A Mutation in Tmem135 Causes Progressive Sensorineural Hearing Loss.

Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135 FUN025/FUN025 ( FUN025 ) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

Evaluating the Validity and Reliability of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Cognition.

OBJECTIVE: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson's disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog). METHODS: We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test-retest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. Spearman's rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. RESULTS: The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). CONCLUSION: Our. RESULTS: demonstrate that the K-SCOPA-Cog has good reliability and validity.

Loss of Esr1 Does Not Affect Hearing and Balance.

Although estrogen affects the structure and function of the nervous system and brain and has a number of effects on cognition, its roles in the auditory and vestibular systems remain unclear. The actions of estrogen are mediated predominately through two classical nuclear estrogen receptors, estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). In the current study, we investigated the roles of ESR1 in normal auditory function and balance performance using 3-month-old wild-type (WT) and Esr1 knockout (KO) mice on a CBA/CaJ background, a normal-hearing strain. As expected, body weight of Esr1 KO females was lower than that of Esr1 KO males. Body weight of Esr1 KO females was higher than that of WT females, while there was no difference in body weight between WT and Esr1 KO males. Similarly, head diameter was higher in Esr1 KO vs. WT females. Contrary to our expectations, there were no differences in auditory brainstem response (ABR) thresholds, ABR waves I-V amplitudes and ABR waves I-V latencies at 8, 16, 32, and 48 kHz, distortion product otoacoustic emission (DPOAE) thresholds and amplitudes at 8, 16, and 32 kHz, and rotarod balance performance (latency to fall) between WT and Esr1 KO mice. Furthermore, there were no sex differences in ABRs, DPOAEs, and rotarod balance performance in Esr1 KO mice. Taken together, our findings show that Esr1 deficiency does not affect auditory function or balance performance in normal hearing mice, and suggest that loss of Esr1 is likely compensated by ESR2 or other estrogen receptors to maintain the structure and function of the auditory and vestibular systems under normal physiological conditions.

Improvement in Yield of Extracellular Vesicles Derived from Edelweiss Callus Treated with LED Light and Enhancement of Skin Anti-Aging Indicators.

The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.

A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10).

PURPOSE: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. MATERIALS AND METHODS: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. RESULTS: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. CONCLUSION: Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Skin Wound Healing and Anti-Wrinkle-Promoting In Vitro Biological Activities of Caragana sinica Flower Absolute and Its Chemical Composition.

Caragana sinica (CS; family Legume) was used as a medicinal material to treat neuralgia and arthritis in folk remedies and has been shown to have antioxidant, neuroprotective, and anti-apoptotic effects. However, CS is unknown for its biological activities related to skin. The present study explored the effects of CS flower absolute (CSFAb) on skin repair responses, viz., wound healing and anti-wrinkle-related responses using keratinocytes. CSFAb was extracted using hexane, and its composition was analyzed by GC/MS. The effects of CSFAb on human keratinocytes (HaCaT cells) were evaluated using Boyden chamber, sprouting, water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, ELISA, zymography, and immunoblotting assays. GC/MS detected 46 components in CSFAb. In addition, in HaCaT cells, CSFAb increased the proliferation, migration, and sprout outgrowth and the phosphorylation of ERK1/2, JNK, p38 MAPK, and AKT, and also increased collagen type I and IV synthesis, reduced TNF-α-increased MMP-2 and MMP-9 activities, and upregulated hyaluronic acid (HA) and HA synthase-2 levels. These effects of CSFAb on wound healing and anti-wrinkle-related responses in keratinocytes suggest its potential use for skin repair and care preparations.

Microparticles as Viral RNA Carriers from Stool for Stable and Sensitive Surveillance.

Since its discovery, polymerase chain reaction (PCR) has emerged as an important technology for the diagnosis and identification of infectious diseases. It is a highly sensitive and reliable nucleic acids (NA) detection tool for various sample types. However, stool, which carries the most abundant micro-organisms and physiological byproducts, remains to be the trickiest clinical specimen for molecular detection of pathogens. Herein, we demonstrate the novel application of hydrogel microparticles as carriers of viral RNA from stool samples without prior RNA purification for real-time polymerase chain reaction (qPCR). In each microparticle of primer-incorporated network (PIN) as a self-sufficient reaction compartment, immobilized reverse transcription (RT) primers capture the viral RNA by hybridization and directly initiate RT of RNA to generate a pool of complementary DNA (PIN-cDNA pool). Through a simple operation with a portable thermostat device, a PIN-cDNA pool for influenza A virus (IAV) was obtained in 20 min. The PIN-cDNA pools can be stored at room temperature, or directly used to deliver cDNA templates for qPCR. The viral cDNA templates were freely released in the subsequent qPCR to allow amplification efficiency of over 91%. The assay displayed good linearity, repeatability, and comparable limit of detection (LoD) with a commercialized viral RNA purification kit. As a proof of concept, this technology carries a huge potential for onsite application to improve human and animal infectious disease surveillance activities using stool samples without the need for a laboratory or centrifuge for sample preparation.

Sex differences in body composition, voluntary wheel running activity, balance performance, and auditory function in CBA/CaJ mice across the lifespan.

Hearing loss is the third most prevalent chronic health condition affecting older adults and age-related hearing loss (ARHL) is the most common form of hearing impairment. Significant sex differences in hearing have been documented in humans and rodents. In general, the results of these studies show that men lose their hearing more rapidly than women. However, the cellular mechanism underlying sex differences in hearing or hearing loss remains largely unknown, and to our knowledge, there is no well-established animal model for studying sex differences in hearing. In the current study, we examined sex differences in body composition, voluntary wheel running activity, balance performance, auditory function, and cochlear histology in young, middle-age, and old CBA/CaJ mice, a model of age-related hearing loss. As expected, body weight of young females was lower than that of males. Similarly, lean mass and total water mass of young, middle-age, and old females were lower than those of males. Young females showed higher voluntary wheel running activity during the dark cycle, an indicator of mobility, physical activity, and balance status, compared to males. Young females also displayed higher auditory brainstem response (ABR) wave I amplitudes at 8 kHz, wave II, III, V amplitudes at 8 and 48 kHz, and wave IV/I and V/I amplitude ratios at 48 kHz compared to males. Collectively, our findings suggest that the CBA/CaJ mouse strain is a useful model to study the cellular mechanisms underlying sex differences in physical activity and hearing.

Disease correction in mucopolysaccharidosis type IIIB mice by intraparenchymal or cisternal delivery of a capsid modified AAV8 codon-optimized NAGLU vector.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal storage disease caused by mutations in the gene that encodes the protein N-acetyl-glucosaminidase (NAGLU). Defective NAGLU activity results in aberrant retention of heparan sulfate within lysosomes leading to progressive central nervous system (CNS) degeneration. Intravenous treatment options are limited by the need to overcome the blood-brain barrier and gain successful entry into the CNS. Additionally, we have demonstrated that AAV8 provides a broader transduction area in the MPS IIIB mouse brain compared with AAV5, 9 or rh10. A triple-capsid mutant (tcm) modification of AAV8 further enhanced GFP reporter expression and distribution. Using the MPS IIIB mouse model, we performed a study using either intracranial six site or intracisterna magna injection of AAVtcm8-codon-optimized (co)-NAGLU using untreated MPS IIIB mice as controls to assess disease correction. Disease correction was evaluated based on enzyme activity, heparan sulfate storage levels, CNS lysosomal signal intensity, coordination, activity level, hearing and survival. Both histologic and enzymatic assessments show that each injection method results in supranormal levels of NAGLU expression in the brain. In this study, we have shown correction of lifespan and auditory deficits, increased CNS NAGLU activity and reduced lysosomal storage levels of heparan sulfate following AAVtcm8-coNAGLU administration and partial correction of NAGLU activity in several peripheral organs in the murine model of MPS IIIB.

Classification of Preschoolers with Low-Functioning Autism Spectrum Disorder Using Multimodal MRI Data.

Multimodal imaging studies targeting preschoolers and low-functioning autism spectrum disorder (ASD) patients are scarce. We applied machine learning classifiers to parameters from T1-weighted MRI and DTI data of 58 children with ASD (age 3-6 years) and 48 typically developing controls (TDC). Classification performance reached an accuracy, sensitivity, and specificity of 88.8%, 93.0%, and 83.8%, respectively. The most prominent features were the cortical thickness of the right inferior occipital gyrus, mean diffusivity of the middle cerebellar peduncle, and nodal efficiency of the left posterior cingulate gyrus. Machine learning-based analysis of MRI data was useful in distinguishing low-functioning ASD preschoolers from TDCs. Combination of T1 and DTI improved classification accuracy about 10%, and large-scale multi-modal MRI studies are warranted for external validation.

Ultrafast Real-Time PCR in Photothermal Microparticles.

As the turnaround time of diagnosis becomes important, there is an increasing demand for rapid, point-of-care testing (POCT) based on polymerase chain reaction (PCR), the most reliable diagnostic tool. Although optical components in real-time PCR (qPCR) have quickly become compact and economical, conventional PCR instruments still require bulky thermal systems, making it difficult to meet emerging needs. Photonic PCR, which utilizes photothermal nanomaterials as heating elements, is a promising platform for POCT as it reduces power consumption and process time. Here, we develop a photonic qPCR platform using hydrogel microparticles. Microparticles consisting of hydrogel matrixes containing photothermal nanomaterials and primers are dubbed photothermal primer-immobilized networks (pPINs). Reduced graphene oxide is selected as the most suitable photothermal nanomaterial to generate heat in pPIN due to its superior light-to-heat conversion efficiency. The photothermal reaction volume of 100 nL (predefined by the pPIN dimensions) provides fast heating and cooling rates of 22.0 ± 3.0 and 23.5 ± 2.6 °C s-1, respectively, enabling ultrafast qPCR within 5 min only with optical components. The microparticle-based photonic qPCR facilitates multiplex assays by loading multiple encoded pPIN microparticles in a single reaction. As a proof of concept, four-plex pPIN qPCR for bacterial discrimination are successfully demonstrated.

Chemical Composition of Impatiens textori Miq. Flower Absolute and Its Potential Wound Repair and Anti-Melanogenesis-Promoting Activities in Skin Cells.

Impatiens textori Miq. (ITM; family Balsaminaceae) is a traditional medicinal plant with many biological activities, which include anti-allergic, anti-inflammatory, and anti-pruritic properties. However, it remains to be determined whether ITM affects biological activities in the skin. Thus, we investigated the effects of ITM flower absolute (ITMFAb) extract on the biological activities of skin, especially those related to skin wound repair and whitening. ITMFAb was extracted with hexane, and its composition was determined through GC/MS. The biological activities of ITMFAb on HaCaT keratinocytes and B16BL6 melanoma cells were analyzed using a water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, a Boyden chamber, an ELISA, a sprouting assay, and by immunoblotting. These analyses were performed in a range of ITMFAb concentrations that did not inhibit the viability of the cells (HaCaT, ≤400 µg/mL; B16BL6, ≤200 µg/m). Forty components were identified in ITMFAb. ITMFAb stimulated proliferation, migration, sprout outgrowth, and type I and IV collagen synthesis and upregulated the activations of ERK1/2, JNK, p38 MAPK, and AKT in HaCaT cells. In addition, ITMFAb attenuated the serum-induced proliferation of B16BL6 cells. ITMFAb inhibited melanin synthesis, tyrosinase activity, and expressions of MITF and tyrosinase in α-MSH-exposed B16BL6 cells. These findings indicate that ITMFAb has beneficial effects on wound repairing and whitening-linked responses in the skin and suggest the potential use of ITMFAb as a natural material for the development of skin wound repair and whitening agents.

In situ diagnosis and simultaneous treatment of cardiac diseases using a single-device platform.

The in situ diagnosis of cardiac activities with simultaneous therapeutic electrical stimulation of the heart is key to preventing cardiac arrhythmia. Here, we present an unconventional single-device platform that enables in situ monitoring even in a wet condition and control of beating heart motions without interferences to the recording signal. This platform consists of the active-matrix array of pressure-sensitive transistors for detecting cardiac beatings, biocompatible, low-impedance electrodes for cardiac stimulations, and an alginate-based hydrogel adhesive for attaching this platform conformally to the epicardium. In contrast to conventional electrophysiological sensing using electrodes, the pressure-sensitive transistors measured mechanophysiological characteristics by monitoring the spatiotemporal distributions of cardiac pressures during heart beating motions. In vivo tests show mechanophysiological readings having good correlation with electrocardiography and negligible interference with the electrical artifacts caused during cardiac stimulations. This platform can therapeutically synchronize the rhythm of abnormal heartbeats through efficient pacing of cardiac arrhythmia.

Methodology in Conventional Head and Neck Reconstruction Following Robotic Cancer Surgery: A Bridgehead Robotic Head and Neck Reconstruction.

PURPOSE: Robotic head and neck surgery is widespread nowadays. However, in the reconstruction field, the use of robotic operations is not. This article aimed to examine methodologies for conventional head and neck reconstruction after robotic tumor surgery in an effort to obtain further options for future reconstruction manipulations. MATERIALS AND METHODS: A retrospective review of all patients who received head and neck robot surgery and conventional reconstructive surgery between October 2016 and September 2021. RESULTS: In total, 53 cases were performed. 67.9% of the tumors were greater than 4 cm. Regarding defect size, 47.2% of the lesions were greater than 8 cm. In terms of TNM stage, stage 3 disease was recorded in 26.4% and stage 4 in 52.8%. To make a deep and narrow field wider, we changed the patient's posture in pre-op field, additional dissection was done. We used radial forearm flap mostly (62.2%). CONCLUSION: Conventional head and neck reconstruction after robotic ENT cancer surgery is possible. One key step is to secure additional space in the deep and narrow space left after robotic surgery. For this, we opted for a radial forearm flap mostly. This can be performed as a bridgehead to perform robotic head and neck reconstruction.

Direct Reverse Transcription Real-Time PCR of Viral RNA from Saliva Samples Using Hydrogel Microparticles.

In recent decades "saliva" has emerged as an important non-invasive biofluid for diagnostic purposes in both human and animal health sectors. However, with the rapid evolution of molecular detection technologies, the limitation has been the lack of an efficient method for the facile amplification of target RNA from such a complex matrix. Herein, we demonstrate the novel application of hydrogel microparticles of primer-immobilized networks (PIN) for direct quantitative reverse transcription PCR (dirRT-qPCR) of viral RNA from saliva samples without prior RNA purification. Each of these highly porous PIN particles operates as an independent reactor. They filter in micro-volumes of the analyte solution. Viral RNA is captured and converted to complementary DNA (cDNA) through the RT step using covalently incorporated RT primers. The PIN with cDNA of the viral target will be ready for subsequent highly specific qPCR. Preceded by heat-treatment for viral lysis, we were able to conduct PIN dirRT-qPCR with 95% efficiency of the matrix (M) gene for influenza A virus (IAV) and 5' untranslated region (5' UTR) for chicken coronavirus spiked into saliva samples. The addition of reverse transcriptase enzyme (RTase) and 10% dilution of the matrix improved the assay sensitivity considerably. PIN particles' compatibility with microfluidic PCR chip technology has significantly reduced total sample processing time to 50 min, instead of an average of 120 min that are normally used by other assays. We anticipate this technology will be useful for other viral RNA targets by changing the incorporated RT primer sequences and can be adapted for onsite diagnostics. Supplementary Information: The online version contains supplementary material available at 10.1007/s13206-022-00065-0.

Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models.

BACKGROUND/AIMS: Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. METHODS: The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. RESULTS: The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-ß signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. CONCLUSION: The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

Characteristics of Dysphagia Based on the Type of ALS in Korean Patients Evaluated Using Videofluoroscopic Study: A Retrospective Analysis.

Dysphagia is one of the main serious issues for amyotrophic lateral sclerosis (ALS) patients because of causing malnutrition and aspiration pneumonia. Early detection and management of dysphagia are essential for the long-term survival. In this study, videofluoroscopic swallowing study (VFSS) results of bulbar and spinal onset ALS patients were compared. VFSS results and revised ALS Functional Rating Scale (ALSFRS-R) score were also analyzed to assess the correlation between dysphagia and functional status of patients. ALS patients with swallowing difficulties who underwent VFSS were recruited retrospectively. Two oral, seven pharyngeal, and two esophageal components of VFSS were evaluated. An ALSRFRS-R bulbar subtype score < 9 was used to divide the groups with severe bulbar symptoms. Total 109 Korean ALS patients (39 bulbar vs 70 spinal) were included. Bulbar ALS patients exhibited a significantly longer oral transit time (OTT) then spinal ALS patients, especially in severe bulbar patients with low ALSRFRS-R bulbar subscale. In bulbar ALS patients, penetration (thick liquid), aspiration, OTT, and Penetration-Aspiration Scale (PAS) were significantly correlated with ALSFRS-R bulbar subscale score. However, in spinal ALS patients, only OTT (thin liquid) and aspiration (thick liquid) were significantly correlated with ALSFRS-R bulbar subscale score. Bulbar ALS patients demonstrated significantly longer OTT than spinal ALS patients, and ALSFRS-R bulbar subscale score also correlated well with bulbar ALS patients. Therefore, high vigilance and aggressive treatment for dysphagia especially in bulbar ALS patients rather than spinal ALS patients are mandatory.

Neurodevelopmental outcomes in very low birthweight infants with retinopathy of prematurity in a nationwide cohort study.

In a nationwide prospective cohort of Korean infants with very low birthweights (VLBW, birth weight < 1500 g) from 70 neonatal intensive care units of the Korean Neonatal Network, we investigated neurodevelopmental outcomes in preterm infants with retinopathy of prematurity (ROP) from 2132 infants with VLBW who had undergone developmental assessments at 18-24 months of corrected age. Motor, cognitive, or language delay was determined using developmental scores that were less than 1 standard deviation from the average. Comparative analyses and multivariate regression analyses were performed to validate the association between ROP or its treatment and developmental delay. Motor (52.8% vs. 36.3%), cognitive (46.8% vs. 31.6%), and language delays (42.5% vs. 28.4%) were noted more frequently in infants with ROP than in those without ROP; this was statistically significant (all P < 0.001). Multivariate analyses showed that motor and cognitive delays were significantly associated with ROP. There were no remarkable differences between the neurodevelopmental outcomes and the treatment modalities (laser photocoagulation, anti-vascular endothelial growth factor injection, or both) for ROP, and both stratification and multivariate regression analyses confirmed no significant association between anti-vascular endothelial growth factor therapy and neurodevelopmental delay. As ROP is significantly associated with poor neurodevelopmental outcomes independent of extreme prematurity, neurodevelopmental functions should be given attention in infants with ROP.

Chemical Composition of Salix koreensis Anderss Flower Absolute and Its Skin Wound Healing Activities In Vitro.

Salix koreensis Anderss (SKA) has been used traditionally to treat inflammation, pain, and edema. SKA has anti-inflammatory and antioxidant effects, but no study has examined its effects on skin wound healing. Here, we aimed to investigate the effects of the absolute extracted from SKA flower (SKAFAb) on skin wound healing-associated responses in keratinocytes. SKAFAb was produced using a solvent extraction method and its chemical composition was analyzed by gas chromatography/mass spectrometry. The effects of SKAFAb on HaCaT cells (a human epidermal keratinocyte cell line) were investigated using a Boyden chamber and 5-bromo-2'-deoxyuridine incorporation, sprout outgrowth, immunoblotting, enzyme-linked immunosorbent, and water-soluble tetrazolium salt assays. Sixteen constituents were identified in SKAFAb. SKAFAb promoted HaCaT cell proliferation, migration, and type I and IV collagen productions. SKAFAb increased sprout outgrowth and increased the phosphorylations of serine/threonine-specific protein kinase (Akt), c-Jun NH2-terminal kinase, extracellular signal-regulated kinase1/2, and p38 mitogen-activated protein kinase (MAPK) in HaCaT cells. These results indicate that SKAFAb promotes keratinocyte proliferation and migration, probably by activating Akt and MAPK signaling pathways, and induces collagen synthesis in keratinocytes. SKAFAb may be a promising material for promoting skin wound healing.