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1.
J Cardiothorac Surg ; 19(1): 416, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961402

ABSTRACT

BACKGROUND: The occurrence of type II endoleaks after endovascular repair of aortic aneurysm has gradually gained increasing attention. We present a case of a patient with an expanding aneurysm after thoracic endovascular aortic repair (TEVAR) for a type II endoleak, in which successful direct ligations of the intercostal artery were performed using a sac incision without cardiopulmonary bypass (CPB) or graft replacement. CASE PRESENTATION: A 62-year-old male patient, previously treated with TEVAR for a descending thoracic aortic aneurysm, presented with ongoing chest discomfort. Based on the diagnosis of a growing aneurysm and type II endoleak, the patient was prepared for CPB and aortic cross-clamping, as a precautions against the possibility of a type I endoleak. A longitudinal opening of the thoracic aortic aneurysm sac was performed following left thoracotomy. Visual confirmation identified the T5 level intercostal artery as the source of the endoleak, and after confirming the absence of a type I endoleak, multiple ligations were applied to the intercostal artery. Follow-up computed tomography confirmed the absence of endoleaks or sac growth. CONCLUSION: In a case involving TEVAR for a thoracic aortic aneurysm, open suture ligations were used to treat type II endoleaks without having to resort to CPB, resulting in successful outcomes.


Subject(s)
Aortic Aneurysm, Thoracic , Endoleak , Endovascular Procedures , Humans , Male , Endoleak/surgery , Endoleak/etiology , Middle Aged , Aortic Aneurysm, Thoracic/surgery , Endovascular Procedures/methods , Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis Implantation/adverse effects , Tomography, X-Ray Computed , Aorta, Thoracic/surgery , Ligation , Endovascular Aneurysm Repair
2.
J Aging Health ; : 8982643241262374, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38881150

ABSTRACT

OBJECTIVES: Relatively little attention has been paid to the underlying processes and conditions leading to loneliness among caregivers of older persons with cognitive impairment (PCI). Drawing upon the caregiver stress-process model and the social relationship expectations framework, this study examined the mediating role of social isolation and the moderating role of caregiver personal mastery in the association between PCI memory and behavioral problems and caregiver loneliness. METHODS: Structural equation modeling was applied to cross-sectional data from 266 caregivers in Singapore. RESULTS: Caregiver-reported PCI memory and behavioral problems were associated with increased levels of caregiver loneliness. Caregiver social isolation partially mediated the association and caregiver personal mastery moderated the association. DISCUSSION: Caregivers with low mastery were more likely to experience loneliness due in part to social isolation resulting from their PCI's memory and behavioral problems. Tailored interventions should address caregiver social isolation and foster caregiver personal mastery.

3.
Proc Natl Acad Sci U S A ; 121(24): e2322009121, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38843187

ABSTRACT

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.


Subject(s)
Cell Differentiation , Lupus Erythematosus, Systemic , Osteopontin , Transcription Factors , Animals , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/pathology , Osteopontin/metabolism , Osteopontin/genetics , Mice , Humans , Transcription Factors/metabolism , Transcription Factors/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , T Follicular Helper Cells/immunology , T Follicular Helper Cells/metabolism , Female , Disease Models, Animal , Mice, Knockout
4.
Korean J Radiol ; 25(7): 613-622, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38942455

ABSTRACT

OBJECTIVE: In Korea, radiology has been positioned towards the early adoption of artificial intelligence-based software as medical devices (AI-SaMDs); however, little is known about the current usage, implementation, and future needs of AI-SaMDs. We surveyed the current trends and expectations for AI-SaMDs among members of the Korean Society of Radiology (KSR). MATERIALS AND METHODS: An anonymous and voluntary online survey was open to all KSR members between April 17 and May 15, 2023. The survey was focused on the experiences of using AI-SaMDs, patterns of usage, levels of satisfaction, and expectations regarding the use of AI-SaMDs, including the roles of the industry, government, and KSR regarding the clinical use of AI-SaMDs. RESULTS: Among the 370 respondents (response rate: 7.7% [370/4792]; 340 board-certified radiologists; 210 from academic institutions), 60.3% (223/370) had experience using AI-SaMDs. The two most common use-case of AI-SaMDs among the respondents were lesion detection (82.1%, 183/223), lesion diagnosis/classification (55.2%, 123/223), with the target imaging modalities being plain radiography (62.3%, 139/223), CT (42.6%, 95/223), mammography (29.1%, 65/223), and MRI (28.7%, 64/223). Most users were satisfied with AI-SaMDs (67.6% [115/170, for improvement of patient management] to 85.1% [189/222, for performance]). Regarding the expansion of clinical applications, most respondents expressed a preference for AI-SaMDs to assist in detection/diagnosis (77.0%, 285/370) and to perform automated measurement/quantification (63.5%, 235/370). Most respondents indicated that future development of AI-SaMDs should focus on improving practice efficiency (81.9%, 303/370) and quality (71.4%, 264/370). Overall, 91.9% of the respondents (340/370) agreed that there is a need for education or guidelines driven by the KSR regarding the use of AI-SaMDs. CONCLUSION: The penetration rate of AI-SaMDs in clinical practice and the corresponding satisfaction levels were high among members of the KSR. Most AI-SaMDs have been used for lesion detection, diagnosis, and classification. Most respondents requested KSR-driven education or guidelines on the use of AI-SaMDs.


Subject(s)
Artificial Intelligence , Societies, Medical , Humans , Republic of Korea , Surveys and Questionnaires , Radiology , Software
5.
Front Immunol ; 15: 1385135, 2024.
Article in English | MEDLINE | ID: mdl-38756783

ABSTRACT

Background: The assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy. Methods: This prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody and neutralizing antibodies (NAb) against wild-type and Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 and EG.5) up to 9 months post-vaccination. T-cell immune responses were measured before and 4 weeks after vaccination. Results: A total of 108 (28 SARS-CoV-2-naïve and 80 previously infected) participants were enrolled. Anti-receptor binding domain immunoglobulin G (U/mL) levels were higher at 9 months post-vaccination than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p<0.001). NAb titers against BQ.1.1, BN.1, and XBB.1 were significantly higher at 9 months post-vaccination than baseline in both groups, whereas NAb against EG.5 was negligible at all time points. The T-cell immune response (median spot forming unit/106 cells) was highly cross-reactive at both baseline (wild-type/BA.5/XBB.1.5, 38.3/52.5/45.0 in SARS-CoV-2-naïve individuals; 51.6/54.9/54.9 in SARS-CoV-2-infected individuals) and 4 weeks post-vaccination, with insignificant boosting post-vaccination. Conclusion: Remarkable cross-reactive neutralization was observed against BQ.1.1, BN.1, and XBB.1 up to 9 months after BA.4/5 bivalent vaccination, but not against EG.5. The T-cell immune response was highly cross-reactive.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunity, Cellular , Immunity, Humoral , SARS-CoV-2 , Vaccination , Humans , Male , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Female , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Middle Aged , Adult , Prospective Studies , Aged , Immunoglobulin G/blood , Immunoglobulin G/immunology , T-Lymphocytes/immunology
7.
RSC Adv ; 14(24): 16846-16858, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38784418

ABSTRACT

Harnessing solar energy for large-scale hydrogen fuel (H2) production shows promise in addressing the energy crisis and ecological degradation. This study focuses on the development of GaN-based photoelectrodes for efficient photoelectrochemical (PEC) water splitting, enabling environmentally friendly H2 production. Herein, a novel nanoflower Au/CuO/GaN hybrid structure was successfully synthesized using a combination of methods including successive ionic layer adsorption and reaction (SILAR), RF/DC sputtering, and metal-organic chemical vapour deposition (MOCVD) techniques. Structural, morphological, and optical characteristics and elemental composition of the prepared samples were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), UV-Vis spectroscopy, and energy-dispersive X-ray (EDX) spectroscopy, respectively. PEC and electrochemical impedance measurements were performed for all samples. The nanoflower Au/CuO/GaN hybrid structure exhibited the highest photocurrent density of ∼4 mA cm-2 at 1.5 V vs. RHE in a Na2SO4 electrolyte with recorded moles of H2 of about 3246 µmol h-1 cm-2. By combining these three materials in a unique structure, we achieved improved performance in the conversion of solar energy into chemical energy. The nanoflower structure provides a large surface area and promotes light absorption while the Au, CuO, and GaN components contribute to efficient charge separation and transfer. This study presents a promising strategy for advancing sustainable H2 production via efficient solar-driven water splitting.

8.
Comput Biol Med ; 175: 108494, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38688124

ABSTRACT

BACKGROUND & OBJECTIVE: Aortic dissection (AD) is a serious condition requiring rapid and accurate diagnosis. In this study, we aimed to improve the diagnostic accuracy of AD by presenting a novel method for aortic segmentation in computed tomography images that uses a combination of a transformer and a UNet cascade network with a Zoom-Out and Zoom-In scheme (ZOZI-seg). METHODS: The proposed method segments each compartment of the aorta, comprising the true lumen (TL), false lumen (FL), and thrombosis (TH) using a cascade strategy that captures both the global context (anatomical structure) and the local detail texture based on the dynamic patch size with ZOZI schemes. The ZOZI-seg model has a two-stage architecture using both a "3D transformer for panoptic context-awareness" and a "3D UNet for localized texture refinement." The unique ZOZI strategies for patching were demonstrated in an ablation study. The performance of our proposed ZOZI-seg model was tested using a dataset from Asan Medical Center and compared with those of existing models such as nnUNet and nnFormer. RESULTS: In terms of segmentation accuracy, our method yielded better results, with Dice similarity coefficients (DSCs) of 0.917, 0.882, and 0.630 for TL, FL, and TH, respectively. Furthermore, we indirectly compared our model with those in previous studies using an external dataset to evaluate its robustness and generalizability. CONCLUSIONS: This approach may help in the diagnosis and treatment of AD in different clinical situations and provide a strong basis for further research and clinical applications.


Subject(s)
Aortic Dissection , Tomography, X-Ray Computed , Humans , Aortic Dissection/diagnostic imaging , Tomography, X-Ray Computed/methods , Algorithms
9.
Fitoterapia ; 175: 105958, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38604262

ABSTRACT

In our quest to discover advanced glycation end products (AGEs) inhibitors from Clinacanthus nutans (Burm.f.) Lindau leaves, we conducted a bioactivity-based molecular networking. This approach integrates LC-MS2 profiling and in vitro antiglycation data to predict bioactive compounds. We began by screening three extracts: 100% ethanol, 70% ethanol and 100% water alongside the in vitro antioxidant activity, total phenolics content (TPC) and schaftoside content. Among these extracts, 100% ethanol extract exhibited the highest total AGEs inhibition effects (IC50 = 80.18 ± 11.6 µg/mL), DPPH scavenging activity (IC50 = 747.40 ± 10.30 µg/mL) and TPC (26.54 ± 2.09 µg GAE /mg extract). Intriguingly, 100% ethanol extract contained the lowest amount of schaftoside, suggesting the involvement of other phytochemicals in the antiglycation effects. The molecular networking and in silico structural annotations of 401 LC-MS features detected in the fractions from 100% ethanol extract predicted 21 bioactive compounds (p < 0.05, r > 0.90), including several C40 carotenoids, alkaloids containing tetrapyrrole structures and fatty acids. On the contrary, all phenolics showed weak correlations with antiglycation effects. These predictions were further validated in vitro, where carotenoid lutein showed half maximal inhibitory concentration, IC50 = 96 ± 8 µM and selected flavonoid-C-glycosides exhibited weaker inhibitions (IC50 between 568 and 1922 µM). Notably, lutein content was higher in freeze-dried leaves (12.42 ± 0.82 mg/100 g) than oven-dried, although the former was associated with elevated mercury levels. In summary, C. nutans exhibited potential antiglycation and antioxidant activity, and lutein was identified as the main bioactive principle.


Subject(s)
Acanthaceae , Antioxidants , Glycation End Products, Advanced , Phenols , Phytochemicals , Plant Extracts , Plant Leaves , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Glycation End Products, Advanced/antagonists & inhibitors , Plant Leaves/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry , Acanthaceae/chemistry , Phenols/pharmacology , Phenols/analysis , Phenols/isolation & purification , Molecular Structure
10.
Res Sq ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38659962

ABSTRACT

Multi-platform mutational, proteomic, and metabolomic spatial mapping was used on the whole-organ scale to identify the molecular evolution of bladder cancer from mucosal field effects. We identified complex proteomic and metabolomic dysregulations in microscopically normal areas of bladder mucosa adjacent to dysplasia and carcinoma in situ. The mutational landscape developed in a background of complex defects of protein homeostasis which included dysregulated nucleocytoplasmic transport, splicesome, ribosome biogenesis, and peroxisome. These changes were combined with altered urothelial differentiation which involved lipid metabolism and protein degradations controlled by PPAR. The complex alterations of proteome were accompanied by dysregulation of gluco-lipid energy-related metabolism. The analysis of mutational landscape identified three types of mutations based on their geographic distribution and variant allele frequencies. The most common were low frequency α mutations restricted to individual mucosal samples. The two other groups of mutations were associated with clonal expansion. The first of this group referred to as ß mutations occurred at low frequencies across the mucosa. The second of this group called γ mutations increased in frequency with disease progression. Modeling of the mutations revealed that carcinogenesis may span nearly 30 years and can be divided into dormant and progressive phases. The α mutations developed gradually in the dormant phase. The progressive phase lasted approximately five years and was signified by the advent of ß mutations, but it was driven by γ mutations which developed during the last 2-3 years of disease progression to invasive cancer. Our study indicates that the understanding of complex alterations involving mucosal microenvironment initiating bladder carcinogenesis can be inferred from the multi-platform whole-organ mapping.

11.
Iran J Basic Med Sci ; 27(6): 755-760, 2024.
Article in English | MEDLINE | ID: mdl-38645496

ABSTRACT

Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that function in all biological processes. Recent findings suggest that exosomes, which are small vesicles abundantly secreted by various cell types, can transport miRNAs to target cells. Here, we elucidated the effect of miRNA-loaded exosomes on lipopolysaccharide (LPS)-induced inflammation in H9c2 cardiomyocytes. Materials and Methods: Exosomes were isolated from mesenchymal stem cells (MSC) and loaded with miR-412-5p. Additionally, the effect of the miR-412-5p-loaded exosomes on LPS-induced inflammation in H9c2 cardiomyocytes was evaluated by assessing the levels of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2). The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inflammatory cytokines, and mitogen-activated protein kinase (MAPK) signaling factors was evaluated using reverse transcription-quantitative PCR and western blotting. Results: miR-412-5p-loaded exosomes inhibited LPS-induced secretion of inflammatory mediators (NO, PGE2, and ROS), pro-inflammatory cytokines (IL-1ß and IL-6), and COX-2 and iNOS expression. Additionally, miR-412-5p-loaded exosomes significantly decreased the expression of MAPK signaling molecules, including p-extracellular signal-regulated kinase (ERK), p-p38, and p-Jun kinase (JNK), in H9c2 cardiomyocytes. Conclusion: These findings showed that miR-412-5p-loaded exosomes ameliorated LPS-induced inflammation in H9c2 cardiomyocytes by inhibiting COX-2 and iNOS expression, inflammatory mediators, and pro-inflammatory cytokines via the MAPK pathway. The findings indicate that miR-412-5p-loaded exosomes may be effective for the prevention of myocardial injury.

12.
BMC Complement Med Ther ; 24(1): 163, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38641782

ABSTRACT

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV. METHODS: A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants. RESULTS: A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant (p = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC (p = 0.04595), younger patients (p = 0.0108), and non-colorectal cancer patients (p = 0.0495) presented significantly lower CINV scores when EMC was applied. CONCLUSION: Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients. TRIAL REGISTRATION: KCT0008200, 17/02/2023, Retrospectively registered.


Subject(s)
Antiemetics , Antineoplastic Agents , Neoplasms , Humans , Quality of Life , Antiemetics/therapeutic use , Antiemetics/adverse effects , Cross-Over Studies , Vomiting/therapy , Vomiting/drug therapy , Nausea/therapy , Nausea/drug therapy , Neoplasms/drug therapy , Antineoplastic Agents/adverse effects
13.
Cell Rep ; 43(5): 114146, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38676926

ABSTRACT

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two of these genes, LPAR6 and CAB39L, are preferentially downregulated in the luminal and basal subtypes of bladder cancer, respectively. Their loss of function dysregulates urothelial differentiation, sensitizing the urothelium to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced cancers, which recapitulate the luminal and basal subtypes of human bladder cancer.


Subject(s)
Carcinogenesis , Cell Differentiation , Urinary Bladder Neoplasms , Urothelium , Aged , Aged, 80 and over , Animals , Female , Humans , Male , Mice , Middle Aged , Carcinogenesis/pathology , Carcinogenesis/genetics , Carcinogenesis/metabolism , Gene Expression Regulation, Neoplastic , Mice, Inbred C57BL , Receptors, Lysophosphatidic Acid/metabolism , Receptors, Lysophosphatidic Acid/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Urothelium/pathology , Urothelium/metabolism
14.
Physiol Behav ; 278: 114520, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38492910

ABSTRACT

Early-life social experiences shape adult phenotype, yet the underlying behavioral mechanisms remain poorly understood. We manipulated early-life social experience in the highly social African cichlid fish Astatotilapia burtoni to investigate the effects on behavior and stress axis function in juveniles. Juveniles experienced different numbers of social partners in stable pairs (1 partner), stable groups (6 fish; 5 partners), and socialized pairs (a novel fish was exchanged every 5 days; 5 partners). Treatments also differed in group size (groups vs. pairs) and stability (stable vs. socialized). We then measured individual behavior and water-borne cortisol to identify effects of early-life experience. We found treatment differences in behavior across all assays: open field exploration, social cue investigation, dominant behavior, and subordinate behavior. Treatment did not affect cortisol. Principal components (PC) analysis revealed robust co-variation of behavior across contexts, including with cortisol, to form behavioral syndromes sensitive to early-life social experience. PC1 (25.1 %) differed by social partner number: juveniles with more partners (groups and socialized pairs) were more exploratory during the social cue investigation, spent less time in the territory, and were more interactive as dominants. PC5 (8.5 %) differed by stability: socialized pairs were more dominant, spent less time in and around the territory, were more socially investigative, and had lower cortisol than stable groups or pairs. Observations of the home tanks provided insights into the social experiences that may underlie these effects. These results contribute to our understanding of how early-life social experiences are accrued and exert strong, lasting effects on phenotype.


Subject(s)
Cichlids , Hydrocortisone , Animals , Social Behavior , Phenotype
15.
J Appl Lab Med ; 9(4): 741-751, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38531067

ABSTRACT

BACKGROUND: Although age negatively correlates with vaccine-induced immune responses, whether the vaccine-induced neutralizing effect against variants of concern (VOCs) substantially differs across age remains relatively poorly explored. In addition, the utility of commercial binding assays developed with the wild-type SARS-CoV-2 for predicting the neutralizing effect against VOCs should be revalidated. METHODS: We analyzed 151 triple-vaccinated SARS-CoV-2-naïve individuals boosted with BNT162b2 (Pfizer-BioNTech). The study population was divided into young adults (age < 30), middle-aged adults (30 ≤ age < 60), and older adults (age ≥ 60). The plaque reduction neutralization test (PRNT) titers against Delta (B.1.617.2) and Omicron (B.1.1.529) variants were compared across age. Antibody titers measured with commercial binding assays were compared with PRNT titers. RESULTS: Age-related decline in neutralizing titers was observed for both Delta and Omicron variants. Neutralizing titers for Omicron were lower than those against Delta in all ages. The multiple linear regression model demonstrated that duration from third dose to sample collection and vaccine types were also significant factors affecting vaccine-induced immunity along with age. The correlation between commercial binding assays and PRNT was acceptable for all age groups with the Delta variant, but relatively poor for middle-aged and older adults with the Omicron variant due to low titers. CONCLUSIONS: This study provides insights into the age-related dynamics of vaccine-induced immunity against SARS-CoV-2 VOCs, corroborating the need for age-specific vaccination strategies in the endemic era where new variants continue to evolve. Moreover, commercial binding assays should be used cautiously when estimating neutralizing titers against VOCs, particularly Omicron.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 , SARS-CoV-2 , Humans , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , SARS-CoV-2/immunology , Adult , Middle Aged , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Male , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Aged , Age Factors , Young Adult , Neutralization Tests/methods , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage
17.
Nat Commun ; 15(1): 1024, 2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38310093

ABSTRACT

Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8-11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.


Subject(s)
Cartilage, Articular , Osteoarthritis , Humans , Male , Animals , Mice , Mesalamine/pharmacology , Mesalamine/therapeutic use , PPAR gamma/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Cartilage, Articular/metabolism , Chondrocytes/metabolism , Disease Models, Animal
18.
Nat Rev Urol ; 21(7): 391-405, 2024 07.
Article in English | MEDLINE | ID: mdl-38321289

ABSTRACT

Bladder cancer is a histologically and clinically heterogenous disease. Most bladder cancers are urothelial carcinomas, which frequently develop distinct histological subtypes. Several urothelial carcinoma histological subtypes, such as micropapillary, plasmacytoid, small-cell carcinoma and sarcomatoid, show highly aggressive behaviour and pose unique challenges in diagnosis and treatment. Comprehensive genomic characterizations of the urothelial carcinoma subtypes have revealed that they probably arise from a precursor subset of conventional urothelial carcinomas that belong to different molecular subtypes - micropapillary and plasmacytoid subtypes develop along the luminal pathway, whereas small-cell and sarcomatoid subtypes evolve along the basal pathway. The subtypes exhibit distinct genomic alterations, but in most cases their biological properties seem to be primarily determined by specific gene expression profiles, including epithelial-mesenchymal transition, urothelial-to-neural lineage plasticity, and immune infiltration with distinct upregulation of immune regulatory genes. These breakthrough studies have transformed our view of bladder cancer histological subtype biology, generated new hypotheses for therapy and chemoresistance, and facilitated the discovery of new therapeutic targets.


Subject(s)
Disease Progression , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Humans , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/classification , Neoplasm Invasiveness , Epithelial-Mesenchymal Transition/genetics
19.
Medicine (Baltimore) ; 103(6): e36917, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38335386

ABSTRACT

Evidence regarding the use of Korean medicine (KM) for the conservative treatment of meniscus tears remains lacking. We aimed to evaluate clinical effectiveness and long-term follow-up outcomes in patients undergoing integrative KM treatment for meniscus tears. We analyzed the electronic medical records (EMRs) of 86 patients with meniscus tears and administered a follow-up survey. Patients treated at 1 of 4 KM hospitals between June 1, 2015, and June 30, 2020, were reviewed. KM treatment comprised herbal medicine, acupuncture, pharmacopuncture, bee venom pharmacopuncture, Chuna therapy, and KM physiotherapy. The primary outcome was the numeric rating scale (NRS) score for knee pain; secondary outcomes were the Western Ontario and McMaster Universities Arthritis Index (WOMAC), EuroQol 5-dimension (EQ-5D) score, range of motion, and patient global impression of change. The NRS for knee pain was reduced by an average of 2.49 (95% confidence interval [CI]: 2.03-2.95) at discharge and 1.97 (95% CI: 2.03-2.95) at follow-up. The WOMAC decreased by an average of 15.52 (95% CI: 10.14-20.89) during hospital stay and 30.72 (95% CI: 24.58-36.87) at follow-up. The EQ-5D score increased by an average of 0.06 (95% CI: -0.14 to 0.02) at discharge and 0.19 (95% CI: -0.29 to -0.09) at follow up. KM treatment effectively reduced knee pain, improved knee joint function, and enhanced the quality of life in patients with a meniscus tear for a relatively long period after treatment.


Subject(s)
Inpatients , Meniscus , Humans , Follow-Up Studies , Retrospective Studies , Quality of Life , Treatment Outcome , Pain , Republic of Korea
20.
J Chest Surg ; 57(2): 225-229, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38185484

ABSTRACT

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a lifesaving technique for patients experiencing respiratory failure. When VV ECMO fails to provide adequate support despite optimal settings, alternative strategies may be employed. One option is to add another venous cannula to increase venous drainage, while another is to insert an additional arterial return cannula to assist cardiac function. Alternatively, a separate ECMO circuit can be implemented to function in parallel with the existing circuit. We present a case in which the parallel ECMO method was used in a 63-year-old man with respiratory failure due to coronavirus disease 2019, combined with cardiac dysfunction. We installed an additional venoarterial ECMO circuit alongside the existing VV ECMO circuit and successfully weaned the patient from both types of ECMO. In this report, we share our experience and discuss this method.

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