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1.
Biomater Sci ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39310945

RESUMO

Bone tissue engineering (BTE) strategies have been developed to address challenges in orthopedic and dental therapy by expediting osseointegration and new bone formation. In this study, we developed irregular porous Ti-6Al-4V scaffolds coated with reduced graphene oxide (rGO), specifically rGO-pTi, and investigated their ability to stimulate osseointegration in vivo. The rGO-pTi scaffolds exhibited unique irregular micropores and high hydrophilicity, facilitating protein adsorption and cell growth. In vitro assays revealed that the rGO-pTi scaffolds increased alkaline phosphatase (ALP) activity, mineralization nodule formation, and osteogenic gene upregulation in MC3T3-E1 preosteoblasts. Moreover, in vivo transplantation of rGO-pTi scaffolds in rabbit calvarial bone defects showed improved bone matrix formation and osseointegration without hemorrhage. These findings highlight the potential of combining rGO with irregular micropores as a promising BTE scaffold for bone regeneration.

2.
Int J Mol Sci ; 25(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39273456

RESUMO

Gastric cancer (GC) is the fifth most common cause of cancer-related death worldwide. Early detection is crucial for improving survival rates and treatment outcomes. However, accurate GC-specific biomarkers remain unknown. This study aimed to identify the metabolic differences between intestinal metaplasia (IM) and GC to determine the pathways involved in GC. A metabolic analysis of IM and tissue samples from 37 patients with GC was conducted using ultra-performance liquid chromatography with tandem mass spectrometry. Overall, 665 and 278 significant features were identified in the aqueous and 278 organic phases, respectively, using false discovery rate analysis, which controls the expected proportion of false positives among the significant results. sPLS-DA revealed a clear separation between IM and GC samples. Steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and arginine and proline metabolism were the most significantly altered pathways. The intensity of 11 metabolites, including N1, N2-diacetylspermine, creatine riboside, and N-formylkynurenine, showed significant elevation in more advanced GC. Based on pathway enrichment analysis and cancer stage-specific alterations, we identified six potential candidates as diagnostic biomarkers: aldosterone, N-formylkynurenine, guanosine triphosphate, arginine, S-adenosylmethioninamine, and creatine riboside. These metabolic differences between IM and GC provide valuable insights into gastric carcinogenesis. Further validation is needed to develop noninvasive diagnostic tools and targeted therapies to improve the outcomes of patients with GC.


Assuntos
Biomarcadores Tumorais , Metaplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Metaplasia/metabolismo , Metaplasia/patologia , Masculino , Feminino , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Idoso , Metaboloma , Metabolômica/métodos , Redes e Vias Metabólicas , Espectrometria de Massas em Tandem/métodos
3.
Medicina (Kaunas) ; 60(9)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39336419

RESUMO

Background/Objectives: A family history of Parkinson's disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients' PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Doença de Parkinson/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Anamnese
4.
Cells ; 13(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39329776

RESUMO

Presbycusis, also referred to as age-related hearing loss (ARHL), is a multifaceted condition caused by the natural aging process affecting the auditory system. Genome-wide association studies (GWAS) in human populations can identify potential genes linked to ARHL. Despite this, our knowledge of the biochemical and molecular mechanisms behind the condition remains incomplete. This study aims to evaluate a potential protective tool for ARHL treatment by comparing human blood-based target gene-miRNA associations regulated in ARHL. To identify promising target genes for ARHL, we utilized an mRNA assay. To determine the role of miRNA in ARHL, we investigated the expression profile of miRNA in whole blood in ARHL patients with real-time polymerase chain reaction (RT-qPCR). A reporter gene assay was performed to confirm the regulation of candidate genes by microRNA. Through RT-qPCR validation analysis, we finally confirmed the relationship between ARHL and the role of the interferon-gamma (IFNG) gene. This gene can be regarded as an age-related gene. Through gene ontology (GO) analysis, it has been found that these genes are enriched in pathways related to apoptosis. Among them, IFNG induces an inflammatory response, apoptotic cell death, and cellular senescence. We found that miR-409-3p downregulates the expression of the IFNG in vitro. In addition, the downregulation of the IFNG by miRNA 409-3p promoted cell apoptosis and suppressed proliferation. In conclusion, our study produced gene signatures and associated microRNA regulation that could be a protective key for ARHL patients. IFNG genes and miR-409-3p should be investigated for their usefulness as a new biomarker for treatment modality.


Assuntos
Interferon gama , MicroRNAs , Transdução de Sinais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/sangue , Interferon gama/metabolismo , Transdução de Sinais/genética , Masculino , Feminino , Envelhecimento/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Presbiacusia/genética , Idoso , Pessoa de Meia-Idade , Regulação da Expressão Gênica , Perda Auditiva/genética , Perda Auditiva/sangue , Apoptose/genética
5.
J Hosp Infect ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39341283

RESUMO

OBJECTIVES: Antimicrobial stewardship programs (ASPs) have gained prominence with increased awareness regarding the importance of appropriate antibiotic use. However, ASP implementation for outpatient antibiotic prescriptions is uncommon, particularly in South Korea. This study aimed to analyse the patterns and appropriateness of outpatient antibiotic prescriptions at a tertiary care hospital in Korea. METHODS: We analysed the patterns of oral antibiotic prescription from June 1, 2018 to May 31, 2023, at the outpatient department of Seoul National University Bundang Hospital. Appropriateness was assessed for prescriptions issued between May 15 and May 19, 2023. The assessment criteria included: indications for antibiotic use, antibiotic choice, duration, dose, and frequency. Pharmacists and infectious diseases specialists performed evaluations. RESULTS: A total of 7,282,407 outpatient visits were recorded within the 5-year duration. Of these, 243,967 (3.4%) were prescribed oral antibiotics. The frequency of antibiotic prescription was highest in dentistry, dermatology, and urology departments. The most commonly prescribed antibiotics were cephalosporins, penicillins, and sulphonamides. Of the 423 prescriptions evaluated, 289 (68.3%) and 134 (31.7%) were for treatment and prophylaxis, respectively. Inappropriate prescriptions were identified in 28.4% (82/289) and 70.9% (95/134) of the treatment and prophylaxis cases, respectively. The primary reason for inadequacy in both treatment and prophylaxis was inappropriate indications, accounting for 46.3% (38/82) of treatment prescriptions and 96.8% (92/95) of prophylaxis prescriptions. CONCLUSIONS: Antibiotics were administered in 3.4% of all outpatient visits, with 28.4% of treatment and 70.9% of prophylactic antibiotics prescribed inappropriately. Proactive and expansive ASP activities by pharmacists should be considered in outpatient settings.

6.
PLoS One ; 19(9): e0311199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39325794

RESUMO

Crop price forecasting is difficult in that supply is not as elastic as demand, therefore, supply and demand should be stabilized through long-term forecasting and pre-response to the price. In this study, we propose a Parametric Seasonal-Trend Autoregressive Neural Network (PaSTANet), which is a hybrid model that includes both a multi-kernel residual convolution neural network model and a Gaussian seasonality-trend model. To compare the performance of the PaSTANet, we used daily data from the Garak market for four crops: onion, radish, Chinese cabbage, and green onion, and performed long-term price forecasts for one year in 2023. The PaSTANet shows good performance on all four crops compared to other conventional statistical and deep learning-based models. In particular, for onion, the (mean absolute error (MAE) for the long-term forecast of 2023 is 107, outperforming the second-best Prophet (152) by 29.6%. Chinese cabbage, radish, and green onion all outperform the existing models with MAE of 2008, 3703, and 557, respectively. Moreover, using the confidence interval, the predicted price was categorized into three intervals: probability, caution, and warning. Comparing the percentage of classified intervals about the true prices in our test set, we found that they accurately detect the large price volatility.


Assuntos
Produtos Agrícolas , Previsões , Redes Neurais de Computação , Estações do Ano , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/economia , Previsões/métodos , Comércio/economia , Raphanus/crescimento & desenvolvimento
7.
RSC Med Chem ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39345719

RESUMO

Due to its essential roles in cell proliferation and apoptosis, the precise regulation of the Hippo pathway through LATS presents a viable biological target for developing new drugs for cancer and regenerative diseases. However, currently available probes for selective and highly drug-like inhibition of LATS require further improvement in terms of both activity, selectivity and drug-like properties. Through scaffold hopping aided by docking studies and AI-assisted prediction of metabolic stabilities, we successfully identified an advanced LATS inhibitor demonstrating potent kinase activity, exceptional selectivity against other kinases, and superior oral pharmacokinetic profiles.

8.
Korean J Med Educ ; 36(3): 267-274, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39246108

RESUMO

PURPOSE: To investigate the form and level of daily caffeine intake recommended above 400 mg in medical students expected to consume caffeinated beverages to enhance their performance. METHODS: From May to June 2023, freshman through senior medical students at a medical school in Korea were administered a seven-item questionnaire designed to measure the amount of caffeine-containing foods consumed, the weekly interval between consumption, the reason for consumption, and the level of caffeine-induced symptoms experienced. RESULTS: Out of 443 students, 361 responded (81.5%). The most commonly consumed caffeine beverages were coffee (79.2%), followed by soda (33.2%), tea (27.4%), chocolate (25.2%), and energy drinks (20.5%). The estimated (average±standard deviation) daily intake was estimated to 274.6±276.5 mg, and they consumed caffeine on an average of 4.25±2.26 days per week. Students who consumed 400 mg or more of caffeine daily consumed 19.9%. The primary motivation for caffeine intake was "to improve academic performance" (60.9%) and "preferred food" (51.8%). Among the responders, 98% of them replied they had symptoms that could be caused by caffeine, in order of palpitations (47.4%), frequent urination (42.9%), anxiety (27.1%), indigestion (17.5%), and excitement (17.5%). A total of 45.7% reported two symptoms, and 24.7% reported three or more. CONCLUSION: Caffeinated beverage consumption was routine among current medical students, with 20% consuming more than the recommended daily amount. Most students experienced at least one caffeine-induced symptom, with two symptoms in half, suggesting the need for policy measures and warnings about caffeine-containing foods.


Assuntos
Cafeína , Café , Bebidas Energéticas , Estudantes de Medicina , Humanos , República da Coreia , Feminino , Masculino , Inquéritos e Questionários , Adulto Jovem , Chá , Chocolate , Bebidas Gaseificadas , Bebidas , Desempenho Acadêmico , Adulto , Motivação , Faculdades de Medicina
9.
Chem Soc Rev ; 53(19): 9446-9489, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39109465

RESUMO

Proteins, which are ubiquitous in cells and critical to almost all cellular functions, are indispensable for life. Fluorescence imaging of proteins is key to understanding their functions within their native milieu, as it provides insights into protein localization, dynamics, and trafficking in living systems. Consequently, the selective labeling of target proteins with fluorophores has emerged as a highly active research area, encompassing bioorganic chemistry, chemical biology, and cell biology. Various methods for selectively labeling proteins with fluorophores in cells and tissues have been established and are continually being developed to visualize and characterize proteins. This review highlights research findings reported since 2018, with a focus on the selective labeling of cellular proteins with small organic fluorophores and their biological applications in studying protein-associated biological events. We also discuss the strengths and weaknesses of each labeling approach for their utility in living systems.


Assuntos
Corantes Fluorescentes , Proteínas , Corantes Fluorescentes/química , Proteínas/química , Proteínas/metabolismo , Humanos , Imagem Óptica , Animais
10.
Healthc Inform Res ; 30(3): 266-276, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39160785

RESUMO

OBJECTIVES: Sepsis is a leading global cause of mortality, and predicting its outcomes is vital for improving patient care. This study explored the capabilities of ChatGPT, a state-of-the-art natural language processing model, in predicting in-hospital mortality for sepsis patients. METHODS: This study utilized data from the Korean Sepsis Alliance (KSA) database, collected between 2019 and 2021, focusing on adult intensive care unit (ICU) patients and aiming to determine whether ChatGPT could predict all-cause mortality after ICU admission at 7 and 30 days. Structured prompts enabled ChatGPT to engage in in-context learning, with the number of patient examples varying from zero to six. The predictive capabilities of ChatGPT-3.5-turbo and ChatGPT-4 were then compared against a gradient boosting model (GBM) using various performance metrics. RESULTS: From the KSA database, 4,786 patients formed the 7-day mortality prediction dataset, of whom 718 died, and 4,025 patients formed the 30-day dataset, with 1,368 deaths. Age and clinical markers (e.g., Sequential Organ Failure Assessment score and lactic acid levels) showed significant differences between survivors and non-survivors in both datasets. For 7-day mortality predictions, the area under the receiver operating characteristic curve (AUROC) was 0.70-0.83 for GPT-4, 0.51-0.70 for GPT-3.5, and 0.79 for GBM. The AUROC for 30-day mortality was 0.51-0.59 for GPT-4, 0.47-0.57 for GPT-3.5, and 0.76 for GBM. Zero-shot predictions using GPT-4 for mortality from ICU admission to day 30 showed AUROCs from the mid-0.60s to 0.75 for GPT-4 and mainly from 0.47 to 0.63 for GPT-3.5. CONCLUSIONS: GPT-4 demonstrated potential in predicting short-term in-hospital mortality, although its performance varied across different evaluation metrics.

11.
Int J Mol Sci ; 25(16)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39201579

RESUMO

Atopic dermatitis (AD) is a common allergic inflammatory skin condition marked by severe itching, skin lichenification, and chronic inflammation. AD results from a complex immune response, primarily driven by T lymphocytes and environmental triggers, leading to a disrupted epidermal barrier function. Traditional treatments, such as topical corticosteroids, have limitations due to long-term side effects, highlighting the need for safer alternatives. Here, we aimed to show that Agrimonia coreana extract (ACext) can be used in treating AD-related dermatologic symptoms. ACext could inhibit CRAC (Calcium Release-Activated Calcium) channel activity, reducing Orai1/CRAC currents and decreasing intracellular calcium signaling. This inhibition was further confirmed by the reduced IL-2 levels and T cell proliferation upon ACext treatment. In a mouse model of AD, ACext significantly ameliorates symptoms, improves histological parameters, and enhances skin barrier function, demonstrating its potential for treating AD.


Assuntos
Agrimonia , Dermatite Atópica , Extratos Vegetais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Camundongos , Agrimonia/química , Modelos Animais de Doenças , Canais de Cálcio Ativados pela Liberação de Cálcio/metabolismo , Canais de Cálcio Ativados pela Liberação de Cálcio/antagonistas & inibidores , Humanos , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Sinalização do Cálcio/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/imunologia
12.
Neurol India ; 72(4): 768-771, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39216031

RESUMO

BACKGROUND: Restless legs syndrome (RLS) is common in Parkinson's disease (PD) patients and can affect the motor symptoms and non-motor symptoms (NMSs) of PD patients. OBJECTIVE: This study aimed to identify the clinical factors affected by RLS in patients with PD. METHODS: We included 369 de novo PD patients. RLS was assessed by face-to-face interviews and the motor symptoms and NMSs of the patients were assessed using relevant scales. RESULTS: RLS frequency in the patients was 12.2% (45/369). PD patients with RLS (PD-RLS) exhibited a greater global Pittsburgh Sleep Quality Index (PSQI) score than those without RLS (PD-No RLS). PD-RLS exhibited significantly greater scores in the daytime dysfunction and sleep disturbances components of the PSQI than PD-No RLS. PD-RLS exhibited a significantly greater score in the sleep/fatigue domain of the Non-Motor Symptoms Scale than PD-No RLS. The International RLS Study Group rating scale score was significantly related to PSQI components scores in the sleep disturbances, sleep latency, habitual sleep efficiency, and subjective sleep quality. CONCLUSIONS: RLS frequency in de novo PD patients is higher than that in the general population, and the main NMS affected by RLS in these patients is sleep disturbances. Therefore, it is necessary to manage RLS in PD patients with sleep disturbances.


Assuntos
Doença de Parkinson , Síndrome das Pernas Inquietas , Humanos , Síndrome das Pernas Inquietas/fisiopatologia , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/complicações , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/epidemiologia , Qualidade do Sono
13.
In Vivo ; 38(5): 2318-2327, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39187315

RESUMO

BACKGROUND/AIM: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial. MATERIALS AND METHODS: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response. RESULTS: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears. CONCLUSION: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments.


Assuntos
Modelos Animais de Doenças , Prurido , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Ratos , Prurido/tratamento farmacológico , Masculino , Pele/efeitos dos fármacos , Pele/patologia , Pele/lesões , Pomadas , Creme para a Pele , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico
14.
J Voice ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39127534

RESUMO

PURPOSE: The purpose of the present study was to determine the extrinsic laryngeal muscle activity and vocal economy during two different singing conditions (straight-tone- vs vibrato singing) over a physiologically relevant singing range. METHODS: Thirty professional singers or voice coaches participated in the study. The participants sang a sustained /a:/ vowel for approximately 5seconds, once in straight-tone singing conditions and once more in vibrato. The target pitches were C3, F3, A3, C4, F4, A4, and C5. Surface electromyographic (sEMG) measures were performed in the infrahyoid (IH)- and the suprahyoid (SH) muscle region. Contact quotient (CQ), sound pressure level (SPL), and fundamental frequencies were measured to derive the electroglottographic-based vocal economy parameter quasi-output cost ratio (QOCR). RESULTS: sEMG measures show that IH and SH muscles significantly increased in activity with ascending pitch. IH and SH muscle activity was also significantly higher when singing in vibrato than straight-tone. Moreover, SPL also increased with ascending pitch and when sung in vibrato. CQ increased and QOCR decreased as pitch ascended but did not significantly change when sung in vibrato. CONCLUSION: Singing higher pitches was generally associated with higher extrinsic laryngeal muscle activity and lower QOCR values. When comparing two singing conditions, extrinsic laryngeal muscle activity was higher during vibrato, implicating that IH and the SH muscles may contribute to rhythmic pulsations of pitch modulation. Although the QOCR value did not show significant differences between the two singing conditions, a significantly higher SPL during vibrato may offer some acoustical and physiological advantages. Results also indicate that extrinsic muscle activity may not be reliably measure vocal economy.

15.
Vaccine ; 42(25): 126118, 2024 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-39025696

RESUMO

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.


Assuntos
Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Imunidade Inata , SARS-CoV-2 , Humanos , Vacinas contra COVID-19/imunologia , ChAdOx1 nCoV-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Corticosteroides , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Animais , Vacinação/métodos , Monócitos/imunologia , Imunogenicidade da Vacina , Vetores Genéticos/genética , Linfócitos T/imunologia , Masculino , Feminino , Adulto
16.
Alzheimers Dement ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39001624

RESUMO

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

17.
Open Forum Infect Dis ; 11(7): ofae348, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39006316

RESUMO

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

18.
Elife ; 122024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953285

RESUMO

We studied lysosomal Ca2+ in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca2+ ([Ca2+]Lys) and increased [Ca2+]i through mitochondrial ROS, which was suppressed in Trpm2-KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated by Trpm2 KO. ER→lysosome Ca2+ refilling occurred after lysosomal Ca2+ release whose blockade attenuated LPS + PA-induced inflammasome. Subsequently, store-operated Ca2+entry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K+ efflux whose inhibition reduced ER Ca2+ content ([Ca2+]ER) and impaired [Ca2+]Lys recovery. LPS + PA activated KCa3.1 channel, a Ca2+-activated K+ channel. Inhibitors of KCa3.1 channel or Kcnn4 KO reduced [Ca2+]ER, attenuated increase of [Ca2+]i or inflammasome activation by LPS + PA, and ameliorated HFD-induced inflammasome or metabolic inflammation. Lysosomal Ca2+ release induced delayed JNK and ASC phosphorylation through CAMKII-ASK1. These results suggest a novel role of lysosomal Ca2+ release sustained by ER→lysosome Ca2+ refilling and K+ efflux through KCa3.1 channel in inflammasome activation and metabolic inflammation.


Assuntos
Cálcio , Retículo Endoplasmático , Inflamassomos , Inflamação , Lisossomos , Camundongos Knockout , Potássio , Animais , Inflamassomos/metabolismo , Camundongos , Lisossomos/metabolismo , Cálcio/metabolismo , Potássio/metabolismo , Inflamação/metabolismo , Retículo Endoplasmático/metabolismo , Lipopolissacarídeos , Canais de Cátion TRPM/metabolismo , Canais de Cátion TRPM/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Masculino , Dieta Hiperlipídica
19.
Korean J Pain ; 37(3): 256-263, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946700

RESUMO

Background: Cervical epidural block (CEB) is an effective intervention for managing cervical radicular pain. This study aimed to investigate the current status of performing CEB in South Korea. Methods: Pain physicians affiliated with the Korean Pain Society were asked to complete anonymous questionnaires regarding CEB between September and October 2022. The questionnaire consisted of 24 questions assessing the current status and methods of CEB in detail. Results: Of the 198 surveys collected, 171 physicians (86.4%) reported performing CEB. Among those, the majority (94.7%) used fluoroscopy during the procedure. The paramedian interlaminar (IL) approach was the most preferred method (50.3%). Respondents performing fluoroscopic-guided IL CEB were categorized into two groups based on clinical experience: those with ≤10 years of experience (≤10-year group, n = 91) and those with >10 years of experience (>10-year group, n = 71). The proportion of physicians obtaining informed consent in the ≤10-year group and >10-year group was 50.5% and 56.3%, respectively. When entering the epidural space during IL CEB, the contralateral oblique view was the second most frequently used in both groups (≤10-year group, 42.9%; >10-year group, 29.6%). In targeting the upper cervical lesions (C3-4), the proportion of respondents who used an IL space higher than C6-7 was 17.6% in the ≤10-year group and 29.5% in the >10-year experience group. Conclusions: This study demonstrated variability in the CEB technique used by pain physicians in South Korea. The findings highlight the need for education on informed consent and techniques to enhance safety.

20.
Infect Chemother ; 56(2): 171-187, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38960737

RESUMO

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively.

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