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1.
Womens Health Nurs ; 30(2): 153-163, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38987919

ABSTRACT

PURPOSE: This study aimed to investigate the experiential meaning of child-rearing for marriage immigrant women in Korea in the context of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Using the hermeneutic descriptive phenomenology framework developed by Colaizzi, 10 marriage immigrant women rearing preschool and school-age children were invited through purposive and snowball sampling from two multicultural support centers in Korea. The participants were rearing one or two children, and their original nationalities were Vietnamese, Japanese, Cambodian, and Chinese. Individual in-depth, face-to-face, semi-structured interviews were conducted from September 1 to November 30, 2021. We extracted significant statements from the transcripts, transformed these into abstract formulations, and organized them into theme clusters and themes to authentically capture the essence of the participants' subjective experiences. RESULTS: Four theme clusters with 14 themes were derived. The four theme clusters identified were "navigating child healthcare alone," "guilt for not providing a social experience," "worry about media-dependent parenting," and "feelings of incompleteness and exclusion." This study explored the perspectives of mothers raising children as marriage migrant women who experienced physical and emotional health crises due to the COVID-19 pandemic. CONCLUSION: The findings underscore that marriage immigrant women encountered heightened challenges in managing their children's health and well-being during the COVID-19 pandemic due to linguistic and cultural barriers limiting access to healthcare and information. Additionally, these women experienced considerable emotional stress from perceived inadequacies in providing a holistic social and developmental environment for their children under extensive social restrictions.


Subject(s)
COVID-19 , Emigrants and Immigrants , Marriage , Parenting , Humans , COVID-19/psychology , COVID-19/epidemiology , COVID-19/ethnology , Female , Republic of Korea/epidemiology , Republic of Korea/ethnology , Emigrants and Immigrants/psychology , Adult , Marriage/psychology , Marriage/ethnology , Parenting/psychology , Parenting/ethnology , SARS-CoV-2 , Child , Mothers/psychology , Child Rearing/psychology , Child Rearing/ethnology , Qualitative Research , Pandemics
2.
Int J Pharm ; : 124415, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960340

ABSTRACT

The human colorectal adenocarcinoma cell line Caco-2, widely used for studying intestinal drug permeability, is typically grown on permeable filter supports and matures in 21 days with frequent media changes. The process is labor-intensive, prone to contamination, and has low throughput, contributing to the overall high utilization cost. Efforts to establish a low-cost, high-throughput, short-duration model have encountered obstacles, such as weaker tight junctions causing monolayer leaks, incomplete differentiation resulting in low transporter expression, intricate and challenging protocols, and cytotoxicity, limiting the usability. Hence, this study aimed to develop a low-cost, efficient, and short-duration model by addressing the aforementioned concerns by customizing the media and finding a safe differentiation inducer. We generated a new rapid model using sodium valerate, which demonstrated sufficient transporter activity, improved monolayer integrity, and higher levels of differentiation markers than the 21-day model. Furthermore, this model exhibited consistent and reliable results when used to evaluate drug permeability over multiple days of repeated use. This study demonstrates the potential of a sodium valerate-assisted abbreviated model for drug permeability assessment with economic and practical advantages.

4.
IBRO Neurosci Rep ; 16: 147-154, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39007089

ABSTRACT

Disruption of the blood-central nervous system barrier (BCB) is increasingly recognized as a pathological factor in diseases and trauma of the central nervous system. Despite the neuropathological impact, current treatment modalities do not target the BCB; strategies to reconstitute the impaired BCB have been restricted to nutritional and dietary remedies. As an integral cell type in the neurovascular unit, pericytes are crucial to the development, maintenance, and repair of the BCB. As such, pericytes are well poised as cellular agents for reconstitution of the impaired BCB. Here, we summarize recent revelations regarding the role of BCB disruption in diseases and trauma of the central nervous system and highlight how pericytes are harnessed to provide targeted therapeutic effect in each case. This review will also address how recent advances in pericyte derivation strategies can serve to overcome practical hurdles in the clinical use of pericytes.

5.
J Control Release ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992622

ABSTRACT

Nanomedicines hold promise for the treatment of various diseases. However, treating cancer metastasis remains highly challenging. In this study, we synthesized gold nanorods (AuNRs) containing (α-GC), an immune stimulator, for the treatment of primary cancer, metastasis, and recurrence of the cancer. Therefore, the AuNR were coated with lipid bilayers loaded with α-GC (α-LA). Upon irradiation with 808 nm light, α-LA showed a temperature increase. Intra-tumoral injection of α-LA in mice and local irradiation of the 4 T1 breast cancer tumor effectively eliminated tumor growth. We found that the presence of α-GC in α-LA activated dendritic cells and T cells in the spleen, which completely blocked the development of lung metastasis. In mice injected with α-LA for primary breast cancer treatment, we observed antigen-specific T cell responses and increased cytotoxicity against 4 T1 cells. We conclude that α-LA is promising for the treatment of both primary breast cancer and its metastasis.

6.
Int J Mol Sci ; 25(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39000052

ABSTRACT

Triacylglycerols (TAGs) are the storage oils of plant seeds, and these lipids provide energy for seed germination and valuable oils for human consumption. Three diacylglycerol acyltransferases (DGAT1, DGAT2, and DGAT3) and phospholipid:diacylglycerol acyltransferases participate in the biosynthesis of TAGs. DGAT1 and DGAT2 participate in the biosynthesis of TAGs through the endoplasmic reticulum (ER) pathway. In this study, we functionally characterized CsDGAT1 and CsDGAT2 from camelina (Camelina sativa). Green fluorescent protein-fused CsDGAT1 and CsDGAT2 localized to the ER when transiently expressed in Nicotiana benthamiana leaves. To generate Csdgat1 and Csdgat2 mutants using the CRISPR/Cas9 system, camelina was transformed with a binary vector carrying Cas9 and the respective guide RNAs targeting CsDGAT1s and CsDGAT2s via the Agrobacterium-mediated floral dip method. The EDD1 lines had missense and nonsense mutations in the CsDGAT1 homoeologs, suggesting that they retained some CsDGAT1 function, and their seeds showed decreased eicosaenoic acid (C20:1) contents and increased C18:3 contents compared to the wild type (WT). The EDD2 lines had a complete knockout of all CsDGAT2 homoeologs and a slightly decreased C18:3 content compared to the WT. In conclusion, CsDGAT1 and CsDGAT2 have a small influence on the seed oil content and have an acyl preference for C20:1 and C18:3, respectively. This finding can be applied to develop oilseed plants containing high omega-3 fatty acids or high oleic acid.


Subject(s)
Brassicaceae , Diacylglycerol O-Acyltransferase , Fatty Acids , Plant Proteins , Seeds , Fatty Acids/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Diacylglycerol O-Acyltransferase/metabolism , Diacylglycerol O-Acyltransferase/genetics , Seeds/metabolism , Seeds/genetics , Brassicaceae/genetics , Brassicaceae/metabolism , CRISPR-Cas Systems , Triglycerides/metabolism , Gene Expression Regulation, Plant , Plants, Genetically Modified/genetics , Mutation , Gene Editing
7.
Alzheimers Dement ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963127

ABSTRACT

INTRODUCTION: This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures. METHODS: For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers. RESULTS: Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials. HIGHLIGHTS: Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures.

9.
Nat Prod Rep ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38984501

ABSTRACT

Correction for 'Biosynthesis, biological activities, and structure-activity relationships of decalin-containing tetramic acid derivatives isolated from fungi' by Hyun Woo Kim et al., Nat. Prod. Rep., 2024, https://doi.org/10.1039/d4np00013g.

10.
Nanomaterials (Basel) ; 14(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38998734

ABSTRACT

The reuse of waste materials has recently become appealing due to pollution and cost reduction factors. Using waste materials can reduce environmental pollution and product costs, thus promoting sustainability. Approximately 95% of calcium carbonate-containing waste eggshells end up in landfills, unused. These eggshells, a form of bio-waste, can be repurposed as catalytic electrode material for various applications, including supercapacitors, after being converted into CaO. Similarly, used waste battery electrode materials pose environmental hazards if not properly recycled. Various types of batteries, particularly lithium-ion batteries, are extensively used worldwide. The recycling of used lithium-ion batteries has become less important considering its low economic benefits. This necessitates finding alternative methods to recover and reuse the graphite rods of spent batteries. Therefore, this study reports the conversion of waste eggshell into calcium oxide by high-temperature calcination and extraction of nanographite from spent batteries for application in energy storage fields. Both CaO and CaO/graphite were characterized for their structural, morphological, and chemical compositions using XRD, SEM, TEM, and XPS techniques. The prepared CaO/graphite nanocomposite material was evaluated for its efficiency in electrochemical supercapacitor applications. CaO and its composite with graphite powder obtained from used lithium-ion batteries demonstrated improved performance compared to CaO alone for energy storage applications. Using these waste materials for electrochemical energy storage and conversion devices results in cheaper, greener, and sustainable processes. This approach not only aids in energy storage but also promotes sustainability through waste management by reducing landfills.

11.
J Clin Med ; 13(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38999448

ABSTRACT

Background: This study investigated the potential link between blood pressure variability (BPV) and the incidence of aortic stenosis (AS) using Korean National Health Insurance Service data from 2002 to 2019. Methods: We collected annual systolic blood pressure variability (SBPV) measurements consisting of three consecutive blood pressure readings each year over three years. The obtained SBPV data was divided into five quantiles, with the highest quintile representing a high fluctuation of blood pressure. Results: Analyzing 9,341,629 individuals with a mean age of 40.7 years, the study found 3981 new AS diagnoses during an average 8.66-year follow-up. Independent predictors for AS included higher blood pressure levels and elevated systolic blood pressure variability (SBPV). The hazard ratios (HR) for different SBPV quintiles compared to the reference (1st quintile) were as follows: 2nd quintile HR 1.09 (p = 0.18), 3rd quintile HR 1.13 (p = 0.04), 4th quintile HR 1.13 (p = 0.04), and 5th quintile HR 1.39 (p < 0.001). Conclusion: Our findings suggest that both hypertension and high fluctuations in SBP during consecutive visits are associated with an increased risk of incident AS. These results emphasize the importance of blood pressure management and stability in the prevention of AS.

12.
J Clin Med ; 13(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38999497

ABSTRACT

Background and Objectives: Colorectal endoscopic submucosal dissection (ESD) is an effective technique for removing colorectal neoplasms with large or cancerous lesions. However, there are few studies on post-ESD electrocoagulation syndrome (PECS), a complication of colorectal ESD. Therefore, this study aimed to investigate the various risk factors for PECS after colorectal ESD. Materials and Methods: We retrospectively analyzed the medical records of 1413 lesions from 1408 patients who underwent colorectal ESD at five tertiary hospitals between January 2015 and December 2020. We investigated the incidence and risk factors associated with PECS. Based on the data, we developed a risk-scoring model to predict the risk of PECS after colorectal ESD. Results: The incidence rate of PECS was 2.6% (37 patients). In multivariate analysis, the use of anti-platelet agents (odds ratio (OR), 2.474; 95% confidence interval (CI), 1.088-5.626; p < 0.031), a lesion larger than 6 cm (OR 3.755; 95% CI, 1.237-11.395; p = 0.028), a deep submucosal invasion (OR 2.579; 95% CI, 1.022-6.507; p = 0.045), and an ESD procedure time ≥ 60 min (OR 2.691; 95% CI, 1.302-5.560; p = 0.008) were independent risk factors of PECS after colorectal ESD. We developed a scoring model for predicting PECS using these four factors. As the score increased, the incidence of PECS also increased, from 1.3% to 16.6%. PECS occurred more frequently in the high-risk group (≥2) (1.8% vs. 12.4%, p < 0.001). Conclusions: In this study, the risk factors for PECS after colorectal ESD were the use of anti-platelet agents, a lesion larger than 6 cm, a deep submucosal invasion, and an ESD procedure time ≥ 60 min. The risk-scoring model developed in this study using these factors could be effective in predicting and preventing PECS.

13.
Int J Mol Sci ; 25(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39000349

ABSTRACT

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.


Subject(s)
Aorta , Cyclic GMP , Emulsions , Labetalol , Nitric Oxide Synthase Type III , Vasodilation , Animals , Vasodilation/drug effects , Rats , Aorta/drug effects , Aorta/metabolism , Labetalol/pharmacology , Male , Nitric Oxide Synthase Type III/metabolism , Cyclic GMP/metabolism , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Rats, Sprague-Dawley , Humans , Lipids , Phosphorylation/drug effects , Calcium/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism
14.
Diagnostics (Basel) ; 14(13)2024 Jul 08.
Article in English | MEDLINE | ID: mdl-39001348

ABSTRACT

Colorectal neoplasms are prevalent in patients with chronic kidney disease (CKD); however, the safety and efficacy of colorectal endoscopic submucosal dissection (ESD) are not well understood. This retrospective analysis included ESD procedures performed in 1266 patients with CKD across five tertiary medical institutions from January 2015 to December 2020. Patients were categorized based on their estimated glomerular filtration rate (eGFR), which ranged from CKD1 to CKD5 (including those on dialysis). We found that en bloc resection rates remained high across all CKD stages, affirming the procedural efficacy of ESD. Notably, the prevalence of cardiovascular comorbidities, such as ischemic heart disease and diabetes mellitus, significantly increased with an advancing CKD stage, with a corresponding increase in the Charlson Comorbidity Index, highlighting the complexity of managing these patients. Despite these challenges, the complete resection rate was lower in the CKD5 group (50%) than in the CKD1 group (83.4%); however, procedural complications, such as perforation and bleeding, did not significantly differ among the groups. The predictive models for complete resection and major complications showed no significant changes with a decreasing eGFR. These findings underscore that ESD is a feasible and safe treatment for colorectal neoplasms in patients with CKD, successfully balancing the inherent procedural risks with clinical benefits.

15.
Microb Pathog ; : 106793, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39004154

ABSTRACT

Genetically, Listeria monocytogenes is closely related to non-L. monocytogenes (L. innocua, L. welshimeri, L. grayi, L. aquatica, and L. fleischimannii). This bacterium is well known for its resistance to harsh conditions including acidity, low temperatures, and high salt concentrations. This study explored the responses of 65 Listeria strains to stress conditions and characterized the prevalence of stress-related genes. The 65 Listeria strains were isolated from different environments and their viability was assessed in four different tests: independent tests for pH 3, 1 °C, and 5% salt concentration and multiple resistance tests that combined pH 3, 1 °C, 5% salt. From the data, the 65 strains were categorized into stress-resistant (56) or stress-sensitive groups (9), with approximately 4 log CFU/mL differences. The PCR assay analyzed the prevalence of two virulence genes prfA and inlA, and eight stress-related genes: three acid (gadB, gadC, and atpD), two low temperature (betL and opuCA) and three salt resistance genes (flaA, cysS, and fbp). Two low temperature (bet and opuCA) and salt resistance (fbp) genes were more prevalent in the stress-resistant strains than in the stress-sensitive Listeria group.

16.
Drug Des Devel Ther ; 18: 2641-2652, 2024.
Article in English | MEDLINE | ID: mdl-38974125

ABSTRACT

Background: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA). Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study. Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects. Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.


Subject(s)
Amlodipine , Cross-Over Studies , Drug Combinations , Ezetimibe , Healthy Volunteers , Rosuvastatin Calcium , Telmisartan , Humans , Telmisartan/administration & dosage , Telmisartan/pharmacokinetics , Rosuvastatin Calcium/pharmacokinetics , Rosuvastatin Calcium/administration & dosage , Amlodipine/pharmacokinetics , Amlodipine/administration & dosage , Male , Ezetimibe/administration & dosage , Ezetimibe/pharmacokinetics , Adult , Young Adult , Benzoates/pharmacokinetics , Benzoates/administration & dosage , Benzimidazoles/pharmacokinetics , Benzimidazoles/administration & dosage , Dose-Response Relationship, Drug , Drug Interactions
17.
Food Sci Anim Resour ; 44(4): 832-848, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38974728

ABSTRACT

This study was carried out to assess the quality properties, components associated with taste and aroma of beef as a function of breed. For this purpose, steers from four Korean native cattle breeds: Hanwoo (n=10), Chikso (n=10), black Hanwoo (n=12, BHW) and Jeju black cattle (n=12, JBC) were used. The steers all were raised under identical conditions and finished at a similar age of around 30-months old. Following 24 h of slaughter, all longissimus lumborum muscles were collected and used for analysis of meat quality, fatty acids, and flavor-related components (metabolic compounds, free amino acids, and aroma volatiles). The Hanwoo presented a significantly higher intramuscular fat content (IMF, 22.85%) than the BHW (11.78%), Chikso (9.25%), and JBC (9.14%; p<0.05). The meat of Hanwoo breed showed lighter and redder color, and lower shear force value (p<0.05). The JBC presented a "healthier" fatty acid profiles as it had a higher total unsaturated fatty acids content (p<0.05). With regard to flavor-related components, Hanwoo also had higher total contents of free amino acids and metabolites associated with umami and sweet tastes, and fat-derived volatile compounds (aldehydes, alcohols, and ketones) associated with fatty aroma. It may be concluded that there was a considerable difference in the meat quality properties among breeds. The variations of IMF content and flavor-related components may be the main factors contributing to the typical flavors of beef among the four Korean native cattle breeds.

18.
Am J Gastroenterol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38976448

ABSTRACT

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker (P-CAB) developed to treat gastroesophageal reflux disease. This study aims to evaluate the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, non-inferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) (P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than esomeprazole group (95.14% (137/144) vs. 87.68% (121/138); P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the two groups (P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

19.
Int Microbiol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977514

ABSTRACT

This study explored the extracellular metabolomic responses of three different Salmonella enterica serotype Typhimurium (S. Typhimurium) strains-ATCC 13311 (STy1), NCCP 16964 (STy4), and NCCP 16958 (STy8)-cultured at refrigeration temperatures. The objective was to identify the survival mechanisms of S. Typhimurium under cold stress by analyzing variations in their metabolomic profiles. Qualitative and quantitative assessments identified significant metabolite alterations on day 6, marking a critical inflection point. Key metabolites such as trehalose, proline, glycerol, and tryptophan were notably upregulated in response to cold stress. Through multivariate analyses, the strains were distinguished using three metabolites-4-aminobutyrate, ethanol, and uridine-as potential biomarkers, underscoring distinct metabolic responses to refrigeration. Specifically, STy1 exhibited unique adaptive capabilities through enhanced metabolism of betaine and 4-aminobutyrate. These findings highlight the variability in adaptive strategies among S. Typhimurium strains, suggesting that certain strains may possess more robust metabolic pathways for enhancing survival in refrigerated conditions.

20.
medRxiv ; 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38978648

ABSTRACT

Importance: Parkinson's disease (PD), the second most common neurodegenerative disease, is pathologically characterized by intraneuronal deposition of misfolded alpha-synuclein aggregates (αSyn D ). αSyn D seeding activities in CSF and skin samples have shown great promise in PD diagnosis, but they require invasive procedures. Sensitive and accurate αSyn D seed amplification assay (αSyn-SAA) for more accessible and minimally invasive samples (such as blood and saliva) are urgently needed for PD pathological diagnosis in routine clinical practice. Objective: To develop a sensitive and accurate αSyn-SAA biomarker using blood and saliva samples for sensitive, accurate and minimally invasive PD diagnosis. Design Setting and Participants: This prospective diagnostic study evaluates serum and saliva samples collected from patients clinically diagnosed with PD or healthy controls (HC) without PD at an academic Parkinson's and Movement Disorders Center from February 2020 to March 2024. Patients diagnosed with non-PD parkinsonism were excluded from this analysis. A total of 124 serum samples (82 PD and 42 HC) and 131 saliva samples (83 PD and 48 HC) were collected and examined by αSyn-SAA. Out of the 124 serum donors, a subset of 74 subjects (48 PD and 26 HC) also donated saliva samples during the same visits. PD patients with serum samples had a mean age of 69.21 years (range 44-88); HC subjects with serum samples had a mean age of 66.55 years (range 44-81); PD patients with saliva samples had a mean age of 69.58 years (range 49-87); HC subjects with saliva samples had a mean age of 64.71 years (range 30-81). Main Outcomes and Measures: Serum and/or saliva αSyn D seeding activities from PD and HC subjects were measured by αSyn-SAA using the Real-Time Quaking-Induced Conversion (RT-QuIC) platform. These PD patients had extensive clinical assessments including MDS-UPDRS. For a subset of PD and HC subjects whose serum and saliva samples were both collected during the same visits, the αSyn D seeding activities in both samples from the same subjects were examined, and the diagnostic accuracies for PD based on the seeding activities in either sample alone or both samples together were compared. Results: RT-QuIC analysis of αSyn D seeding activities in the 124 serum samples revealed a sensitivity of 80.49%, a specificity of 90.48%, and an accuracy of 0.9006 (AUC of ROC, 95% CI, 0.8472-0.9539, p <0.0001) for PD diagnosis. RT-QuIC analysis of αSyn D seeding activity in 131 saliva samples revealed a sensitivity of 74.70%, a specificity of 97.92%, and an accuracy of 0.8966 (AUC of ROC, 95% CI, 0.8454-0.9478, p <0.0001). When aSyn D seeding activities in the paired serum-saliva samples from the subset of 48 PD and 26 HC subjects were considered together, sensitivity was 95.83%, specificity was 96.15%, and the accuracy was 0.98 (AUC of ROC, 95% CI, 0.96-1.00, p <0.001), which are significantly better than when αSyn D seeding activities in either serum or saliva were used alone. For the paired serum-saliva samples, when specificity was set at 100% by elevating the αSyn-SAA cutoff values, a sensitivity of 91.7% and an accuracy of 0.9457 were still attained. Detailed correlation analysis revealed that αSyn D seeding activities in the serum of PD patients were correlated inversely with Montreal Cognitive Assessment (MoCA) score ( p =0.04), positively with Hamilton Depression Rating Scale (HAM-D) ( p =0.03), and weakly positively with PDQ-39 cognitive impairment score ( p =0.07). Subgroup analysis revealed that the inverse correlation with MoCA was only seen in males ( p =0.013) and weakly in the ≥70 age group ( p =0.07), and that the positive correlation with HAM-D was only seen in females ( p =0.04) and in the <70 age group ( p =0.01). In contrast, αSyn D seeding activities in the saliva of PD patients were inversely correlated with age at diagnosis ( p =0.02) and the REM sleep behavior disorder (RBD) status ( p =0.04), but subgroup analysis showed that the inverse correlation with age at diagnosis was only seen in males ( p =0.04) and in the <70 age group ( p =0.01). Conclusion and Relevance: Our data show that concurrent RT-QuIC assay of αSyn D seeding activities in both serum and saliva can achieve high diagnostic accuracies comparable to that of CSF αSyn-SAA, suggesting that αSyn D seeding activities in serum and saliva together can potentially be used as a valuable biomarker for highly sensitive, accurate, and minimally invasive diagnosis of PD in routine clinical practice. αSyn D seeding activities in serum and saliva of PD patients correlate differentially with some clinical characteristics and in an age and sex-dependent manner. KEY POINTS: Question: Are αSyn D seeding activities in serum and saliva together a more sensitive and accurate diagnostic PD biomarker than αSyn D seeding activities in either sample type alone? Are αSyn D seeding activities in either serum or saliva correlated with any clinical characteristics? Findings: Examinations of αSyn D seeding activities in 124 serum samples and 131 saliva samples from PD and heathy control subjects show that αSyn D seeding activities in both serum and saliva samples together can provide significantly more sensitive and accurate diagnosis of PD than either sample type alone. αSyn D seeding activities in serum or saliva exhibit varied inverse or positive correlations with some clinical features in an age and sex-dependent manner. Meaning: αSyn D seeding activities in serum and saliva together can potentially be used as a valuable pathological biomarker for highly sensitive, accurate, and minimally invasive PD diagnosis in routine clinical practice and clinical studies, and αSyn D seeding activities in serum or saliva correlate with some clinical characteristics in an age and sex-dependent manner, suggesting some possible clinical utility of quantitative serum/saliva αSyn-SAA data.

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