3D Artificial Skin Platform for Investigating Pregnancy-Related Skin Pigmentation.

In this study, we created a 3D Artificial Skin Platform that can be used for the treatment of pigmentation by artificially realizing the skin of pregnant women. For the stable realization of 3D artificial skin, a bilayer hydrogel composed of collagen type I and fibrin was designed and applied to the study to reduce the tension-induced contraction of collagen type I, the extracellular matrix (ECM) of artificial skin, by dynamic culture. Oxygen concentration and 17ß-Estradiol (E2) concentration, which are highly related to melanin production, were selected as parameters of the pregnancy environment and applied to cell culture. Oxygen concentration, which is locally reduced in the first trimester (2.5-3%), and E2, which is upregulated in the third trimester, were applied to the cell culture process. We analyzed whether the 3D artificial skin implemented in the 3D Artificial Skin Platform could better represent the tendency of melanin expression in pregnant women than cells cultured under the same conditions in 2D. The expression levels of melanin and melanin-related genes in the 2D cell culture did not show a significant trend that was similar to the melanin expression trend in pregnant women. However, the 3D artificial skin platform showed a significant trend towards a 2-6-fold increase in melanin expression in response to low oxygen concentrations (2.5%) and E2 concentrations (17 ng/mL), which was similar to the trend in pregnant women in vivo. These results suggest that 3D artificial skin cultured on the Artificial Skin Platform has the potential to be used as a substitute for human pregnant skin in various research fields related to the treatment of pigmentation.

Microfluidics in High-Throughput Drug Screening: Organ-on-a-Chip and C. elegans-Based Innovations.

The development of therapeutic interventions for diseases necessitates a crucial step known as drug screening, wherein potential substances with medicinal properties are rigorously evaluated. This process has undergone a transformative evolution, driven by the imperative need for more efficient, rapid, and high-throughput screening platforms. Among these, microfluidic systems have emerged as the epitome of efficiency, enabling the screening of drug candidates with unprecedented speed and minimal sample consumption. This review paper explores the cutting-edge landscape of microfluidic-based drug screening platforms, with a specific emphasis on two pioneering approaches: organ-on-a-chip and C. elegans-based chips. Organ-on-a-chip technology harnesses human-derived cells to recreate the physiological functions of human organs, offering an invaluable tool for assessing drug efficacy and toxicity. In parallel, C. elegans-based chips, boasting up to 60% genetic homology with humans and a remarkable affinity for microfluidic systems, have proven to be robust models for drug screening. Our comprehensive review endeavors to provide readers with a profound understanding of the fundamental principles, advantages, and challenges associated with these innovative drug screening platforms. We delve into the latest breakthroughs and practical applications in this burgeoning field, illuminating the pivotal role these platforms play in expediting drug discovery and development. Furthermore, we engage in a forward-looking discussion to delineate the future directions and untapped potential inherent in these transformative technologies. Through this review, we aim to contribute to the collective knowledge base in the realm of drug screening, providing valuable insights to researchers, clinicians, and stakeholders alike. We invite readers to embark on a journey into the realm of microfluidic-based drug screening platforms, fostering a deeper appreciation for their significance and promising avenues yet to be explored.

Oral/taste sensitivity to non-esterified long-chain fatty acids with varying degrees of unsaturation.

Understanding human oral/taste sensitivity to long-chain non-esterified fatty acids (NEFA) with varying physicochemical properties is essential to reducing the intake of fats and altering the intake composition. This study investigated the differences in human taste sensitivity to two NEFA: oleic acid and linoleic acid. Twenty-four female subjects were divided into two equal sensitivity groups, and they performed discrimination tests for both fatty acids against bottled water using either the triangle or the DR A-Not A test. To achieve an accurate measurement of NEFA sensitivity, the stimulus was carefully prepared, avoiding additives that could interfere with the binding of fatty acids to receptors. Stimuli concentrations were selected to be within the lowest range (9.9 to 177.3 µM) evaluated in previous research. Through a systematic stimulus control process, this study confirmed that greater sensitivity was exhibited to linoleic acid than oleic acid, resulting in better discrimination than previous studies.

Characterization of Spheno-occipital Synchondrosis Fusion From Preadolescents to Young Adults Using Age and Cervical Vertebrae Maturation Index.

The purpose of this study was to characterize the spheno-occipital synchondrosis fusion (SOSF) from preadolescents to young adults. A total of 630 Korean subjects (308 men, 322 women; age range, 6-18 y) were divided into 26 groups according to sex and age. After 3-dimensional computed tomography (CT) images were reoriented using the Frankfort horizontal (FH) plane, mid-sagittal plane, and frontal plane via ON3D software (3DONS), the cervical vertebrae maturation index (CVMI) and SOSF stages were identified using 6-stage and 5-stage scoring systems, respectively. The distributions of stage in each group were statistically investigated. Women showed early appearance and a short range of onset (CVMI stage 2, SOSF stage 2), middle (CVMI stage 4, SOSF stage 3 and stage 4), and completion (CVMI stage 6, SOSF stage 5), indicating rapid skeletal maturation compared with men. In both males and females, there were strong positive correlations between age and CVMI stage (rs=0.902, rs=0.890), between age and SOSF stage (rs=0.887, rs=0.885), and between CVMI and SOSF stages (rs=0.955, rs=0.964) (all P<0.001). The mean ages at SOSF stage 3 and stage 4 (12.7~13.9 y in males and 11.0~12.5 y in females) could be used as indicators of the pubertal growth peak. Regression equations for SOSF stage (y), age (a), and CVMI stage (b) were as follows: y=1.355-(0.133×a)+(0.29007×b)+(0.041×a×b) for males (r2=0.9496); y=1.305-(0.158×a)+(0.455×b)+(0.036×a×b) for females (r2=0.9606). Ordinal logistic regression analyses with the proportional odds model showed that females had more advanced SOSF stages than males (odds ratio: 1.972; 95% CI: 1.063-3.658, P<0.05). Our findings may provide basic references for CVMI and SOSF from preadolescents to young adults.

Elucidating the Molecular Interactions between Lipids and Lysozyme: Evaporation Resistance and Bacterial Barriers for Dry Eye Disease.

Dry eye disease (DED) is a chronic condition characterized by ocular dryness and inflammation. The tear film lipid layer (TFLL) is the outermost layer composed of lipids and proteins that protect the ocular surface. However, environmental contaminants can disrupt its structure, potentially leading to DED. Although the importance of tear proteins in the TFLL functionality has been clinically recognized, the molecular mechanisms underlying TFLL-protein interactions remain unclear. In this study, we investigated tear protein-lipid interactions and analyzed their role in the TFLL functionality. The results show that lysozyme (LYZ) increases the stability of the TFLL by reducing its surface tension and increasing its surface pressure, resulting in increased TFLL evaporation and bacterial invasion resistance, with improved wettability and lubrication performance. These findings highlight the critical role of LYZ in maintaining ocular health and provide potential avenues for investigating novel approaches to DED treatment and patient well-being.

Portable Colorimetric Hydrogel Beads for Point-of-Care Antimicrobial Susceptibility Testing.

Sepsis is a life-threatening condition with systemic inflammatory responses caused by bacterial infections. Considering the emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), sepsis is a great threat to public health. The gold standard methods for antimicrobial susceptibility testing (AST), however, take at least approximately 3 days to implement the entire blood culture, pure culture, and AST processes. To overcome the time-consuming nature of conventional AST, a method employing a chromatic biosensor composed of poly(diacetylene), alginate, and LB broth (PAL) is introduced in this study. Compared to the gold standards, AST with PAL biosensors can be completed within a time frame as short as 16 h. Such a significant reduction in time is possible because the consecutive cultures and AST are carried out simultaneously by encapsulating the bacterial nutrients and detection molecules into a single component. The bead-like hydrogel sensors were used in their freeze-dried form, which endows them with portability and stability, thus making them adequate for point-of-care testing. The PAL biosensor yields minimum inhibitory concentrations comparable to those from the Clinical and Laboratory Standards Institute, and the applicability of the biosensor is further shown in MRSA-infected mice.

Endometriosis and Adverse Pregnancy Outcomes: A Nationwide Population-Based Study.

Endometriosis is a major cause of infertility, and considering its pathophysiology, it is expected to affect pregnancy outcomes as well. This study aimed to evaluate whether endometriosis is associated with adverse pregnancy outcomes after successful conception. Data from singleton pregnancy deliveries between January 2014 and October 2019 were obtained from the Korean Health Insurance Review and Assessment Service database. We compared the clinical characteristics and adverse pregnancy outcomes of women with and without endometriosis. A total of 1,251,597 pregnant women were enrolled; of these, 32,951 (2.6%) were assigned to the endometriosis group. Women with endometriosis had significantly more adverse pregnancy outcomes than those without endometriosis. Adverse pregnancy outcomes associated with endometriosis included preterm labor, preterm birth, preeclampsia, fetal growth restriction, placenta previa, placental abruption, antepartum and postpartum hemorrhage, and stillbirth. This study also showed an increased risk of postpartum hemorrhage, blood transfusion, uterine artery embolization, and cesarean hysterectomy in the endometriosis group compared to the non- endometriosis group. The cesarean delivery rate was significantly higher in the endometriosis group than in the non-endometriosis group, even after excluding cases of antenatal obstetric complications that could increase the risk of cesarean delivery. Women with endometriosis not only have difficulty conceiving, but also have a significantly higher risk of adverse pregnancy outcomes.

Multicomponent-Loaded Vesosomal Drug Carrier for Controlled and Sustained Compound Release.

Liposomes have been extensively adopted in drug delivery systems with clinically approved formulations. However, hurdles remain in terms of loading multiple components and precisely controlling their release. Herein, we report a vesosomal carrier composed of liposomes encapsulated inside the core of another liposome for the controlled and sustained release of multiple contents. The inner liposomes are made of lipids with different compositions and are co-encapsulated with a photosensitizer. Upon induction of reactive oxygen species (ROS), the contents of the liposomes are released, with each type of liposome displaying distinct kinetics due to the variance in lipid peroxidation for differential structural deformation. In vitro experiments demonstrated immediate content release from ROS-vulnerable liposomes, followed by sustained release from ROS-nonvulnerable liposomes. Moreover, the release trigger was validated at the organismal level using Caenorhabditis elegans. This study demonstrates a promising platform for more precisely controlling the release of multiple components.

The Skin Antiseptic agents at Vaginal dElivery (SAVE) trial: study protocol for a randomized controlled trial.

BACKGROUND: Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. METHODS: In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. DISCUSSION: This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 2021.

Trophoblast Migration with Different Oxygen Levels in a Gel-Patterned Microfluidic System.

In the placenta, substances such as nutrients, oxygen, and by-products are exchanged between the mother and the fetus, and the proper formation of the placenta determines the success of pregnancy, including the growth of the fetus. Preeclampsia is an obstetric disease in which the incomplete formation of the placenta occurs, which is known to occur when there is an abnormality in the invasion of trophoblast cells. The invasion of trophoblast cells is controlled by oxygen concentration, and HIF-1α changes according to oxygen concentration, showing a difference in cell mobility. MMP-2 and MMP-9 are observed to be high in the endometrium involved in trophoblast invasion, and the expression is regulated according to the oxygen concentration. In this experiment, cell culture was conducted using a gel-patterned system with a hypoxic chamber. Before the chip experiment, the difference in the expression of MMP-2 and MMP-9 according to the oxygen concentration was confirmed using a hypoxia chamber. After that, trophoblast cells (HTR8/SVneo) and endothelial cells (HUVECs) were separated and cultured through a physical barrier through a hydrogel on a microfluidic chip. Cells were cultured in a hypoxic chamber under controlled oxygen levels. It was confirmed that the mobility of trophoblast cells in culture on the chip was upregulated in a hypoxic environment through oxygen control. This suggests that the formation of a hypoxic environment in the endometrium where the invasion of trophoblast cells occurs plays a role in increasing cell mobility.

Multi-Modal Locomotion of Caenorhabditis elegans by Magnetic Reconfiguration of 3D Microtopography.

Miniaturized untethered soft robots are recently exploited to imitate multi-modal curvilinear locomotion of living creatures that perceive change of surrounding environments. Herein, the use of Caenorhabditis elegans (C. elegans) is proposed as a microscale model capable of curvilinear locomotion with mechanosensing, controlled by magnetically reconfigured 3D microtopography. Static entropic microbarriers prevent C. elegans from randomly swimming with the omega turns and provide linear translational locomotion with velocity of ≈0.14 BL s-1 . This velocity varies from ≈0.09 (for circumventing movement) to ≈0.46 (for climbing) BL s-1 , depending on magnetic bending and twisting actuation coupled with assembly of microbarriers. Furthermore, different types of neuronal mutants prevent C. elegans from implementing certain locomotion modes, indicating the potential for investigating the correlation between neurons and mechanosensing functions. This strategy promotes a platform for the contactless manipulation of miniaturized biobots and initiates interdisciplinary research for investigating sensory neurons and human diseases.

Development of early prediction model for pregnancy-associated hypertension with graph-based semi-supervised learning.

Clinical guidelines recommend several risk factors to identify women in early pregnancy at high risk of developing pregnancy-associated hypertension. However, these variables result in low predictive accuracy. Here, we developed a prediction model for pregnancy-associated hypertension using graph-based semi-supervised learning. This is a secondary analysis of a prospective study of healthy pregnant women. To develop the prediction model, we compared the prediction performances across five machine learning methods (semi-supervised learning with both labeled and unlabeled data, semi-supervised learning with labeled data only, logistic regression, support vector machine, and random forest) using three different variable sets: [a] variables from clinical guidelines, [b] selected important variables from the feature selection, and [c] all routine variables. Additionally, the proposed prediction model was compared with placental growth factor, a predictive biomarker for pregnancy-associated hypertension. The study population consisted of 1404 women, including 1347 women with complete follow-up (labeled data) and 57 women with incomplete follow-up (unlabeled data). Among the 1347 with complete follow-up, 2.4% (33/1347) developed pregnancy-associated HTN. Graph-based semi-supervised learning using top 11 variables achieved the best average prediction performance (mean area under the curve (AUC) of 0.89 in training set and 0.81 in test set), with higher sensitivity (72.7% vs 45.5% in test set) and similar specificity (80.0% vs 80.5% in test set) compared to risk factors from clinical guidelines. In addition, our proposed model with graph-based SSL had a higher performance than that of placental growth factor for total study population (AUC, 0.71 vs. 0.80, p < 0.001). In conclusion, we could accurately predict the development pregnancy-associated hypertension in early pregnancy through the use of routine clinical variables with the help of graph-based SSL.

The effect of a trunk stabilization exercise program using weight loads on balance and gait in stroke patients: A randomized controlled study.

BACKGROUND: The effects of trunk stabilization exercise programs and exercises applying weight loads for stroke patients are well presented. However, there is not enough objective research to prove the effects of trunk stabilization exercise programs using weight loads for stroke patients. OBJECTIVE: In this study, a trunk stabilization exercise program using weight loads was performed to investigate its impact on the balance and gait ability of stroke patients. METHODS: Thirty patients with stroke were randomly divided into three groups. Experiment group 1 followed a trunk stabilization exercise program using weight loads, experiment group 2 followed a trunk stabilization exercise program, and the control group followed general physiotherapy. Patients' balance ability was assessed using balance measurement equipment BT-4 (postural sway area (PSA), postural sway length (PSL), limit of stability (LOS)), Berg Balance Scale (BBS), and Time Up and Go test (TUG). Gait speed was measured to examine gait ability. RESULT: After the intervention, the PSA, PFSL in experimental groups 1 and 2 decreased but that of the control group increased. BBS, TUG, and LOS scores of experimental group 1 were significantly improved compared to experimental group 2 and the control group. Also, gait speed was significantly improved in experimental group 1 compared to experimental group 2 and the control group. CONCULSION: This study may be used as a basic material for an effective trunk stabilization exercise method for stroke patients and might be of significance as an intervention method for stroke patients requiring long-term treatment.

Elucidation of the Interactions of Reactive Oxygen Species and Antioxidants in Model Membranes Mimicking Cancer Cells and Normal Cells.

Photosensitizers (PSs) used in photodynamic therapy (PDT) have been developed to selectively destroy tumor cells. However, PSs recurrently reside on the extracellular matrix or affect normal cells in the vicinity, causing side effects. Additionally, the membrane stability of tumor cells and normal cells in the presence of reactive oxygen species (ROS) has not been studied, and the effects of ROS at the membrane level are unclear. In this work, we elucidate the stabilities of model membranes mimicking tumor cells and normal cells in the presence of ROS. The model membranes are constructed according to the degree of saturation in lipids and the bilayers are prepared either in symmetric or asymmetric form. Interestingly, membranes mimicking normal cells are the most vulnerable to ROS, while membranes mimicking tumor cells remain relatively stable. The instability of normal cell membranes may be one cause of the side effects of PDT. Moreover, we also show that ROS levels are controlled by antioxidants, helping to maintain an appropriate amount of ROS when PDT is applied.

Simple and rapid detection of common fetal aneuploidies using peptide nucleic acid probe-based real-time polymerase chain reaction.

To examine the detection performance of a peptide nucleic acid (PNA) probe-based real-time time polymerase chain reaction (PCR) assay to detect common aneuploidies. Using amniotic fluid samples, PNA probe based real-time PCR (Patio DEP Detection Kit; SeaSun Biomaterials, Korea) assay was performed. PNA probe was designed to hybridize to similar sequences located on different segments of target chromosomes (21, 18, and 13) and a reference chromosome. Amplification of target sequences and melting curve analysis was performed. When analyzing the melting curve, the ratio of the peak height of the target and reference chromosome was calculated and determined as aneuploidy if the ratio of peak height was abnormal. All the results from the PNA probe-based real-time PCR and melting curve analyses were compared to those from conventional karyotyping. Forty-two cases with common aneuploidies (24 of trisomy 21, 12 of trisomy 18, and 6 of trisomy 13) and 131 cases with normal karyotype were analyzed. When comparing the karyotyping results, the sensitivity and specificity of the PNA probe-based real-time PCR assay were both 100%. The level of agreement was almost perfect (k = 1.00). PNA real-time PCR assay is a rapid and easy method for detecting common aneuploidies.

Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods.

BACKGROUND/AIMS: To develop an early prediction model for gestational diabetes mellitus (GDM) using machine learning and to evaluate whether the inclusion of nonalcoholic fatty liver disease (NAFLD)-associated variables increases the performance of model. METHODS: This prospective cohort study evaluated pregnant women for NAFLD using ultrasound at 10-14 weeks and screened them for GDM at 24-28 weeks of gestation. The clinical variables before 14 weeks were used to develop prediction models for GDM (setting 1, conventional risk factors; setting 2, addition of new risk factors in recent guidelines; setting 3, addition of routine clinical variables; setting 4, addition of NALFD-associated variables, including the presence of NAFLD and laboratory results; and setting 5, top 11 variables identified from a stepwise variable selection method). The predictive models were constructed using machine learning methods, including logistic regression, random forest, support vector machine, and deep neural networks. RESULTS: Among 1,443 women, 86 (6.0%) were diagnosed with GDM. The highest performing prediction model among settings 1-4 was setting 4, which included both clinical and NAFLD-associated variables (area under the receiver operating characteristic curve [AUC] 0.563-0.697 in settings 1-3 vs. 0.740-0.781 in setting 4). Setting 5, with top 11 variables (which included NAFLD and hepatic steatosis index), showed similar predictive power to setting 4 (AUC 0.719-0.819 in setting 5, P=not significant between settings 4 and 5). CONCLUSION: We developed an early prediction model for GDM using machine learning. The inclusion of NAFLDassociated variables significantly improved the performance of GDM prediction. (ClinicalTrials.gov Identifier: NCT02276144).

Metabolic Dysfunction-Associated Fatty Liver Disease and Subsequent Development of Adverse Pregnancy Outcomes.

BACKGROUND & AIMS: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), rather than nonalcoholic fatty liver disease (NAFLD), was proposed to better describe liver disease associated with metabolic dysfunction (MD). In this study, we attempted to investigate the impact of MAFLD on pregnancy complications. METHODS: The current study is a secondary analysis of a multicenter prospective cohort designed to examine the risk of NAFLD during pregnancy. In the first trimester, enrolled pregnant women were evaluated for hepatic steatosis by liver ultrasonography, and blood samples were collected for biochemical measurements. The study population was divided into 3 groups: no NAFLD, hepatic steatosis but without metabolic dysfunction (non-MD NAFLD), and MAFLD. The primary outcome was the subsequent development of adverse pregnancy outcomes, including gestational diabetes mellitus, pregnancy-associated hypertension, preterm birth, and fetal growth abnormalities. RESULTS: The study population consisted of 1744 pregnant women, including 1523 with no NAFLD, 43 with non-MD NAFLD, and 178 with MAFLD. The risk of subsequent development of adverse pregnancy outcomes was higher in MAFLD than in non-MD NAFLD (adjusted odds ratio, 4.03; 95% CI, 1.68-9.67), whereas the risk was not significantly different between no NAFLD and non-MD NAFLD. Among women with no NAFLD, the presence of MD increased the risk of adverse pregnancy outcomes. However, women with MAFLD were at higher risk for adverse pregnancy outcomes than women with no NAFLD without MD or those with no NAFLD with MD. CONCLUSIONS: In pregnant women, MAFLD may be associated with an increased risk of subsequent adverse pregnancy outcomes.

A simple strategy for signal enhancement in lateral flow assays using superabsorbent polymers.

To enhance the sensitivity of lateral flow assays (LFAs), a simple strategy is proposed using a nitrocellulose membrane modified with a superabsorbent polymer (SAP). SAP was incorporated into a nitrocellulose membrane for the flow control of detection probes. When absorbing aqueous solutions, SAP promoted the formation of biomolecule complexes to achieve up to a tenfold sensitivity improvement for the detection of human IgG. The assay time was optimized experimentally and numerically to within 20 min using this strategy. Moreover, fluid saturation in LFAs modified with SAP was mathematically simulated to better understand the underlying process, and molecular dynamics simulations were carried out to determine the effect of SAP. The proposed design was also applied to samples spiked with human immunoglobulin-depleted serum to test its applicability. The strategy presented is unique in that it preserves the characteristics of conventional LFAs, as it minimizes user intervention and is simple to manufacture at scale.

Maternal dyslipidemia and altered cholesterol metabolism in early pregnancy as a risk factor for small for gestational age neonates.

We evaluated the relationship between maternal cholesterol levels and its biologically active precursors and metabolites in the first trimester and subsequent risk for small-for-gestational-age birthweight (SGA). This is a secondary analysis of a prospective cohort study which enrolled healthy singleton pregnancies (n = 1337). Maternal fasting blood was taken in the first trimester and followed up till delivery. The lipid parameters were compared between women who delivered SGA neonates (SGA-group, birthweight < 10th percentile, n = 107) and women who did not (non-SGA-group, n = 1230). In addition, metabolic signatures of cholesterol were evaluated in a subset consisting of propensity-score matched SGA (n = 56) and control group (n = 56). Among lipid parameters, maternal high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in SGA-group than in non-SGA-group (p = 0.022). The risk for SGA was negatively correlated with maternal serum HDL-C quartiles (p = 0.003), and this association remained significant after adjustment for confounding variables. In metabolic signatures of cholesterol, the cholesterol/lathosterol ratio in SGA-group was significantly higher than non-SGA-group [(2.7 (1.6-3.7) vs. 2.1 (1.5-2.9), respectively; p = 0.034)], suggesting increased endogenous cholesterol biosynthesis. We demonstrated that dyslipidemia and increased cholesterol biosynthesis led to delivery of SGA neonates even in early pregnancy.

Quantitative Analysis of the Membrane Affinity of Local Anesthetics Using a Model Cell Membrane.

Local anesthesia is a drug that penetrates the nerve cell membrane and binds to the voltage gate sodium channel, inhibiting the membrane potential and neurotransmission. It is mainly used in clinical uses to address the pain of surgical procedures in the local area. Local anesthetics (LAs), however, can be incorporated into the membrane, reducing the thermal stability of the membrane as well as altering membrane properties such as fluidity, permeability, and lipid packing order. The effects of LAs on the membrane are not yet fully understood, despite a number of previous studies. In particular, it is necessary to analyze which is the more dominant factor, the membrane affinity or the structural perturbation of the membrane. To analyze the effects of LAs on the cell membrane and compare the results with those from model membranes, morphological analysis and 50% inhibitory concentration (IC50) measurement of CCD-1064sk (fibroblast, human skin) membranes were carried out for lidocaine (LDC) and tetracaine (TTC), the most popular LAs in clinical use. Furthermore, the membrane affinity of the LAs was quantitatively analyzed using a colorimetric polydiacetylene assay, where the color shift represents their distribution in the membrane. Further, to confirm the membrane affinity and structural effects of the membranes, we performed an electrophysiological study using a model protein (gramicidin A, gA) and measured the channel lifetime of the model protein on the free-standing lipid bilayer according to the concentration of each LA. Our results show that when LAs interact with cell membranes, membrane affinity is a more dominant factor than steric or conformational effects of the membrane.