Mental health effects associated with COVID-19 financial assistance in South Korea: a comparison of employment status.

BACKGROUND: COVID-19 has created tensions across different sectors of the society, but the impact has been unequal. Vulnerable people have been most affected, especially those with insecure employment and who have experienced economic hardships due to unemployment and lost wages. The combination of social change and economic hardships due to the pandemic increases the risk of poor mental health. Some countries have utilized financial assistance to alleviate economic hardships caused by COVID-19, and in South Korea, the central and local governments have implemented COVID-19 financial assistance. This study analysed the impact of financial assistance on mental health associated with working status during the COVID-19 pandemic in South Korea. METHODS: The participants of this study were randomly selected from residents of Gyeonggi-do after being proportionally allocated by resident registration population status. A total of 1,000 adult males and females aged 19 years or older in Gyeonggi-do who received financial assistance from the central and local governments were selected. A retrospective pre-post-study design was applied, and mental health surveys including the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item scale (GAD-7) were applied. RESULTS: The results show that depression scores averaged 5.5 and anxiety scores averaged 4.4 before COVID-19 Financial Assistance. It is similar to the national average of 5.1 and 4.5 respectively at that time. After the assistance, depression scores dropped to 4.5, and anxiety scores dropped to 3.2. Before the assistance, depression and anxiety were higher among temporary day labourers with less job security, and they showed the most significant improvement in mental health. For full-time workers, there was no significant change in anxiety or depression after receiving the assistance. CONCLUSIONS: Financial assistance can provide material resources and also positively affect mental health. In particular, it had a greater impact on the relatively vulnerable groups, such as those in unstable employment.

Arabidopsis OSMOTIN 34 Functions in the ABA Signaling Pathway and Is Regulated by Proteolysis.

Plants have evolutionarily established resistance responses to a variety of abiotic stress conditions, in which ABA mediates the integrated regulation of these stress responses. Numerous proteins function at the transcription level or at the protein level when contributing to controls of the ABA signaling process. Although osmotin is identified as a salt-inducible protein, its function in the abiotic stress response is yet to be elucidated. To examine the role of Arabidopsis OSMOTIN 34 (OSM34) in the ABA signaling pathway, a deletion mutant osm34 generated by a CRISPR/Cas9 system and the double mutant osm34 osml (osmotin 34-like) were analyzed for various ABA responses. Both osm34 and osm34 osml showed reduced levels of ABA responses in seeds and leaves. Moreover, proline level and expression of the proline biosynthesis gene P5CS1 was significantly reduced in osm34 osml. Interestingly, OSM34 binds to SKP2A, an F-Box protein whose transcription is induced by ABA. The protein stability of OSM34 was determined to be under the control of the 26S proteasome. In conclusion, our data suggest that OSM34 functions as a positive regulator in the generation of ABA responses and is under post-translational control.

Portable ultrasound-guided high-intensity focused ultrasound with functions for safe and rapid ablation: prospective clinical trial for uterine fibroids-short-term and long-term results.

OBJECTIVES: To investigate the efficacy and safety of a new portable ultrasound-guided high-intensity focused ultrasound system (USgHIFU) with advanced targeting and beam steering technology for the treatment of uterine fibroids. METHODS: Fifty-nine uterine fibroids from 36 participants (mean age, 44.9 ± 4.1 years) were included from November 2013 to November 2015. All participants were treated with HIFU, with 3D electronic steering. MR imaging studies were performed before HIFU, immediately after HIFU, and 1 month and 3 (or 5) months after the HIFU treatment. The non-perfused volume ratio (NPVR), fibroid volume shrinkage (FVS), symptom improvement, quantified life quality assessment, and safety were analyzed. A long-term follow-up was conducted in July to December 2017 (mean, 32.2 months). RESULTS: The volume of the treated uterine fibroids ranged from 7.5 to 274.4 cm3 (mean, 69.8 cm3; SD, 64.3 cm3). The mean NPVR on the immediate post-HIFU MR imaging was 74.8 ± 25.2%. The mean FVS was 17.3% at 1 month, 33.3% at 3 months, and 45.1% at 5 months after HIFU treatment. The mean treatment time was 44.6 ± 28.2 min per fibroid and 72.9 ± 31.4 min per participant. Uterine fibroid-related symptoms and quality of life showed statistically significant improvement after the HIFU treatment. No significant symptoms related to safety or complications occurred. In the long-term follow-up, 78.8% of those surveyed were satisfied with their HIFU treatment. CONCLUSION: This clinical trial showed that a portable USgHIFU with advanced functions may safely and effectively treat uterine fibroids. KEY POINTS: • A portable compact ultrasound-guided high-intensity focused ultrasound (HIFU) can effectively and safely treat uterine fibroids. • Advanced functions, such as portability, targeted forecasting, electronic beam steering, and interleaved scanning, might be helpful in enhancing the clinical applicability of ultrasound-guided high-intensity focused ultrasound. • In the long-term follow-up of more than 2 years, approximately 80% of those surveyed were satisfied with their HIFU treatment.

In vivo study of enhanced chemotherapy combined with ultrasound image-guided focused ultrasound (USgFUS) treatment for pancreatic cancer in a xenograft mouse model.

OBJECTIVES: This study was designed to investigate whether focused ultrasound (FUS) treatment with a higher mechanical index (MI) can enhance the effects of combined chemotherapy more than with a lower MI, and to evaluate the feasibility of the chemotherapy combined with FUS at a higher MI as an alternative treatment protocol. METHODS: Mice in the first study were divided into six groups: control, chemotherapy only (GEM), two groups treated with FUS only at two different MIs, and two groups treated with chemotherapy and FUS (GEM + FUS). Mice were treated with a single-session treatment; one session consisted of three weekly treatments and 1 week of follow-up monitoring. In the second study, mice were assigned to two groups (GEM, GEM + FUS) and treated with four treatment sessions. RESULTS: In the single-session treatment, tumor growth was most effectively suppressed in GEM + FUS group with a higher MI. Tumor growth rate was significantly lower in GEM + FUS group than in GEM group for multiple-session treatment. Specifically, three of ten mice in GEM + FUS group showed complete remission. CONCLUSIONS: This study demonstrated that FUS at a higher MI can enhance chemotherapy outcomes more than at a lower MI and demonstrated the potential of FUS in combination with chemotherapy as a new cancer treatment protocol. KEY POINTS: • Combined treatment of chemotherapy and focused ultrasound can effectively suppress tumor growth. • For the focused ultrasound treatment conditions used in this study, focused ultrasound with relatively higher mechanical index shows more enhanced therapeutic outcomes than with the lower mechanical index. • Combination therapy shows the possibility as a new cancer treatment protocol.

Production of ABA responses requires both the nuclear and cytoplasmic functional involvement of PYR1.

Abscisic acid (ABA) enhances stress tolerant responses in plants against unfavorable environmental conditions. In Arabidopsis, ABA promotes interactions between PYR/PYL/RCARs and PP2C, thereby allowing SnRK2s to phosphorylate downstream components required for the regulation of gene expression or for gating ion channels. Because PYR1 is known to localize to nucleus and cytoplasm it is a question whether nuclear or cytoplasmic PYR1 confer different functions to the ABA signaling pathway, as has been previously shown for regulatory proteins. In order to answer this question, transgenic lines expressing nuclear PYR1 were generated in an ABA insensitive mutant background. Enforced nuclear expression of PYR1 was examined by confocal microscopy and western blot analysis. Physiological analyses of the transgenic lines demonstrated that nuclear PYR1 is sufficient to generate ABA responses, such as, the inhibition of seed germination, root growth inhibition, the induction of gene expression, and stomatal closing movement. However, for the full recovery of ABA responses in the mutant background cytoplasmic PYR1 was required. The study suggests both nuclear and cytoplasmic PYR1 participate in the control of ABA signal transduction.

Xylitol induces cell death in lung cancer A549 cells by autophagy.

Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.

Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection.

Porphyromonas gingivalis, a major periodontopathogen, is involved in the pathogenesis of periodontitis. Interleukin-1ß (IL-1ß), a proinflammatory cytokine, regulates innate immune responses and is critical for the host defense against bacterial infection. However, excessive IL-1ß is linked to periodontal destruction. IL-1ß synthesis, maturation, and secretion are tightly regulated by Toll-like receptor (TLR) signaling and inflammasome activation. We found much higher levels of inflammasome components in the gingival tissues from patients with chronic periodontitis than in those from healthy controls. To investigate the molecular mechanisms by which P. gingivalis infection causes IL-1ß secretion, we examined the characteristics of P. gingivalis-induced signaling in differentiated THP-1 cells. We found that P. gingivalis induces IL-1ß secretion and inflammatory cell death via caspase-1 activation. We also found that P. gingivalis-induced IL-1ß secretion and pyroptic cell death required both NLRP3 and AIM2 inflammasome activation. The activation of the NLRP3 inflammasome was mediated by ATP release, the P2X7 receptor, and lysosomal damage. In addition, we found that the priming signal via TLR2 and TLR4 activation precedes P. gingivalis-induced IL-1ß release. Our study provides novel insight into the innate immune response against P. gingivalis infection which could potentially be used for the prevention and therapy of periodontitis.

Tumor suppression effect of ultrasound-sensitive nanoparticles with focused ultrasound in a pancreas cancer xenograft model.

BACKGROUND: We investigated the tumor suppression effect of an ultrasound-sensitive doxorubicin-loaded liposome-based nanoparticle, IMP301, to enhance the synergistic effect with focused ultrasound (FUS) in an animal model of pancreatic cancer. METHODS: Thirty nude mice with xenografts of PANC-1 human pancreatic cancer cells were randomly and prospectively allocated to 6 different groups (5 per group) each for Study-1 (dose-response test) and Study-2 (synergistic effect test). Study-1 consisted of control, gemcitabine, Doxil with FUS, and three different doses of IMP301 (2, 4, 6 mg/kg) with FUS groups. Study-2 consisted of control, FUS only, gemcitabine, Doxil with FUS, and IMP301 (4 mg/kg) with or without FUS groups. Differences in tumor volume and growth rate were evaluated by one-way ANOVA and Student-Newman-Keuls test. RESULTS: In Study-1, 4 mg/kg or greater IMP301 with FUS groups showed lower tumor growth rates of 14 ± 4 mm3/day (mean ± standard deviation) or less, compared to the control, gemcitabine, and Doxil with FUS groups with rates exceeding 28 ± 5 (p < 0.050). The addition of FUS in Study-2 decreased the tumor growth rate in the IMP301-treated groups from 36 ± 17 to 9 ± 6, which was lower than the control, FUS only, gemcitabine, and Doxil with FUS groups (p < 0.050). CONCLUSIONS: IMP301 combined with FUS exhibited higher tumor growth suppression compared to the use of a conventional drug alone or the combination with FUS. The present study showed the potential of IMP301 to enhance the synergistic effect with FUS for the treatment of pancreatic cancer. RELEVANCE STATEMENT: This article aims to evaluate the synergistic effect of FUS and ultrasound-responsive liposomal drug in tumor growth suppression by using xenograft mouse model of pancreatic ductal adenocarcinoma. FUS-induced ultrasound-sensitive drug release may be a potential noninvasive repeatable treatment option for patients with locally advanced or unresectable pancreatic cancer. KEY POINTS: • Modification of conventional drugs combined with FUS would maximize tumor suppression. • IMP301 with FUS had higher tumor suppression effect compared to conventional chemotherapy. • This image-guided drug delivery would enhance therapeutic effects of systemic chemotherapy.

Characteristics of novel root-end filling material using epoxy resin and Portland cement.

OBJECTIVES: The aim of this study was to evaluate the physical properties and cytotoxicity of a novel root-end filling material (EPC) which is made from epoxy resin and Portland cement as a mineral trioxide aggregate (MTA) substitute. MATERIALS AND METHODS: EPC, developed as a root-end filling material, was compared with MTA and a mixture of AH Plus sealer and MTA (AMTA) with regard to the setting time, radio-opacity, and microleakage. Setting times were evaluated using Vicat apparatus. Digital radiographs were taken to evaluate the aluminium equivalent radio-opacity using an aluminium step wedge. Extracted single-rooted teeth were used for leakage test using methylene blue dye. After canal shaping and obturation, the apical 3-mm root was resected, and a root-end cavity with a depth of 3 mm was prepared. The root-end cavities were filled with MTA, AMTA, and EPC for 15 specimens in each of three groups. After setting in humid conditions for 24 h, the specimens were tested for apical leakage. For evaluation of the biocompatibility of EPC, cell (human gingival fibroblast) viability was compared for MTA and Portland cement by MTT assay, and cell morphological changes were compared for MTA and AH Plus by fluorescence microscopy using DAPI and F-actin staining. The setting time, radio-opacity, and microleakage were compared using one-way ANOVA and Scheffe's post hoc comparison, and the cytotoxicity was compared using the nonparametric Kruskal-Wallis rank sum test. Statistical significance was set at 95%. RESULTS: EPC had a shorter setting time and less microleakage compared with MTA (p < 0.05). EPC showed 5-mm aluminium thickness radio-opacity and similar biocompatibility to MTA. CONCLUSIONS: Under the conditions of this study, EPC, a novel composite made from a mixture of epoxy resin and Portland cement, was found to be a useful material for root-end filling, with favourable radio-opacity, short setting time, low microleakage, and clinically acceptable low cytotoxicity. CLINICAL RELEVANCE: The novel root-end filling material would be a potentially useful material for a surgical endodontic procedure with favourable properties.

Development of exosome membrane materials-fused microbubbles for enhanced stability and efficient drug delivery of ultrasound contrast agent.

Lipid-coated microbubbles are widely used as an ultrasound contrast agent, as well as drug delivery carriers. However, the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system, and the difficulty of surface modification of microbubbles for active targeting. The exosome, a type of extracellular vesicle, has a preferentially targeting ability for its original cell. In this study, exosome-fused microbubbles (Exo-MBs) were developed by embedding the exosome membrane proteins into microbubbles. As a result, the stability of Exo-MBs is improved over the conventional microbubbles. On the same principle that under the exposure of ultrasound, microbubbles are cavitated and self-assembled into nano-sized particles, and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles (Exo-NPs). The Exo-NPs showed favorable targeting properties to their original cells. A photosensitizer, chlorin e6, was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier. Much higher therapeutic efficacy of photodynamic therapy was confirmed, followed by cancer immunotherapy from immunogenic cell death. We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.

First report on the persist time of the free radical produced by shock wave pulses employed in clinical ESWL.

The shock wave used in extracorporeal shock wave lithotripsy (ESWL) induces strong cavitation and generates a large amount of free radicals (FR). In order to evaluate the harmfulness of FR in the ESWL, information on the incidence and persist time of FR caused by shock waves is required. FR markers can estimate the amount of FR generated, but not how long the FRs will survive. The OH* FR generated by the ESWL shock wave reacts with luminol and emits blue light, which is called sonochemical luminescence (SCL) phenomenon. In this study, FR generation and persist time were measured by recording SCL phenomenon with a sensitive photomultiplier tube (PMT) that responds in nanoseconds. As a result of measurement with the PMT, when the electromagnetic shock wave used in clinical practice was irradiated to the luminol solution, the amount of light emitted per unit time reached its maximum value within a very short time (< ∼600us) and then exponentially decreased for a long time (∼several hundred ms). The measured FR persist time reaches a maximum of 1000 ms. As the output setting of the shock wave generator increases, the minimum or average FR persist time increases, but the maximum value does not show a high correlation with the output setting. The amount of generated FR shows a very high correlation with the shock wave setting, and when the setting is changed from low to high, it increases very sensitively, rapidly and non-linearly. In order to reduce the risk of FR in patient treatment using lithotripsy, the output setting of the shock wave should be minimized, and the interval between the shock wave pulses should be sufficiently larger than the FR persist time. Therefore, it is recommended to avoid increasing the output setting and setting the shock wave irradiation frequency below 1 Hz to shorten the treatment time in clinical practice. For the purpose of formulating these recommendations, additional studies on the generation and persist time of FR depending on the shock wave generation method and set conditions in living tissue or similar environment are required in the future.

Properties of Central and Peripheral Concepts of Emotion in Japanese and Korean: An Examination Using a Multi-Dimensional Model.

The concept of emotion can be organized within a hypothetical space comprising a limited number of dimensions representing essential properties of emotion. The present study examined cultural influences on such conceptual structure by comparing the performance of emotion word classification between Japanese and Korean individuals. Two types of emotional words were used; central concepts, highly typical examples of emotion, and less typical peripheral concepts. Participants classified 30 words into groups based on conceptual similarity. MDS analyses revealed a three-dimensional structure with valence, social engagement, and arousal dimensions for both cultures, with the valence dimension being the most salient one. The Japanese prioritized the social engagement over the arousal while the Koreans showed sensitivities to the arousal dimension. Although the conceptual structure was similar for the two countries, the weight of importance among the three dimensions seems to be different, reflecting each culture's values and communication styles.

Efficacy of Immune Checkpoint Inhibitors against Advanced or Metastatic Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis of the treatment efficacy of immune checkpoint inhibitors (ICIs) in advanced/metastatic neuroendocrine neoplasms (NENs). MEDLINE and EMBASE were searched to identify studies that provide data on treatment response and/or survival outcomes of advanced/metastatic NEN patients treated with ICIs. The overall response rate (ORR) was pooled using a random-effects model. Meta-regression was performed to explore factors influencing the ORR. Individual patient data (IPD) meta-analysis of survival was performed using stratified Cox regression. Ten studies (464 patients) were included. The overall pooled ORR was 15.5% (95% confidence interval (CI), 9.5-24.3%), and it varied according to the primary site (thoracic, 24.7%; gastro-entero-pancreatic, 9.5%), tumor differentiation (poorly differentiated, 22.7%; well-differentiated, 10.4%), and drug regimen (combination, 25.3%; monotherapy, 10.1%). All these variables significantly influenced the ORR. Tumor differentiation was associated with both overall survival and progression-free survival (hazard ratio of poorly differentiated tumors, 4.2 (95% CI, 2.0-8.7) and 2.6 (95% CI, 1.6-4.4), respectively). Thus, the treatment efficacy of ICIs for advanced/metastatic NENs varied according to primary site, tumor differentiation, and drug regimen. Poorly differentiated NENs showed a better ORR than well-differentiated NENs but had a negative impact on survival.

Impact of national Covid-19 vaccination Campaign, South Korea.

BACKGROUND: We evaluate the overall effectiveness of the nationwide vaccination campaign using ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines in preventing Covid-19 in South Korea. METHODS: The National Surveillance System with the National Immunization Registry were linked to form a large-linked database for assessment. Age-adjusted incidence of SARS-CoV-2 infection, severe disease, and death by vaccination status are calculated. Weekly vaccine effectiveness was calculated based on incidence rate ratio (IRR) between fully-vaccinated and unvaccinated persons, as: IRR = incidence rate of vaccinated / incidence rate of unvaccinated. We estimate the cumulative SARS-CoV-2 outcome overtime comparing the observed case with predicted cases without vaccination. RESULTS: Age-adjusted incidence in unvaccinated persons (5.69 per 100,000 person-day) was 2.7 times the rate in fully vaccinated (2.13 per 100,000 person-day) persons, resulting effectiveness against SARS-CoV-2 infection of 63%. Vaccine effectiveness against severe disease and death were 93% and 95%, respectively. Between March and October 2021, estimated Covid-19 related outcomes averted by vaccinations were: 46,508 infections, 3,424 severe diseases, and 718 deaths. CONCLUSIONS: We found significant protection for national Covid-19 vaccination campaign against Covid-19 severe disease, and death in target populations, but there was an unexpected decreased protection against SARS-CoV-2 infection, highlighting the importance of continued surveillance and assessment.

Clinical significance of high on-treatment platelet reactivity in patients with prolonged clopidogrel therapy.

BACKGROUND/AIMS: Prolonged dual antiplatelet therapy (DAPT) with aspirin and clopidogrel beyond 1 year has been shown to reduce ischemic events at the expense of increased bleeding. However, limited data are available on the clinical significance of platelet reactivity (PR) at 1 year. METHODS: We retrospectively identified 331 patients who underwent percutaneous coronary intervention (PCI) and assessed the on-clopidogrel PR using VerifyNow P2Y12 assay at 1 year in a single center. Two hundred eleven patients were on DAPT for > 1 year. The relationship between high on-treatment platelet reactivity (HPR) at 1 year and clinical outcomes beyond 1 year, as well as the longitudinal change in PR was analyzed. RESULTS: At 1 year, 135 (64%) patients showed HPR and 76 (36%) did not. There was a significant increase in ischemic endpoint events, including cardiovascular death, non-fatal myocardial infarction, and stroke/transient ischemic attack in patients with compared to without HPR at 1 year (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.06 to 6.77; p = 0.036). However, the incidence of any Bleeding Academic Research Consortium bleeding was significantly lower in the HPR group (HR, 0.11; 95% CI, 0.02 to 0.65; p = 0.015). In the longitudinal analysis, PR significantly decreased from post-load to 1 year after index PCI in the non-HPR group. Conversely, the HPR group showed high PR from baseline through 1 year. CONCLUSION: HPR at 1 year may be a useful surrogate for predicting ischemic and bleeding events in patients on prolonged DAPT. Patients with and without HPR at 1 year showed different patterns of longitudinal change in PR.

Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer's disease model.

Drainage of parenchymal waste through the lymphatic system maintains brain homeostasis. Age-related changes of glymphatic-lymphatic clearance lead to the accumulation beta-amyloid (Aß) in dementia models. In this study, focused ultrasound treatment in combination with microbubbles (FUS-MB) improved Aß drainage in early dementia model mice, 5XFAD. FUS-MB enhanced solute Aß clearance from brain, but not plaques, to cerebrospinal fluid (CSF) space and then deep cervical lymph node (dCLN). dCLN ligation exaggerated memory impairment and progress of plaque formation and also the beneficial effects of FUS-MB upon Aß removal through CSF-lymphatic routes. In this ligation model, FUS-MB improved memory despite accumulation of Aß in CSF. In conclusion, FUS-MB enhances glymphatic-lymphatic clearance of Aß mainly by increasing brain-to-CSF Aß drainage. We suggest that FUS-MB can delay dementia progress in early period and benefits of FUS-MB depend on the effect of Aß disposal through CSF-lymphatics.

Synergistic Effects of Pulsed Focused Ultrasound and a Doxorubicin-Loaded Microparticle-Microbubble Complex in a Pancreatic Cancer Xenograft Mouse Model.

The synergistic effects of a doxorubicin (Dox)-loaded microparticle-microbubble complex (DMMC) and focused ultrasound (FUS) with a short duty cycle (5%) were evaluated in a pancreatic cancer xenograft model established by inoculating immunodeficient mice with CFPAC-1 cells. The efficacy of the DMMC with FUS (study 1), the effect of conjugating the particles as opposed to mixing them (study 2) and the levels of tumor apoptosis and intracellular Dox (study 3) were evaluated. The DMMC with FUS exhibited the lowest tumor growth rate (30.8 mm3/wk) and the highest intracellular Dox uptake (8.8%) and tumor cell apoptosis rate (58.7%) among all treatments. DMMC had a significantly lower growth rate than the mixture of Dox-loaded microparticles and microbubbles (44.2 mm3/wk, p < 0.01) when they were combined with FUS. In conclusion, DMMC with short-duty-cycle FUS holds promise for tumor growth suppression, which may be attributed to high intracellular Dox uptake.

Quadratic inference functions in marginal models for longitudinal data.

The quadratic inference function (QIF) is a new statistical methodology developed for the estimation and inference in longitudinal data analysis using marginal models. This method is an alternative to the popular generalized estimating equations approach, and it has several useful properties such as robustness, a goodness-of-fit test and model selection. This paper presents an introductory review of the QIF, with a strong emphasis on its applications. In particular, a recently developed SAS MACRO QIF is illustrated in this paper to obtain numerical results.

Zinc modulation of glycine receptors in acutely isolated rat CA3 neurons.

Glycine and GABA are the primary inhibitory neurotransmitters in the spinal cord and brain stem, with glycine exerting its physiological roles by activating strychnine-sensitive ionotropic receptors. Glycine receptors are also expressed in the brain, including the cortex and hippocampus, but their physiological roles and pharmacological properties are largely unknown. Here, we report the pharmacological properties of functional glycine receptors in acutely isolated rat CA3 neurons using conventional whole-cell patch clamp techniques. Both glycine and taurine, which are endogenous agonists of glycine receptors, elicited Cl(-) currents in a concentration-dependent manner. The glycine-induced current (I(Gly)) was inhibited by strychnine, picrotoxin or cyclothiazide in a concentration-dependent manner. At lower concentrations (0.01-1 microM), ICS-205,930 potentiated I(Gly), but at higher concentrations (>10 microM) it inhibited I(Gly). These pharmacological properties strongly suggest that CA3 neurons express functional strychnine-sensitive glycine receptors containing alpha2 subunits. Furthermore, at lower concentrations (1-30 microM), Zn(2+) potentiated I(Gly), but at higher concentrations (>100 microM) it inhibited I(Gly). Considering that Zn(2+) is synaptically co-released with glutamate from mossy fiber terminals that make excitatory synapses onto CA3 neurons, these results suggest that endogenous Zn(2+) modulation of these glycine receptors may have an important role in the excitability of CA3 neurons.

Toxicity identification and reduction of wastewaters from a pigment manufacturing factory.

In this study, major toxicants in pigment wastewaters (i.e. raw wastewater and effluent) were determined by toxicity identification evaluations (TIEs), and changes in their toxicities due to combined gamma-ray (gamma-ray) and ozone treatments were evaluated. From TIE results using Daphnia magna, Cr(VI) and o-toluidine were identified as major toxicants in the raw wastewater with concentrations of 2.47 and 25.3mg l(-1), respectively. This was confirmed by subsequent spiking and mass balance approaches. For effluent, TIE results suggested that organic anions were likely responsible for the observed toxicities. Toxicity reduction tests showed that gamma-rays with ozone treatment after coagulation was more efficient in reducing toxicities in the raw wastewater (3.9-2.0 TU) than gamma-ray treatment alone (3.9-3.1 TU). For pigment effluent, gamma-ray/O3 treatment resulted in a complete removal of the acute toxicity.