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Abstract Patients with diabetes mellitus (DM) are at a higher risk of infectious diseases, and exercise is an important treatment modality for DM. Despite their susceptibility to infection in diabetic patients, the association between the amount of physical activity and the incidence of infective endocarditis (IE) is unclear. We attempted to demonstrate risk reduction by physical activity in diabetic patients with IE. From the National Health Insurance database, patients with DM were verified, and the incidence of IE was investigated. The level of physical activity was categorized into

Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P

Sphingosine 1-phosphate (S1P) is a signaling lipid molecule involved in various cellular processes. It is important to develop a quantitative method for S1P to determine endogenous levels and to investigate its functions. As S1P is a tiny lipid component of most biological samples, highly sensitive analysis by LC-MS/MS is required. The main challenge in S1P analysis by chromatography is peak-broadening due to the presence of a polar phosphate and the fact that S1P is indeed a zwitterion itself. In this study, we used hydrogen fluoride (HF) to efficiently remove a phosphate and then analyzed the surrogate, sphingosine, as a sharp peak by LC-ESI-MS/MS. We optimized the dephosphorylation reaction in terms of temperature and reaction time. Multiple reaction monitoring (MRM) for a dephosphorylated form of S1P and C17-S1P as an internal standard at m/z transition 300.4 > 282.4 (quantification ion), 300.4 > 262.4 (qualification ion), 286.3 > 268.2 (internal standard) was conducted. This method was validated by essential parameters such as specificity, linearity, range, LOQ, LOD, accuracy, precision, and repeatability. To confirm this new method, we quantified S1P levels in various serum products (100.0~284.4 nM). In the sample pretreatment conditions for extracting S1P, the concern about potential sphingosine contamination in serum was negligible. The dephosphorylation efficiency by this method was about two-fold higher than that of alkaline phosphatase (APase). To apply the method in vivo, we analyzed S1P in plasma and kidney tissues obtained from a chronic kidney disease (CKD) mouse model. S1P levels were increased only in CKD kidney tissue but not in plasma. In conclusion, by applying the dephosphorylation step with HF, we established a new, sensitive LC-MS/MS quantitative method for S1P that can be applied to biological samples.

This paper aims to provide the most useful method of determining an optimum LCB position and design direction of fore- and aft-body hull shape for a SLBV. It is known that the SLBV has a lower length-to-beam ratio, larger Cb and simpler stern shape designed for the installation of azimuth thrusters comparing to those of conventional LNG carriers. Due to these specific particulars of SLBV, the optimum LCB position was very different to that of conventional LNG carrier. And various approaches were applied to determine the optimum fore- and aft-body hull shape. The design direction for the optimum hull-form was evaluated as the minimization of the total resistance which includes the wave-making resistance and form-drag with numerical simulation.

This study investigates the effect of Licochalcone A (Lico-A), a flavonoid from licorice roots known for its anti-inflammatory, anti-cancer, and antioxidant properties, on NMDA-induced neurotoxicity in primary cultured rat hippocampal neurons. The study measured cell survival following NMDA and Lico-A exposure, revealing that Lico-A at a 2.5 μg/ml significantly improved cell viability, countering the detrimental effects of NMDA. The study also analyzed synaptic changes by examining both postsynaptic density 95 (PSD95) and synaptophysin-targeted imaging, showing that Lico-A treatment resulted in a significant increase in synaptic puncta, contrasting with the reduction observed under NMDA exposure. Furthermore, levels of phosphorylated mixed lineage kinase domain-like pseudokinase (P-MLKL) and phosphorylated receptor-interacting serine/threonine-protein kinase 3 (P-RIP3), key necroptosis regulators, were measured using Western blotting. The results showed an increase in P-MLKL and P-RIP3 in neurons exposed to NMDA, which was reduced following Lico-A treatment. The response of astrocyte and microglia was also evaluated by immunostaining for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA-1) and tumor necrosis factor alpha (TNF-α). These markers exhibited heightened expression in the NMDA group, which was substantially reduced by Lico-A treatment. These findings suggest that Lico-A has neuroprotective effects against NMDA-induced neurotoxicity, potentially contributing to synaptic preservation, inhibition of neuronal necroptosis, and modulation of glial activation. Therefore, Lico-A shows promise as a neuroprotective agent for conditions associated with NMDA-related neurotoxicity.

Background: With improvements in cardiopulmonary resuscitation (CPR) techniques, the quality and the effectiveness of CPR have been established; nevertheless, the survival rate after cardiac arrest still remains poor. Recently, many reports have shown good outcomes in cases where extracorporeal membrane oxygenation (ECMO) was used during prolonged CPR. Accordingly, we attempted to evaluate the impact of extracorporeal cardiopulmonary resuscitation (ECPR) on the survival of patients who experienced a prolonged cardiac arrest and compared it with that of conventional CPR (CCPR). Methods: Between March 2009 and April 2014, CPR, including both in-hospital and out-of-hospital CPR, was carried out in 955 patients. The ECPR group, counted from the start of the ECPR program in March 2010, included 81 patients in total, and the CCPR group consisted of 874 patients. All data were retrospectively collected from the patients’ medical records. Results: The return of spontaneous circulation (ROSC) rate was 2.24 times better in CPR of in-hospital cardiac arrest (IHCA) patients than in CPR of out-of-hospital CA (OHCA) patients (p=0.0012). For every 1-minute increase in the CPR duration, the ROSC rate decreased by 1% (p=0.0228). Further, for every 10-year decrease in the age, the rate of survival discharge increased by 31%. The CPR of IHCA patients showed a 2.49 times higher survival discharge rate than the CPR of OHCA patients (p=0.03). For every 1-minute increase in the CPR duration, the rate of survival discharge was decreased by 4%. ECPR showed superiority in terms of the survival discharge in the univariate analysis, although with no statistical significance in the multivariate analysis. Conclusion: The survival discharge rate of the ECPR group was comparable to that of the CCPR group. As the CPR duration increased, the survival discharge and the ROSC rate decreased. Therefore, a continuous effort to reduce the time for the decision of ECMO initiation and ECMO team activation is necessary, particularly during the CPR of relatively young patients and IHCA patients.

A 38-year-old male was admitted with symptoms of upper respiratory infection. Despite medical treatment, his symptoms of dyspnea and anxiety became aggravated, and bilateral lung infiltration was noted on radiological imaging studies. His hypoxemia failed to improve even after the application of endotracheal intubation with mechanical ventilator care, and we therefore decided to initiate venovenous extracorporeal membrane oxygenation (VV ECMO) for additional pulmonary support. On his twentieth day of hospitalization, hypotension and desaturation (arterial saturated oxygen ＜85%) developed, and right ventricular failure was confirmed by two-dimensional echocardiography. Therefore, we changed from VV ECMO to venoarteriovenous (VAV) ECMO, and the patient ultimately recovered. In this case, right ventricular dysfunction and volume overloading were induced by long-term VV ECMO therapy, and we successfully treated these conditions by changing to VAV ECMO.

ObjectivesHearing impairment (HI) is the most common sensory deficit in human. The Gap Junction Protein, Beta-2 (GJB2) gene encodes the protein connexin 26, and this gene accounts for up to half of the cases of autosomal recessive nonsyndromic HI. This study was conducted to obtain a set of sequence variations (SVs) of the GJB2 gene among Koreans from the general population for making molecular genetic diagnoses and performing genetic counseling.MethodsWe resequenced the GJB2 gene in 192 chromosomes from 96 adult individuals of Korean descent and who were without a history of hearing difficulty. The data of the SVs was obtained and the haplotypes were reconstructed from the data.ResultsFive SVs were observed, including a novel one (c.558G>A; p.T186T), with the allele frequencies ranging from 0.5% (1/192) to 41% (79/192). The linkage disequilibrium study and haplotype construction showed that some of the SVs are in tight linkage, resulting in a limited number of haplotypes.ConclusionWe observed SVs of the GJB2 gene with different allele frequencies, and a limited number of haplotypes were constructed. The data from this study can be used as reference data for GJB2-related hearing genetic studies, including studies on the founder effect and population genetics, and this data is particularly relevant to people of East Asian decent.

Spinal cord injury (SCI) is one of the most devastating medical conditions; however, currently, there are no effective pharmacological interventions for SCI. Ginsenoside Rg3 (GRg3) is one of the protopanaxadiols that show anti-inflammatory, anti-oxidant, and neuroprotective effects. The present study investigated the neuroprotective effect of GRg3 following SCI in rats. SCI was induced using a static compression model at vertebral thoracic level 10 for 5 min. GRg3 was administrated orally at a dose of 10 or 30 mg/kg/day for 14 days after the SCI. GRg3 (30 mg/kg) treatment markedly improved behavioral motor functions, restored lesion size, preserved motor neurons in the spinal tissue, reduced Bax expression and number of TUNEL-positive cells, and suppressed mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. GRg3 also attenuated the over-production of cyclooxygenase-2 and inducible nitric oxide synthase after SCI. Moreover, GRg3 markedly suppressed microglial activation in the spinal tissue. In conclusion, GRg3 treatment led to a remarkable recovery of motor function and a reduction in spinal tissue damage by suppressing neuronal apoptosis and inflammatory responses after SCI. These results suggest that GRg3 may be a potential therapeutic agent for the treatment of SCI.

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinson's disease (PD) related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD.

Background The recent advent of genome-wide molecular platforms has facilitated our understanding of the human genome and disease, particularly copy number aberrations. We performed genome-wide single nucleotide polymorphism-array in hereditary coagulopathy to delineate the extent of copy number mutations and to assess its diagnostic utility.Design and Methods The study subjects were 17 patients with hereditary coagulopathy from copy number mutations in coagulation genes detected by multiple ligation-dependent probe amplification. Eleven had hemophilia (7 hemophilia A and 4 hemophilia B) and 6 had thrombophilia (4 protein S deficiency and 2 antithrombin deficiency). Single nucleotide polymorphism-array experiments were performed using Affymetrix Genome-Wide Human SNP arrays 6.0.Results Copy number mutations were identified by single nucleotide polymorphism-array in 9 patients, which ranged in length from 51 Kb to 6,288 Kb harboring 2 to ~160 genes. Single nucleotide polymorphism-array showed a neutral copy number status in 8 patients including 7 with either a single-exon copy number mutation or duplication mutations of PROS1.Conclusions This study revealed unexpectedly heterogeneous lengths of copy number mutations underlying human coagulopathy. Single nucleotide polymorphism-array had limitations in detecting copy number mutations involving a single exon or those of a gene with homologous sequences such as a pseudogene.

The molecular basis of heat shock response (HSR), a cellular defense mechanism against various stresses, is not well understood. In this, the first comprehensive analysis of gene expression changes in response to heat shock and MG132 (a proteasome inhibitor), both of which are known to induce heat shock proteins (Hsps), we compared the responses of normal mouse fibrosarcoma cell line, RIF-1, and its thermotolerant variant cell line, TR-RIF-1 (TR), to the two stresses. The cellular responses we examined included Hsp expressions, cell viability, total protein synthesis patterns, and accumulation of poly-ubiquitinated proteins. We also compared the mRNA expression profiles and kinetics, in the two cell lines exposed to the two stresses, using microarray analysis. In contrast to RIF-1 cells, TR cells resist heat shock caused changes in cell viability and whole-cell protein synthesis. The patterns of total cellular protein synthesis and accumulation of poly-ubiquitinated proteins in the two cell lines were distinct, depending on the stress and the cell line. Microarray analysis revealed that the gene expression pattern of TR cells was faster and more transient than that of RIF-1 cells, in response to heat shock, while both RIF-1 and TR cells showed similar kinetics of mRNA expression in response to MG132. We also found that 2,208 genes were up-regulated more than 2 fold and could sort them into three groups: 1) genes regulated by both heat shock and MG132, (e.g. chaperones); 2) those regulated only by heat shock (e.g. DNA binding proteins including histones); and 3) those regulated only by MG132 (e.g. innate immunity and defense related molecules). This study shows that heat shock and MG132 share some aspects of HSR signaling pathway, at the same time, inducing distinct stress response signaling pathways, triggered by distinct abnormal proteins.

Conclusions: Frailty, but not prefrailty, appeared to be an independent factor associated with poor analgesic efficacy of ESI in elderly patients with symptomatic degenerative lumbar spinal disease receiving conservative care.

Introduction: The rapid spread of COVID-19 worldwide within 2 months demonstrated the vulnerability of the world's population to infectious diseases. In 2015, the Global Antimicrobial Resistance and Use Surveillance System (GLASS) was launched to combat antimicrobial resistance (AMR). However, there has been no comprehensive assessment of the decade-long global battle against AMR based on GLASS data. Methods: South Korea established Kor-GLASS (Korean-GLASS) to proactively monitor data quality and enable international collaborations. A unique feature of Kor-GLASS is the quality control center (QCC), which uses network hubs and ensures standardized, high-quality data through interlaboratory proficiency testing (IPT) and external quality assessment (EQA). In addition, the QCC multifaceted endeavors for integrated data quality management. Results: Since 2020, high-quality AMR data have indicated fluctuating antibiotic resistance rates in South Korea. This trend does not align with the decrease in antibiotic usage seen in humans but coincides with non-human antibiotic sales, indicating a need for greater monitoring of non-human antibiotic resistance. Comprehensive and robust management taking account of the intricate interplay among humans, animals, and the environment is essential. Kor-GLASS has been expanded into a "One Health" multiagency collaborative initiative. Discussion: Although a standardized solution is not suitable for all countries, it must alignwith the local context and international standards. A centralized top-down management structure such as that of the QCC is essential to ensure continuous data quality coordination. Sustained efforts and surveillance systems are crucial for monitoring and managing AMR and safeguarding human health. [ABSTRACT FROM AUTHOR]

Purpose: The global older adult population is rapidly growing, intensifying the burden of elderly care. To alleviate this challenge of an aging society, interventions utilizing artificial intelligence (AI) technology are becoming widespread. This review aimed to examine the effects of AI robot interventions on the psychological outcomes of community-dwelling older adults through a systematic literature review. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was employed to identify and select relevant studies. Seven electronic databases were thoroughly searched for eligible studies from June 1st to 30th, 2023. Methodological quality was assessed using RoB 2.0 or RoBANS 2. Results: Thirteen studies (five randomized controlled trials and eight quasi-experimental studies) were selected in the systematic review. Among the selected studies, eight provided AI robot interventions individually, whereas five used a group format, primarily addressing older adults with cognitive impairment or dementia. Depression was the most frequently addressed psychological outcome, with six of ten studies reporting significant effects. Additionally, five studies each highlighted significant effects on emotions, such as positive expressiveness and enjoyment. However, quality of life, anxiety, and loneliness revealed divergent results. Conclusion: AI robots show potential in alleviating psychological challenges for older adults. However, due to the scarcity of high-quality studies, the review recommends conducting more randomized controlled trials with rigorous designs. This review is expected to provide valuable insights for planning and executing AI robot interventions to improve psychological outcomes for community-dwelling older adults in future research. [ABSTRACT FROM AUTHOR]

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1–3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4–18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the efficacy and safety of baclofen and gabapentin in reducing leg pain from nocturnal calf cramps in lumbar spinal stenosis patients. Design: In a randomized clinical trial, the patients with lumbar spinal stenosis who commonly experienced nocturnal calf cramps were included. Patients were randomly assigned to either the baclofen or gabapentin group. Overall leg pain intensity, nocturnal calf cramp frequency and severity, sleep disturbances and functional disability were assessed at baseline and after 4 and 12 wks. Results: Thirty-six patients completed the 3-mo study. Both gabapentin and baclofen groups showed a significant reduction in overall leg pain, calf cramp frequency and intensity, and insomnia severity index scores frombaseline to the endpoint. However, therewere no significant differences between the two groups in terms of symptom reduction at different time points. The baclofen group also demonstrated a significant decrease in Oswestry Disability Index scores (P < 0.001), while the gabapentin group did not (P = 0.344). No adverse effects were reported in either group. Conclusions: Baclofen seems to be as effective and as safe as gabapentin in treating nocturnal calf cramps in lumbar spinal stenosis patients and even shows superiority in enhancing functional outcomes. [ABSTRACT FROM AUTHOR]

Normal variants refer to imaging findings that are generally asymptomatic and discovered incidentally, yet may exhibit findings similar to those observed in pathological conditions. Recognizing normal variants in pediatric bone requires comprehension of the developmental process of long tubular bones and secondary ossification centers. Familiarity with various radiological findings of normal variants can prevent unnecessary follow-up imaging tests, as well as incorrect diagnosis and treatment. In this review, we will discuss the characteristic imaging findings of normal variants seen in growing pediatric bones, along with strategies for distinguishing them from pathologic conditions. [ABSTRACT FROM AUTHOR]

Perovskite solar cells (PSCs) have shown remarkable advancements and achieved impressive power conversion efficiencies since their initial introduction in 2012. However, challenges regarding stability, quality, and sustainability must be addressed for their successful commercial use. This review analyses the recent studies and challenges related to the operating life and end-of-life utilization of PSCs. Strategies to enhance the stability and mitigate the toxic Pb leakage in operational and recycling approaches of discarded PSCs post their end-of-life are examined to establish a viable and sustainable PSC industry. Additionally, future research directions are proposed for the advancements in the PSC industry. The goal is to ensure high efficiency as well as economic and environmental sustainability throughout the lifecycle of PSCs. [ABSTRACT FROM AUTHOR]