptual differences. Various two-dimensional rooms and reverberation times are tested with a three-alternative forced-choice listening test. Results reveal that for the presented cases, the threshold stands between a relative root mean square error of 1% and 0.1%, where the reduced order model stimulus results in a statistically significant difference.

Sound propagation in realistic interactive 3D scenes with parameterized sources using deep neural operators.

We address the challenge of acoustic simulations in three-dimensional (3D) virtual rooms with parametric source positions, which have applications in virtual/augmented reality, game audio, and spatial computing. The wave equation can fully describe wave phenomena such as diffraction and interference. However, conventional numerical discretization methods are computationally expensive when simulating hundreds of source and receiver positions, making simulations with parametric source positions impractical. To overcome this limitation, we propose using deep operator networks to approximate linear wave-equation operators. This enables the rapid prediction of sound propagation in realistic 3D acoustic scenes with parametric source positions, achieving millisecond-scale computations. By learning a compact surrogate model, we avoid the offline calculation and storage of impulse responses for all relevant source/listener pairs. Our experiments, including various complex scene geometries, show good agreement with reference solutions, with root mean squared errors ranging from 0.02 to 0.10 Pa. Notably, our method signifies a paradigm shift as-to our knowledge-no prior machine learning approach has achieved precise predictions of complete wave fields within realistic domains.

Esthetic reconstruction of a localized severely resorbed anterior maxilla associated with peri-implantitis: A clinical report.

This clinical report described the esthetic reconstruction of a localized severely resorbed right anterior maxilla associated with peri-implantitis. For vertical bone augmentation, guided bone regeneration surgery was performed by raising a flap with the remote incision technique, followed by soft tissue grafting and vestibuloplasty. The biologically oriented preparation technique was used to improve the health and stability of the peri-implant tissues. The surgical treatment and a novel method of prosthetic rehabilitation provided excellent esthetic and functional outcomes.

Micellized protein transduction domain-bone morphogenetic protein-2 accelerates bone healing in a rat tibial distraction osteogenesis model.

The clinical application of growth factors such as recombinant human bone morphogenetic protein-2 (rh-BMP-2), for functional bone regeneration remains challenging due to limited in vivo efficacy and adverse effects of previous modalities. To overcome the instability and short half-life of rh-BMP-2 in vivo, we developed a novel osteogenic supplement by fusing a protein transduction domain (PTD) with BMP-2, effectively creating a prodrug of BMP-2. In this study, we first created an improved PTD-BMP-2 formulation using lipid nanoparticle (LNP) micellization, resulting in downsizing from micrometer to nanometer scale and achieving a more even distribution. The micellized PTD-BMP-2 (mPTD-BMP-2) demonstrated improved distribution and aggregation profiles. As a prodrug of BMP-2, mPTD-BMP-2 successfully activated Smad1/5/8 and induced mineralization with osteogenic gene induction in vitro. In vivo pharmacokinetic analysis revealed that mPTD-BMP-2 had a much more stable pharmacokinetic profile than rh-BMP-2, with a 7.5-fold longer half-life. The in vivo BMP-responsive element (BRE) reporter system was also successfully activated by mPTD-BMP-2. In the in vivo rat tibia distraction osteogenesis (DO) model, micro-computed tomography (micro-CT) scan findings indicated that mPTD-BMP-2 significantly increased bone volume, bone surface, axis moment of inertia (MOI), and polar MOI. Furthermore, it increased the expression of osteogenesis-related genes, and induced bone maturation histologically. Based on these findings, mPTD-BMP-2 could be a promising candidate for the next-generation osteogenesis drug to promote new bone formation in DO surgery. STATEMENT OF SIGNIFICANCE: This study introduces micellized bone morphogenetic protein-2 (mPTD-BMP-2), a next-generation osteogenic supplement that combines protein transduction domain (PTD) and nano-sized micelle formulation technique to improve transduction efficiency and stability. The use of PTD represents a novel approach, and our results demonstrate the superiority of mPTD-BMP-2 over rh-BMP-2 in terms of in vivo pharmacokinetic profile and osteogenic potential, particularly in a rat tibial model of distraction osteogenesis. These findings have significant scientific impact and potential clinical applications in the treatment of bone defects that require distraction osteogenesis. By advancing the field of osteogenic supplements, our study has the potential to contribute to the development of more effective treatments for musculoskeletal disorders.

Reduced order modelling using parameterized non-uniform boundary conditions in room acoustic simulations.

Quick simulations for iterative evaluations of multi-design variables and boundary conditions are essential to find the optimal acoustic conditions in building design. We propose to use the reduced basis method (RBM) for realistic room acoustic scenarios where the surfaces have inhomogeneous acoustic properties, which enables quick evaluations of changing absorption materials for different surfaces in room acoustic simulations. The RBM has shown its benefit to speed up room acoustic simulations by 3 orders of magnitude for uniform boundary conditions. This study investigates the RBM with two main focuses: (1) various source positions in diverse geometries, e.g., square, rectangular, L-shaped, and disproportionate room, (2) two-dimensional and three-dimensional (3D) inhomogeneous surface absorption by parameterizing numerous acoustic parameters of surfaces, e.g., the thickness of a porous material, cavity depth, switching between a frequency independent (e.g., hard surface) and frequency dependent boundary condition. Results of numerical experiments show speedups of more than 2 orders of magnitude compared to a high fidelity numerical solver in a 3D case where reverberation time varies within one just noticeable difference in all the frequency octave bands.

Enhancement of Immune Responses Elicited by Nanovaccines through a Cross-Presentation Pathway.

Numerous studies have aimed to develop novel advanced vaccines, in part because traditional vaccines have been unsuccessful in preventing rapidly emerging and reemerging viral and bacterial infections. There is a need for an advanced vaccine delivery system to ensure the successful induction of humoral and cellular immune responses. In particular, the ability of nanovaccines to modulate intracellular antigen delivery by inducing exogenous antigens (loaded onto major histocompatibility complex class 1 molecules) in CD8+ T cells, the so-called cross-presentation pathway, has attracted a great deal of attention. Protection against viral and intracellular bacterial infections relies on cross-presentation. This review discusses the advantages, requirements, and preparation of nanovaccines, the cross-presentation mechanism, the several parameters affecting cross-presentation by nanovaccines, and future perspectives.

Enhancement of Immune Responses Elicited by Nanovaccines through a Cross-Presentation Pathway

Numerous studies have aimed to develop novel advanced vaccines, in part because traditional vaccines have been unsuccessful in preventing rapidly emerging and reemerging viral and bacterial infections. There is a need for an advanced vaccine delivery system to ensure the successful induction of humoral and cellular immune responses. In particular, the ability of nanovaccines to modulate intracellular antigen delivery by inducing exogenous antigens (loaded onto major histocompatibility complex class 1 molecules) in CD8+ T cells, the so-called cross-presentation pathway, has attracted a great deal of attention. Protection against viral and intracellular bacterial infections relies on cross-presentation.This review discusses the advantages, requirements, and preparation of nanovaccines, the cross-presentation mechanism, the several parameters affecting cross-presentation by nanovaccines, and future perspectives.

Intranasal Immunization With Nanoparticles Containing an Orientia tsutsugamushi Protein Vaccine Candidate and a Polysorbitol Transporter Adjuvant Enhances Both Humoral and Cellular Immune Responses.

Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy. Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8+ and CD4+ T cells. Furthermore, the vaccines containing PST improved the mouse survival against O. tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

Hidden energies around surfaces, edges, and corners in rooms.

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.

Glycogen Synthase Kinase-3 Interaction Domain Enhances Phosphorylation of SARS-CoV-2 Nucleocapsid Protein.

A structural protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), nucleocapsid (N) protein is phosphorylated by glycogen synthase kinase (GSK)-3 on the serine/arginine (SR) rich motif located in disordered regions. Although phosphorylation by GSK-3ß constitutes a critical event for viral replication, the molecular mechanism underlying N phosphorylation is not well understood. In this study, we found the putative alpha-helix L/FxxxL/AxxRL motif known as the GSK-3 interacting domain (GID), found in many endogenous GSK-3ß binding proteins, such as Axins, FRATs, WWOX, and GSKIP. Indeed, N interacts with GSK-3ß similarly to Axin, and Leu to Glu substitution of the GID abolished the interaction, with loss of N phosphorylation. The N phosphorylation is also required for its structural loading in a virus-like particle (VLP). Compared to other coronaviruses, N of Sarbecovirus lineage including bat RaTG13 harbors a CDK1-primed phosphorylation site and Gly-rich linker for enhanced phosphorylation by GSK-3ß. Furthermore, we found that the S202R mutant found in Delta and R203K/G204R mutant found in the Omicron variant allow increased abundance and hyper-phosphorylation of N. Our observations suggest that GID and mutations for increased phosphorylation in N may have contributed to the evolution of variants.

A round-robin approach provides a detailed assessment of biomolecular small-angle scattering data reproducibility and yields consensus curves for benchmarking.

Through an expansive international effort that involved data collection on 12 small-angle X-ray scattering (SAXS) and four small-angle neutron scattering (SANS) instruments, 171 SAXS and 76 SANS measurements for five proteins (ribonuclease A, lysozyme, xylanase, urate oxidase and xylose isomerase) were acquired. From these data, the solvent-subtracted protein scattering profiles were shown to be reproducible, with the caveat that an additive constant adjustment was required to account for small errors in solvent subtraction. Further, the major features of the obtained consensus SAXS data over the q measurement range 0-1 Å-1 are consistent with theoretical prediction. The inherently lower statistical precision for SANS limited the reliably measured q-range to <0.5 Å-1, but within the limits of experimental uncertainties the major features of the consensus SANS data were also consistent with prediction for all five proteins measured in H2O and in D2O. Thus, a foundation set of consensus SAS profiles has been obtained for benchmarking scattering-profile prediction from atomic coordinates. Additionally, two sets of SAXS data measured at different facilities to q > 2.2 Å-1 showed good mutual agreement, affirming that this region has interpretable features for structural modelling. SAS measurements with inline size-exclusion chromatography (SEC) proved to be generally superior for eliminating sample heterogeneity, but with unavoidable sample dilution during column elution, while batch SAS data collected at higher concentrations and for longer times provided superior statistical precision. Careful merging of data measured using inline SEC and batch modes, or low- and high-concentration data from batch measurements, was successful in eliminating small amounts of aggregate or interparticle interference from the scattering while providing improved statistical precision overall for the benchmarking data set.

Acceleration of bone formation by octacalcium phosphate composite in a rat tibia critical-sized defect.

Background: The osteogenic capabilities and biodegradability of octacalcium phosphate (OCP) composites make them unique. Despite the excellent characteristics of OCP, their use is limited due to handling difficulties. In this study, we aimed to evaluate and compare three types of OCPs (cemented OCP (C-OCP), C-OCP with collagen (OCP/Col), and synthetic OCP (S-OCP) with alginate (OCP/Alg)) versus commercially available ß-tricalcium phosphate (ß-TCP) regarding their potential to accelerate bone formation in defective rat tibias. Methods: The specimens with OCP composite were manufactured into 5 â€‹mm cubes and inserted into the segmental defects of rat tibias fixed with an external fixator. In addition, 3 â€‹mm-hole defects in rat tibias were evaluated to compare the graft material properties in different clinical situations. Serial X-ray studies were evaluated weekly and the tibias were harvested at postoperative 6 weeks or 8 weeks for radiologic evaluation. Histological and histomorphometric analyses were performed to evaluate the acceleration of bone formation. Results: In the critical-defect model, OCP/Alg showed bone bridges between segmentally resected bone ends that were comparable to those of ß-TCP. However, differences were observed in the residual graft materials. Most ß-TCP was maintained until 8 weeks postoperatively; however, OCP/Alg was more biodegradable. In addition calcification in the ß-TCP occurred at the directly contacted area between graft particles and bony ingrowth was observed in the region adjacent resected surface of tibia. In contrast, no direct bony ingrowth was observed in OCP-based materials, but osteogenesis induced from resected surface of tibia was more active. In the hole-defect model, OCP/Col accelerated bone formation. ß-TCP and OCP/Alg showed similar patterns with relatively higher biodegradability. In histology, among the OCP-based materials, directly contacted new bone was formed only in OCP/Alg group. The new bone formation in the periphery area of graft materials was much more active in the OCP-based materials, and the newly formed bone showed a thicker trabecular and more mature appearance than the ß-TCP group. Conclusions: In this study, OCP/Alg was equivalent to ß-TCP in the acceleration of bone formation with better biodegradability appropriate for clinical situations in different circumstances. Our OCP/Col composite showed fast degradation, which makes it unsuitable for use in mechanical stress conditions in clinical orthopedic settings. The Translational Potential of this Article: In our research, we compared our various manufactured OCP composites to commercially available ß-TCP in critical-defect rat tibia model. OCP/Col showed acceleration in hole-defect model as previous studies in dental field but in our critical-sized defect model it resorbed fast without acceleration of bony union. OCP/Alg showed matched results compared to ß-TCP and relatively fast resorption so we showed market value in special clinical indication depending on treatment strategy. This is the first OCP composite study in orthopaedics with animal critical-sized tibia bone study and further study should be considered for clinical application based on this study.

Reduced basis methods for numerical room acoustic simulations with parametrized boundaries.

The use of model-based numerical simulations of wave propagation in rooms for engineering applications requires that acoustic conditions for multiple parameters are evaluated iteratively, which is computationally expensive. We present a reduced basis method (RBM) to achieve a computational cost reduction relative to a traditional full-order model (FOM) for wave-based room acoustic simulations with parametrized boundaries. The FOM solver is based on the spectral-element method; however, other numerical methods could be applied. The RBM reduces the computational burden by solving the problem in a low-dimensional subspace for parametrized frequency-independent and frequency-dependent boundary conditions. The problem is formulated in the Laplace domain, which ensures the stability of the reduced-order model (ROM). We study the potential of the proposed RBM in terms of computational efficiency, accuracy, and storage requirements, and we show that the RBM leads to 100-fold speedups for a two-dimensional case and 1000-fold speedups for a three-dimensional case with an upper frequency of 2 and 1 kHz, respectively. While the FOM simulations needed to construct the ROM are expensive, we demonstrate that the ROM has the potential of being 3 orders of magnitude faster than the FOM when four different boundary conditions are simulated per room surface.

Characterization of winter air pollutant gradients near a major highway.

Traffic-related air pollutants (TRAP) including nitric oxide (NO), nitrogen oxide (NOx), carbon monoxide (CO), ultrafine particles (UFP), black carbon (BC), and fine particulate matter (PM2.5) were simultaneously measured at near-road sites located at 10 m (NR10) and 150 m (NR150) from the same side of a busy highway to provide insights into the influence of winter time meteorology on exposure to TRAP near major roads. The spatial variabilities of TRAP were examined for ambient temperatures ranging from -11 °C to +19 °C under downwind, upwind, and stagnant air conditions. The downwind TRAP concentrations at NR10 were higher than the upwind concentrations by a factor of 1.4 for CO to 13 for NO. Despite steep downwind reductions of 38 % to 75 % within 150 m, the downwind concentrations at NR150 were still well above upwind concentrations. Near-road concentrations of NOx and UFP increased as ambient temperatures decreased due to elevated emissions of NOx and UFP from vehicles under colder temperatures. Traffic-related PM2.5 sources were identified using hourly PM2.5 chemical components including organic/inorganic aerosol and trace metals at both sites. The downwind concentrations of primary PM2.5 species related to tailpipe and non-tailpipe emissions at NR10 were substantially higher than the upwind concentrations by a factor of 4 and 32, respectively. Traffic-related PM2.5 sources accounted for almost half of total PM2.5 mass under downwind conditions, leading to a rapid change of PM2.5 chemical composition. Under stagnant air conditions, the concentrations of most TRAP and related PM2.5 including tailpipe emissions, secondary nitrate, and organic aerosol were comparable to, or even greater than, the downwind concentrations under windy conditions, especially at NR150. This study demonstrates that stagnant air conditions further widen the traffic-influenced area and people living near major roadways may experience increased risks from elevated exposure to traffic emissions during cold and stagnant winter conditions.

Progress of Polysaccharide-Contained Polyurethanes for Biomedical Applications.

Polyurethane (PU) has been widely examined and used for biomedical applications, such as catheters, blood oxygenators, stents, cardiac valves, drug delivery carriers, dialysis devices, wound dressings, adhesives, pacemaker, tissue engineering, and coatings for breast implants due to its mechanical flexibility, high tear strength, biocompatibility, and tailorable foams although bio-acceptability, biodegradability and controlled drug delivery to achieve the desired properties should be considered. Especially, during the last decade, the development of bio-based PUs has raised public awareness because of the concern with global plastic waste for creating more environmentally friended materials. Therefore, it is desirable to discuss polysaccharide (PS)-contained PU for the wound dressing and bone tissue engineering among bio-based PUs because PS has several advantages, such as biocompatibility, reproducibility from the natural resources, degradability, ease of incorporation of bioactive agents, ease of availability and cost-effectiveness, and structural feature of chemical modification to meet the desired needs to overcome the disadvantages of PU itself by containing the PS into the PU.

In vitro photodynamic therapy of methylene blue-loaded acetyl resistant starch nanoparticles.

BACKGROUND: Combination therapies comprising multiple methods, such as photodynamic therapy have been applied to be complements chemotherapy as they increase the therapeutic efficiency by enabling the intelligent drug delivery to target sites by exposing the photosensitizer to light and activating it in the tumor tissue. This study evaluated in vitro photodynamic therapy of methylene blue (MB)-loaded acetyl resistant starch (ARS) nanoparticles (NPs). METHODS: ARS was synthesized by the reaction between resistant starch (RS) and acetic anhydride. MB-loaded ARS NPs and ARS NPs were prepared by a single emulsion method. Synthesized ARS was measured by NMR. Prepared ARS NPs and MB-loaded ARS NPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction, UV/Vis, and circular dichroism (CD). MB-loaded ARS NPs were treated in mouse colon cancer cells (CT-26) and they were treated under near-infrared (NIR) laser irradiation. RESULTS: Synthesis of ARS was confirmed by NMR and the degree of substitutions in the ARS was 7.1. The morphologies of ARS NPs observed by TEM were spherical shapes and the particle sizes of ARS NPs were 173.4 nm with a surface charge of - 17.24 mV. The d-spacing of ARS NPs was smaller than those of RS and the conformational changes of RS occurred by the formation of self-assembled polymeric NPs with induction of CD of the MB by chiral ARS NPs. The phototoxicity of CT-26 cells treated by MB-loaded ARS NPs dramatically decreased in a dose-dependent manner under NIR laser irradiation compared to free MB. CONCLUSION: This study demonstrated the ordered nanosized structures in the ARS NPs and conformational change from random coil structure of RS to alpha-helices one of ARS occurred and CD of the achiral MB was induced. The MB-loaded ARS NPs showed a higher generation of reactive oxygen species (ROS) in the CT-26 cells than free MB with the NIR laser irradiation and resulting in phototoxicity under irradiation.