Clinical Utility of Impact of Event Scale-Revised for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition Posttraumatic Stress Disorder.

OBJECTIVE: The Impact of Event Scale-Revised (IES-R) is a widely used self-report for assessing posttraumatic stress disorder (PTSD), originally aligned with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic criteria. This study aimed to evaluate the applicability of the IES-R under the DSM-5 guidelines and establish a cutoff point for DSM-5 PTSD diagnosis. METHODS: A total of 238 participants recruited from multiple psychiatric centers, including 67 patients with PTSD, 72 patients with psychiatric controls, and 99 healthy controls, were included in the study. All participants completed the Korean version of the Structured Clinical Interview for the DSM-5 research version to confirm the presence of PTSD, the Korean version of PTSD Checklist for DSM-5 (PCL-5), the Beck Depression Inventory-II, the Beck Anxiety Inventory, and the Spielberger State Trait Anxiety Inventory. RESULTS: The IES-R demonstrated good internal consistency and a high correlation with the PCL-5. Through factor analysis, 5 distinct dimensions emerged within the IES-R: sleep disturbance, intrusion, hyperarousal, avoidance, and numbness-dissociation. A proposed cutoff score of 25 on the IES-R was suggested for identifying patients with PTSD. CONCLUSION: These findings underscore the scale's concurrent validity with the DSM-5 PTSD criteria and its effectiveness as a screening tool. Implementing a cutoff score of 25 on the IES-R can enhance its utility in identifying DSM-5 PTSD cases.

Battery-Free, Wireless Multi-Modal Sensor, and Actuator Array System for Pressure Injury Prevention.

Simultaneous monitoring of critical parameters (e.g., pressure, shear, and temperature) at bony prominences is essential for the prevention of pressure injuries in a systematic manner. However, the development of wireless sensor array for accurate mapping of risk factors has been limited due to the challenges in the convergence of wireless technologies and wearable sensor arrays with a thin and small form factor. Herein, a battery-free, wireless, miniaturized multi-modal sensor array is introduced for continuous mapping of pressure, shear, and temperature at skin interfaces. The sensor array includes an integrated pressure and shear sensor consisting of 3D strain gauges and micromachined components. The mechanically decoupled design of the integrated sensor enables reliable data acquisition of pressure and shear at skin interfaces without the need for additional data processing. The sensor platform enables the analysis of interplay among localized pressure, shear, and temperature in response to changes in the patient's movement, posture, and bed inclination. The validation trials using a novel combination of wireless sensor arrays and customized pneumatic actuator demonstrate the efficacy of the platform in continuous monitoring and efficient redistribution of pressure and shear without repositioning, thereby improving the patient's quality of life.

Development and validation of QuEChERS-based LC-MS/MS method for simultaneous quantification of eleven N-nitrosamines in processed fish meat, processed meat, and salted fish products.

N-Nitrosamines (NAs) pose a threat to food safety due to their carcinogenic and mutagenic properties. In this study, we developed and validated a QuEChERS-based LC-MS/MS method for the simultaneous analysis of 11 NAs in 74 processed fish meat, processed meat, and salted fish products. Sample preparation was optimized by screening two versions of QuEChERS buffer, four extraction methods, and eight purification methods. The optimal analytical approach was validated for three product categories in terms of linearity, matrix effects, accuracy, and precision. Satisfactory precision and accuracy were demonstrated, with relative recoveries of 70-120% for the 11 NAs. The limits of detection for fish meat, processed meat, and salted fish products were 0.12-7.50, 0.12-4.14, and 0.10-7.81 ng·g-1, respectively. Among the 11 NAs, nine were detected in all 74 samples. This methodology could be applied to monitor NA levels to ensure the safety and quality of food products.

Effect of diabetes on mortality and liver transplantation in alcoholic liver cirrhotic patients with acute decompensation.

BACKGROUND: Previous studies have investigated the influence of diabetes on alcoholic liver cirrhosis patients, leaving its impact unclear. Thus, we conducted a study to reveal the association of diabetes and clinical outcomes of such patients. MATERIALS AND METHODS: We prospectively collected data from multicenter pertaining to 965 patients diagnosed with alcoholic liver cirrhosis, all of whom were admitted due to acute decompensation between 2015 and 2019. Risk of major precipitating factors and incidences of death or liver transplantation in patients with and without diabetes was comparatively assessed. Propensity score (PS) matching was performed at a 1:2 ratio for accurate comparisons. RESULTS: The mean age was 53.4 years, and 81.0% of the patients were male. Diabetes was prevalent in 23.6% of the cohort and was positively correlated with hepatic encephalopathy and upper gastrointestinal bleeding, although not statistically significant. During a median follow-up of 903.5 person-years (PYs), 64 patients with and 171 without diabetes died or underwent liver transplantation, with annual incidence of 33.6/100 PYs and 24.0/100 PYs, respectively. In the PS-matched cohort, the incidence of death or liver transplantation was 36.8/100 PYs and 18.6/100 PYs in the diabetes and matched control group, respectively. After adjusting for various factors, coexisting diabetes significantly heightened the risk of death or liver transplantation in the short and long term, in addition to prolonged prothrombin time, low serum albumin, elevated total bilirubin and creatinine, and decreased serum sodium levels. CONCLUSIONS: Diabetes increases the risk of death or liver transplantation in patients with alcoholic liver cirrhosis.

A Food Odorant, α-Ionone, Inhibits Skin Cancer Tumorigenesis by Activation of OR10A6.

SCOPE: This study aims to investigate the anticancer properties of α-ionone in squamous cell carcinoma (SCC). METHODS AND RESULTS: The expression of OR10A6 together with olfactory receptor signaling components is demonstrated in A431 human SCC cells via RT-PCR and qRT-PCR analysis. OR10A6 activation in A431 cells using the ligand α-ionone inhibits proliferation and migration but induces apoptosis which is confirmed by proliferation assay, colony formation, and western blotting. The mechanism involves the core proteins of the Hippo pathway, where the phosphorylation of large tumor suppressor kinase (LATS), yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) is confirmed by western blotting. However, the anticancer effects of α-ionone are abrogated in A431 cells with OR10A6 gene knockdown. In A431 xenograft mouse model, the injection of α-ionone suppresses tumor growth, induces apoptosis, and increases phosphorylation of the LATS-YAP-TAZ signaling axis in the Hippo pathway. None of these effects are observed in xenografted tumors with OR10A6 gene knockdown. CONCLUSION: These findings collectively demonstrate that activation of ectopic OR OR10A6 by α-ionone in SCC cells stimulates the Hippo pathway and suppresses tumorigenesis both in vitro and in vivo, suggesting a novel therapeutic candidate for the treatment of SCC.

7-Amino-3-phenyl-2-methyl-pyrazolopyrimidine derivatives inhibit human rhinovirus replication.

Small molecules that exhibit broad-spectrum enteroviral inhibitory activity by targeting viral replication proteins are highly desired in antiviral drug discovery studies. To discover new human rhinovirus (hRV) inhibitors, we performed a high-throughput screening of 100,000 compounds from the Korea Chemical Bank library. This search led to identification of two phosphatidylinositol-4-kinase IIIß (PI4KIIIß) inhibitors having the pyrazolo-pyrimidine core structure, which display moderate anti-rhinoviral activity along with mild cytotoxicity. The results of a study aimed at optimizing the activity of the hit compounds showed that the pyrazolo-pyrimidine derivative 6f exhibits the highest activity (EC50 = 0.044, 0.066, and 0.083 µM for hRV-B14, hRV-A16, and hRV-A21, respectively) and moderate toxicity (CC50 = 31.38 µM). Furthermore, 6f has broad-spectrum activities against various hRVs, coxsackieviruses and other enteroviruses, such as EV-A71, EV-D68. An assessment of kinase inhibition potencies demonstrated that 6f possesses a high and selective kinase inhibition activity against PI4KIIIß (IC50 value of 0.057 µM) and not against PI4KIIIα (>10 µM). Moreover, 6f exhibits modest hepatic stability (46.9 and 55.3 % remaining after 30 min in mouse and human liver microsomes, respectively). Finally, an in vivo study demonstrated that 6f possesses a desirable pharmacokinetic profile reflected in low systemic clearance (0.48 L∙h-1 kg-1) and modest oral bioavailability (52.4 %). Hence, 6f (KR-26549) appears to be an ideal lead for the development of new antiviral drugs.

Facile synthesis of elastin nanogels encapsulated decursin for castrated resistance prostate cancer therapy.

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/ßcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.

GIS-Based Analysis of Volatile Organic Compounds in Bucheon, Korea, Using Mobile Laboratory and Proton-Transfer-Reaction Time-of-Flight Mass Spectrometry Methods.

Recently, volatile organic compounds (VOCs) have been shown to act as precursors of secondary organic particles that react with ultraviolet rays in the atmosphere and contribute to photochemical smog, global warming, odor, and human health risks, highlighting the importance of VOC management. In this study, we measured VOC concentrations in various contexts including industrial and residential areas of Bucheon, Korea, through mobile laboratory and proton-transfer-reaction time-of-flight mass spectrometry methods to determine winter VOC concentrations and visualized the data based on spatial information. Regional characteristics, temperature/humidity, atmospheric conditions, wind speed, traffic volume, etc., during the measurement period of the study site were comprehensively reviewed. For this purpose, global information system (GIS)-based air quality data and various environmental variables were comprehensively reviewed to assess spatial and temporal concentrations in three dimensions rather than in tables and graphs. Among VOCs, the levels of toluene, methanol, and n + i-butene were relatively high, with average concentrations of 48.3 ± 67.2, 34.4 ± 102.7, and 32.6 ± 57.7 ppb, respectively, at the end of the working day. The highest concentrations occurred near the Ojeong Industrial Complex. Mobile pollution sources are also a major driver of VOCs, highlighting the necessity of comprehensively reviewing traffic variables such as road level, estimated traffic volume, and average speed when identifying hotspots of air pollution. GIS-based visualization analysis techniques will improve the efficiency of air quality management.

Isoxazolyl-urea derivative evokes apoptosis and paraptosis by abrogating the Wnt/ß-catenin axis in colon cancer cells.

Deregulated activation of the Wnt/ß-catenin pathway is observed in many types of human malignancies including colon cancer. Abrogation of the Wnt/ß-catenin pathway has been demonstrated as an effective way of inducing cancer cell death. Herein, a new isoxazolyl-urea (QR-5) was synthesized and examined its efficacy on the viability of colon cancer cell lines. QR-5 displayed selective cytotoxicity towards colon cancer cells over normal counterparts. QR-5 induced apoptosis as evidenced by elevation in sub-G1 cells, decrease in Bcl-2, MMP-9, COX-2, VEGF and cleavage of PARP and caspase-3. QR-5 reduced the mitochondrial membrane potential, decreased the expression of Alix and elevated the expression of ATF4 and CHOP indicating the induction of paraptosis. The inhibitor of apoptosis (Z-DEVD-FMK) and paraptosis (CHX) could not restore Alix expression and PARP cleavage in QR-5 treated cells, respectively suggesting the complementation between the two cell death pathways. QR-5 suppressed the expression of Wnt/ß-catenin pathway proteins which was also evidenced by the downregulation of nuclear and cytoplasmic ß-catenin. The dependency of QR-5 on ß-catenin for inducing apoptosis and paraptosis was demonstrated by knockdown experiments using ß-catenin specific siRNA. Overall, QR-5 induces apoptosis as well as paraptosis by mitigating the Wnt/ß-catenin axis in colon cancer cells.

The role of prolactin in amniotic membrane regeneration: Therapeutic potential for premature rupture of membranes.

INTRODUCTION: Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. METHODS: We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and anti-oxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. RESULTS: PRL had a dose-dependent effect on hAESCs in vitro. 500 ng/mL PRL significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the up-regulation of CCN2 expression and down-regulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via down-regulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. Top ten specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. CONCLUSION: PRL improves the viability and anti-oxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.

Fangchinoline targets human renal cell carcinoma cells through modulation of apoptotic and non­apoptotic cell deaths.

The process of apoptosis is one of the essential processes involved in maintenance of homeostasis in the human body. It can aid to remove misfolded proteins or cellular organelles. This sequence is especially necessary in cancer cells. However, specifically targeting already apoptotic pathways can induce drug resistance in cancer cells and hence drugs can induce cell death by alternative mechanism. We investigated whether fangchinoline (FCN) can target renal carcinoma cells by inducing multiple cell death mechanisms. Both paraptosis, autophagy, and apoptosis were induced by FCN through stimulation of diverse molecular signaling pathways. FCN induced ROS production with GSH/GSSG imbalance, and ER stress. In addition, formation of autophagosome and autophagy related markers were stimulated by FCN. Moreover, FCN induced cell cycle arrest and PARP cleavage. Except for blocking protein synthesis, these three cell death pathways were found to be complementarily working together with each other. FCN also exhibited synergistic effects with paclitaxel in inducing programmed cell death in RCC cells. Our data indicates that FCN could induce apoptotic cell death and non-apoptotic cell death pathways and can be con-tribute to development of novel cancer prevention or therapy.

Retraction Notice to: Decreased Lung Tumor Development in SwAPP Mice through the Downregulation of CHI3L1 and STAT 3 Activity via the Upregulation of miRNA342-3p.

[This retracts the article DOI: 10.1016/j.omtn.2019.02.007.].

The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer's disease.

Although the role of gut microbiota (GMB)-derived metabolites in mitochondrial and endolysosomal dysfunction in Alzheimer's disease (AD) under metabolic syndrome remains unclear, deciphering these host-metabolite interactions represents a major public health challenge. Dysfunction of mitochondria and endolysosomal networks (ELNs) plays a crucial role in metabolic syndrome and can exacerbate AD progression, highlighting the need to study their reciprocal regulation for a better understanding of how AD is linked to metabolic syndrome. Concurrently, metabolic disorders are associated with alterations in the composition of the GMB. Recent evidence suggests that changes in the composition of the GMB and its metabolites may be involved in AD pathology. This review highlights the mechanisms of metabolic syndrome-mediated AD development, focusing on the interconnected roles of mitochondrial dysfunction, ELN abnormalities, and changes in the GMB and its metabolites. We also discuss the pathophysiological role of GMB-derived metabolites, including amino acids, fatty acids, other metabolites, and extracellular vesicles, in mediating their effects on mitochondrial and ELN dysfunction. Finally, this review proposes therapeutic strategies for AD by directly modulating mitochondrial and ELN functions through targeting GMB metabolites under metabolic syndrome.

Biotechnological valorization of levulinic acid as a non-sugar feedstock: New paradigm in biorefineries.

Due to the severe climate crisis, biorefineries have been highlighted as replacements for fossil fuel-derived refineries. In traditional sugar-based biorefineries, levulinic acid (LA) is a byproduct. Nonetheless, in 2002, the US Department of Energy noted that LA is a significant building block obtained from biomass, and the biorefinery paradigm has shifted from being sugar-based to non-sugar-based. Accordingly, LA is of interest in this review since it can be converted into useful precursors and ultimately can broaden the product spectrum toward more valuable products (e.g., fuels, plastics, and pharmaceuticals), thereby enabling the construction of economically viable biorefineries. This study comprehensively reviews LA production techniques utilizing various bioresources. Recent progress in enzymatic and microbial routes for LA valorization and the LA-derived product spectrum and its versatility are discussed. Finally, challenges and future outlooks for LA-based non-sugar biorefineries are suggested.

Prognosis of remaining fetus in twin pregnancy after demise of one fetus according to its location.

BACKGROUND: To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised fetus. METHODS: This was a retrospective study of twin pregnancies with one fetal demise after the first trimester (14 weeks of gestation) delivered between September 2004 and September 2022. The study population was divided into two groups based on the location of the demised fetus as determined by the last recorded ultrasonography results: Group 1 included twin pregnancies where the presenting fetus was demised (n = 36) and Group 2 included twin pregnancies where the non-presenting fetus was demised (n = 44). The obstetric and neonatal outcomes were also reviewed. RESULTS: A total of 80 pregnant women were included. The median gestational age for the diagnosis of fetal demise was 24.1 weeks. The gestational age of the demised fetus was not different between Groups 1 and 2; however, the gestational age of the remaining fetus at delivery was significantly earlier in Group 1 than it was in Group 2 (33.8 vs. 37.3 weeks, P = .004). The rate of preterm birth before 28 weeks was almost five times higher in Group 1 than in Group 2 (22.2% vs. 4.5%, P = .037). Regression analysis demonstrated significant differences between Groups 1 and 2. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, and jaundice were more common in Group 1 than in Group 2; however, the association was not significant after adjusting for gestational age at delivery. CONCLUSIONS: When the presenting fetus is demised in a twin pregnancy, the remaining fetus tends to be delivered earlier than when the non-presenting fetus is demised.

Comparison of One-Person Technique and Two-Person Technique for Colonoscope Insertion: A Randomized Controlled Trial.

Background: The one-person technique (OPT) for colonoscope insertion is recommended by professional societies and regarded as standard practice. However, the two-person technique (TPT) has shown several advantages over the OPT. The aim of this study was to evaluate the performance of the TPT compared to the OPT. Methods: In this prospective study, consecutive individuals presenting for outpatient colonoscopy were randomized to undergo colonoscopy by OPT or by TPT. The colonoscopies were performed by six endoscopists, two of whom were beginners, two with intermediate skills, and two who were experts. The primary endpoints were quality indicators for colonoscopy, including adenoma detection rate, cecal intubation rate, cecal insertion time, and total colonoscopy time. A secondary outcome was procedure tolerability, as assessed by both the patients and the endoscopists. Results: Two hundred and four subjects (117 males, mean age 54.3) were randomized to either one- (n = 102) or two-person (n = 102) colonoscopy. The adenoma detection rate was 30.4% in OPT group and 34.3% in TPT group. (p = 0.55). No significant differences between the two groups were found in terms of cecal intubation rate (98/102 vs. 98/102), insertion time (411 vs. 381 s), and total examination time (1426 vs. 1296 s). However, patients receiving the TPT had lower pain scores than patients receiving the OPT. Endoscopist fatigue measured with the FACIT-F was also significantly lower in the TPT group. Conclusion: The two-person colonoscopy method was not shown to be technically or clinically inferior. Rather, the TPT can improve patient tolerance and reduce endoscopist fatigue.

Novel Developments and Progress in Two-Dimensional Correlation Spectroscopy (2D-COS).

This first of the two-part series of the comprehensive survey review on the progress of the two-dimensional correlation spectroscopy (2D-COS) field during the period 2021-2022, covers books, reviews, tutorials, novel concepts and theories, and patent applications that appeared in the last two years, as well as some inappropriate use or citations of 2D-COS. The overall trend clearly shows that 2D-COS is continually growing and evolving with notable new developments. The technique is well recognized as a powerful analytical tool that provides deep insights into systems in many science fields.

Efficacy of RCI001 as a therapeutic candidate of dry eye disease in a modified mixed dry eye model.

BACKGROUND: To evaluate the therapeutic effects of topical RCI001 (RCI) and compare its efficacy with that of 1% prednisolone acetate (PDE) and 5% Lifitegrast in a modified mixed dry eye disease (DED) model. METHODS: The environmental DED model was induced in BALB/c mice in a dry chamber with scopolamine. The eyes of the mice were treated topically with phosphate buffered saline (PBS), PDE, Lifitegrast or RCI twice daily for 1 week. Ocular surface staining (OSS), tear secretion, inflammatory cytokines in the ocular surface and lacrimal gland, and immunofluorescence staining in the conjunctiva and cornea(CC) were assessed. RESULTS: The RCI group demonstrated better improvement of OSS and tear secretion than the PBS group (OSS, PBS: 13.0 ± 1.6, RCI: 9.4 ± 3.0; tear secretion, PBS: 5.0 ± 0.4 mm, RCI: 7.0 ± 0.3 mm, each P < 0.001) and better clinical efficacy than PDE and Lifitegrast groups on Day 7 (improvement rate of OSS, RCI: 32.45%, Lifitegrast: 13.13%, PDE: 12.25%). The RCI group resulted in significantly lower expression of oxidative stress markers in the CC than the PBS group (4-HNE, NOX2, and NOX4 in the conjunctiva; NOX2 in the cornea, each P < 0.05). However, the PDE and Lifitegrast groups did not show significant differences compared with the PBS group. There were no significant differences of inflammatory cytokines in the ocular surface and lacrimal gland between all groups. CONCLUSION: Topical RCI001 showed excellent therapeutic effects in environmental DED models by stimulating tear secretion, modulating oxidative stress and improving corneal epithelial healing compared to 1% PDE and 5% Lifitegrast.

Diverse Applications of Two-Dimensional Correlation Spectroscopy (2D-COS).

This second of the two-part series of a comprehensive survey review provides the diverse applications of two-dimensional correlation spectroscopy (2D-COS) covering different probes, perturbations, and systems in the last two years. Infrared spectroscopy has maintained its top popularity in 2D-COS over the past two years. Fluorescence spectroscopy is the second most frequently used analytical method, which has been heavily applied to the analysis of heavy metal binding, environmental, and solution systems. Various other analytical methods including laser-induced breakdown spectroscopy, dynamic mechanical analysis, differential scanning calorimetry, capillary electrophoresis, seismologic, and so on, have also been reported. In the last two years, concentration, composition, and pH are the main effects of perturbation used in the 2D-COS fields, as well as temperature. Environmental science is especially heavily studied using 2D-COS. This comprehensive survey review shows that 2D-COS undergoes continuous evolution and growth, marked by novel developments and successful applications across diverse scientific fields.