Neuromodulation of inhibitory control using phase-lagged transcranial alternating current stimulation.

BACKGROUND: Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance. METHODS: The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power. RESULTS: We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity. CONCLUSIONS: These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Risk factors for sodium overcorrection in non-hypovolemic hyponatremia patients treated with tolvaptan.

PURPOSE: In this study, the risk factors associated with sodium overcorrection were investigated with an optimal cutoff for baseline serum sodium for use in daily clinical practice. METHODS: Electronic medical records of patients who received tolvaptan for non-hypovolemic hyponatremia were reviewed. Demographic and clinical data including age, sex, weight, height, comorbidity, cause of hyponatremia, hypertonic saline use, and comedication were collected. Baseline laboratory parameters measured included serum sodium, serum potassium, serum creatinine, blood urea nitrogen, serum tonicity, ALT, AST, and urine osmolality. The primary outcome was the overcorrection of serum sodium, which was defined as an increase in serum sodium by more than 10 mmol/L in 24 h. RESULTS: From a total of 77 patients included in the analysis, 24 (31.2%) showed sodium overcorrection (> 10 mmol/L/24 h); 2 (2.6%) in heart failure cohort, 17 (22.1%) in SIADH cohort, and 5 (6.5%) in unknown cause cohort. More than half of patients (51.9%) were administered hypertonic saline prior to tolvaptan. Hypertension, cancer, diuretics, baseline serum sodium, and SIADH were associated with the risk of overcorrection in the univariable analysis. Significant factors for the overcorrection from multivariable analysis were lower body mass index, presence of cancer (adjusted odds ratio, 10.87; 95% CI, 1.23-96.44), and lower serum sodium at baseline (adjusted odds ratio, 0.76 for every 1 mEq/L increase; 95% CI, 0.61-0.94). CONCLUSION: The overcorrection of hyponatremia in non-hypovolemic patients treated with tolvaptan was significantly associated with lower body mass index, presence of cancer, and lower serum sodium at baseline. In subgroup analysis using SIADH patients, baseline sodium and cancer were found to be significant factors of overcorrection.

A Multi-Component Analysis of CPTED in the Cyberspace Domain.

The visual fidelity of a virtual environment lacks the exceedingly complex layers from the physical world, but the continuous improvements of image rendering technology and computation powers have led to greater demands for virtual simulations. Our study employs Crime Prevention through Environmental Design (CPTED) as a risk control measure and utilizes two principles: Access Control and Natural Surveillance. We conducted an experiment with (n-sample: 100) graduate students. For the experiment, we utilized the Factor Analysis of Information Risk (FAIR) to quantitatively analyze the risk. Furthermore, we adopted the lme4 package for R to estimate the mixed effect of the 6,242,880 observations retrieved from Kaggle. Based on the two experiments, we were able to critically evaluate the contributions of CPTED through a multi-component analysis. Our study investigates how spatial syntax and territorial demarcation may translate in the cyberspace realm. We found that the corollaries of the mophology in the virtual environment effects the distribution of crime. The results of our study discusses how to determine the criminogenic designs and capacity in the cyberspace realm.

The influence of vitamin C on the urine dipstick tests in the clinical specimens: a multicenter study.

BACKGROUND: Vitamin C may interfere with the results of urine dipstick tests. We investigated the incidence of urinary vitamin C and its interference with urine dipstick reagents using a vitamin C dipstick. METHODS: The incidence of urinary vitamin C was determined in patients and healthy individuals undergoing routine medical check-ups. Interference tests were performed using samples with various amounts of added vitamin C. For clinical samples, we identified false-negative dipstick glucose, hemoglobin, and leukocyte esterase results based on the urine sediment and serum glucose results. RESULTS: Vitamin C was found in the urine of 18.1% of the subjects overall, and 23.1% of those undergoing medical check-ups. Dipstick results for glucose, leukocyte esterase, and hemoglobin differed between samples without vitamin C and with added vitamin C. When vitamin C was detected in clinical urine samples, 42.3%, 10.6%, and 8.2% of the glucose, hemoglobin, and leukocyte esterase dipstick tests were rated as false negative, respectively. CONCLUSIONS: Vitamin C was frequently found in clinical urine samples, and its concentration was higher in individuals undergoing medical check-ups. Urinary vitamin C can interfere with the urine dipstick results. This study gives useful information for predicting false-negative rates of urine dipstick tests caused by vitamin C.

Quantitative model for the blood pressure-lowering interaction of valsartan and amlodipine.

AIMS: The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. METHODS: PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. RESULTS: A two-compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an Imax model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D1  + D2 ) +ALPHA×(D1 × D2 ). D1 and D2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were -0.171 (95% CI: -0.218, -0.143) for SBP and -0.0312 (95% CI: -0.07739, -0.00283) for DBP. These infra-additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. CONCLUSION: PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra-additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified.

Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

OBJECTIVE: As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. METHODS: This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. RESULTS: 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test treatments. CONCLUSIONS: Our findings suggest that the telmisartan/rosuvastatin FDC is bioequivalent to coadministration of separate tablets, and both treatments were safe and well tolerated. Administration of this FDC tablet is expected to improve patient compliance.

Circulating matrix metalloproteinase-9 level is associated with cerebral white matter hyperintensities in non-stroke individuals.

BACKGROUNDS: The pathogenesis of cerebral white matter hyperintensities (WMH) has been poorly understood. Our aim was to investigate the association of circulating proteins, the biomarkers of inflammation, blood-brain barrier (BBB) dysfunction, and thrombosis with WMH in non-stroke individuals. METHODS: Demographic, laboratory, and brain magnetic resonance imaging parameters were prospectively analyzed in 137 subjects. The relationship between plasma interleukin-6, tumor necrosis factor-α, matrx-metalloproteinase-9 (MMP-9), plasminogen activator inhibitor-1 and overt WMH (Fazekas grading score ≥2) was analyzed. RESULTS: In univariate analysis, old age, high blood pressure, history of hypertension, and elevated plasma MMP-9 level were associated with overt WMH. In multivariate analysis, plasma MMP-9 still maintained a significant association with WMH. Plasma MMP-9 level was weakly but significantly associated with WMH volume (r = 0.232, p = 0.006). All the other circulating proteins examined failed to demonstrate a significant relationship with WMH. CONCLUSIONS: Plasma MMP-9 is associated with pathophysiology of WMH development.

Genome assembly and population genomic data of a pulmonate snail Ellobium chinense.

Ellobium chinense is an airbreathing, pulmonate gastropod species that inhabits saltmarshes in estuaries of the northwestern Pacific. Due to a rapid population decline and their unique ecological niche in estuarine ecosystems, this species has attracted special attention regarding their conservation and the genomic basis of adaptation to frequently changing environments. Here we report a draft genome assembly of E. chinense with a total size of 949.470 Mb and a scaffold N50 of 1.465 Mb. Comparative genomic analysis revealed that the GO terms enriched among four gastropod species are related to signal transduction involved in maintaining electrochemical gradients across the cell membrane. Population genomic analysis using the MSMC model for 14 re-sequenced individuals revealed a drastic decline in Korean and Japanese populations during the last glacial period, while the southern Chinese population retained a much larger effective population size (Ne). These contrasting demographic changes might be attributed to multiple environmental factors during the glacial-interglacial cycles. This study provides valuable genomic resources for understanding adaptation and historical demographic responses to climate change.

Asymmetric TMO-Metal-TMO Structure for Enhanced Efficiency and Long-Term Stability of Si-Based Heterojunction Solar Cells.

In this study, we fabricated Si-based heterojunction solar cells (HSCs) with an asymmetric TMO-metal-TMO (TMT) structure using both MoO3 and V2O5 as the hole-selective contacts. Our HSCs offer enhanced long-term stability and effective passivation for crystal defects on the Si sur-face. We analyzed the oxygen vacancy state and surface morphology of the MoO3- and V2O5-TMO thin films using X-ray photoelectron spectroscopy and atomic force microscopy to investigate their passivation characteristics for Si surface defects. From the measured minority carrier lifetime, V2O5 revealed a highly improved lifetime (590 µs) compared to that of MoO3 (122.3 µs). In addition, we evaluated the long-term stability of each TMO thin film to improve the operation stability of the HSCs. We deposited different types of TMOs as the top- and bottom-TMO layers and assessed the effect of the thickness of each TMO layer. The fabricated asymmetric TMT/Si HSCs showed noticeable improvements in efficiency (7.57%) compared to 6.29% for the conventional symmetric structure which used the same TMO material for both the top and bottom layers. Furthermore, in terms of long-term stability, the asymmetric TMT/Si HSCs demonstrated an efficiency that was 250% higher than that of symmetric TMT/Si HSCs, as determined via power conversion efficiency degradation over 2000 h which is mainly attributed by the lower oxygen vacancy of the top-TMO, V2O5. These results suggest that the asymmetric TMT structure is a promising approach for the fabrication of low-cost and high-efficiency Si-based HSCs with enhanced long-term stability.

Safety, tolerability, pharmacokinetic/pharmacodynamic characteristics of bersiporocin, a novel prolyl-tRNA synthetase inhibitor, in healthy subjects.

Bersiporocin, a novel first-in-class prolyl-tRNA synthetase (PRS) inhibitor currently under clinical development, was shown to exert an antifibrotic effect through the downregulation of collagen synthesis in various pulmonary fibrosis models. The aim of this first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-dose, dose-escalation study was to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of bersiporocin in healthy adults. A total of 40 and 32 subjects were included in a single- (SAD) and multiple-ascending dose (MAD) study, respectively. No severe or serious adverse events were observed after a single oral dose up to 600 mg and multiple oral doses up to 200 mg twice daily for 14 days. The most common treatment-emergent adverse events were gastrointestinal adverse events. To improve the tolerability, initial bersiporocin solution was changed to the enteric-coated formulation. Afterward, the enteric-coated tablet was used in the last cohort of SAD and in the MAD study. Bersiporocin showed dose-proportional PK characteristics after a single dose up to 600 mg and multiple doses up to 200 mg. Upon reviewing the safety and PK data, the final SAD cohort (800 mg enteric-coated tablet) was canceled by the Safety Review Committee. The levels of pro-peptide of type 3 procollagen were lower after treatment with bersiporocin than after the placebo in the MAD study, whereas no significant change was observed in other idiopathic pulmonary fibrosis (IPF) biomarkers. In conclusion, the safety, PK, and PD profile of bersiporocin supported its further investigation in patients with IPF.

Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301.

PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1. RESULTS: Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116). Observed safety of both treatments was consistent with their previously reported safety profiles. CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

Characterization of Nonaflatoxigenic Aspergillus flavus/oryzae Strains Isolated from Korean Traditional Soybean Meju.

Filamentous fungi that could be classified into Aspergillus flavus/oryzae were isolated from traditionally fermented meju commercially available in Korea. The samples were analyzed for aflatoxin B1 and ochratoxin A contamination by HPLC; however, no toxin was detected. In addition, fungal and bacterial metagenomic sequencing were performed to analyze the microbial distribution in the samples. The results revealed that the distribution and abundance of fungi and bacteria differed considerably depending on the production regions and fermentation conditions of the meju samples. Through morphological analysis, ITS region sequencing, and assessment of the aflatoxin-producing ability, a total of 32 A. flavus/oryzae strains were identified. PCR analysis of six regions with a high mutation frequency in the aflatoxin gene cluster (AGC) revealed a total of six types of AGC breaking point patterns. The A. flavus/oryzae strains did not exhibit the high amylase activity detected in the commercial yellow koji strain (starter mold). However, their peptidase and lipase activities were generally higher than that of the koji isolates. We verified the safety of the traditionally fermented meju samples by analyzing the AGC breaking point pattern and the enzyme activities of A. flavus/oryzae strains isolated from the samples. The isolated strains could possibly be used as starter molds for soybean fermentation.

A Pharmacometric Model to Predict Chemotherapy-Induced Myelosuppression and Associated Risk Factors in Non-Small Cell Lung Cancer.

Chemotherapy often induces severe neutropenia due to the myelosuppressive effect. While predictive pharmacokinetic (PK)/pharmacodynamic (PD) models of absolute neutrophil count (ANC) after anticancer drug administrations have been developed, their deployments to routine clinics have been limited due to the unavailability of PK data and sparseness of PD (or ANC) data. Here, we sought to develop a model describing temporal changes of ANC in non-small cell lung cancer patients receiving (i) combined chemotherapy of paclitaxel and cisplatin and (ii) granulocyte colony stimulating factor (G-CSF) treatment when needed, under such limited circumstances. Maturation of myelocytes into blood neutrophils was described by transit compartments with negative feedback. The K-PD model was employed for drug effects with drug concentration unavailable and the constant model for G-CSF effects. The fitted model exhibited reasonable goodness of fit and parameter estimates. Covariate analyses revealed that ANC decreased in those without diabetes mellitus and female patients. Using the final model obtained, an R Shiny web-based application was developed, which can visualize predicted ANC profiles and associated risk of severe neutropenia for a new patient. Our model and application can be used as a supportive tool to identify patients at the risk of grade 4 neutropenia early and suggest dose reduction.

Comparing SARS-CoV-2 Antibody Responses after Various COVID-19 Vaccinations in Healthcare Workers.

Coronavirus disease 2019 (COVID-19) vaccination began for healthcare workers in South Korea at the end of February 2021. This study investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses after various COVID-19 vaccinations in healthcare workers. Blood specimens of 497 vaccinated healthcare workers were collected. Inoculated vaccines were ChAdOx1 (AstraZeneca/Oxford), BNT162b2 (Pfizer/BioNTech), JNJ-78436735 (Janssen), and mRNA-1273 (Moderna). Each specimen was tested for antibodies against SARS-CoV-2 using Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics), SARS-CoV-2 IgG II Quant assay (Abbott), and R-FIND SARS-CoV-2 Neutralizing Antibody kit (SG medical Inc.). A questionnaire was used to investigate adverse events related to vaccination. We found that 99.5% of the subjects showed a 96-100% positive rate in all three antibody assays, regardless of the vaccine type. The antibody-positive rate of completed vaccination groups reached 96-100%, and antibody quantities significantly increased 2 weeks after vaccination. The antibody values measured approximately 3 months after BNT162b2 inoculation significantly correlated with adverse events.

3,6'- and 1,6'-Dithiopomalidomide Mitigate Ischemic Stroke in Rats and Blunt Inflammation.

(1) Background: An important concomitant of stroke is neuroinflammation. Pomalidomide, a clinically available immunomodulatory imide drug (IMiD) used in cancer therapy, lowers TNF-α generation and thus has potent anti-inflammatory actions. Well-tolerated analogs may provide a stroke treatment and allow evaluation of the role of neuroinflammation in the ischemic brain. (2) Methods: Two novel pomalidomide derivatives, 3,6'-dithiopomalidomide (3,6'-DP) and 1,6'-dithiopomalidomide (1,6'-DP), were evaluated alongside pomalidomide in a rat middle cerebral artery occlusion (MCAo) stroke model, and their anti-inflammatory actions were characterized. (3) Results: Post-MCAo administration of all drugs lowered pro-inflammatory TNF-α and IL1-ß levels, and reduced stroke-induced postural asymmetry and infarct size. Whereas 3,6'- and 1,6'-DP, like pomalidomide, potently bound to cereblon in cellular studies, 3,6'-DP did not lower Ikaros, Aiolos or SALL4 levels-critical intermediates mediating the anticancer/teratogenic actions of pomalidomide and IMiDs. 3,6'-DP and 1,6'-DP lacked activity in mammalian chromosome aberration, AMES and hERG channel assays -critical FDA regulatory tests. Finally, 3,6'- and 1,6'-DP mitigated inflammation across rat primary dopaminergic neuron and microglia mixed cultures challenged with α-synuclein and mouse LPS-challenged RAW 264.7 cells. (4) Conclusion: Neuroinflammation mediated via TNF-α plays a key role in stroke outcome, and 3,6'-DP and 1,6'-DP may prove valuable as stroke therapies and thus warrant further preclinical development.

Fire-Safe Polymer Composites: Flame-Retardant Effect of Nanofillers.

Currently, polymers are competing with metals and ceramics to realize various material characteristics, including mechanical and electrical properties. However, most polymers consist of organic matter, making them vulnerable to flames and high-temperature conditions. In addition, the combustion of polymers consisting of different types of organic matter results in various gaseous hazards. Therefore, to minimize the fire damage, there has been a significant demand for developing polymers that are fire resistant or flame retardant. From this viewpoint, it is crucial to design and synthesize thermally stable polymers that are less likely to decompose into combustible gaseous species under high-temperature conditions. Flame retardants can also be introduced to further reinforce the fire performance of polymers. In this review, the combustion process of organic matter, types of flame retardants, and common flammability testing methods are reviewed. Furthermore, the latest research trends in the use of versatile nanofillers to enhance the fire performance of polymeric materials are discussed with an emphasis on their underlying action, advantages, and disadvantages.

Protective role of glucagon-like peptide-1 against glucosamine-induced cytotoxicity in pancreatic beta cells.

High doses of glucosamine have been known to induce apoptosis of pancreatic beta cells. The mechanism for this phenomenon has not been clearly elucidated. We aimed to explore the potential mechanisms for glucosamine toxicity in the rat insulinoma cell line INS-1 and in rat native beta cells. We also investigated whether glucagon-like peptide (GLP)-1 could be protective against glucosamine. Glucosamine exhibited dose-dependent inhibition of cell survival and an increase in the cell population at the sub-G1 phase. Glucosamine was revealed to inhibit cellular glucose uptake, resulting in the activation of AMP-activated protein kinase (AMPK). Accordingly, phosphorylation of P70S6K and ribosomal protein S6 (S6RP) was decreased. Protein glycosylation appeared not to be involved in this cytotoxicity. Pretreatment with GLP-1 alleviated glucosamine-mediated inhibition of glucose uptake and lessened AMPK activation, thus allowing recovery of the phosphorylation levels of P70S6K and S6RP. The effect of GLP-1 was blocked by the adenylyl cyclase inhibitor MDL12330A but not by the protein kinase A inhibitor H89. Taken together, these data demonstrate that glucosamine may inhibit beta-cell survival by diminishing cellular glucose uptake independent of glycosylation. This glucosamine toxicity can be blocked by GLP-1, which leads to recovery of the glucose uptake through a PKA-independent, cAMP-dependent mechanism.

Development of the Jordanian Arabic early speech perception test.

INTRODUCTION: The Early Speech Perception (ESP) test has been previously used to assess speech perception skills in young hearing-impaired children. As the Arabic language is known to be diglossic, the purpose of this study was to develop a Colloquial Jordanian Arabic version (JAESP) of the ESP test and to check its usefulness. METHODS: The JAESP test encompasses four categories: detection of speech sounds, speech pattern perception, disyllabic word identification, and monosyllabic word identification. Picture boards representing the test materials were created and two equivalent lists for each test category were made. The word identification task was used to test a total of 43 children with reported normal-hearing abilities (15 children aged 3 years, 15 aged 4 years, and 13 aged 5 years). RESULTS: The scores for all age groups were 98-100% for all test materials. Statistical analysis showed that there was no significant difference between age groups and between lists (p ˃ 0.05). CONCLUSION: The findings of this study indicate that the JAESP test materials are appropriate for Jordanian children who are at least 3 years old. Additional studies are needed to verify the validity of the test materials for Jordanian hearing-impaired children.

Retronectin enhances lentivirus-mediated gene delivery into hematopoietic progenitor cells.

Genetic modification of hematopoietic stem cells holds great promise in the treatment of hematopoietic disorders. However, clinical application of gene delivery has been limited, in part, by low gene transfer efficiency. To overcome this problem, we investigated the effect of retronectin (RN) on lentiviral-mediated gene delivery into hematopoietic progenitor cells (HPCs) derived from bone marrow both in vitro and in vivo. RN has been shown to enhance transduction by promoting colocalization of lentivirus and target cells. We found that RN enhanced lentiviral transfer of the VENUS transgene into cultured c-Kit(+) Lin(-) HPCs. As a complementary approach, in vivo gene delivery was performed by subjecting mice to intra-bone marrow injection of lentivirus or a mixture of RN and lentivirus. We found that co-injection with RN increased the number of VENUS-expressing c-Kit(+) Lin(-) HPCs in bone marrow by 2-fold. Further analysis of VENUS expression in colony-forming cells from the bone marrow of these animals revealed that RN increased gene delivery among these cells by 4-fold. In conclusion, RN is effective in enhancing lentivirus-mediated gene delivery into HPCs.