Differential Impact of Surface Conduction and Electroosmotic Flow on Ion Transport Enhancement by Microscale Auxiliary Structures.

Our research investigates the impact of auxiliary structures on ion transport in electrochemical systems such as batteries and microscale desalination units, whose importance for sustainable development has increased dramatically in recent decades. The electrochemical systems typically feature ion-selective surfaces, such as electrodes and ion exchange membranes, where ion depletion can cause performance issues including metal dendrite formation and flow instability. Recent research has shown that auxiliary structures in these electrochemical systems can enhance ion transfer near ion-selective surfaces, thereby resolving the instability problem and improving the energy conversion efficiency of the system. Our study leverages recent advancements in nanoscale electrokinetics to model these auxiliary structures as pillar arrays near an ion exchange membrane in a microchannel. We examine how these structures enhance ion transports relative to the characteristic length scale of microchannel depth and pillars' proximity to the ion-selective surface. Results show that the effect of the pillars varies significantly with their placement. Specifically, in deeper microchannels, where electrokinetic convection is stronger, the closer the auxiliary structure is to the ion-selective membrane, the better the ion transfer. However, in the thinner microchannel, the proximity of the auxiliary structure to the ion selective membrane has a less significant correlation with the ion transfer. Therefore, this finding highlights the importance of spatial arrangement of the auxiliary structures in improving the performance of electrochemical devices. Conclusively, this study can help to better understand energy conversion systems such as fuel cells, salinity gradient power generation systems, and electrochemical desalination systems, where auxiliary structures can be used in the vicinity of ion-selective surfaces. Especially, our fundamental electrokinetic study provides an effective means for designing the efficient electrochemical platforms utilizing micro/nanofluidics.

Therapeutic Effects of Aß-Specific Regulatory T Cells in Alzheimer's Disease: A Study in 5xFAD Mice.

The aging global population is placing an increasing burden on healthcare systems, and the social impact of Alzheimer's disease (AD) is on the rise. However, the availability of safe and effective treatments for AD remains limited. Adoptive Treg therapy has been explored for treating neurodegenerative diseases, including AD. To facilitate the clinical application of Treg therapy, we developed a Treg preparation protocol and highlighted the therapeutic effects of Tregs in 5xFAD mice. CD4+CD25+ Tregs, isolated after Aß stimulation and expanded using a G-rex plate with a gas-permeable membrane, were adoptively transferred into 5xFAD mice. Behavioral analysis was conducted using Y-maze and passive avoidance tests. Additionally, we measured levels of Aß, phosphorylated tau (pTAU), and nitric oxide synthase 2 (NOS2) in the hippocampus. Real-time RT-PCR was employed to assess the mRNA levels of pro- and anti-inflammatory markers. Our findings indicate that Aß-specific Tregs not only improved cognitive function but also reduced Aß and pTAU accumulation in the hippocampus of 5xFAD mice. They also inhibited microglial neuroinflammation. These effects were observed at doses as low as 1.5 × 103 cells/head. Collectively, our results demonstrate that Aß-specific Tregs can mitigate AD pathology in 5xFAD mice.

Injury of the Vestibulocerebellar Tract and Signs of Ataxia in Patients with Cerebellar Stroke.

BACKGROUND: The vestibulocerebellar tract (VCT) is responsible for maintaining balance, spatial orientation, and coordination. Damage to the vestibular system is accompanied by symptoms of balance disorder or ataxia. This study aimed to compare cerebellar dysfunction according to VCT damage in patients with cerebellar stroke. METHODS: Six patients with cerebellum injury were recruited. This study measured ataxia and hand function related to visuomotor integration and manual dexterity using the Purdue pegboard test. The primary and bilateral secondary VCTs were reconstructed to investigate the integrity of pathways using diffusion tensor imaging (DTI). RESULTS: The ataxia sign was positive in five patients (83%) at onset. In the result of the pegboard test, all patients had hand dysfunction in the dominant hand (100%). Likewise, all patients also had non-dominant hand dysfunction (100%). On the DTI tractography, the left and right primary VCTs of the patients demonstrated a 25% injury rate. Furthermore, the injury rates of ipsilateral and contralateral secondary VCTs were 50% and 58%. CONCLUSIONS: Ataxia is related to secondary VCTs, and hand dysfunction is also related to VCTs. Therefore, we believe that the current study will be helpful in evaluating and providing a clinical intervention strategy for patients with ataxia and hand dysfunction following cerebellar injury.

TAMpepK Suppresses Metastasis through the Elimination of M2-Like Tumor-Associated Macrophages in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) accounts for approximately 10-15% of all breast cancer cases and is characterized by high invasiveness, high metastatic potential, relapse proneness, and poor prognosis. M2-like tumor-associated macrophages (TAMs) contribute to tumorigenesis and are promising targets for inhibiting breast cancer metastasis. Therefore, we investigated whether melittin-conjugated pro-apoptotic peptide (TAMpepK) exerts therapeutic effects on breast cancer metastasis by targeting M2-like TAMs. TAMpepK is composed of M2-like TAM binding peptide (TAMpep) and pro-apoptotic peptide d(KLAKLAK)2 (dKLA). A metastatic mouse model was constructed by injecting 4T1-luc2 cells either orthotopically or via tail vein injection, and tumor burden was quantified using a bioluminescence in vivo imaging system. We found that TAMpepK suppressed lung and lymph node metastases of breast cancer by eliminating M2-like TAMs without affecting the viability of M1-like macrophages and resident macrophages in the orthotopic model. Furthermore, TAMpepK reduced pulmonary seeding and the colonization of tumor cells in the tail vein injection model. The number of CD8+ T cells in contact with TAMs was significantly decreased in tumor nodules treated with TAMpepK, resulting in the functional activation of cytotoxic CD8+ T cells. Taken together, our findings suggest that TAMpepK could be a novel therapeutic agent for the inhibition of breast cancer metastasis by targeting M2-like TAMs.

The Use of Personal Protective Equipment among Frontline Nurses in a Nationally Designated COVID-19 Hospital during the Pandemic.

BACKGROUND: The appropriate use of personal protective equipment (PPE) can significantly reduce the risk of infection associated with caring for patients. This study aimed to investigate the knowledge, awareness, and behaviors related to the PPE usage among frontline nurses in a nationally designated coronavirus disease 2019 (COVID-19) hospital during the COVID-19 pandemic. MATERIALS AND METHODS: The study was performed in two phases: (1) a questionnaire survey to assess the knowledge, awareness, and behaviors related to PPE use, and (2) in-depth personal interviews to elaborate the survey findings. The questionnaires were distributed to all 121 registered nurses in three isolation wards and an intensive care unit which dedicated for patients with COVID-19 and 102 nurses completed survey (84.3% response rate). In-depth interviews were conducted with a total of 7 nurses. RESULTS: Among the survey participant, 100% stated that they knew how to protect themselves while providing nursing care and 93.1% stated that they knew the recommended PPE by task. Most survey participant mainly wore gloves, face shield, N95 or equivalent respirator, and a long-sleeved gown, but one-third of the participants sometimes used coveralls instead of long-sleeved gown. In-depth interviews, the importance of timely updated and specific guidelines for selecting the appropriate type of PPE was highlighted. The adequate supply of PPE, convenience at work, and the role of responsible leadership mainly determined behaviors related to the PPE. CONCLUSION: As new information on COVID-19 continues to emerge, the up-to-date and specific PPE guideline with evidence should be prepared. The spread of accurate information, the role of accountable leadership, and the active communication under positive organizational culture are important for the proper use of PPE.

Age as a Moderator of Social Skills Intervention Response Among Korean Adolescents with Autism Spectrum Disorder.

Few studies have investigated the effect of age on treatment effectiveness of evidence-based social skills training in autism spectrum disorder (ASD) adolescents. This study evaluated the effectiveness of Program for the Education and Enrichment of Relational Skills (PEERS®) in different ages of ASD adolescents. A total of 110 ASD adolescents aged 11-19 years were divided into early, middle, and late adolescence groups, and the changes in outcome measures following intervention were compared among the three groups. We found that the improvements in social competence after PEERS® were significant, but the treatment effects were not significantly different among the three age groups. The findings suggest that PEERS® is beneficial for ASD adolescents regardless of patient age and adolescence stage.

Surface Conduction in a Microchannel.

Ionic current through a microchannel has drawn significant attention not only for fundamental electrokinetic research but also for the development of novel micro/nanofluidic applications. Among various ion transport mechanisms, surface conduction, which is a predominant mechanism in micro/nanofluidic devices, has been theoretically characterized based on two-dimensional analysis. However, its infinite axis assumption has become a barrier for direct application in practical micro/nanochannel networks. In this work, we conducted rigorous experiments to include all of the three-dimensional length scales. There, L/ A, the perimeter to area ratio of the microchannel cross-section, came up as a single parameter to quantitatively interpret the surface conductive ion transportation. Overlimiting conductance of microchannel devices increased with larger perimeter, which is equivalent to specific surface area, even with the same cross sectional area. Finally, a micro/nanofluidic diode with a different L/ A value on its forward and reverse channel was demonstrated as a simple application. The analysis presented could provide a practical guideline to design a micro/nanofluidic application.

Balance Deficit and Brain Connectivity in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: We aimed to assess disturbances in postural and gait balance and functional connectivity within the brain regions controlling balance in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Thirteen children with ADHD and 13 age- and sex-matched controls were recruited. Gait balance was assessed by the difference in the center of pressure (COP) between the left and right foot, as well as the difference in plantar pressure between the left and right foot during gait. Neuroimaging data were acquired using a 3.0 Tesla MRI scanner. Functional connectivity between the vermis of the cerebellum and all other brain regionswas assessed. RESULTS: The difference in plantar pressure between the left foot and right foot in the ADHD group was greater than that observed in the control group. The average COP jerk score of the right foot in the ADHD group was higher than that observed in the control group. A higher functional connectivity between the cerebellum and the right middle frontal gyrus (premotor cortex) and medial frontal gyrus (cingulate gyrus) was observed in the control group relative to the ADHD group. In the ADHD group, the difference in plantar pressure between the left and right foot was also negatively correlated with the beta-value within the middle frontal gyrus. CONCLUSION: Children with ADHD had disturbance of balance as assessed by plantar pressure. Decreased brain connectivity from the cerebellum to the premotor cortex and anterior cingulate was associated with disturbances of posture and balance in children with ADHD.

Ion Concentration Polarization by Bifurcated Current Path.

Ion concentration polarization (ICP) is a fundamental electrokinetic process that occurs near a perm-selective membrane under dc bias. Overall process highly depends on the current transportation mechanisms such as electro-convection, surface conduction and diffusioosmosis and the fundamental characteristics can be significantly altered by external parameters, once the permselectivity was fixed. In this work, a new ICP device with a bifurcated current path as for the enhancement of the surface conduction was fabricated using a polymeric nanoporous material. It was protruded to the middle of a microchannel, while the material was exactly aligned at the interface between two microchannels in a conventional ICP device. Rigorous experiments revealed out that the propagation of ICP layer was initiated from the different locations of the protruded membrane according to the dominant current path which was determined by a bulk electrolyte concentration. Since the enhancement of surface conduction maintained the stability of ICP process, a strong electrokinetic flow associated with the amplified electric field inside ICP layer was significantly suppressed over the protruded membrane even at condensed limit. As a practical example of utilizing the protruded device, we successfully demonstrated a non-destructive micro/nanofluidic preconcentrator of fragile cellular species (i.e. red blood cells).

Antiobesity Effects of Salvia plebeia R. Br. Extract in High-Fat Diet-Induced Obese Mice.

This study was designed to investigate the antiobesity effects of Salvia plebeia R. Br. ethanolic extracts (SPE) in mice fed high-fat diets (HFD). Male C57BL/6J mice were randomly assigned to four groups: normal diet (Chow), high-fat diet (HFD, 45% fat), HFD+SPE 200 (200 mg/kg b.w.), and HFD+SPE 400 (400 mg/kg b.w.). Extracts were administered orally every day for 8 weeks. Increases in body/fat weight and feed efficiency ratio were monitored in all mice. In addition, obesity resulting from feeding HFD to the mice was confirmed by the increase of glucose level, aspartate transaminase, alanine transaminase, triglyceride (TG), high-density lipoprotein cholesterol, very low-density lipoprotein-c, leptin, and adiponectin in blood. The SPE-treated mice gained less body and mesenteric/subcutaneous adipose tissues weights and had lower TG, very low-density lipoprotein cholesterol, leptin, and glucose level in serum, compared to the HFD group. Moreover, histopathological examinations revealed that the size of adipocytes in liver and adipose tissue was significantly decreased by SPE, compared to the HFD group. The expression of adipogenesis transcription factors (e.g., peroxisome proliferator activated receptor γ and CCAAT/enhancer binding protein α) and lipogenesis-related target genes (adipocyte fatty acid-binding protein 2, lipoprotein lipase, fatty acid synthase, and sterol regulatory element-binding transcription factor 1c) in HFD-induced obese mice was decreased by SPE treatment. These results suggest that SPE attenuates the fat accumulation in HFD-induced obese mice by suppressing the expressions of genes related to adipogenesis and lipogenesis activity. Therefore, SPE could be developed as a potential therapy for reduction of body weight and antiobesity intervention.

Non-Negligible Diffusio-Osmosis Inside an Ion Concentration Polarization Layer.

The first experimental and theoretical evidence was provided for the non-negligible role of a diffusio-osmosis in the ion concentration polarization (ICP) layer, which had been reported to be in a high Peclet number regime. Under the assumption that the hydrated shells of cations were stripped out with the amplified electric field inside the ICP layer, its concentration profile possessed a steep concentration gradient at the stripped location. Since the concentration gradient drove a strong diffusio-osmosis, the combination of electro-osmotic and diffusio-osmotic slip velocity had a form of an anomalous nonmonotonic function with both a single- and multiple-cationic solution. A direct measurement of electrolytic concentrations around the layer quantitatively validated our new investigations. This non-negligible diffusio-osmotic contribution in a micro- and nanofluidic platform or porous medium would be essential for clarifying the fundamental insight of nanoscale electrokinetics as well as guiding the engineering of ICP-based electrochemical systems.

Capillarity ion concentration polarization as spontaneous desalting mechanism.

To overcome a world-wide water shortage problem, numerous desalination methods have been developed with state-of-the-art power efficiency. Here we propose a spontaneous desalting mechanism referred to as the capillarity ion concentration polarization. An ion-depletion zone is spontaneously formed near a nanoporous material by the permselective ion transportation driven by the capillarity of the material, in contrast to electrokinetic ion concentration polarization which achieves the same ion-depletion zone by an external d.c. bias. This capillarity ion concentration polarization device is shown to be capable of desalting an ambient electrolyte more than 90% without any external electrical power sources. Theoretical analysis for both static and transient conditions are conducted to characterize this phenomenon. These results indicate that the capillarity ion concentration polarization system can offer unique and economical approaches for a power-free water purification system.

Experimental verification of overlimiting current by surface conduction and electro-osmotic flow in microchannels.

Direct evidence is provided for the transition from surface conduction (SC) to electro-osmotic flow (EOF) above a critical channel depth (d) of a nanofluidic device. The dependence of the overlimiting conductance (OLC) on d is consistent with theoretical predictions, scaling as d(-1) for SC and d(4/5) for EOF with a minimum around d=8 µm. The propagation of transient deionization shocks is also visualized, revealing complex patterns of EOF vortices and unstable convection with increasing d. This unified picture of surface-driven OLC can guide further advances in electrokinetic theory, as well as engineering applications of ion concentration polarization in microfluidics and porous media.

Astragalin inhibits autophagy-associated airway epithelial fibrosis.

BACKGROUND: Fibrotic remodeling of airway and lung parenchymal compartments is attributed to pulmonary dysfunction with an involvement of reactive oxygen species (ROS) in chronic lung diseases such as idiopathic pulmonary fibrosis and asthma. METHODS: The in vitro study elucidated inhibitory effects of astragalin, kaempferol-3-O-glucoside from leaves of persimmon and green tea seeds, on oxidative stress-induced airway fibrosis. The in vivo study explored the demoting effects of astragalin on epithelial to mesenchymal transition in BALB/c mice sensitized with ovalbumin (OVA). RESULTS: The exposure of 20 µM H2O2 for 72 h accelerated E-cadherin loss and vimentin induction in airway epithelial BEAS-2B cells, which was reversed by non-toxic astragalin at 1-20 µM. Astragalin allayed the airway tissue levels of ROS and vimentin enhanced by OVA challenge. Collagen type 1 production increased in H2O2-exposed epithelial cells and collagen fiber deposition was observed in OVA-challenged mouse airways. This study further investigated that the oxidative stress-triggered autophagic regulation was responsible for inducing airway fibrosis. H2O2 highly enhanced the expression induction of the autophagy-related beclin-1 and light chains 3A/B (LC3A/B) within 4 h and astragalin blocked such induction by H2O2. This compound deterred the ROS-promoted autophagosome formation in BEAS-2B cells. Consistently, in OVA-sensitized mice the expression of beclin-1 and LC3A/B was highly induced, and oral administration of astragalin suppressed the autophagosome formation with inhibiting the induction of these proteins in OVA-challenged airway subepithelium. Induction of autophagy by spermidine influenced the epithelial induction of E-cadherin and vimentin that was blocked by treating astragalin. CONCLUSION: These results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial fibrosis through inhibiting autophagosome formation in airways.

Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children.

BACKGROUND: Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms. OBJECTIVES: We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains. METHODS: Blood lead concentrations were measured in a general population of 1,001 children 8-11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A). RESULTS: Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (-7.23; 95% CI: -13.39, -1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: -0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models. CONCLUSIONS: Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD.

Blood manganese levels in relation to comorbid behavioral and emotional problems in children with attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) appear to be more vulnerable to the development of other psychiatric disorders than the general population. The proposed neurotoxic mechanisms of manganese involve striatal dopamine neurotransmission, implicated in the pathophysiology of ADHD. We investigated whether the adverse impact of manganese is particularly pronounced in children with ADHD. Blood manganese concentration and diagnosis of ADHD were assessed in a general population of 890 children, aged 8-11 years. The main outcome measure was the Child Behavior Checklist (CBCL). A significant interaction was found between ADHD status and blood manganese level in predicting CBCL total problems score as well as anxiety/depression, social problems, delinquent behavior, aggressive behavior, internalizing problems, and externalizing problems. The directions of the interactions indicated that blood manganese level was more positively correlated with CBCL scores in ADHD children than in the healthy population. In ADHD children, only the fifth quintile of blood manganese concentration was significantly associated with the CBCL total problems score. ADHD children may be more vulnerable than the general school-age population to the neurotoxic effects of manganese exposure, which lead to an elevated risk of developing comorbid mental conditions.

Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling.

BACKGROUND: Eotaxin proteins are a potential therapeutic target in treating the peribronchial eosinophilia associated with allergic airway diseases. Since inflammation is often associated with an increased generation of reactive oxygen species (ROS), oxidative stress is a mechanistically imperative factor in asthma. Astragalin (kaempferol-3-O-glucoside) is a flavonoid with anti-inflammatory activity and newly found in persimmon leaves and green tea seeds. This study elucidated that astragalin inhibited endotoxin-induced oxidative stress leading to eosinophilia and epithelial apoptosis in airways. METHODS: Airway epithelial BEAS-2B cells were exposed to lipopolysaccharide (LPS) in the absence and presence of 1-20 µM astragalin. Western blot and immunocytochemical analyses were conducted to determine induction of target proteins. Cell and nuclear staining was also performed for ROS production and epithelial apoptosis. RESULTS: When airway epithelial cells were exposed to 2 µg/ml LPS, astragalin nontoxic at ≤ 20 µM suppressed cellular induction of Toll-like receptor 4 (TLR4) and ROS production enhanced by LPS. Both LPS and H2O2 induced epithelial eotaxin-1 expression, which was blocked by astragalin. LPS activated and induced PLCγ1, PKCß2, and NADPH oxidase subunits of p22phox and p47phox in epithelial cells and such activation and induction were demoted by astragalin or TLR4 inhibition antagonizing eotaxin-1 induction. H2O2-upregulated phosphorylation of JNK and p38 MAPK was dampened by adding astragalin to epithelial cells, while this compound enhanced epithelial activation of Akt and ERK. H2O2 and LPS promoted epithelial apoptosis concomitant with nuclear condensation or caspase-3 activation, which was blunted by astragalin. CONCLUSIONS: Astragalin ameliorated oxidative stress-associated epithelial eosinophilia and apoptosis through disturbing TLR4-PKCß2-NADPH oxidase-responsive signaling. Therefore, astragalin may be a potent agent antagonizing endotoxin-induced oxidative stress leading to airway dysfunction and inflammation.

Overlimiting current through ion concentration polarization layer: hydrodynamic convection effects.

In this work, we experimentally investigated an effect of the hydrodynamic convective flow on ion transport through a nanoporous membrane in a micro/nanofluidic modeled system. The convective motion of ions in an ion concentration polarization (ICP) layer was controlled by external hydrodynamic inflows adjacent to the nanoporous membrane. The ion depletion region, which is regarded as a high electrical resistance, was spatially confined to a triangular shape with the additional hydrodynamic convective flow, resulting in a significant alteration in the classical ohmic-limiting-overlimiting current characteristics. Furthermore, the extreme spatial confinement can completely eliminate the limiting current region at a higher flow rate, while the ICP layer still exists. The presented results enable one to obtain a high current value which turns out to be a high electrical power efficiency. Therefore, this mechanism could be utilized as an optimizing power consumption strategy for various electrochemical membrane systems such as fuel-cells, electro-desalination systems and nanofluidic preconcentrators, etc.

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice.

Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, submucosal fibrosis and epithelial shedding. Epithelial-to-mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF-ß. In the in vitro study, we investigated whether 1-20 µM kaempferol inhibited lipopolysaccharide (LPS)-induced bronchial EMT in BEAS-2B cells. The in vivo study explored demoting effects of 10-20 mg/kg kaempferol on airway fibrosis in BALB/c mice sensitized with ovalbumin (OVA). LPS induced airway epithelial TGF-ß1 signaling that promoted EMT with concurrent loss of E-cadherin and induction of α-smooth muscle actin (α-SMA). Nontoxic kaempferol significantly inhibited TGF-ß-induced EMT process through reversing E-cadherin expression and retarding the induction of N-cadherin and α-SMA. Consistently, OVA inhalation resulted in a striking loss of epithelial morphology by displaying myofibroblast appearance, which led to bronchial fibrosis with submucosal accumulation of collagen fibers. Oral administration of kaempferol suppressed collagen deposition, epithelial excrescency and goblet hyperplasia observed in the lung of OVA-challenged mice. The specific inhibition of TGF-ß entailed epithelial protease-activated receptor-1 (PAR-1) as with 20 µM kaempferol. The epithelial PAR-1 inhibition by SCH-79797 restored E-cadherin induction and deterred α-SMA induction, indicating that epithelial PAR-1 localization was responsible for resulting in airway EMT. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.

A randomized controlled trial of the Korean version of the PEERS(®) parent-assisted social skills training program for teens with ASD.

Impaired social functioning is a hallmark feature of autism spectrum disorder (ASD), often requiring treatment throughout the life span. PEERS(®) (Program for the Education and Enrichment of Relational Skills) is a parent-assisted social skills training for teens with ASD. Although PEERS(®) has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America, the efficacy of this treatment has yet to be established in cross-cultural validation trials. The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS(®) for enhancing social skills through a randomized controlled trial (RCT).The English version of the PEERS(®) Treatment Manual (Laugeson & Frankel, 2010) was translated into Korean and reviewed by 21 child mental health professionals. Items identified as culturally sensitive were surveyed by 447 middle school students, and material was modified accordingly. Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient (IQ) ≥ 65. Eligible teens were randomly assigned to a treatment group (TG) or delayed treatment control group (CG). Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD. Secondary outcome measures included scales for depressive symptoms, anxiety, and other behavioral problems. Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS(®) treatment. Independent samples t-tests revealed no significant differences at baseline across the TG and CG conditions with regard to age (14.04 ± 1.64 and 13.54 ± 1.50 years), IQ (99.39 ± 18.09 & 100.67 ± 16.97), parental education, socioeconomic status, or ASD symptoms (p < 0.05), respectively. Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule, interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale (p's < 0.01), social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge-Revised (p < 0.01), and decreased depressive symptoms on the Child Depression Inventory following treatment (p < 0.05). Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables (p < 0.05). Despite cultural and linguistic differences, the PEERS(®) social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment. In an RCT, participants receiving the PEERS(®) treatment showed significant improvement in social skills knowledge, interpersonal skills, and play/leisure skills, as well as a decrease in depressive symptoms and ASD symptoms. This study represents one of only a few cross-cultural validation trials of an established evidence-based treatment for adolescents with ASD.