Optimizing protein crosslinking control: Synergistic quenching effects of glycine, histidine, and lysine on glutaraldehyde reactions.

Glutaraldehyde (GA) is a protein crosslinker widely used in biochemical and pharmaceutical research because it can rapidly stabilize and immobilize substrates via amine group interactions. However, controlling GA crosslinking is challenging owing to its swift reactivity and the influence of various solution conditions, such as pH and concentrations of the substrate and crosslinker. Although extensive research has focused on GA cross-linking mechanisms, studies on quenching, which is critical for preventing non-specific aggregation during prolonged storage, remain sparse. This study examines the quenching efficiency of a combined amino acid mixture of glycine, histidine, and lysine, which are commonly used as individual quenchers. Our findings, confirmed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis, demonstrate that this amino acid blend offers superior quenching compared to single amino acids, enhancing quenching activity across a wide pH spectrum. These results provide a novel approach for mitigating the high reactivity of GA with implications for improving sample preservation and stabilization in a range of biochemical applications, including microscopy and cell fixation.

A study on the 10-year trend of surgeries performed for lumbar disc herniation and comparative analysis of prescribed opioid analgesics and hospitalization duration: 2010-2019 HIRA NPS Data.

BACKGROUND: This study, utilizing the claims data from the Health Insurance Review and Assessment Service of Korea, aimed to examine the 10-year (2010-2019) trends in various types of lumbar spine surgeries performed on patients diagnosed with lumbar herniated intervertebral disc (HIVD), and the current status of opioid prescriptions, as well as the duration of postoperative hospital stays based on the type of surgery performed. METHOD: This retrospective cross-sectional study examined patients with one or more national health insurance claims carrying a primary or secondary diagnosis of HIVD (ICD-10 codes: M511, M518, M519) over a 10-year period (2010-2019). From the patients undergoing lumbar spine surgery, we selected those who did not require reoperation within 30 days following the initial lumbar surgery. Our final study sample comprised patients who underwent only one type of surgery. RESULTS: Among the patients diagnosed with HIVD and subsequently undergoing lumbar surgery between 2010 and 2019, a slight downward trend was observed in those undergoing open discectomy (OD); however, OD persistently accounted for the highest proportion over the 10 years. Percutaneous endoscopic lumbar discectomy (PELD) demonstrated a consistent upward trend from 2016 to 2018. When inspecting trends, we noted a consistent escalation over the decade in the postoperative opioid prescription rates of strong opioids (50.7% in 2010 to 77.8% in 2019) and tramadol (50.9% in 2010 to 76.8% in 2019). Analyzing these trends by surgery type, spinal fusion exhibited a slightly higher rate of opioid prescriptions than other lumbar surgeries. Regarding the length of postoperative hospital stays, patients undergoing PELD recorded the shortest stay (7.04 ± 6.78 days), while spinal fusion necessitated the longest (20.14 ± 12.18 days). CONCLUSION: This study analyzed the trends in types of lumbar spine surgeries, opioid analgesic prescriptions, and length of hospital stays over 10 years (2010-2019) among patients with HIVD in Korea. Our data and findings provide valuable evidence that may prove beneficial for clinicians and researchers involved in HIVD-related practices.

Characterizing different patterns of digital competence and their associations with loneliness and social isolation among older adults: findings from South Korea.

OBJECTIVES: With the advent of worldwide internet networks in the digital age, digital competence can play an important role in decreasing loneliness and social isolation in older adults. This study characterized different patterns of digital competence among older adults and examined their associations with loneliness and social isolation. METHOD: The sample included 315 older Korean adults (M = 68.79, range = 65-84) who completed an online survey. RESULTS: Latent profile analysis identified four different profiles of digital competence, including 1) low activity (28%) who did not choose digital participation despite advanced technical skills, 2) unskilled (13%) who had limited technical skills, 3) passive participation (25%) who was motivated for digital interactions even with insufficient technical skills, and 4) active participation (34%) who were involved in digital activities with the necessary skills. Additionally, the unskilled profile had relatively higher levels of loneliness than did the active participation profile. The passive participation and low activity profiles showed the highest level of social isolation, followed by the unskilled, and active participation profiles. CONCLUSION: The present findings suggest that understanding different profiles of digital competence and facilitating active digital participation related to specific profiles can be an effective strategy to reduce older adults' social isolation and loneliness.

Osteoporosis Associated with Breast Cancer Treatments Based on Types of Hormonal Therapy: A Cross-Sectional Study Using Korean National Sample Data.

Background and Objectives: This study aimed to investigate osteoporosis-related treatments and the overall anticancer drug treatment tendencies, with a focus on selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), in Korean patients with breast cancer from 2010 to 2019. Materials and Methods: Data were obtained from the Health Insurance Review and Assessment Service. Patients with breast cancer (International Classification of Diseases, 10th Revision code: C50) as a principal diagnosis at least once from 2010 to 2019 were included. Those with osteoporosis (M80, M81, or M82) as a principal or sub-diagnosis or those who received osteoporosis treatment at least once were categorized as the osteoporosis-related treatment group, and others as the non-osteoporosis-related treatment group. The trends of drug prescriptions and treatment costs in patient groups were evaluated using descriptive statistics. Results: Among all included patients, those aged 45-54 years (40.20%) without osteoporosis treatment and those aged 55-64 years (34.11%) with osteoporosis treatment were the most common. SERM was the most commonly prescribed anticancer drug (29.20%) in the entire patient group, followed by AIs (20.83%). Patients without osteoporosis treatment had the highest prescription rate of SERM (31.48%), and those with osteoporosis treatment had a higher prescription rate of AIs (34.28%). Additionally, SERM and AIs were prescribed most frequently before and after the age of 55 years, respectively, regardless of the presence of treatment. Conclusions: This study found that osteoporosis-related treatment and patient age were associated with anticancer drug prescriptions. The present findings would help clinicians and researchers in the clinical diagnosis and treatment of breast cancer.

GSK-3ß regulates the synaptic expression of NMDA receptors via phosphorylation of phosphatidylinositol 4 kinase type IIα.

Deregulation of GSK-3ß is strongly implicated in a variety of serious brain conditions, such as Alzheimer disease, bipolar disorder and schizophrenia. To understand how GSK-3ß becomes dysregulated in these conditions, it is important to understand its physiological functions in the central nervous system. In this context, GSK-3ß plays a role in the induction of NMDA receptor-dependent long-term depression (LTD) and several substrates for GSK-3ß have been identified in this form of synaptic plasticity, including KLC-2, PSD-95 and tau. Stabilization of NMDA receptors at synapses has also been shown to involve GSK-3ß, but the substrates involved are currently unknown. Recent work has identified phosphatidylinositol 4 kinase type IIα (PI4KIIα) as a neuronal GSK-3ß substrate that can potentially regulate the surface expression of AMPA receptors. In the present study, we investigated the synaptic role of PI4KIIα in organotypic rat hippocampal slices. We found that knockdown of PI4KIIα has no effect on synaptic AMPA receptor-mediated synaptic transmission but substantially reduces NMDA receptor-mediated synaptic transmission. Furthermore, the ability of the selective GSK-3 inhibitor, CT99021, to reduce the amplitude of NMDA receptor-mediated currents was occluded in shRNA-PI4KIIα transfected neurons. The effects of knocking down PI4KIIα were fully rescued by a shRNA-resistant wild-type construct, but not by a mutant construct that cannot be phosphorylated by GSK-3ß. These data suggest that GSK-3ß phosphorylates PI4KIIα to stabilize NMDA receptors at the synapse.

Docetaxel-loaded PLGA nanoparticles to increase pharmacological sensitivity in MDA-MB-231 and MCF-7 breast cancer cells.

This study aimed to develop docetaxel (DTX) loaded poly(lactic-coglycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and -26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The in vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC50 values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

Neur1 and Neur2 are required for hippocampus-dependent spatial memory and synaptic plasticity.

Neur1 and Neur2, mouse homologs of the Drosophila neur gene, consist of two neuralized homology repeat domains and a RING domain. Both Neur1 and Neur2 are expressed in the whole adult brain and encode E3 ubiquitin ligases, which play a crucial role in the Notch signaling pathways. A previous study reported that overexpression of Neur1 enhances hippocampus-dependent memory, whereas the role of Neur2 remains largely unknown. Here, we aimed to elucidate the respective roles of Neur1 and Neur2 in hippocampus-dependent memory using three lines of genetically modified mice: Neur1 knock-out, Neur2 knock-out, and Neur1 and Neur2 double knock-out (D-KO). Our results showed that spatial memory was impaired when both Neur1 and Neur2 were deleted, but not in the individual knock-out of either Neur1 or Neur2. In addition, basal synaptic properties estimated by input-output relationships and paired-pulse facilitation did not change, but a form of long-term potentiation that requires protein synthesis was specifically impaired in the D-KO mice. These results collectively suggest that Neur1 and Neur2 are crucially involved in hippocampus-dependent spatial memory and synaptic plasticity.

Outcoupling efficiency enhancement of a bottom-emitting OLED with a visible parylene film.

We have investigated an effective and a single-step chemical vapor deposition (CVD) method to achieve conformal visible poly-dichloro-para-xylylene (parylene C) film for light extraction enhancement in bottom-emitting organic light-emitting diodes (OLEDs) at room temperature. We report that sublimed parylene dimers pyrolyzed between 400 °C and 500 °C resulted in visible parylene films with tunable transmittance and haze, exhibiting light scattering properties due to the formation of uniformly distributed dimer crystals. We achieved a novel conformal visible parylene film with total transmittance and high haze of 79.5% and 93.6%, respectively. It is observed that the outcoupling efficiency of the OLEDs employing the visible parylene film is enhanced up to 45.8%. Additionally, the OLED with the visible parylene light extraction film shows limited angle-dependency of emission spectrum over viewing angles. The single-step room temperature fabrication process of this conformal outcoupling film paves the way to achieving commercial high-performance OLEDs.

Cytotoxicity induced by the mixture components of nickel and poly aromatic hydrocarbons.

Although particulate matter (PM) is composed of various chemicals, investigations regarding the toxicity that results from mixing the substances in PM are insufficient. In this study, the effects of low levels of three PAHs (benz[a]anthracene, benzo[a]pyrene, and dibenz[a,h]anthracene) on Ni toxicity were investigated to assess the combined effect of Ni-PAHs on the environment. We compared the difference in cell mortality and total glutathione (tGSH) reduction between single Ni and Ni-PAHs co-exposure using A549 (human alveolar carcinoma). In addition, we measured the change in Ni solubility in chloroform that was triggered by PAHs to confirm the existence of cation-π interactions between Ni and PAHs. In the single Ni exposure, the dose-response curve of cell mortality and tGSH reduction were very similar, indicating that cell death was mediated by the oxidative stress. However, 10 µM PAHs induced a depleted tGSH reduction compared to single Ni without a change in cell mortality. The solubility of Ni in chloroform was greatly enhanced by the addition of benz[a]anthracene, which demonstrates the cation-π interactions between Ni and PAHs. Ni-PAH complexes can change the toxicity mechanisms of Ni from oxidative stress to others due to the reduction of Ni2+ bioavailability and the accumulation of Ni-PAH complexes on cell membranes. The abundant PAHs contained in PM have strong potential to interact with metals, which can affect the toxicity of the metal. Therefore, the mixture toxicity and interactions between diverse metals and PAHs in PM should be investigated in the future.

Correction: Eu2+-Eu3+ valence transition in double, Eu-, and Na-doped PbSe from transport, magnetic, and electronic structure studies.

Correction for 'Eu2+-Eu3+ valence transition in double, Eu-, and Na-doped PbSe from transport, magnetic, and electronic structure studies' by Bartlomiej Wiendlocha et al., Phys. Chem. Chem. Phys., 2017, 19, 9606-9616.

Eu2+-Eu3+ valence transition in double, Eu-, and Na-doped PbSe from transport, magnetic, and electronic structure studies.

The Eu atoms in Pb1-xEuxSe have long been assumed to be divalent. We show that p-type doping of this magnetic semiconductor alloy with Na can modify the effective Eu valence: a mixed, Eu2+-Eu3+ state appears in Pb1-x-yEuxNaySe at particular values of y. Magnetization, carrier concentration, resistivity, and thermopower of Pb1-x-yEuxNaySe are reported for a number of samples with different x and y. A pronounced increase in thermopower at a given carrier concentration was identified and attributed to the presence of enhanced ionized impurity scattering. A strong decrease in the hole concentration is observed in Pb1-yNaySe when Eu is added to the system, which we attribute to a Eu2+-Eu3+ self-ionization process. This is evidenced by magnetization measurements, which reveal a significant reduction of the magnetic moment of Pb1-xEuxSe upon alloying with Na. Further, a deviation of magnetization from a purely paramagnetic state, described by a Brillouin function, identifies antiferromagnetic interactions between the nearest-neighbor Eu atoms: a value of Jex/kB = -0.35 K was found for the exchange coupling parameter. The conclusion of a Eu2+-Eu3+ self-ionization process being in effect is supported further by the electronic structure calculations, which show that an instability of the 4f7 configuration of the Eu2+ ion appears with Na doping. Schematically, it was found that the Eu 4f levels form states near enough to the Fermi energy that hole doping can lower the Fermi energy and trigger a reconfiguration of a 4f electronic shell.

Trends in healthcare utilization by patients with gout: A cross-sectional study using Health Insurance Review and Assessment Service data.

This study aimed to analyze the distribution of gout patients and the utilization of healthcare services in South Korea to provide valuable recommendations to clinicians and policymakers. A cross-sectional study was conducted. Claims data from the Health Insurance Review and Assessment Service spanning 2010 to 2019 were utilized, and a sample of 69,680 patients was included in the study. The incidence of gout was observed to be high in male patients over the age of 40, with most patients receiving outpatient care for gout management. Nonsteroidal anti-inflammatory drugs and urate-lowering agents were the most frequently prescribed medications, with prescriptions for colchicine and febuxostat increasing among urate-lowering agents. Musculoskeletal disorders were found to be the most common comorbidities among gout patients. Although the total costs of gout management increased, there was no significant increase in cost per patient. This study provides insights into the current state of healthcare utilization for gout patients in South Korea and trends in the disease burden and use of medications. The findings have crucial implications for clinicians and policymakers involved in decision-making regarding the management and treatment of gout.

Changes in lymph node surgery in breast cancer and preoperative drug prescription analysis for postoperative pain management: A retrospective, cross-sectional study.

This study aimed to investigate the changes in lymph node surgery types and prescription patterns of postoperative medications for pain management in patients with breast cancer using national health insurance claim data from South Korea. The study population comprised patients with at least one record of a principal diagnosis of breast cancer (ICD-10 code: C50) from the national health insurance claim database between 2010 and 2019. Patients who underwent mastectomy or lumpectomy only once were selected for the analysis. Patients who underwent axillary lymph node dissection (ALND) with mastectomy or lumpectomy on the day of surgery were included in the ALND group, whereas those who underwent sentinel lymph node biopsy (SLNB) were included in the SLNB group. Prescription records of opioids before, after and on the date of breast cancer surgery were collected and categorized according to the opioid type. Multivariate logistic regression modeling was used to compare postoperative opioid prescriptions. The proportion of those undergoing ALND among 3,080 patients decreased consistently after 2014, while the proportion undergoing SLNB increased. Although the rate of pain medication prescription on the day of surgery was similar between the two groups, the rate of prescription of postoperative pain medication and anticancer agents was lower in the SLNB group than in the ALND group. Logistic regression modeling showed that the SLNB group had lower odds of receiving opioids than did the ALND group (Odds ratio (OR) = 0.727, Confidence Interval (CI) = 0.546-0.970). A consistent trend was observed when the model was adjusted for neoadjuvant chemotherapy and the use of preoperative pain medications (OR = 0.718, CI = 0.538-0.959). To manage postoperative pain and prevent chronic pain with minimal side effects, sufficient discussion among clinicians, patients, and other healthcare professionals is imperative, along with adequate treatment planning.

Designing a Placebo Microneedle Stamp: Modeling and Validation in a Clinical Control Trial.

Recently, several clinical studies have been conducted using microneedles (MNs), and various devices have been developed. This study aimed to propose and confirm the feasibility of a placebo control for activating MN clinical research. A 0.5 mm MN stamp with 42 needles was used as a treatment intervention, and a placebo stamp with four acupressure-type needles that did not penetrate was proposed and designed as a control for comparison. First, to check whether the placebo stamp did not invade the skin and to set an appropriate level of pressure to be provided during skin stimulation, two participants were stimulated with five different forces on the forearm, and then the skin was dyed. Secondly, to evaluate the validity of the placebo control group, a blinded study between the MN and placebo stamps was performed on 15 participants. We confirmed that the placebo stamp did not penetrate the skin at any intensity or location. Both types of stamps reported relatively low pain levels, but the MN stamp induced higher pain compared to the placebo stamp. Based on the speculation regarding the type of intervention received, the MN stamp was successfully blinded (random guess), whereas the placebo stamp was unblinded. However, according to a subgroup analysis, it was confirmed that the group with low skin sensitivity was completely blind. Blinding the placebo MN stamp had limited success in participants with low skin sensitivity. Future research on suitable placebo controls, considering the variations in MN stamp length and needle count, is warranted.

Role of sodium doping in lead chalcogenide thermoelectrics.

The solubility of sodium and its effects on phonon scattering in lead chalcogenide PbQ (Q = Te, Se, S) family of thermoelectric materials was investigated by means of transmission electron microscopy and density functional calculations. Among these three systems, Na has the highest solubility limit (~2 mol %) in PbS and the lowest ~0.5 mol %) in PbTe. First-principles electronic structure calculations support the observations, indicating that Na defects have the lowest formation energy in PbS and the highest in PbTe. It was also found that in addition to providing charge carriers (holes) for PbQ, Na introduces point defects (solid solution formation) and nanoscale precipitates; both reduce the lattice thermal conductivity by scattering heat-carrying phonons. These results explain the recent reports of high thermoelectric performance in p-type PbQ materials and may lead to further advances in this class of materials.

High-performance tellurium-free thermoelectrics: all-scale hierarchical structuring of p-type PbSe-MSe systems (M = Ca, Sr, Ba).

We present a systematic study of the characterization and thermoelectric properties of nanostructured Na-doped PbSe embedded with 1-4% MSe (M = Ca, Sr, Ba) phases as endotaxial inclusions. The samples were powder-processed by the spark plasma sintering technique, which introduces mesoscale-structured grains. The hierarchical architectures on the atomic scale (Na and M solid solution), nanoscale (MSe nanoprecipitates), and mesoscale (grains) were confirmed by transmission electron microscopy. These structures produce a great reduction in the lattice thermal conductivity relative to pristine PbSe without appreciably affecting the power factor. The lattice thermal conductivity can be reduced by up to ∼29% when the second phase is added. The highest ZT value achieved was ∼1.3 at 923 K for both 2% SrSe-and 3% BaSe-containing samples, while the sample containing 4% CaSe showed a ZT value of ∼1.2 at 923 K. The optimal samples have hole carrier concentration of 1-2 × 10(20) cm(-3). We attribute the high ZT values to the combination of broad-based phonon scattering on multiple length scales and favorable charge transport through coherent interfaces between the PbSe matrix and MSe.

High thermoelectric performance via hierarchical compositionally alloyed nanostructures.

Previous efforts to enhance thermoelectric performance have primarily focused on reduction in lattice thermal conductivity caused by broad-based phonon scattering across multiple length scales. Herein, we demonstrate a design strategy which provides for simultaneous improvement of electrical and thermal properties of p-type PbSe and leads to ZT ~ 1.6 at 923 K, the highest ever reported for a tellurium-free chalcogenide. Our strategy goes beyond the recent ideas of reducing thermal conductivity by adding two key new theory-guided concepts in engineering, both electronic structure and band alignment across nanostructure-matrix interface. Utilizing density functional theory for calculations of valence band energy levels of nanoscale precipitates of CdS, CdSe, ZnS, and ZnSe, we infer favorable valence band alignments between PbSe and compositionally alloyed nanostructures of CdS1-xSex/ZnS1-xSex. Then by alloying Cd on the cation sublattice of PbSe, we tailor the electronic structure of its two valence bands (light hole L and heavy hole Σ) to move closer in energy, thereby enabling the enhancement of the Seebeck coefficients and the power factor.

Do expressive writing interventions have positive effects on Koreans?: a meta-analysis.

Introduction: Expressive Writing (EW) is an intervention that focuses on individuals' writing down their thoughts and feelings about trauma or stressful events. Meta-analyses on EW studies have confirmed that EW has a positive effect. However, the heterogeneity of studies is high, so many studies have investigated boundary conditions and moderators. One of these moderators is the cultural difference in emotional suppression. Since EW focuses on the expression of suppressed thoughts and emotions, its effect might be slightly different for people in Asian cultures who show a high tendency to suppress their emotions. This study attempted to confirm the effect size of the EW interventions in Korea and examine whether these studies have different effect size from those based on Western cultures. Method: A total of 29 studies published in Korea until 2021 were analyzed. The effect size was calculated using the "dmetar," "meta," and "metafor" packages of the statistical program R 4.0.4. Results: The results were as follows. First, the effect size of EW intervention was 0.16, and we found that studies in the Korean context showed no significant difference from studies based on western meta-analysis. Second, the moderating variables that influenced the EW intervention were the writing type, the number of sessions, the time per session, and the measurement time. Discussion: The results of this study suggest that EW interventions benefit Koreans. And it is at least harmless and has a positive effect considering the efficiency and conciseness of interventions. Furthermore, the finding shows that EW interventions can be helpful even in the general population without apparent psychological problems. By considering moderators, we could structure more effective form of EW interventions for Koreans.

Real-world data analysis on effectiveness of integrative therapies: A practical guide to study design and data analysis using healthcare databases.

Real world data (RWD) is increasingly used to investigate health outcomes and treatment efficacy in the field of integrative medicine. Due to the fact that the majority of RWDs are not intended for research, their secondary use in research necessitates complex study designs to account for bias and confounding. To conduct a robust analysis of RWD in integrative medicine, a comprehensive study design process that reflects the characteristics of integrative therapies is necessary. In this paper, we present a guide for designing comparative effectiveness RWE research in integrative medicine. We discuss key factors to consider when selecting RWDs for research on integrative medicine. We provide practical steps for developing a research question, formulating the PICOT objectives (population, intervention, comparator, outcome, and time horizon), and selecting and defining covariates with a summary table. Specific study designs are depicted with corresponding diagrams. Finally, data analysis procedures are introduced. We hope this article clarifies the importance of RWE research design and related processes in order to improve the rigor of RWD studies in the field of integrative medicine research.