Comparative analysis of child injuries in passenger vehicles and school buses: a multicentre cross-sectional study.

OBJECTIVE: This study investigated the differences in injury profiles and safety device effectiveness among children with road traffic injuries (RTIs) involving passenger vehicles and school buses. METHODS: Using data from the Emergency Department-based Injury In-depth Surveillance database, this multicentre cross-sectional study investigated the injury profiles of 14 669 children aged 12 years old and younger who experienced RTIs from 2011-2021. Demographic factors, injury distribution, severity and effect of safety device use between RITs involving passenger vehicles and school buses were compared. RESULTS: RTIs in children most frequently occurred between 12:00 and 18:00 hours (46.9%). School bus-related RTIs peaked during school commute hours, that is, from 06:00 to 12:00 hours, and were associated with a higher prevalence of head (63.1% vs 58.9%, p<0.05) and extremity injuries (upper extremity: 8.0% vs 6.4% and lower extremity: 11.1% vs 7.6 %, p<0.05) compared with those involving passenger vehicles. However, passenger vehicle crashes showed higher proportions of neck and chest injuries, along with injuries requiring hospitalisation and intensive care. Safety devices exhibited preventive effects against head and lower extremity injuries in both vehicle types. While safety devices showed effective in reducing hospital admissions and severe injuries in passenger vehicles, their effectiveness in school buses was not observed. CONCLUSION: This study highlights the different epidemiology and injury profiles of RTIs among children involving passenger vehicles and school buses. Improved safety devices, particularly in school buses, are necessary to ensure the comprehensive protection of child passengers and reduce the risk of severe injuries during road traffic incidents.

Formation of Multiscale Pattern Structures by Combined Patterning of Nanotransfer Printing and Laser Micromachining.

Various lithography techniques have been widely used for the fabrication of next-generation device applications. Micro/nanoscale pattern structures formed by lithographic methods significantly improve the performance capabilities of the devices. Here, we introduce a novel method that combines the patterning of nanotransfer printing (nTP) and laser micromachining to fabricate multiscale pattern structures on a wide range of scales. Prior to the formation of various nano-in-micro-in-millimeter (NMM) patterns, the nTP process is employed to obtain periodic nanoscale patterns on the target substrates. Then, an optimum laser-based patterning that effectively engraves various nanopatterned surfaces, in this case, spin-cast soft polymer film, rigid polymer film, a stainless still plate, and a Si substrate, is established. We demonstrate the formation of well-defined square and dot-shaped multiscale NMM-patterned structures by the combined patterning method of nTP and laser processes. Furthermore, we present the generation of unusual text-shaped NMM pattern structures on colorless polyimide (CPI) film, showing optically excellent rainbow luminescence based on the configuration of multiscale patterns from nanoscale to milliscale. We expect that this combined patterning strategy will be extendable to other nano-to-micro fabrication processes for application to various nano/microdevices with complex multiscale pattern geometries.

High-Resolution Nanotransfer Printing of Porous Crossbar Array Using Patterned Metal Molds by Extreme-Pressure Imprint Lithography.

High-resolution nanotransfer printing (nTP) technologies have attracted a tremendous amount of attention due to their excellent patternability, high productivity, and cost-effectiveness. However, there is still a need to develop low-cost mold manufacturing methods, because most nTP techniques generally require the use of patterned molds fabricated by high-cost lithography technology. Here, we introduce a novel nTP strategy that uses imprinted metal molds to serve as an alternative to a Si stamp in the transfer printing process. We present a method by which to fabricate rigid surface-patterned metallic molds (Zn, Al, and Ni) based on the process of direct extreme-pressure imprint lithography (EPIL). We also demonstrate the nanoscale pattern formation of functional materials, in this case Au, TiO2, and GST, onto diverse surfaces of SiO2/Si, polished metal, and slippery glass by the versatile nTP method using the imprinted metallic molds with nanopatterns. Furthermore, we show the patterning results of nanoporous crossbar arrays on colorless polyimide (CPI) by a repeated nTP process. We expect that this combined nanopatterning method of EPIL and nTP processes will be extendable to the fabrication of various nanodevices with complex circuits based on micro/nanostructures.

Vasohibin-1 promotes osteoclast differentiation in periodontal disease by stimulating the expression of RANKL in gingival fibroblasts.

Vasohibin-1 (VASH1) is a key inhibitor of vascular endothelial growth factor-induced angiogenesis. Although the involvement of VASH1 in various pathological processes has been extensively studied, its role in periodontal disease (PD) remains unclear. We aimed to investigate the role of VASH1 in PD by focusing on osteoclastogenesis regulation. We investigated VASH1 expression in PD by analyzing data from the online Gene Expression Omnibus (GEO) database and using a mouse ligature-induced periodontitis model. The effects of VASH1 on osteoclast differentiation and osteoclastogenesis-supporting cells were assessed in mouse bone marrow-derived macrophages (BMMs) and human gingival fibroblasts (GFs). To identify the stimulant of VASH1, we used culture broth from Porphyromonas gingivalis (Pg), a periopathogen. The GEO database and mouse periodontitis model revealed that VASH1 expression was upregulated in periodontitis-affected gingival tissues, which was further supported by immunohistochemistry and qRT-PCR analyses. VASH1 expression was significantly stimulated in GFs after treatment with the Pg broth. Direct treatment with recombinant VASH1 protein did not stimulate osteoclast differentiation in BMMs but did contribute to osteoclast differentiation by inducing RANKL expression in GFs through a paracrine mechanism. Small interfering RNA-mediated silencing of VASH1 in GFs abrogated RANKL-mediated osteoclast differentiation in BMMs. Additionally, VASH1-activated RANKL expression in GFs was significantly suppressed by MK-2206, a selective inhibitor of AKT. These results suggest that Pg-induced VASH1 may be associated with RANKL expression in GFs in a paracrine manner, contributing to osteoclastogenesis via an AKT-dependent mechanism during PD progression.

Oriented Crystal Growth during Perovskite Surface Reconstruction.

Surface passivation has become a key strategy for an improvement in power conversion efficiency (PCE) of perovskite solar cells (PSCs) since PSCs experienced a steep increase in PCE and reached a comparably matured point. Recently, surface passivation using a mixed salt of fluorinated alkyl ammonium iodide and formamidinium bromide demonstrated a remarkable improvement in both performance and stability, which can be tuned by the length of the alkyl chain. Nevertheless, the role of the alkyl chain in manipulating surface-limited crystal growth was not fully understood, preventing a further progress in interface control. In this study, we found that the length of the fluorine-substituted alkyl chain governed the crystal formation dynamics by manipulating surface tensions of different crystal orientations. The overall enhancement of the (001) plane, being the most favored, commonly resulted from the surface reformation of the perovskite film regardless of the chain length, while the highly oriented (001) over (111) was monitored with a particular chain length. The enhanced crystal orientation during surface recrystallization was responsible for the low trap density and thus effectively suppressed charge recombination at the interface, resulting in a considerable increase in open-circuit voltage and fill factor.

Virulence factors released from Porphyromonas gingivalis induce electrophysiological dysfunction in human pluripotent stem cell-derived cardiomyocytes.

Background/purpose: Periodontal disease development correlates with the occurrence of systemic diseases. The present study investigated the association between periodontal disease and the development of cardiac arrhythmia. Materials and methods: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were treated with Porphyromonas gingivalis (Pg). Cardiotoxicity and electrophysiological properties of hESC-CMs were measured using the cell counting kit-8 assay and a multi-electrode array, respectively. Reverse-transcription-quantitative polymerase chain reaction (RT-qPCR) revealed the mRNA expression of S100 calcium binding protein A1 (S100A1), calsequestrin 2 (CASQ2), troponin I3 (TNNI3), myosin light chain 2 (MYL2), integrin subunit beta 1 (ITGB1), and cadherin 2 (CDH2) in hESC-CMs. Results: Treatment with Pg broth significantly decreased the beat period, field potential duration, spike amplitude, and conduction velocity without affecting the viability of hESC-CMs. In addition, the mRNA expression of CASQ2, TNNI3, and MYL2, which are all associated with calcium handling, were downregulated by Pg broth treatment. Conclusion: These findings indicate that Pg may induce cardiac arrhythmia mediated by virulence factors.

Immunomodulatory Effect of Hispolon on LPS-Induced RAW264.7 Cells and Mitogen/Alloantigen-Stimulated Spleen Lymphocytes of Mice.

Hispolon is a potent anticancer, anti-inflammatory, antioxidant, and antidiabetic agent isolated from Phellinus linteus, an oriental medicinal mushroom. However, the immunomodulatory mechanisms by which hispolon affects macrophages and lymphocytes remain poorly characterized. We investigated the immunomodulatory effects of hispolon on oxidative stress, inflammatory responses, and lymphocyte proliferation using lipopolysaccharide (LPS)-treated RAW264.7 macrophages or mitogen/alloantigen-treated mouse splenocytes. Hispolon inhibited LPS-induced reactive oxygen and nitrogen species (ROS/RNS) generation and decreased total sulfhydryl (SH) levels in a cell-free system and RAW264.7 cells. Hispolon exerted significant anti-inflammatory effects by inhibiting production of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) and activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) in LPS-treated RAW264.7 cells. Hispolon also modulated NF-κB and STAT3 activation by suppressing the NF-κB p65 interaction with phospho-IκBα and the STAT3 interaction with JAK1, as determined via coimmunoprecipitation analysis. Additionally, hispolon significantly decreased lymphocyte proliferation, T cell responses and T helper type 1 (Th1)/type 2 (Th2) cytokines production in mitogen/alloantigen-treated splenocytes. We conclude that hispolon exerts immunomodulatory effects on LPS-treated macrophages or mitogen/alloantigen-treated splenocytes through antioxidant, anti-inflammatory, and antiproliferative activities. Thus, hispolon may be a therapeutic agent for treating immune-mediated inflammatory diseases.

The Role of Physiotherapy in the Management of Functional Neurological Disorder in Children and Adolescents.

Children and adolescents with functional neurological (conversion) disorder (FND) present with symptoms of impaired motor and sensory function. FND involves complex interactions between the brain, mind, body, and lived experience of the child. The gold standard for treatment is therefore a holistic, biopsychosocial approach with multimodal interventions delivered by a multidisciplinary team. In this narrative review we examine the role of physiotherapy in managing FND in children. We searched Embase, Medline, PsycINFO, and PubMed (back to 2000) for relevant physiotherapy articles and also manually searched their reference lists. Two review articles and ten observational studies were identified. Data were extracted concerning the type of study, therapies involved, outcome measures, and comorbid mental health outcomes. FND symptoms resolved in 85% to 95% of the patients, and about two-thirds returned to full-time school after completing the multidisciplinary intervention. Ongoing mental health concerns at follow-up were associated with poorer functional outcomes. Key themes included the following: use of psychological interventions embedded in the physiotherapy intervention; integration of play, music, and dance; role of physical exercise in modulating physiological, neural, and endocrine systems; need for FND-specific outcome measures; ethical issues pertaining to randomized trials; and need to develop alternate study methodologies for assessing combined treatments. Clinical vignettes were included to highlight a range of physiotherapy interventions. In conclusion, the emerging literature suggests that physiotherapy for children with FND is a useful intervention for improving motor dysfunction and for addressing other concurrent issues such as physical deconditioning, neuroprotection, chronic pain, disturbed sleep, anxiety and depression, and resilience building.

Bone Reconstruction Using Two-Layer Porcine-Derived Bone Scaffold Composed of Cortical and Cancellous Bones in a Rabbit Calvarial Defect Model.

In this study, we aimed to investigate the bone regeneration efficiency of two-layer porcine-derived bone scaffolds composed of cancellous and cortical bones in a rabbit calvarial defect model. Four circular calvaria defects were formed on cranium of rabbit and were filled with block bone scaffolds of each group: cortical bone block (Cortical group), cancellous bone block (Cancellous group), and two-layer bone block (2layer group). After 8 weeks, new bones were primarily observed in cancellous parts of the Cancellous and 2layer groups, while the Cortical group exhibited few new bones. In the results of new bone volume and area analyses, the Cancellous group showed the highest value, followed by the 2layer group, and were significantly higher than the Cortical group. Within the limitations of this study, the cancellous and two-layer porcine-derived bone scaffolds showed satisfactory bone regeneration efficiency; further studies on regulating the ratio of cortical and cancellous bones in two-layer bones are needed.

Trends and Determinants in Breastfeeding among Korean Women: A Nationwide Population-Based Study.

Many efforts have been launched to promote breastfeeding in Korea. However, breastfeeding trends and associated factors with breastfeeding in Korea remain unknown. This study aimed to examine trends and determinants in breastfeeding using the Korea National Health and Nutrition Examination Survey (KNHANES) (2010-2018). We analyzed data from the KNHANES V (2010-2012), VI (2013-2015), and VII (2016-2018). A total of 9232 women aged 19-49 years were included in this study. We performed multivariable logistic regression analyses to investigate breastfeeding prevalence trends and associated factors with breastfeeding. Compared to 2010-2012, the odds ratio associated with breastfeeding during 2013-2015 and 2016-2018 increased to 1.30 (95% confidence interval (CI): 1.11-1.51) and 1.40 (95% CI: 1.21-1.63), respectively. The breastfeeding rate was associated with 40-49 years (OR, 95% CI: 0.47, 0.34-0.64 compared to 19-29 years), richer and poorer income (1.20, 1.03-1.39 in richer group and 1.24, 1.05-1.46 in poorer group compared to richest group), education level (0.74, 0.65-0.86 in ≤12 years of education compared to ≥13 years of education), smoking status (1.77, 1.38-2.28 in non-smoking compared to smoking), and self-rated health (1.40, 1.14-1.70 in good and 1.20, 1.00-1.44 in average compared to bad). Education programs and policies such as the Baby-Friendly Hospital Initiative (BFHI) and mother-friendly workplaces are necessary to increase the rates of breastfeeding in these groups.

TRIB2 Stimulates Cancer Stem-Like Properties through Activating the AKT-GSK3ß-ß-Catenin Signaling Axis.

Tribbles homolog 2 (TRIB2) is implicated in tumorigenesis and drug resistance in various types of cancers. However, the role of TRIB2 in the regulation of tumorigenesis and drug resistance of cancer stem cells (CSCs) is still elusive. In the present study, we showed increased expression of TRIB2 in spheroid-forming and aldehyde dehydrogenase-positive CSC populations of A2780 epithelial ovarian cancer cells. Short hairpin RNA-mediated silencing of TRIB2 expression attenuates the spheroid-forming, migratory, tumorigenic, and drug-resistant properties of A2780 cells, whereas overexpression of TRIB2 increases the CSC-like characteristics. TRIB2 overexpression induced GSK3ß inactivation by augmenting AKT-dependent phosphorylation of GSK3ß at Ser9, followed by increasing ß-catenin level via reducing the GSK3ß-mediated phosphorylation of ß-catenin. Treatment of TRIB2-ovexpressed A2780 cells with the phosphoinositide-3-kinase inhibitor LY294002 abrogated TRIB2-stimulated proliferation, migration, drug resistance of A2780 cells. These results suggest a critical role for TRIB2 in the regulation of CSC-like properties by increasing the stability of ß-catenin protein via the AKT-GSK3ß-dependent pathways.

Exosomal delivery of NF-κB inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models.

Accumulation of immune cells and activation of the pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-κB activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-κB inhibitor, termed super-repressor (SR) IκBα. Treatment with SR exosomes (1 × 1010 per intraperitoneal injection) after lipopolysaccharide (LPS) challenge on gestation day 15 (E15) prolonged gestation by over 24 hours (PTB ≤ E18.5) and reduced maternal inflammation (n ≥ 4). Furthermore, using a transgenic model in which fetal tissues express the red fluorescent protein tdTomato while maternal tissues do not, we report that LPS-induced PTB in mice is associated with influx of fetal innate immune cells, not maternal, into feto-maternal uterine tissues. SR packaged in exosomes provides a stable and specific intervention for reducing the inflammatory response associated with PTB.

Elevated Expression of Cathepsin K in Periodontal Ligament Fibroblast by Inflammatory Cytokines Accelerates Osteoclastogenesis via Paracrine Mechanism in Periodontal Disease.

Cathepsin K (CTSK) is a cysteine protease that is mainly produced from mature osteoclasts and contributes to the destruction of connective tissues and mineralized matrix as a consequence of periodontal disease (PD). However, few studies have reported its regulatory role in osteoclastogenesis-supporting cells in inflammatory conditions. Here, we investigated the role of CTSK in osteoclastogenesis-supporting cells, focusing on the modulation of paracrine function. Microarray data showed that CTSK was upregulated in PD patients compared with healthy individuals, which was further supported by immunohistochemistry and qPCR analyses performed with human gingival tissues. The expression of CTSK in the osteoclastogenesis-supporting cells, including dental pulp stem cells, gingival fibroblasts, and periodontal ligament fibroblasts (PDLFs) was significantly elevated by treatment with inflammatory cytokines such as TNFα and IL-1ß. Moreover, TNFα stimulation potentiated the PDLF-mediated osteoclastogenesis of bone marrow-derived macrophages. Interestingly, small interfering RNA-mediated silencing of CTSK in PDLF noticeably attenuated the TNFα-triggered upregulation of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor, and RANKL/osteoprotegerin ratio, thereby abrogating the enhanced osteoclastogenesis-supporting activity of PDLF. Collectively, these results suggest a novel role of CTSK in the paracrine function of osteoclastogenesis-supporting cells in periodontal disease.

Cut-off value of serum homocysteine in relation to increase of coronary artery calcification.

A recent study reported that coronary artery calcification (CAC) and serum homocysteine were well associated; however, no report is available for the cut-off value of serum homocysteine according to increase of coronary-artery calcification volume score (CVS). The data of 469 out of 777 subjects in 1 health promotion center located in Seoul were selected after exclusion of the missing data of serum homocysteine and CVS. CVS was categorized into 2 groups: CVS=0 and CVS>0. Serum homocysteine according to the CVS groups was compared, and the cut-off value of serum homocysteine according to the increase of CVS (>0) was calculated using the receiver operating characteristic curve. Mean age was 54.5 years and the proportion of females was 22.2%. Mean serum homocysteine concentration and CVS were 11.2 µmol/L and 50.4, respectively. After adjustments for age and sex, serum homocysteine was associated with CVS (r=0.167, p=0.001), and Log(Homocysteine) also showed a significant difference according to the CVS groups. The cut-off value of serum homocysteine according to the increase of CVS (>0) was 9.45 µmol/L (area under the curve=0.569 (95% CI 0.512 to 0.625), p=0.015). The cut-off value of serum homocysteine was 9.45 µmol/L according to the increase of coronary-artery CVS.

Enhancement of Drought-Stress Tolerance of Brassica oleracea var. italica L. by Newly Isolated Variovorax sp. YNA59.

Drought is a major abiotic factor and has drastically reduced crop yield globally, thus damaging the agricultural industry. Drought stress decreases crop productivity by negatively affecting crop morphological, physiological, and biochemical factors. The use of drought tolerant bacteria improves agricultural productivity by counteracting the negative effects of drought stress on crops. In this study, we isolated bacteria from the rhizosphere of broccoli field located in Daehaw-myeon, Republic of Korea. Sixty bacterial isolates were screened for their growth-promoting capacity, in vitro abscisic acid (ABA), and sugar production activities. Among these, bacterial isolates YNA59 was selected based on their plant growth-promoting bacteria traits, ABA, and sugar production activities. Isolate YNA59 highly tolerated oxidative stress, including hydrogen peroxide (H2O2) and produces superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activities in the culture broth. YNA59 treatment on broccoli significantly enhanced plant growth attributes, chlorophyll content, and moisture content under drought stress conditions. Under drought stress, the endogenous levels of ABA, jasmonic acid (JA), and salicylic acid (SA) increased; however, inoculation of YNA59 markedly reduced ABA (877 ± 22 ng/g) and JA (169.36 ± 20.74 ng/g) content, while it enhanced SA levels (176.55 ± 9.58 ng/g). Antioxidant analysis showed that the bacterial isolate YNA59 inoculated into broccoli plants contained significantly higher levels of SOD, CAT, and APX, with a decrease in GPX levels. The bacterial isolate YNA59 was therefore identified as Variovorax sp. YNA59. Our current findings suggest that newly isolated drought tolerant rhizospheric Variovorax sp. YNA59 is a useful stress-evading rhizobacterium that improved droughtstress tolerance of broccoli and could be used as a bio-fertilizer under drought conditions.

Multivalent-Interaction-Driven Assembly of Discrete, Flexible, and Asymmetric Supramolecular Protein Nano-Prisms.

Current approaches to design monodisperse protein assemblies require rigid, tight, and symmetric interactions between oligomeric protein units. Herein, we introduce a new multivalent-interaction-driven assembly strategy that allows flexible, spaced, and asymmetric assembly between protein oligomers. We discovered that two polygonal protein oligomers (ranging from triangle to hexagon) dominantly form a discrete and stable two-layered protein prism nanostructure via multivalent interactions between fused binding pairs. We demonstrated that protein nano-prisms with long flexible peptide linkers (over 80 amino acids) between protein oligomer layers could be discretely formed. Oligomers with different structures could also be monodispersely assembled into two-layered but asymmetric protein nano-prisms. Furthermore, producing higher-order architectures with multiple oligomer layers, for example, 3-layered nano-prisms or nanotubes, was also feasible.

Effect of Ammonia and Indole-3-acetic Acid Producing Endophytic Klebsiella pneumoniae YNA12 as a Bio-Herbicide for Weed Inhibition: Special Reference with Evening Primroses.

Information on the use of endophytic bacteria as a bio-herbicide for the management of weed control in agricultural fields is limited. The current study aimed to isolate endophytic bacteria from evening primroses and to screen them for their bio-herbicidal activity. Two isolated endophytic bacteria (Pantoea dispersa YNA11 and Klebsiella pneumoniae YNA12) were initially screened for citrate utilization and for indole-3-acetic acid (IAA) and catalase production. The preliminary biochemical assessment showed YNA12 as a positive strain. Ammonia, catalase, and IAA in its culture filtrate were quantified. Gas Chromatography/Mass Spectroscopy- Selective Ion Monitoring (GC/MS-SIM) analysis revealed the production of IAA by YNA12 in a time-dependent manner. YNA12 also exhibited significant ammonia-producing potential and catalase activity against hydrogen peroxide. The YNA12 culture filtrate significantly inhibited the germination rate of evening primrose seeds, resulting in a marked reduction in seedling length and biomass compared with those of the control seeds. Moreover, the culture filtrate of YNA12 significantly accelerated the endogenous abscisic acid (ABA) production and catalase activity of evening primrose seedlings. Macronutrient regulation was adversely affected in the seedlings exposed to the culture filtrate of YNA12, leading to inhibition of seed germination. The current results suggest that endophytic YNA12 may be used as a potent bio-herbicidal agent for controlling weed growth and development.

Clinical Implications of Ventricular Repolarization Parameters on Long-Term Risk of Atrial Fibrillation　- Longitudinal Follow-up Data From a General Ambulatory Korean Population.

BACKGROUND: This study investigated 12-lead electrocardiogram (ECG) predictors associated with atrial fibrillation (AF) or flutter (AFL), specifically whether ventricular repolarization abnormalities in surface ECG (i.e., non-specific ST-T abnormalities [NSSTTA], QT prolongation, early repolarization [ER]) were associated with the development of AF or AFL.Methods and Results:This study included 16,793 ambulatory Koreans (mean age 48.2 years, 62.3% male) who underwent medical check-ups at Asan Medical Center in 2002 (NSSTTA, n=1,037 [6.2%]; ER, n=1,493 [8.9%]). The primary outcome was the incidence of ECG-documented AF or AFL. During follow-up, new-onset AF or AFL was documented in 334 subjects (2.0%). The incidence of AF or AFL at the 10-year follow-up was higher in patients with than without NSSTTA (3.5% vs. 1.6%; hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.28-2.50). The QT interval was associated with a higher risk of AF or AFL (HR 1.12 [95% CI 1.07-1.17] per 10 ms), and the risk was even higher in patients with multiple-region NSSTTA (HR 2.30; 95% CI 1.64-3.21) and NSSTTA with QT prolongation (HR 4.06; 95% CI 2.14-7.69). ER was not associated with a higher risk of AF or AFL (HR 1.02; 95% CI 0.71-1.46). CONCLUSIONS: NSSTTA and QT prolongation, but not ER, were associated with a higher risk of future AF or AFL in a general ambulatory population after adjusting for parameters of atrial depolarization.

Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality.

As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes. We showed that intraperitoneal injection of purified srIκB-loaded exosomes (Exo-srIκBs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srIκBs were observed mainly in the neutrophils, and in monocytes to a lesser extent, in the spleens and livers of mice. Moreover, we found that Exo-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.

Gastrin-Releasing Peptide (GRP) Stimulates Osteoclastogenesis in Periodontitis.

Periodontitis is a chronic inflammatory disease with alveolar bone resorption and subsequent tooth loss as its ultimate outcomes. Gastrin-releasing peptide (GRP) is a neuropeptide with growth-stimulatory and tumorigenic properties, and neuropeptides have previously been suggested to play a role in the complex cascade of chemical activity associated with periodontal inflammation. In this study, GRP treatment enhanced the differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts, and gastrin-releasing peptide receptor (GRPR) antagonists suppressed the pro-osteoclastogenic effect of GRP. Grpr-siRNA knockdown resulted in a significantly lower number of osteoclasts formed as compared with the control. Interestingly, gene expression analysis indicated downregulation of Grp and Grpr expressions in BMMs during osteoclastogenesis. Moreover, ligature-induced periodontitis model in mice and gingival samples from patients with periodontitis displayed increased immunostaining of GRP in the oral epithelium. Subsequently, stimulation of mouse primary epithelial cells (ECs) and HaCaT cells, human epidermal keratinocytes, with lipopolysaccharides (LPS) of Porphyromonas gingivalis or live P. gingivalis upregulated Grp and Grpr expressions. Finally, coculture of P. gingivalis-stimulated ECs and BMMs using Transwell system revealed that the differentiation of BMMs was induced when subjected to paracrine activation by LPS- as well as live-P. gingivalis stimulated ECs. Taken together, our results demonstrate that the pro-osteoclastogenic properties of BMMs may be modulated by GRP produced by ECs in the periodontal microenvironment.