Assessment of acid catalytic properties of ferrosilicate MFI zeolite by methanol-to-hydrocarbon conversion.

Four representative synthetic methods were employed to prepare Fe-containing siliceous MFI zeolites. The obtained Fe-MFI zeolites exhibited markedly different catalytic performances in the methanol-to-hydrocarbon (MTH) conversion reaction depending on the type of Fe incorporation within the siliceous framework. The catalytically active Brønsted acid sites were analyzed using pyridine adsorption experiments combined with Fourier transform infrared spectroscopy, providing characteristic signal intensities according to the acid-base interactions. Based on the MTH conversion results and acidity analyses, a suitable synthetic method was identified for the incorporation of Fe within the MFI zeolite framework. However, compared to other catalytic reactions, structural analyses by transmission electron microscopy, ultraviolet-visible spectroscopy, and X-ray absorption spectroscopy were much less conclusive.

Genotype-Phenotype Correlations in 83 Korean X-linked Retinoschisis Patients: Impact of RS1 Secretion Profiles on Clinical Phenotypes.

PURPOSE: To assess the correlation between genotype and phenotype severity in X-linked juvenile retinoschisis (XLRS) by examining clinical and genetic features of a cohort of Korean XLRS patients. DESIGN: Retrospective, observational study. PARTICIPANTS: Data from 83 consecutive male patients with molecularly confirmed XLRS were collected retrospectively. METHODS: Clinical evaluation included best-corrected visual acuity (BCVA), fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinography (ERG). MAIN OUTCOME MEASURES: The phenotypic characteristics of a cohort of pediatric Korean XLRS patients, based on mutation types (truncating versus missense) and secretory profile (secretion versus non-secretion), were assessed. RESULTS: One hundred sixty-six eyes of 83 patients were included. The mean age at diagnosis was 6.1 ± 8.8 years (range, 0.5-20.7 years), with a mean follow-up time of 9.2 ± 7.0 years (range, 0.6-24.3 years). The BCVA at first and last examination ranged from light perception to 0.1 logarithm of the minimum angle of resolution (mean ± SD, 0.75 ± 0.59 and 0.82 ± 0.65, respectively). There were no significant differences in the first and last BCVA measurements between the truncating (0.71 ± 0.51 and 0.75 ± 0.44) and missense (0.77 ± 0.59 and 0.84 ± 0.66) variants (P = 0.678 and 0.551, respectively). Additionally, there were no differences in clinical parameters from fundus photography, SD-OCT, and full-field ERG. However, the BCVA at the first and last measurement were better for patients in the secretion group (0.51 ± 0.24 and 0.61 ± 0.30) compared to patients in the non-secretion group (0.65 ± 0.71 and 0.87 ± 0.81). The last BCVA showed a statistically significant difference between the two groups (P = 0.021). In OCT findings, the frequency of ellipsoid zone disruption was higher in patients with non-secretion variants than those with secretion variants (P = 0.030), with no significant differences in other parameters. CONCLUSIONS: The secretion profile of RS1 could influence the severity of XLRS phenotypes. Patients with RS1-secreted mutants, particularly with intact octamerization, exhibit more homogeneous phenotypes and better visual acuity than the RS1-non-secreted group. This data provides insights for studying genotype and phenotype correlations in both clinical and research fields.

Role of NOX1 and NOX5 in protein kinase C/reactive oxygen species­mediated MMP­9 activation and invasion in MCF­7 breast cancer cells.

NADPH oxidases (NOXs) are a family of membrane proteins responsible for intracellular reactive oxygen species (ROS) generation by facilitating electron transfer across biological membranes. Despite the established activation of NOXs by protein kinase C (PKC), the precise mechanism through which PKC triggers NOX activation during breast cancer invasion remains unclear. The present study aimed to investigate the role of NOX1 and NOX5 in the invasion of MCF­7 human breast cancer cells. The expression and activity of NOXs and matrix metalloprotease (MMP)­9 were assessed by reverse transcription­quantitative PCR and western blotting, and the activity of MMP­9 was monitored using zymography. Cellular invasion was assessed using the Matrigel invasion assay, whereas ROS levels were quantified using a FACSCalibur flow cytometer. The findings suggested that NOX1 and NOX5 serve crucial roles in 12­O­tetradecanoylphorbol­13­acetate (TPA)­induced MMP­9 expression and invasion of MCF­7 cells. Furthermore, a connection was established between PKC and the NOX1 and 5/ROS signaling pathways in mediating TPA­induced MMP­9 expression and cellular invasion. Notably, NOX inhibitors (diphenyleneiodonium chloride and apocynin) significantly attenuated TPA­induced MMP­9 expression and invasion in MCF­7 cells. NOX1­ and NOX5­specific small interfering RNAs attenuated TPA­induced MMP­9 expression and cellular invasion. In addition, knockdown of NOX1 and NOX5 suppressed TPA­induced ROS levels. Furthermore, a PKC inhibitor (GF109203X) suppressed TPA­induced intracellular ROS levels, MMP­9 expression and NOX activity in MCF­7 cells. Therefore, NOX1 and NOX5 may serve crucial roles in TPA­induced MMP­9 expression and invasion of MCF­7 breast cancer cells. Furthermore, the present study indicated that TPA­induced MMP­9 expression and cellular invasion were mediated through PKC, thus linking the NOX1 and 5/ROS signaling pathways. These findings offer novel insights into the potential mechanisms underlying their anti­invasive effects in breast cancer.

Guidelines for Antibacterial Treatment of Carbapenem-Resistant Enterobacterales Infections.

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.

Deciphering the links: Fragmented polystyrene as a driver of skin inflammation.

Nano- and microplastics (NMPs), ubiquitous in the environment, pose significant health risks. We report for the first time a comprehensive study using in-vitro, in-vivo, and ex-vivo models to investigate the penetration and inflammatory effects of fragmented polystyrene (fPS) on human skin, including the analysis of both penetration depth and fPS amounts that penetrate the skin. Human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells exposed to fPS exhibited notable internalization and cytotoxicity. In a 3D human skin model, fPS particles penetrated the dermal layer within one hour, with an average maximum penetration of 4.7 µg for particles smaller than 2 µm. Similarly, mouse dorsal skin and human abdominal skin models confirmed fPS penetration. RNA sequencing revealed substantial upregulation of inflammatory genes, including IL-1α, IL-1ß, IL-18, IL-6, IL-8, ICAM-1, FOS, and JUN, following fPS exposure. These findings were validated at both the mRNA and protein levels, indicating a robust inflammatory response. Notably, the inflammatory response in both the 3D human skin and mouse models increased in a dose-dependent manner, underscoring the toxicological impact of fPS on skin health. This study provides crucial insights into the mechanisms through which NMPs affect human health and underscores the need for further research to develop effective mitigation strategies.

Epidemiologic characteristics and risk factors of Clostridioides difficile infection in patients with active tuberculosis in the Republic of Korea: A nationwide population-based study.

BACKGROUND: The relationship between anti-tuberculosis (TB) agents and Clostridioides difficile infection (CDI) remains unclear. This study aimed to investigate the epidemiological characteristics and risk factors for CDI in patients with TB. METHODS: This nationwide, population-based cohort study was conducted in the Republic of Korea (ROK) between January 2018 and December 2022. Data were extracted from the National Health Insurance Service (NHIS) National Health Information Database. The risk factors for CDI in patients with TB were identified through multivariate logistic regression analysis using a 1:4 greedy matching method based on age and sex. RESULTS: During the study period, CDI developed in 2,901 of the 131,950 patients with TB who were prescribed anti-TB agents. The incidence of CDI in patients with TB has increased annually in the ROK from 12.31/1000 in 2018 to 33.51/1000 in 2022. Oral metronidazole (81.94%) was the most common first-line treatment for CDI. The in-hospital mortality rate of patients with concomitant CDI and tuberculosis was 9.9% compared with 6.9% in those with TB alone (P<0.0001). Multivariate logistic regression analysis found intensive care unit admission, Charlson Comorbidity Index ≥3, antibiotics exposure, standard regimen, multidrug resistant TB, and extrapulmonary TB as significant risk factors for development of CDI in patients with TB. CONCLUSION: CDI is uncommon in patients with TB, but it results in a significantly increased mortality rate. Patients being treated for TB should be carefully monitored for the development of CDI. Further clinical research is warranted to identify effective interventions for preventing and controlling CDI during TB treatment.

Thermodynamic phase control of Cu-Sn alloy electrocatalysts for selective CO2 reduction.

In the electrochemical CO2 reduction reaction (CO2RR), Cu alloy electrocatalysts can control the CO2RR selectivity by modulating the intermediate binding energy. Here, we report the thermodynamic-based Cu-Sn bimetallic phase control in heterogeneous catalysts for selective CO2 conversion. Starting from the thermodynamic understanding about Cu-Sn bimetallic compounds, we established the specific processing window for Cu-Sn bimetallic phase control. To modulate the Cu-Sn bimetallic phases, we controlled the oxygen partial pressure (pO2) during the calcination of electrospun Cu and Sn ions-incorporated nanofibers (NFs). This resulted in the formation of CuO-SnO2 NFs (full oxidation), Cu-SnO2 NFs (selective reduction), Cu3Sn/CNFs, Cu41Sn11/CNFs, and Cu6Sn5/CNFs (full reduction). In the CO2RR, CuO-SnO2 NFs exhibited formate (HCOO-) production and Cu-SnO2 NFs showed carbon monoxide (CO) production with the faradaic efficiency (FE) of 65.3% at -0.99 V (vs. RHE) and 59.1% at -0.89 V (vs. RHE) respectively. Cu-rich Cu41Sn11/CNFs and Cu3Sn/CNFs enhanced the methane (CH4) production with the FE of 39.1% at -1.36 V (vs. RHE) and 34.7% at -1.50 V (vs. RHE). However, Sn-rich Cu6Sn5/CNFs produced HCOO- with the FE of 58.6% at -2.31 V (vs. RHE). This study suggests the methodology for bimetallic catalyst design and steering the CO2RR pathway by controlling the active sites of Cu-Sn alloys.

Plectalibertellenone A suppresses colorectal cancer cell motility and glucose metabolism by targeting TGF-ß/Smad and Wnt pathways.

Colorectal cancer (CRC) is the second most common cause of cancer-related death and represents a serious worldwide health problem. CRC metastasis decreases the survival rate of cancer patients, underscoring the need to identify novel anticancer agents and therapeutic targets. Here, we introduce Plectalibertellenone A (B) as a promising agent for the inhibition of CRC cell motility and glucose metabolism and explore its mechanism of action in CRC cells. Plectalibertellenone A suppressed TGF-ß gene expression and the activation of the TGF-ß/Smad signaling pathway, leading to reverse epithelial to mesenchymal transition (EMT) by modulating the expressions of EMT markers and transcriptional factors such as E-cadherin, N-cadherin, vimentin, Slug, Snail, Twist, and ZEB1/2. Furthermore, disruption of Wnt signaling inhibited CRC motility and glucose metabolism including glycolysis and oxidative phosphorylation, primarily affecting glycolytic enzymes, GLUT1, HK2, PKM2, LDHA, and HIF-1α under hypoxic condition. Therefore, Plectalibertellenone A is a potential drug candidate that can be developed into a promising anticancer treatment to prevent CRC metastasis and inhibit glucose metabolism.

Comparative analysis of body composition using torso CT from PET/CT with bioelectrical impedance and muscle strength in healthy adults.

The role of torso computed tomography (CT) in evaluating body composition has been unexplored. This study assessed the potential of low-dose torso CT from positron emission tomography (PET)/CT for analyzing body composition and its relation to muscle strength. We retrospectively recruited 384 healthy Korean adults (231 men, 153 women) who underwent torso 18F-FDG PET/CT, bioelectrical impedance analysis (BIA), and muscle strength tests (handgrip strength [HGS] and knee extension strength [KES]). CT images were segmented into three compartments: torso volumetric, abdominal volumetric, and abdominal areal. Muscle amounts from each compartment were indexed to height (m2). BIA and HGS served as reference standards, with correlation coefficients (r) calculated. Torso muscle volumetric index (TorsoMVI) had the strongest correlations with BIA-derived values (r = 0.80 for men; r = 0.73 for women), surpassing those from the abdominal compartments. TorsoMVI was also correlated significantly with HGS (r = 0.39, p < 0.01) and differentiated between normal and possible sarcopenia in men (n = 225, 5960 ± 785 cm3/m2 vs. n = 6, 5210 ± 487 cm3/m2, p = 0.02). In women, KES correlated more strongly with muscle parameters than HGS. Despite gender-specific variations, torso CT-derived parameters show promise for evaluating body composition and sarcopenia.

Terpenoids and steroids from aerial parts of Achillea alpina L. as PTP1B inhibitors: Kinetic analysis and molecular docking studies.

Achillea alpina L. (Alpine yarrow) is a noteworthy herb in the genus Achillea with many uses in vegetables and traditionally used to treat stomach disorders. In our continuous research on the chemical constituents and biological activities of medicinal plants, ten previously undescribed terpenoids including eight eudesmane-type sesquiterpenes (1-8), one nor-eudesmane-type sesquiterpene (9), one cyclo-geraniol derivative (10), and twenty-one known compounds were isolated and structurally elucidated from the aerial parts of A. alpina. Structures and absolute configurations of the undescribed terpenoids were identified using comprehensive spectroscopic analysis (NMR, HRESI-MS, and CD data) and computational methods (ECD and NMR calculation). Enzyme inhibitory assays showed that the isolated sesquiterpene (19), triterpene (22), and sterol (26) were protein tyrosine phosphatase 1B (PTP1B) inhibitors with IC50 values ranging from 14.87 to 23.09 µM in comparison with positive control - ursolic acid, showing IC50 value of 5.93 ± 0.16 µM. Further enzyme kinetics and molecular docking studies were performed to provide valuable insights into their mechanism of action.

Progress of Metal Chalcogenides as Catalysts for Efficient Electrosynthesis of Hydrogen Peroxide.

Hydrogen peroxide (H2O2) is a high-demand chemical, valued as a powerful and eco-friendly oxidant for various industrial applications. The traditional industrial method for producing H2O2, known as the anthraquinone process, is both costly and environmentally problematic. Electrochemical synthesis, which produces H2O2 using electricity, offers a sustainable alternative, particularly suited for small-scale, continuous on-site H2O2 generation due to the portability of electrocatalytic devices. For efficient H2O2 electrosynthesis, electrocatalysts must exhibit high selectivity, activity, and stability for the two-electron pathway-oxygen reduction reaction (2e- ORR). Transition-metal chalcogenide (TMC)-based materials have emerged as promising candidates for effective 2e- ORR due to their high activity in acidic environments and the abundance of their constituent elements. This review examines the potential of TMC-based catalysts in H2O2 electrosynthesis, categorizing them into noble-metal and non-noble-metal chalcogenides. It underscores the importance of achieving high selectivity, activity, and stability in 2e- ORR. By reviewing recent advancements and identifying key challenges, this review provides valuable insights into the development of TMC-based electrocatalysts for sustainable H2O2 production.

Functional-hydrogel-based electronic-skin patch for accelerated healing and monitoring of skin wounds.

Conductive hydrogels feature reasonable electrical performance as well as tissue-like mechanical softness, thus positioning them as promising material candidates for soft bio-integrated electronics. Despite recent advances in materials and their processing technologies, however, facile patterning and monolithic integration of functional hydrogels (e.g., conductive, low-impedance, adhesive, and insulative hydrogels) for all-hydrogel-based soft bioelectronics still poses significant challenges. Here, we report material design, fabrication, and integration strategies for an electronic-skin (e-skin) patch based on functional hydrogels. The e-skin patch was fabricated by using photolithography-compatible functional hydrogels, such as poly(2-hydroxyethyl acrylate) (PHEA) hydrogel (substrate), Ag flake hydrogel (interconnection; conductivity: ∼571.43 S/cm), poly(3,4-ethylenedioxythiophene:polystyrene) (PEDOT:PSS) hydrogel (working electrode; impedance: ∼69.84 Ω @ 1 Hz), polydopamine (PDA) hydrogel (tissue adhesive; shear strength: ∼725.1 kPa), and poly(vinyl alcohol) (PVA) hydrogel (encapsulation). The properties of these functional hydrogels closely resemble those of human tissues in terms of water content and Young's modulus, enabling stable tissue-device interfacing in dynamically changing physiological environments. We demonstrated the efficacy of the e-skin patch through its application to accelerated healing and monitoring of skin wounds in mouse models - efficient fibroblast migration, proliferation, and differentiation promoted by electric field (EF) stimulation and iontophoretic drug delivery, and monitoring of the accelerated healing process through impedance mapping. The all-hydrogel-based e-skin patch is expected to create new opportunities for various clinically-relevant tissue interfacing applications.

Quality Characteristics of Meat Analogs through the Incorporation of Textured Vegetable Protein and Tenebrio molitor Larvae in the Presence of Transglutaminase.

Alternative protein sources with greater nutritional value and a lower environmental footprint have recently attracted interest in the production of meat substitutes. However, it is required that these alternatives mimic the texture and structure of meat. This study investigated varying ratios of textured vegetable proteins (TVP) to Tenebrio molitor larvae (brown mealworm; TM) with the addition of transglutaminase (TG) to determine the quality characteristics of these emulsions. The results demonstrated low protein solubility of the emulsions as TVP content increased. Furthermore, when the proportion of TM was high, the TG-treated emulsion had a low pH. Additionally, when there was a high TM ratio to TVP in the TG treatment, the emulsions demonstrated better thermal stability and water holding capacity. Regarding the rheological properties of the emulsion, both the frequency-dependent storage modulus (G') and loss modulus (G'') increased as the proportion of TVP in the emulsion increased with and without the addition of TG. Differential scanning calorimetry analyses demonstrated two protein denaturation peaks in all treatments, with high peak temperatures for both treatments with a high proportion of TM. The hardness and chewiness of the emulsion were highest in the treatment (T6 and T8) with TG, and the gumminess of the emulsion was greatest when TM only or when equal ratios of TVP and TM were treated with TG, respectively. In conclusion, the addition of TM to TVP with TG improves the overall texture of the protein mixture, making it a suitable meat alternative.

Urethral diverticulum in pregnancy: Rare case report and brief literature review.

OBJECTIVE: Female urethral diverticulum (UD), an evagination of the urethral mucosa into the surrounding connective tissue, is extremely rare in pregnancy. No clear guidelines on the optimal management of UD have been established, except for a common conservative approach. Here, we discuss how to manage UD with pregnancy. CASE REPORT: A 39-year-old gravida 4, para 0, abortion 3 (G4P0A3) woman at 34+0 gestational weeks (GW) visited our outpatient department with a 6-cm septate vaginal mass. Transvaginal ultrasound sonography (TVUS) revealed a 5.5 x 4.9-cm multicystic mass, which was confirmed as UD with pelvic MRI. She was admitted because of preterm labor. A cesarean section was performed at 36+5 GW due to a previous myomectomy, and a healthy male baby was born. UD was still observed in the patient two months after delivery. Periurethral diverticulectomy was performed, and pathological analysis revealed UD with chronic inflammation and edema. CONCLUSION: Previous reports and our case report show that UD can develop during pregnancy and that pelvic MRI is suitable for its accurate diagnosis. Vaginal delivery is possible in pregnant women with the small size of the UD. UD aspiration can permit vaginal delivery in a few cases; however, pus can occur at the aspirated site after the operation. If UD is still observed after delivery, urethral diverticulectomy is recommended.

Polaribacter ponticola sp. nov., isolated from seawater, reclassification of Polaribacter undariae as a later heterotypic synonym of Polaribacter sejongensis, and emended description of Polaribacter sejongensis Kim et al. 2013.

A Gram-stain-negative, yellow-pigmented, and strictly aerobic bacterium, designated as strain MSW5T, was isolated from seawater of the Yellow Sea in South Korea. The cells were non-motile rods exhibiting oxidase- and catalase-positive activities. Growth was observed at 15-25 °C (optimum, 25 °C) and pH 5.0-9.0 (optimum, pH 7.0-8.0) and in the presence of 1.0-5.0% (w/v) NaCl (optimum, 2.0%). Menaquinone-6 was the sole respiratory quinone, and iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C15 : 0 3-OH, and C15 : 1 ω6c were the major cellular fatty acids. Major polar lipids included phosphatidylethanolamine, two unidentified aminolipids, and three unidentified lipids. Phylogenetic analyses based on 16S rRNA gene sequences and 92 concatenated core protein sequences revealed that strain MSW5T formed a distinct lineage within the genus Polaribacter. The genome of strain MSW5T was 3582 kb in size with a 29.1 mol% G+C content. Strain MSW5T exhibited the highest similarity to Polaribacter atrinae WP25T, with a 97.9% 16S rRNA gene sequence similarity. However, the average nucleotide identity and digital DNA-DNA hybridization values were 79.4 and 23.3%, respectively, indicating that strain MSW5T represents a novel species. Based on its phenotypic, chemotaxonomic, and phylogenetic characteristics, strain MSW5T is proposed to represent a novel species, with the name Polaribacter ponticola sp. nov. The type strain is MSW5T (=KACC 22340T=NBRC 116025T). In addition, whole genome sequence comparisons and phenotypic features suggested that Polaribacter sejongensis and Polaribacter undariae belong to the same species, with P. undariae proposed as a later heterotypic synonym of P. sejongensis. An emended description of Polaribacter sejongensis is also proposed.

Radiographic and neurological outcomes of Gamma Knife radiosurgery for lower cranial nerve schwannomas: a single-institution experience.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is widely used for treating small- to medium-sized or postoperative residual, recurrent lower cranial nerve schwannomas (LCNSs). This study aimed to evaluate the radiographic and neurological outcomes of GKRS for LCNS. METHODS: A total of 60 patients with 47 jugular foramen schwannomas (JFSs) and 13 hypoglossal nerve schwannomas (HNSs) who underwent GKRS were included. Dysphagia (40.4%) and hoarseness (23.4%) were the most common preexisting symptoms associated with JFS, whereas tongue deviation (53.8%) was prevalent in HNS. The median tumor volumes were 3.2 cm3 and 2.2 cm3 for JFSs and HNSs, respectively. The median marginal dose administered to the tumor was 13 Gy (range 12-15 Gy). The median follow-up duration was 52.8 months. RESULTS: Local tumor control was achieved in 91.5% of JFSs and 92.3% of HNSs. The preexisting neurological symptoms improved in 48.9% of patients with JFS and remained stable in 29.8%. However, 10 patients (21.3%) experienced exacerbation of symptoms associated with cranial nerves VII, VIII, IX, X, and XI. Among these, 3 patients (6.4%) exhibited persistent symptomatic deterioration. Patients with HNSs demonstrated a stable trajectory without symptom aggravation. Larger tumor volume and cystic portion were significantly associated with tumor progression (p = 0.017 and 0.003, respectively), and post-GKRS transient swelling was associated with neurological deterioration (p = 0.044). CONCLUSIONS: GKRS is an alternative treatment option for LCNS that reduces surgical morbidity and enhances tumor control. However, GKRS can potentially lead to neurological deterioration, necessitating extreme caution throughout the procedure, specifically for JFSs.

Association of smoking cessation with dynapenia among older lifetime smokers in Korea.

INTRODUCTION: Muscle strength is known to play an important role in the health of older adults. The health burden of cigarette smoking among older adults remains significant. We investigated the association between smoking cessation and dynapenia among older lifetime smokers in Korea. METHODS: This study is a secondary dataset analysis of cross-sectional data from theKorea National Health and Nutrition Examination Survey (KNHANES) 2016- 2019. We included 1450 participants aged 65-79 years, excluding those who had never smoked. Dynapenia was defined as grip strength <28 kg for men and <18 kg for women based on the Asian Working Group for Sarcopenia 2019 criteria. Multivariable logistic regression analysis evaluated the association between smoking cessation and dynapenia. RESULTS: Compared with current smokers, the adjusted odds ratio (AOR) of dynapenia in former smokers was 0.66 (95% CI: 0.44-0.99). The AORs for smoking cessation periods of ≤10 years, 10-20 years, 20-30 years, and >30 years were 0.67 (95% CI: 0.39-1.16), 0.61 (95% CI: 0.36-1.03), 0.65 (95% CI: 0.37-1.14), and 0.52 (95% CI: 0.25-1.06), respectively. The AOR for dynapenia significantly decreased with the years since smoking cessation (p for trend=0.043). CONCLUSIONS: Our findings suggest that smoking cessation can reduce the likelihood of dynapenia among older lifetime smokers, with a decreasing likelihood trend associated with longer cessation periods.

Categorizing Monogenic Epilepsies by Genetic Mechanisms May Predict Efficacy of the Ketogenic Diet.

BACKGROUND: The ketogenic diet (KD) is an effective treatment for epilepsy. In recent years, studies have shown favorable efficacy of KD in epilepsy from genetic disorders. In this study, we propose an approach to KD in monogenic epilepsy: we evaluate the utility of categorizing genetic variants based on rational associations with the known mechanisms of KD. METHODS: Patients with monogenic epilepsy treated with KD were reviewed. The genetic etiologies were categorized into five groups: (1) conditions causing cellular energy impairment, (2) GABA-pathies, (3) mToR-pathies, (4) ion channelopathies, and (5) no known mechanisms associated with KD mechanisms. Treatment response was defined as a median reduction in seizure frequency of greater than 50%. RESULTS: Of 35 patients, 24 (69%) were responders at three months. Based on categories, Group 1 had the highest response rate with seven of seven (100%), followed by Group 2, six of seven (86%), and Group 3, two of three (67%). Patients in Groups 4 and 5 had poorer responses with three of seven (43%) and four of 11 (36%) response rates, respectively (P < 0.01). Median percentage of seizure reduction showed Group 1 with the highest reduction of 97.5%, Group 2 at 94%, and Groups 3, 4, and 5 at 62.5%, 30%, and 40%, respectively (P = 0.036). CONCLUSION: Our findings show a favorable response to KD in patients with monogenic epilepsy (69% at three months) with the highest response in patients with conditions involving cellular energy impairment and GABA-pathies. The KD, therefore, should be considered early in patients with monogenic epilepsy, especially those involving genes associated with cellular energy impairment or GABA-pathies.

Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence.

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence.