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1.
Front Bioeng Biotechnol ; 12: 1392269, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100623

RESUMEN

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis.

2.
Cardiol J ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115461

RESUMEN

BACKGROUND: Diabetes mellitus (DM) is a significant factor in increased mortality rates among patients with acute myocardial infarction (AMI), but research on its impact on the long-term outcomes in patients with MI with nonobstructive coronary arteries (MINOCA) is limited. Thus, a comparison of the 3-year clinical outcomes between the DM and non-DM groups among patients with MINOCA was undertaken. METHODS: From the Korea AMI Registry-National Institute of Health dataset, 10,774 AMI patients were enrolled. After applying the exclusion criteria, 379 patients with MINOCA were included. The primary clinical outcomes were major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction (MI), repeat coronary revascularization, and stroke. The secondary outcomes were the individual components of MACCE. RESULTS: The adjusted hazard ratios for 3-year MACCE (2.287, p = 0.010), all-cause death (2.845, p = 0.004), and non-cardiac death (non-CD, 3.914, p = 0.008) were higher in the DM group than in the non-DM group. It is speculated that the higher non-CD rate in the MINOCA group is attributable to a higher proportion of patients with non-ST-segment elevation MI in the total study population. The CD, recurrent MI, revascularization, and stroke rates were similar between the DM and non-DM groups. DM, advanced age, cardiopulmonary resuscitation on admission, and non-use of statin medications were significant predictors of MACCE. CONCLUSIONS: In this study involving patients with MINOCA, the DM group exhibited a higher 3-year mortality rate than the non-DM group. Thus, DM demonstrated a hazardous effect even in patients with MINOCA.

3.
Life Sci ; : 122954, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128820

RESUMEN

Neuropathic pain, a common symptom of several disorders, exerts a substantial socioeconomic burden worldwide. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel predominantly ex-pressed in nociceptive neurons, plays a pivotal role in nociception, by detecting various endogenous and exogenous stimuli, including heat, pro-inflammatory mediators, and physical stressors. Dysregulation of TRPV1 signaling further contributes to the pathophysiology of neuropathic pain. Therefore, targeting TRPV1 is a promising strategy for developing novel analgesics with improved efficacy and safety profiles. Several pharmacological approaches to modulate TRPV1 activity, including agonists, antagonists, and biological TRPV1 RNA interference (RNAi, small interfering RNA [siRNA]) have been explored. Despite preclinical success, the clinical translation of TRPV1-targeted therapies has encountered challenges, including hyperthermia, hypothermia, pungency, and desensitization. Nevertheless, ongoing research efforts aim to refine TRPV1-targeted interventions through structural modifications, development of selective modulators, and discovery of natural, peptide-based drug candidates. Herein, we provide guidance for researchers and clinicians involved in the development of new interventions specifically targeting TRPV1 by reviewing the existing literature and highlighting current research activities. This study further discusses potential future research endeavors for enhancing the efficacy, safety, and tolerability of TRPV1 candidates, and thereby facilitates the translation of these discoveries into effective clinical interventions to alleviate neuropathic pain disorders.

4.
J Cardiovasc Imaging ; 32(1): 22, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39113162

RESUMEN

BACKGROUND: Right ventricular (RV) systolic dysfunction is an established prognostic factor in patients with severe tricuspid regurgitation (TR). However, accurate assessment of RV systolic function using conventional echocardiography remains challenging. We investigated the accuracy of strain measurement using speckle tracking echocardiography (STE) for evaluating RV systolic function in patients with severe TR. METHODS: We included consecutive patients with severe TR who underwent echocardiography and cardiac magnetic resonance imaging (CMR) within 30 days between 2011 and 2023. Two-dimensional STE was used to measure RV free wall longitudinal strain (RVFWLS) and global longitudinal strain (RVGLS). These values were compared with the RV ejection fraction (RVEF) from CMR. RV systolic dysfunction was defined as a CMR-derived RVEF < 35%. RESULTS: A total of 87 patients with severe TR were identified during the study period. Among echocardiographic RV strain measurements, RVFWLS was the best correlate of CMR-derived RVEF (r = -0.37, P < 0.001), followed by RVGLS (r = -0.27, P = 0.012). Receiver operating characteristic (ROC) curve analysis revealed that RVFWLS provided better discrimination of RV systolic dysfunction, yielding an area under the ROC curve (AUC) of 0.770 (95% confidence interval [CI], 0.696-0.800) than RV fractional area change (AUC, 0.615; 95% CI, 0.500-0.859). CONCLUSIONS: In patients with severe TR, STE-derived RVFWLS showed the best correlation with RVEF on CMR and displayed superior discrimination of RV systolic dysfunction compared with the RV fractional area change. This study suggests the potential usefulness of STE in assessing RV systolic function in this population.

5.
Int J Surg ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39116451

RESUMEN

BACKGROUND: The increasing use of kidneys from elderly donors raises concerns due to age-related nephron loss. Combined with nephrectomy, this loss of nephrons markedly increases the risk of developing chronic kidney disease (CKD). This study aimed to investigate the prognostic value of preoperative kidney cortex volume in predicting the loss of kidney function in elderly donors, by developing an artificial intelligence (AI)-based model for precise kidney volume measurement and applying it to living kidney donors. MATERIALS METHODS: A multicenter retrospective cohort study using data from living donors who underwent donor nephrectomy between January 2010 and December 2020 was conducted. An AI segmentation model was developed and validated to measure kidney cortex volume from pre-donation computer tomographic (CT) images. The association between measured preoperative kidney volumes and post-nephrectomy renal function was analyzed through a generalized additive model. RESULTS: A total of 1074 living kidney donors were included in the study. Validation of the developed kidney cortex volume model showed a Dice similarity coefficient of 0.97 and a Hausdorff distance of 0.76 mm. The measured cortex volumes exhibited an age-related decrease, which correlated with declining kidney function. Elderly donors showed greater decreases in estimated glomerular filtration rates (eGFR) post-donation compared to young donors (P=0.041). Larger preoperative remnant kidney cortex volume was associated with significantly less decline of eGFR post-donation than those with smaller preoperative remnant kidney cortex volume (P<0.001). CONCLUSION: This study highlights the critical role of preoperative kidney cortex volume in the donor assessment process, particularly for elderly donors. The fully automated model for measuring kidney cortex volume provides a valuable tool for predicting post-donation renal function and holds promise for enhancing donor evaluation and safety.

6.
Psychiatry Res ; 340: 116092, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39116687

RESUMEN

Treatment-resistant depression (TRD) is defined as patients diagnosed with depression having a history of failure with different antidepressants with an adequate dosage and treatment duration. The NMDA receptor antagonist ketamine rapidly reduces depressive symptoms in TRD. We examined neural correlates of treatment response to ketamine in TRD through a systematic review of brain magnetic resonance imaging (MRI) studies. A comprehensive search in PubMed was performed using "ketamine AND depression AND magnetic resonance." The time span for the database queries was "Start date: 2018/01/01; End date: 2024/05/31." Total 41 original articles comprising 1,396 TRD and 587 healthy controls (HC) were included. Diagnosis of depression was made using the Structured Clinical Interview for DSM Disorders (SCID), the Mini-International Neuropsychiatric Interview (MINI), and/or the clinical assessment by psychiatrists. Patients with affective psychotic disorders were excluded. Most studies applied ketamine [0.5mg/kg racemic ketamine and/or 0.25mg/kg S-ketamine] diluted in 60cc of normal saline via intravenous infusion over 40 min one time, four times, or six times spaced 2-3 days apart over 2 weeks. Clinical outcome was defined as either remission, response, and/or percentage changes of depressive symptoms. Brain MRI of the T2*-weighted imaging (resting-state or task performance), arterial spin labeling, diffusion weighted imaging, and T1-weighted imaging were acquired at baseline and mainly 1-3days after the ketamine administration. Only the study results replicated by ≥ 2 studies and were included in the default-mode, salience, fronto-parietal, subcortical, and limbic networks were regarded as meaningful. Putative brain-based markers of treatment response to ketamine in TRD were found in the structural/functional features of limbic (subgenual ACC, hippocampus, cingulum bundle-hippocampal portion; anhedonia/suicidal ideation), salience (dorsal ACC, insula, cingulum bundle-cingulate gyrus portion; thought rumination/suicidal ideation), fronto-parietal (dorsolateral prefrontal cortex, superior longitudinal fasciculus; anhedonia/suicidal ideation), default-mode (posterior cingulate cortex; thought rumination), and subcortical (striatum; anhedonia/thought rumination) networks. Brain features of limbic, salience, and fronto-parietal networks could be useful in predicting the TRD with better response to ketamine in relief of anhedonia, thought rumination, and suicidal ideation.

7.
Nanomaterials (Basel) ; 14(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39120353

RESUMEN

Morphology plays a crucial role in defining the optical, electronic, and mechanical properties of halide perovskite microcrystals. Therefore, developing strategies that offer precise control over crystal morphology during the growth process is highly desirable. This work presents a simple scheme to simultaneously grow distinct geometries of cesium lead bromide (CsPbBr3) microcrystals, including microrods (MR), microplates (MP), and microspheres (MS), in a single chemical vapor deposition (CVD) experiment. By strategically adjusting precursor evaporation temperatures, flux density, and the substrate temperature, we surpass previous techniques by achieving simultaneous yet selective growth of multiple CsPbBr3 geometries at distinct positions on the same substrate. This fine growth control is attributed to the synergistic variation in fluid flow dynamics, precursor substrate distance, and temperature across the substrate, offering regions suitable for the growth of different morphologies. Pertinently, perovskite MR are grown at the top, while MP and MS are observed at the center and bottom regions of the substrate, respectively. Structural analysis reveals high crystallinity and an orthorhombic phase of the as-grown perovskite microcrystals, while persistent photonic lasing manifests their nonlinear optical characteristics, underpinning their potential application for next-generation photonic and optoelectronic devices.

8.
Medicine (Baltimore) ; 103(32): e39230, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39121261

RESUMEN

Percutaneous lumbar nucleoplasty (PLN) and intradiscal electrothermal therapy (IDET) are effective treatment options for discogenic low back pain (D-LBP). We evaluated the effectiveness of PLN and IDET and the positive predictive factors associated with intradiscal procedures. We reviewed the medical records of 205 patients who underwent IDET or PLN in patients with D-LBP followed by positive provocation discography. A successful outcome was defined as ≥ 50% pain relief on the numerical rating scale (NRS) pain score at the 6-month follow-up visit. The relationship between the outcome of the intradiscal procedure and clinical variables was investigated using multivariate analyses. Of the 142 patients (89 with PLN and 53 with IDET), 86 (60.5%) experienced a successful outcome, which was more substantial in PLN (n = 61, 68.5%) than in IDET (n = 25, 47.2%; P = .010). The high-grade Modified Dallas Discogram Scale in provocation discography and a procedure at the L3/L4 spinal level were independent positive predictors of successful outcomes (P = .023 and .010, respectively). Coexisting psychiatric disorders, such as depression and anxiety, were negative predictors of successful treatment (P = .007). No serious complications related to the intradiscal procedures were reported during the 6-month follow-up period. PLN and IDET might be effective for managing low back pain (LBP) from internal disc disruption (IDD). The high-grade Modified Dallas Discogram, a procedure at the L3/4 spinal level, and the absence of neuropsychiatric disorders could be positive factors for the successful outcome of the intradiscal procedure.


Asunto(s)
Dolor de la Región Lumbar , Vértebras Lumbares , Humanos , Femenino , Masculino , Estudios Retrospectivos , Dolor de la Región Lumbar/terapia , Persona de Mediana Edad , Adulto , Vértebras Lumbares/cirugía , Resultado del Tratamiento , Discectomía Percutánea/métodos , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/terapia , Desplazamiento del Disco Intervertebral/cirugía , Dimensión del Dolor , Degeneración del Disco Intervertebral/complicaciones , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/cirugía
9.
Stem Cell Res ; 80: 103510, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39121651

RESUMEN

E-cadherin, a transmembrane protein, is essential for maintaining the integrity and structure of human pluripotent stem cells (hPSCs) by facilitating strong cell-cell adhesion and communication, which is crucial for their colony formation and pluripotency. Here, we used the CRISPR/Cas9 system to introduce the enhanced green fluorescent protein (EGFP)-tagged CDH1 into the AAVS1 locus, a safe harbour site, of human induced pluripotent stem cells (hiPSCs). The engineered cell line, KSCBi002-A-3, expressed functional CDH1-EGFP fusion protein, exhibited normal cell morphology, maintained a normal karyotype, and retained pluripotent state.

10.
Int J Mol Sci ; 25(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39125628

RESUMEN

Staphylococcus aureus, particularly drug-resistant strains, poses significant challenges in healthcare due to its ability to form biofilms, which confer increased resistance to antibiotics and immune responses. Building on previous knowledge that several flavonoids exhibit antibiofilm activity, this study sought to identify a novel flavonoid capable of effectively inhibiting biofilm formation and virulence factor production in S. aureus strains including MRSA. Among the 19 flavonoid-like compounds tested, 3,2'-dihydroxyflavone (3,2'-DHF) was identified for the first time as inhibiting biofilm formation and virulence factors in S. aureus with an MIC 75 µg/mL. The antibiofilm activity was further confirmed by microscopic methods. Notably, 3,2'-DHF at 5 µg/mL was effective in inhibiting both mono- and polymicrobial biofilms involving S. aureus and Candida albicans, a common co-pathogen. 3,2'-DHF reduces hemolytic activity, slime production, and the expression of key virulence factors such as hemolysin gene hla and nuclease gene nuc1 in S. aureus. These findings highlight the potential of 3,2'-DHF as a novel antibiofilm and antivirulence agent against both bacterial and fungal biofilms, offering a promising alternative to traditional antibiotics in the treatment of biofilm-associated infections.


Asunto(s)
Antibacterianos , Biopelículas , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Factores de Virulencia , Biopelículas/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Factores de Virulencia/genética , Antibacterianos/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/patogenicidad , Flavonas/farmacología , Flavonoides/farmacología , Virulencia/efectos de los fármacos , Humanos
12.
J Chest Surg ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115199

RESUMEN

Background: This study aimed to examine the clinical implications of selective station 4L lymph node dissection (S4L-LND) on survival in non-small cell lung cancer (NSCLC) and to evaluate its potential advantages. Methods: We enrolled patients with primary left-sided NSCLC who underwent upfront video-assisted thoracoscopic surgery with R0 resection including lobectomy and segmentectomy, with or without S4L-LND, at our institution between January 2007 and December 2021. Following 1:1 propensity score matching (PSM), we compared overall survival (OS) and recurrence-free survival (RFS) between patients with and without S4L-LND. Results: The study included 2,601 patients, of whom 1,126 underwent S4L-LND and 1,475 did not. PSM yielded 1,036 patient pairs. Among those who underwent S4L-LND, 87 (7.7%) exhibited S4L-LN involvement. Neither OS (p=0.12) nor RFS (p=0.24) differed significantly between matched patients with and without S4L-LND. In patients with S4L-LN involvement, metastases were more common in the left upper lobe (LUL) than in the left lower lobe (LLL) (3.6% vs. 2.0%, p=0.061). Metastasis became significantly more frequent with more advanced clinical N (cN) stage (cN0, 2.3%; cN1, 5.8%; cN2, 32.6%; p<0.001). Multivariate logistic regression analysis revealed that cN stage and tumor location were independently associated with S4L-LN involvement (p<0.001 for both). Conclusion: OS and RFS did not differ significantly between matched patients with and without S4L-LND. Among participants with S4L-LN involvement, metastases occurred more frequently in the LUL than the LLL, and their incidence increased significantly with more advanced cN stage. Thus, patients with LUL or advanced cN lung cancers may benefit from S4L-LND.

13.
Nat Commun ; 15(1): 6569, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39095374

RESUMEN

Liquid-liquid phase separation (LLPS) facilitates the formation of membraneless organelles within cells, with implications in various biological processes and disease states. AT-rich interactive domain-containing protein 1A (ARID1A) is a chromatin remodeling factor frequently associated with cancer mutations, yet its functional mechanism remains largely unknown. Here, we find that ARID1A harbors a prion-like domain (PrLD), which facilitates the formation of liquid condensates through PrLD-mediated LLPS. The nuclear condensates formed by ARID1A LLPS are significantly elevated in Ewing's sarcoma patient specimen. Disruption of ARID1A LLPS results in diminished proliferative and invasive abilities in Ewing's sarcoma cells. Through genome-wide chromatin structure and transcription profiling, we identify that the ARID1A condensate localizes to EWS/FLI1 target enhancers and induces long-range chromatin architectural changes by forming functional chromatin remodeling hubs at oncogenic target genes. Collectively, our findings demonstrate that ARID1A promotes oncogenic potential through PrLD-mediated LLPS, offering a potential therapeutic approach for treating Ewing's sarcoma.


Asunto(s)
Ensamble y Desensamble de Cromatina , Proteínas de Unión al ADN , Proteína EWS de Unión a ARN , Sarcoma de Ewing , Factores de Transcripción , Humanos , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Línea Celular Tumoral , Proteína EWS de Unión a ARN/metabolismo , Proteína EWS de Unión a ARN/genética , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Proteínas de Fusión Oncogénica/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteína Proto-Oncogénica c-fli-1/metabolismo , Proteína Proto-Oncogénica c-fli-1/genética , Cromatina/metabolismo , Carcinogénesis/genética , Animales , Ratones , Dominios Proteicos , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Separación de Fases
14.
Front Cell Dev Biol ; 12: 1411529, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39105172

RESUMEN

Introduction: Prion diseases are deadly neurodegenerative disorders in both animals and humans, causing the destruction of neural tissue and inducing behavioral manifestations. Heat shock proteins (Hsps), act as molecular chaperones by supporting the appropriate folding of proteins and eliminating the misfolded proteins as well as playing a vital role in cell signaling transduction, cell cycle, and apoptosis control. SW02 is a potent activator of Hsp 70 kDa (Hsp70). Methods: In the current study, the protective effects of SW02 against prion protein 106-126 (PrP106-126)-induced neurotoxicity in human neuroblastoma cells (SH-SY5Y) were investigated. In addition, the therapeutic effects of SW02 in ME7 scrapie-infected mice were evaluated. Results: The results showed that SW02 treatment significantly increased Hsp70 mRNA expression levels and Hsp70 ATPase activity (p < 0.01). SW02 also significantly inhibited cytotoxicity and apoptosis induced by PrP106-126 (p < 0.01) and promoted neurite extension. In vivo, intraperitoneal administration of SW02 did not show a statistically significant difference in survival time (p = 0.16); however, the SW02-treated group exhibited a longer survival time of 223.6 ± 6.0 days compared with the untreated control group survival time of 217.6 ± 5.4 days. In addition, SW02 reduced the PrPSc accumulation in ME7 scrapie-infected mice at 5 months post-injection (p < 0.05). A significant difference was not observed in GFAP expression, an astrocyte marker, between the treated and untreated groups. Conclusion: In conclusion, the potential therapeutic role of the Hsp70 activator SW02 was determined in the present study and may be a novel and effective drug to mitigate the pathologies of prion diseases and other neurodegenerative diseases. Further studies using a combination of two pharmacological activators of Hsp70 are required to maximize the effectiveness of each intervention.

15.
Stroke ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101205

RESUMEN

BACKGROUND: Previous studies have demonstrated conflicting results regarding the effects of rehabilitation therapy on poststroke mortality. We aimed to investigate the association between rehabilitation therapy, including both inpatient and outpatient treatment, within the first 6 months after stroke and long-term all-cause mortality in patients with stroke using the Korean National Health Insurance System data. METHODS: A total of 10 974 patients newly diagnosed with stroke using the International Classification of Diseases, Tenth Revision, codes (I60-I64) between 2003 and 2019 were enrolled and followed up for all-cause mortality until 2019. Follow-up for mortality began 6 months after the index event. Poststroke patients were categorized into 3 groups according to the frequency of rehabilitation therapy: no rehabilitation therapy, ≤40 sessions and >40 sessions. Cox proportional hazards models were used to assess the mortality risk according to rehabilitation therapy stratified by disability severity measured based on activities of daily living 6 months after stroke onset. RESULTS: Within 6 months after stroke, 6738 patients (61.4%) did not receive rehabilitation therapy, whereas 2122 (19.3%) received ≤40 sessions and 2114 (19.3%) received >40 sessions of rehabilitation therapy. Higher frequency of rehabilitation therapy was associated with significantly lower poststroke mortality in comparison to no rehabilitation therapy (hazard ratio [HR], 0.88 [95% CI, 0.79-0.99]), especially among individuals with severe disability after stroke (mild to moderate: HR, 1.02 [95% CI, 0.77-1.35]; severe: HR, 0.74 [95% CI, 0.62-0.87]). In the context of stroke type, higher frequency of rehabilitation therapy was associated with reduced mortality rates compared with no rehabilitation therapy only in patients with hemorrhagic stroke (ischemic: HR, 1.04 [95% CI, 0.91-1.18]; hemorrhagic: HR, 0.60 [95% CI, 0.49-0.74]). CONCLUSIONS: We found a positive association between rehabilitation therapy within 6 months after stroke onset and long-term mortality in patients with stroke. A higher frequency of rehabilitation therapy would be recommended for poststroke patients, especially those with hemorrhagic stroke and severe disability.

16.
J Med Chem ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102524

RESUMEN

The P2X3 receptor (P2X3R), an ATP-gated cation channel predominantly expressed in C- and Aδ-primary afferent neurons, has been proposed as a drug target for neurological inflammatory diseases, e.g., neuropathic pain, and chronic cough. Aiming to develop novel, selective P2X3R antagonists, tetrazolopyrimidine-based hit compound 9 was optimized through structure-activity relationship studies by modifying the tetrazole core as well as side chain substituents. The optimized antagonist 26a, featuring a cyclopropane-substituted triazolopyrimidine core, displayed potent P2X3R-antagonistic activity (IC50 = 54.9 nM), 20-fold selectivity versus the heteromeric P2X2/3R, and high selectivity versus other P2XR subtypes. Noncompetitive P2X3R blockade was experimentally confirmed by calcium influx assays. Cryo-electron microscopy revealed that 26a stabilizes the P2X3R in its desensitized state, acting as a molecular barrier to prevent ions from accessing the central pore. In vivo studies in a rat neuropathic pain model (spinal nerve ligation) showed dose-dependent antiallodynic effects of 26a, thus presenting a novel, promising lead structure.

18.
Heliyon ; 10(14): e34749, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39130470

RESUMEN

Climate change is an imminent threat, particularly affecting agricultural productivity, which relies heavily on weather conditions. Understanding the specific impacts of climate change on key crops is crucial for developing effective adaptation strategies to ensure food security. The growth patterns of onions and garlic were observed at over ten different locations in South Korea, and the yield data from the past 40 years were analyzed. The yield was significantly correlated with temperature and strongly affected by the frequent and unexpected patterns of precipitation. The increase in mean temperature during winter and the spatial and temporal concentration of precipitation are expected to be the most influential factors for Allium crop production in the future. In addition, the yields of onions and garlic can serve as good indicators for predicting the impacts of weather on agricultural productivity, given their extended cultivation periods and significant correlations with temperature and precipitation. As climate change scenarios become available, the results of this study can serve as a basis for predicting changes in agricultural production in the future and identifying opportunities to adapt cultivation systems for food security.

19.
J Cardiothorac Surg ; 19(1): 416, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961402

RESUMEN

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.


Asunto(s)
Aneurisma de la Aorta Torácica , Endofuga , Procedimientos Endovasculares , Humanos , Masculino , Endofuga/cirugía , Endofuga/etiología , Persona de Mediana Edad , Aneurisma de la Aorta Torácica/cirugía , Procedimientos Endovasculares/métodos , Implantación de Prótesis Vascular/métodos , Implantación de Prótesis Vascular/efectos adversos , Tomografía Computarizada por Rayos X , Aorta Torácica/cirugía , Ligadura , Reparación Endovascular de Aneurismas
20.
Infect Chemother ; 56(2): 256-265, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38960739

RESUMEN

BACKGROUND: Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. MATERIALS AND METHODS: We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. RESULTS: Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/ß-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. CONCLUSION: This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

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