Study on the feasibility of using livestock blood as a fetal bovine serum substitute for cultured meat.

Fetal bovine serum (FBS) accounts for the largest portion of the cost of cultured meat production or cell culture experiments and is highly controversial in terms of animal welfare because it is taken from the fetus of a pregnant cow during slaughtering. Nevertheless, FBS is the most important supplement in the cell culture manufacturing process. This study aimed to develop an FBS substitute from slaughterhouse waste blood to reduce the cost of FBS in cultured meat production through various experiments. Our study successfully demonstrated that adult livestock blood obtained from slaughterhouses can effectively replace FBS. Our substitute, when cultured with bovine myosatellite cells, demonstrated cell growth that was either equivalent to or superior to that of commercial FBS. In the process of muscle generation through differentiation, the substitutes from bovine and chicken formed 70%-75% more bovine muscle compared to the control group using FBS. Furthermore, using the FBS substitute can reduce cell culture costs by approximately 61% compared to using commercial FBS. Therefore, the groundbreaking FBS substitute will not only contribute to the development of technology to mass-produce cultured meat using livestock byproducts but will also lower the production cost of media for experimental cell culture or vaccine production.

Gene Therapy for Cardiovascular Disease: Clinical Perspectives.

Cardiovascular disease (CVD) stands as one of the leading causes of death in the United States, with its prevalence steadily on the rise. Traditional therapeutic approaches, such as pharmacological treatment, cardiovascular intervention, and surgery, have inherent limitations. In response to these challenges, cardiac gene therapy has emerged as a promising alternative for treating CVD patients. However, several obstacles persist, including the low efficiency of gene transduction, immune reactions to vectors or transduced cells, and the occurrence of off-target effects. While preclinical research has demonstrated significant success in various CVD model in both small and large animals, the translation of these findings to clinical applications has, for the most part, yielded disappointing results, except for some early, albeit small, trials. This review aims to provide a comprehensive summary of recent preclinical and clinical studies on gene therapy for various CVDs. Additionally, we discuss the existing limitations and challenges that hinder the widespread clinical application of cardiac gene therapy.

Functional Role of Piezo1 in the Human Eosinophil Cell Line AML14.3D10: Implications for the Immune and Sensory Nervous Systems.

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected Piezo1 mRNA expression, but not Piezo2 expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd3+, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems.

Anticancer Effects of BAF312 (Siponimod) in Epithelial Ovarian Cancer.

BACKGROUND/AIM: Epithelial ovarian cancer (EOC) is a lethal disease that is the fifth leading cause of cancer-related death in women. BAF312 (siponimod) is a potent and selective sphingosine-1-phosphate (S1P) receptor modulator that has been approved as a treatment for multiple sclerosis. In addition to its immunomodulatory action, BAF312 shows preclinical antitumor effects in several cancer types. This study sought to determine whether BAF312 had anticancer properties against EOC using in vitro and in vivo models. MATERIALS AND METHODS: EOC cell lines A2780, SKOV3ip1, A2780-CP20, and SKOV3-TR were treated with BAF312 and tested for cell proliferation, apoptosis, and migration using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence-activated cell sorting, and migration assays. We investigated the expression of sphingosine-1-phosphate receptor 1 (S1PR1) in most EOC cell lines through western blot analysis. To investigate potential mechanisms, western blot analysis was used to assess the expression of AKT serine/threonine kinase 1 (AKT) and extracellular-regulated kinase (ERK) after BAF312 treatment. We also created poly(D,L-lactide-co-glycolide) nanoparticles encapsulating BAF312 (PLGA-NP-BAF312) for in vivo therapy. The average size and zeta potential of PLGA-NP-BAF312 were determined using dynamic light scattering. The therapeutic efficacy of PLGA-NP-BAF312 was tested in an A2780 tumor-bearing orthotopic mouse model of EOC. RESULTS: S1PR1 was overexpressed in most EOC cell lines. BAF312 significantly reduced cell proliferation and migration while inducing significant apoptosis in all EOC cell lines. PLGA-NP-BAF312 treatment significantly reduced tumor weights in A2780 tumor-bearing mice. Furthermore, the anticancer effects of BAF312 were associated with reduced phosphorylation of ERK and AKT. CONCLUSION: Our findings show that BAF312 has significant anticancer effects in EOC cells by inhibiting the ERK and AKT pathways, and might potentially be used to treat EOCs.

The Gastroprotective Effect of Sicyos angulatus Against Hydrochloric Acid/Ethanol-Induced Acute Gastritis and Gastric Ulcer in Mice.

Gastritis and gastric ulcers are common gastric diseases that are caused by infection, drugs, alcohol consumption, or stress. These conditions lead to increased inflammatory cytokines and recruitment of leukocytes, which damage the stomach mucosa and exacerbate disease severity. Sicyos angulatus (SA), an annual vine in the Cucurbitaceae family, is known to have an anti-inflammatory effect, but its efficacy for preventing gastritis and gastric ulcers has not yet been evaluated. In the present study, we investigated the gastroprotective effect of SA using a hydrochloric acid/ethanol-induced gastric mucosal injury mouse model and lipopolysaccharide (LPS)-stimulated KATO III cells. Macroscopic analysis revealed a reduction in gastric ulcer area. Similarly, histopathological analysis showed a dose-dependent decrease in gastric mucosal injury, with significant improvement at 750 mg/kg of SA treatment. Gene expressions of inflammatory cytokines, chemokines, and adhesion molecule were reduced in the SA-administered group. Immunohistochemical staining indicated that SA significantly decreased neutrophil infiltration in the lamina propria and epithelium of the stomach. Kaempferol, a major bioactive flavonoid of SA, also improved gastric injury by reducing macroscopic and microscopic lesions, inflammatory mediator gene expression, and neutrophil infiltration. Furthermore, both SA and kaempferol downregulated LPS-mediated increases in inflammatory cytokines and chemokines following inhibition of p38 and c-Jun N-terminal kinase (JNK) phosphorylation in KATO III cells. These results suggest that SA can ameliorate gastric mucosal injury by inhibiting the recruitment of inflammatory cells, particularly neutrophils, and by suppressing p38 and JNK phosphorylation.

Extracellular microvesicle microRNAs, along with imaging metrics, improve detection of aggressive prostate cancer.

Prostate cancer is the most commonly diagnosed cancer in men worldwide. Early diagnosis of the disease provides better treatment options for these patients. Magnetic resonance imaging (MRI) provides an overall assessment of prostate disease. Quantitative metrics (radiomics) from the MRI provide a better evaluation of the tumor and have been shown to improve disease detection. Recent studies have demonstrated that plasma extracellular vesicle microRNAs (miRNAs) are functionally linked to cancer progression, metastasis, and aggressiveness. In our study, we analyzed a matched cohort with baseline blood plasma and MRI to access tumor morphology using imaging-based radiomics and cellular characteristics using miRNAs-based transcriptomics. Our findings indicate that the univariate feature-based model with the highest Youden's index achieved average areas under the receiver operating characteristic curve (AUC) of 0.76, 0.82, and 0.84 for miRNA, MR-T2W, and MR-ADC features, respectively, in identifying clinically aggressive (Gleason grade) disease. The multivariable feature-based model demonstrated an average AUC of 0.88 and 0.95 using combinations of miRNA markers with imaging features in MR-ADC and MR-T2W, respectively. Our study demonstrates combining miRNA markers with MRI-based radiomics improves predictability of clinically aggressive prostate cancer.

Laparoscopic management of bowel perforation secondary to levonorgestrel-releasing intrauterine device migration: a case report and review of literature.

Bowel perforation secondary to a levonorgestrel-releasing intrauterine device is exceptionally rare. We present the case of a woman who exhibited abnormal findings during a colonoscopy examination. Despite undergoing an intrauterine device (IUD) insertion procedure for contraception in 2000, attempts for its removal in 2007 were unsuccessful due to the inability to locate the IUD. In 2022, she presented with intermittent hematochezia and lower left abdominal pain. Subsequent colonoscopy and abdominal computed tomography confirmed the presence of the IUD penetrating the uterine wall and entering the colon. Laparoscopic anterior resection was performed, and the patient's postoperative recovery was uneventful, indicating the viability of laparoscopic treatment as a valuable option.

Anticancer effect of the antipsychotic agent penfluridol on epithelial ovarian cancer.

OBJECTIVE: Chemoresistant-epithelial ovarian cancer (EOC) has a poor prognosis, prompting the search for new therapeutic drugs. The diphenylbutylpiperidine (DPBP) class of antipsychotic drugs used in schizophrenia has shown anticancer effects. This study aimed to investigate the preclinical efficacy of penfluridol, fluspirilene, and pimozide (DPBP) using in vitro and in vivo models of EOC. METHODS: Human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with penfluridol, fluspirilene, and pimozide, and cell proliferation, apoptosis, and migration were assessed. The preclinical efficacy of DPBP was also investigated using in vivo mouse models, including cell lines and patient-derived xenografts (PDX) of EOC. RESULTS: DPBP drugs significantly decreased cell proliferation in chemosensitive (A2780, HeyA8, and SKOV3ip1) and chemoresistant (A2780-CP20, HeyA8-MDR, and SKOV3-TR) cell lines. Among these drugs, penfluridol exerted a relatively stronger cytotoxic effect on all cell lines. Penfluridol significantly increased apoptosis and inhibited migration of EOC cells. In the cell line xenograft mouse model with HeyA8, the penfluridol group showed significantly decreased tumor weight compared with the control group. In the paclitaxel-resistant model with HeyA8-MDR, the penfluridol group had significantly decreased tumor weight compared with the paclitaxel or control groups. Penfluridol exerted anticancer effects on the PDX model. CONCLUSION: Penfluridol exerted significant anticancer effects on EOC cells and xenograft models, including PDX. Thus, penfluridol therapy, as a drug repurposing strategy, might be a potential therapeutic for EOCs.

Prime-boost immunization with inactivated human adenovirus type 55 combined with an adjuvant enhances neutralizing antibody responses in mice.

BACKGROUND: Human adenovirus type 55 (hAd55) infection can lead to acute respiratory diseases that often present with severe symptoms. Despite its persistent prevalence in military camps and communities, there are no commercially available vaccines or vaccine candidates undergoing clinical evaluation; therefore, there is an urgent need to address this. In this study, we evaluated the immunogenicity of inactivated hAd55 isolates and investigated the effects of adjuvants and various immunization intervals. METHODS AND RESULTS: To select a vaccine candidate, four hAd55 strains (6-9, 6-15 (AFMRI 41014), 28-48 (AFMRI 41013), and 12-164 (AFMRI 41012)) were isolated from infected patients in military camps. Sequence analysis revealed no variation in the coding regions of structural proteins, including pentons, hexons, and fibers. Immunization with inactivated hAd55 isolates elicited robust hAd55-specific binding and neutralizing antibody responses in mice, with adjuvants, particularly alum hydroxide (AH), enhancing antibody titers. Co-immunization with AH also induced hAd14-specific neutralizing antibody responses but did not induce hAd11-specific neutralizing antibody responses. Notably, booster immunization administered at a four-week interval resulted in superior immune responses compared with shorter immunization intervals. CONCLUSIONS: Prime-boost immunization with the inactivated hAd55 isolate and an AH adjuvant shows promise as a potential approach for preventing hAd55-induced respiratory disease. Further research is needed to evaluate the efficacy and safety of these vaccine candidates in preventing hAd55-associated respiratory illnesses.

Damage-Free Plasma Source for Atomic-Scale Processing.

As atomic-scale etching and deposition processes become necessary for manufacturing logic and memory devices at the sub-5 nm node, the limitations of conventional plasma technology are becoming evident. For atomic-scale processes, precise critical dimension control at the sub-1 nm scale without plasma-induced damage and high selectivity between layers are required. In this paper, a plasma with very low electron temperature is applied for damage-free processing on the atomic scale. In plasmas with an ultralow electron temperature (ULET, Te < 0.5 eV), ion energies are very low, and the ion energy distribution is narrow. The absence of physical damage in ULET plasma is verified by exposing 2D structural material. In the ULET plasma, charging damage and radiation damage are also expected to be suppressed due to the extremely low Te. This ULET plasma source overcomes the limitations of conventional plasma sources and provides insights to achieve damage-free atomic-scale processes.

Case Report: Superior mesenteric artery vasculitis causing aneurysm following COVID-19 infection.

Objective: Arteritis refers to all infectious and non-infectious conditions that lead to inflammation of the arterial wall. However, little is known about its presence in patients with coronavirus disease 2019 (COVID-19). Most patients improved with steroids along with conservative treatments in a few studies. We report our experience with superior mesenteric artery (SMA) arteritis causing an aneurysm following COVID-19 infection. Case presentation: A 66-year-old female patient who was infected with COVID-19 1 month prior presented with abdominal pain. A computed tomography scan revealed proximal SMA arteritis. Although preliminary antibacterial treatment was initiated, the follow-up CT revealed an aggressive and fast-growing 5.7-cm SMA aneurysm. Subsequently, an open interposition bypass of the SMA aneurysm was performed successfully. As the specimens retrieved during surgery showed no bacterial colonization in the tissue or blood cultures, the patient was discharged without complications. Conclusions: The mechanism of arteritis in patients with COVID-19 has not been elucidated. In the absence of evidence of bacterial infection in arteritis, it is necessary to consider the possibility of viral infection caused by COVID-19 during the COVID-19 pandemic era and start with high-dose steroid therapy promptly.

Sensitive label free imaging of 3D cell models with minimal toxicity using confocal reflectance.

Confocal reflectance imaging typically suffers from high background and poor sensitivity. We demonstrate sensitive and low-background reflectance imaging of cells encapsulated in transparent 3D hydrogels. Nanoscale cell morphology is visualized with sensitivity similar to confocal fluorescence, with low laser power, minimal specimen preparation, and reduced toxicity.

Detecting M-Protein via Mass Spectrometry and Affinity Beads: Enrichment With Mixed Kappa-Lambda Beads Enables Prompt Application in Clinical Laboratories.

Background: Detecting monoclonal protein (M-protein), a hallmark of plasma cell disorders, traditionally relies on methods such as protein electrophoresis, immune-electrophoresis, and immunofixation electrophoresis (IFE). Mass spectrometry (MS)-based methods, such as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization-quadrupole time-of-flight (ESI-qTOF) MS, have emerged as sensitive methods. We explored the M-protein-detection efficacies of different MS techniques. Methods: To isolate immunoglobulin and light chain proteins, six types of beads (IgG, IgA, IgM, kappa, lambda, and mixed kappa and lambda) were used to prepare samples along with CaptureSelect nanobody affinity beads (NBs). After purification, both MALDI-TOF MS and liquid chromatography coupled with Synapt G2 ESI-qTOF high-resolution MS analysis were performed. We purified 25 normal and 25 abnormal IFE samples using NBs and MALDI-TOF MS (NB-MALDI-TOF). Results: Abnormal samples showed monoclonal peaks, whereas normal samples showed polyclonal peaks. The IgG and mixed kappa and lambda beads showed monoclonal peaks following the use of daratumumab (an IgG/kappa type of monoclonal antibody) with both MALDI-TOF and ESI-qTOF MS analysis. The limits of detection for MALDI-TOF MS and ESI-qTOF MS were established as 0.1 g/dL and 0.025 g/dL, respectively. NB-MALDI-TOF and IFE exhibited comparable sensitivity and specificity (92% and 92%, respectively). Conclusions: NBs for M-protein detection, particularly with mixed kappa-lambda beads, identified monoclonal peaks with both MALDI-TOF and ESI-qTOF analyses. Qualitative analysis using MALDI-TOF yielded results comparable with that of IFE. NB-MALDI-TOF might be used as an alternative method to replace conventional tests (such as IFE) to detect M-protein with high sensitivity.

Minimal Access vs Conventional Nipple-Sparing Mastectomy.

Importance: While nipple-sparing mastectomy (NSM) for breast cancer was only performed using the open method in the past, its frequency using endoscopic and robotic surgical instruments has been increasing rapidly. However, there are limited studies regarding postoperative complications and the benefits and drawbacks of minimal access NSM (M-NSM) compared with conventional NSM (C-NSM). Objective: To examine the differences in postoperative complications between C-NSM and M-NSM. Design, Setting, Participants: This was a retrospective multicenter cohort study enrolling 1583 female patients aged 19 years and older with breast cancer who underwent NSM at 21 university hospitals in Korea between January 2018 and December 2020. Those with mastectomy without preserving the nipple-areolar complex (NAC), clinical or pathological malignancy in the NAC, inflammatory breast cancer, breast cancer infiltrating the chest wall or skin, metastatic breast cancer, or insufficient medical records were excluded. Data were analyzed from November 2021 to March 2024. Exposures: M-NSM or C-NSM. Main Outcomes and Measures: Clinicopathological factors and postoperative complications within 3 months of surgery were assessed. Statistical analyses, including logistic regression, were used to identify the factors associated with complications. Results: There were 1356 individuals (mean [SD] age, 45.47 [8.56] years) undergoing C-NSM and 227 (mean [SD] age, 45.41 [7.99] years) undergoing M-NSM (35 endoscopy assisted and 192 robot assisted). There was no significant difference between the 2 groups regarding short- and long-term postoperative complications (<30 days: C-NSM, 465 of 1356 [34.29%] vs M-NSM, 73 of 227 [32.16%]; P = .53; <90 days: C-NSM, 525 of 1356 [38.72%] vs M-NSM, 73 of 227 [32.16%]; P = .06). Nipple-areolar complex necrosis was more common in the long term after C-NSM than M-NSM (C-NSM, 91 of 1356 [6.71%] vs M-NSM, 5 of 227 [2.20%]; P = .04). Wound infection occurred more frequently after M-NSM (C-NSM, 58 of 1356 [4.28%] vs M-NSM, 18 of 227 [7.93%]; P = .03). Postoperative seroma occurred more frequently after C-NSM (C-NSM, 193 of 1356 [14.23%] vs M-NSM, 21 of 227 [9.25%]; P = .04). Mild or severe breast ptosis was a significant risk factor for nipple or areolar necrosis (odds ratio [OR], 4.75; 95% CI, 1.66-13.60; P = .004 and OR, 8.78; 95% CI, 1.88-41.02; P = .006, respectively). Conversely, use of a midaxillary, anterior axillary, or axillary incision was associated with a lower risk of necrosis (OR for other incisions, 32.72; 95% CI, 2.11-508.36; P = .01). Necrosis occurred significantly less often in direct-to-implant breast reconstruction compared to other breast reconstructions (OR, 2.85; 95% CI, 1.11-7.34; P = .03). Conclusions and Relevance: The similar complication rates between C-NSM and M-NSM demonstrates that both methods were equally safe, allowing the choice to be guided by patient preferences and specific needs.

Thermomechanical Processing for Improved Mechanical Properties of HT9 Steels.

Thermomechanical processing (TMP) of ferritic-martensitic (FM) steels, such as HT9 (Fe-12Cr-1MoWV) steels, involves normalizing, quenching, and tempering to create a microstructure of fine ferritic/martensitic laths with carbide precipitates. HT9 steels are used in fast reactor core components due to their high-temperature strength and resistance to irradiation damage. However, traditional TMP methods for these steels often result in performance limitations under irradiation, including embrittlement at low temperatures (<~430 °C), insufficient strength and toughness at higher temperatures (>500 °C), and void swelling after high-dose irradiation (>200 dpa). This research aimed to enhance both fracture toughness and strength at high temperatures by creating a quenched and tempered martensitic structure with ultrafine laths and precipitates through rapid quenching and unconventional tempering. Mechanical testing revealed significant variations in strength and fracture toughness depending on the processing route, particularly the tempering conditions. Tailored TMP approaches, combining rapid quenching with limited tempering, elevated strength to levels comparable to nano-oxide strengthened ferritic alloys while preserving fracture toughness. For optimal properties in high-Cr steels for future reactor applications, this study recommends a modified tempering treatment, i.e., post-quench annealing at 500 °C or 600 °C for 1 h, possibly followed by a brief tempering at a slightly higher temperature.

Decreased Serum Cocaine- and Amphetamine-Regulated Transcript Level in Internet Gaming Disorder.

OBJECTIVE: Vulnerability to internet gaming disorder (IGD) has increased as internet gaming continues to grow. Cocaine- and amphetamine-regulated transcript (CART) is a hormone that plays a role in reward, anxiety, and stress. The purpose of this study was to identify the role of CART in the pathophysiology of IGD. METHODS: The serum CART levels were measured by enzyme-linked immunosorbent assay, and the associations of the serum CART level with psychological variables were analyzed in patients with IGD (n=31) and healthy controls (HC) (n=42). RESULTS: The serum CART level was significantly lower in the IGD than HC group. The IGD group scored significantly higher than the HC group on the psychological domains of depression, anxiety, the reward response in the Behavioral Activation System and Behavioral Inhibition System. There were no significant correlations between serum CART level and other psychological variables in the IGD group. CONCLUSION: Our results indicate that a decrease in the expression of the serum CART level is associated with the vulnerability of developing IGD. This study supports the possibility that CART is a biomarker in the pathophysiology of IGD.

PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation.

The mRNA 5'cap-binding eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in the control of mRNA translation in health and disease. One mechanism of regulation of eIF4E activity is via phosphorylation of eIF4E by MNK kinases, which promotes the translation of a subset of mRNAs encoding pro-tumorigenic proteins. Work on eIF4E phosphatases has been paltry. Here, we show that PPM1G is the phosphatase that dephosphorylates eIF4E. We describe the eIF4E-binding motif in PPM1G that is similar to 4E-binding proteins (4E-BPs). We demonstrate that PPM1G inhibits cell proliferation by targeting phospho-eIF4E-dependent mRNA translation.

Nanoporous Carbon Materials as Solid Contacts for Microneedle Ion-Selective Sensors.

Continuous sensing of biomarkers, such as potassium ions or pH, in wearable patches requires miniaturization of ion-selective sensor electrodes. Such miniaturization can be achieved by using nanostructured carbon materials as solid contacts in microneedle-based ion-selective and reference electrodes. Here we compare three carbon materials as solid contacts: colloid-imprinted mesoporous (CIM) carbon microparticles with ∼24-28 nm mesopores, mesoporous carbon nanospheres with 3-9 nm mesopores, and Super P carbon black nanoparticles without internal porosity but with textural mesoporosity in particle aggregates. We compare the effects of carbon architecture and composition on specific capacitance of the material, on the ability to incorporate ion-selective membrane components in the pores, and on sensor performance. Functioning K+ and H+ ion-selective electrodes and reference electrodes were obtained with gold-coated stainless-steel microneedles using all three types of carbon. The sensors gave near-Nernstian responses in clinically relevant concentration ranges, were free of potentially detrimental water layers, and showed no response to O2. They all exhibited sufficiently low long-term potential drift values to permit calibration-free, continuous operation for close to 1 day. In spite of the different specific capacitances and pore architecture of the three types of carbon, no significant difference in potential stability for K+ ion sensing was observed between electrodes that used each material. In the observed drift values, factors other than the carbon solid contact are likely to play a role, too. However, for pH sensing, electrodes with CIM as a carbon solid contact, which had the highest specific capacitance and best access to the pores, exhibited better long-term stability than electrodes with the other carbon materials.

Association between E-Cigarette Smoking and Insulin Resistance Using the Triglyceride-Glucose Index in Korean Adults: Korea National Health and Nutrition Examination Survey.

Background: Insulin resistance contributes to the development of cardiovascular disease and type 2 diabetes mellitus. Smoking leads to an increase in triglyceride levels, which, in turn, increases insulin resistance. Although the number of e-cigarette users has increased in recent years, few studies have investigated the association between ecigarette use and insulin resistance. Therefore, this study aimed to determine the association between e-cigarette use and insulin resistance using the triglyceride-glucose (TyG) index in Korean adults. Methods: This study included 4,404 healthy adults aged ≥20 years who participated in the Korea National Health and Nutrition Examination Survey between 2019 and 2020. Participants were categorized as never-smokers or ecigarette users, and the TyG index was categorized into low- and high-TyG index groups according to the median value (9.22). A logistic regression analysis was performed to determine the association between e-cigarette smoking and insulin resistance. Results: E-cigarette users had a higher TyG index than never smokers (e-cigarette: mean=3.95; never: mean=9.18; P<0.001). The e-cigarette users had a higher risk of being in the high TyG index group than never-smokers (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.03-1.84). In the subgroup analysis stratified by sex, age, and body mass index, a higher OR for a high TyG index was observed in men (OR, 1.46; 95% CI, 1.03-2.08) and individuals aged 60 years or older (OR, 3.74; 95% CI, 1.14-12.30). Conclusion: Our findings suggest that e-cigarette use is significantly associated with insulin resistance.

Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.

BACKGROUND: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.