Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 598
Filtrar
1.
J Korean Med Sci ; 39(18): e151, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38742291

RESUMO

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) account for a large proportion of healthcare-associated infections and have a significant impact on morbidity, length of hospital stay, and mortality. Adherence to the recommended infection prevention practices can effectively reduce the incidence of CAUTIs. This study aimed to assess the characteristics of CAUTIs and the efficacy of prevention programs across hospitals of various sizes. METHODS: Intervention programs, including training, surveillance, and monitoring, were implemented. Data on the microorganisms responsible for CAUTIs, urinary catheter utilization ratio, rate of CAUTIs per 1,000 device days, and factors associated with the use of indwelling catheters were collected from 2017 to 2019. The incidence of CAUTIs and associated data were compared between university hospitals and small- and medium-sized hospitals. RESULTS: Thirty-two hospitals participated in the study, including 21 university hospitals and 11 small- and medium-sized hospitals. The microorganisms responsible for CAUTIs and their resistance rates did not differ between the two groups. In the first quarter of 2018, the incidence rate was 2.05 infections/1,000 device-days in university hospitals and 1.44 infections/1,000 device-days in small- and medium-sized hospitals. After implementing interventions, the rate gradually decreased in the first quarter of 2019, with 1.18 infections/1,000 device-days in university hospitals and 0.79 infections/1,000 device-days in small- and medium-sized hospitals. However, by the end of the study, the infection rate increased to 1.74 infections/1,000 device-days in university hospitals and 1.80 infections/1,000 device-days in small- and medium-sized hospitals. CONCLUSION: We implemented interventions to prevent CAUTIs and evaluated their outcomes. The incidence of these infections decreased in the initial phases of the intervention when adequate support and personnel were present. The rate of these infections may be reduced by implementing active interventions such as consistent monitoring and adherence to guidelines for preventing infections.


Assuntos
Infecções Relacionadas a Cateter , Infecções Urinárias , Humanos , Infecções Urinárias/prevenção & controle , Infecções Urinárias/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Incidência , Controle de Infecções/métodos , Cateterismo Urinário/efeitos adversos , Cateteres de Demora/efeitos adversos , Hospitais Universitários , Cateteres Urinários/efeitos adversos
2.
Eur Heart J Digit Health ; 5(3): 260-269, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38774376

RESUMO

Aims: Augmenting echocardiography with artificial intelligence would allow for automated assessment of routine parameters and identification of disease patterns not easily recognized otherwise. View classification is an essential first step before deep learning can be applied to the echocardiogram. Methods and results: We trained two- and three-dimensional convolutional neural networks (CNNs) using transthoracic echocardiographic (TTE) studies obtained from 909 patients to classify nine view categories (10 269 videos). Transthoracic echocardiographic studies from 229 patients were used in internal validation (2582 videos). Convolutional neural networks were tested on 100 patients with comprehensive TTE studies (where the two examples chosen by CNNs as most likely to represent a view were evaluated) and 408 patients with five view categories obtained via point-of-care ultrasound (POCUS). The overall accuracy of the two-dimensional CNN was 96.8%, and the averaged area under the curve (AUC) was 0.997 on the comprehensive TTE testing set; these numbers were 98.4% and 0.998, respectively, on the POCUS set. For the three-dimensional CNN, the accuracy and AUC were 96.3% and 0.998 for full TTE studies and 95.0% and 0.996 on POCUS videos, respectively. The positive predictive value, which defined correctly identified predicted views, was higher with two-dimensional rather than three-dimensional networks, exceeding 93% in apical, short-axis aortic valve, and parasternal long-axis left ventricle views. Conclusion: An automated view classifier utilizing CNNs was able to classify cardiac views obtained using TTE and POCUS with high accuracy. The view classifier will facilitate the application of deep learning to echocardiography.

3.
Ultraschall Med ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593859

RESUMO

PURPOSE: To develop and evaluate artificial intelligence (AI) algorithms for ultrasound (US) microflow imaging (MFI) in breast cancer diagnosis. MATERIALS AND METHODS: We retrospectively collected a dataset consisting of 516 breast lesions (364 benign and 152 malignant) in 471 women who underwent B-mode US and MFI. The internal dataset was split into training (n = 410) and test datasets (n = 106) for developing AI algorithms from deep convolutional neural networks from MFI. AI algorithms were trained to provide malignancy risk (0-100%). The developed AI algorithms were further validated with an independent external dataset of 264 lesions (229 benign and 35 malignant). The diagnostic performance of B-mode US, AI algorithms, or their combinations was evaluated by calculating the area under the receiver operating characteristic curve (AUROC). RESULTS: The AUROC of the developed three AI algorithms (0.955-0.966) was higher than that of B-mode US (0.842, P < 0.0001). The AUROC of the AI algorithms on the external validation dataset (0.892-0.920) was similar to that of the test dataset. Among the AI algorithms, no significant difference was found in all performance metrics combined with or without B-mode US. Combined B-mode US and AI algorithms had a higher AUROC (0.963-0.972) than that of B-mode US (P < 0.0001). Combining B-mode US and AI algorithms significantly decreased the false-positive rate of BI-RADS category 4A lesions from 87% to 13% (P < 0.0001). CONCLUSION: AI-based MFI diagnosed breast cancers with better performance than B-mode US, eliminating 74% of false-positive diagnoses in BI-RADS category 4A lesions.

4.
BMC Med Genomics ; 17(Suppl 1): 92, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632583

RESUMO

BACKGROUND: Repressor element 1 (RE1) silencing transcription factor (REST) is a transcriptional repressor abundantly expressed in aging human brains. It is known to regulate genes associated with oxidative stress, inflammation, and neurological disorders by binding to a canonical form of sequence motif and its non-canonical variations. Although analysis of genomic sequence motifs is crucial to understand transcriptional regulation by transcription factors (TFs), a comprehensive characterization of various forms of RE1 motifs in human cell lines has not been performed. RESULTS: Here, we analyzed 23 ENCODE REST ChIP-seq datasets from diverse human cell lines and identified a non-redundant set of 68,975 loci with ChIP-seq peaks. Our systematic characterization of these binding sites revealed that the canonical form of REST binding motif was found primarily in ChIP-seq peaks shared across multiple cell lines, while non-canonical forms of motifs were identified in both cell-line-specific binding sites and those shared across cell lines. Remarkably, we observed a notable prevalence of non-canonical motifs that corresponded to half segments of the canonical motif. Furthermore, our analysis unveiled the presence of cell-line-specific REST binding patterns, as evidenced by the clustering of ChIP-seq experiments according to their respective cell lines. This observation underscores the cell-line specificity of REST binding at certain genomic loci, implying intricate cell-line-specific regulatory mechanisms. CONCLUSIONS: Overall, our study provides a comprehensive characterization of REST binding motifs in human cell lines and genome-wide RE1 motif profiles. These findings contribute to a deeper understanding of REST-mediated transcriptional regulation and highlight the importance of considering cell-line-specific effects in future investigations.


Assuntos
Regulação da Expressão Gênica , Proteínas Repressoras , Fatores de Transcrição , Humanos , Sítios de Ligação , Linhagem Celular , Genômica , Fatores de Transcrição/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
5.
JAMA ; 331(18): 1544-1557, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38557703

RESUMO

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.


Assuntos
Anti-Infecciosos Locais , Infecções Bacterianas , Infecção Hospitalar , Farmacorresistência Bacteriana Múltipla , Instalações de Saúde , Controle de Infecções , Idoso , Humanos , Administração Intranasal , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/uso terapêutico , Infecções Bacterianas/economia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/prevenção & controle , Banhos/métodos , California/epidemiologia , Clorexidina/administração & dosagem , Clorexidina/uso terapêutico , Infecção Hospitalar/economia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Infecção Hospitalar/prevenção & controle , Instalações de Saúde/economia , Instalações de Saúde/normas , Instalações de Saúde/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Hospitais/normas , Hospitais/estatística & dados numéricos , Controle de Infecções/métodos , Iodóforos/administração & dosagem , Iodóforos/uso terapêutico , Casas de Saúde/economia , Casas de Saúde/normas , Casas de Saúde/estatística & dados numéricos , Transferência de Pacientes , Melhoria de Qualidade/economia , Melhoria de Qualidade/estatística & dados numéricos , Higiene da Pele/métodos , Precauções Universais
6.
NPJ Biofilms Microbiomes ; 10(1): 19, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467678

RESUMO

Lower socioeconomic status (SES) is related to increased incidence and mortality due to chronic diseases in adults. Association between SES variables and gut microbiome variation has been observed in adults at the population level, suggesting that biological mechanisms may underlie the SES associations; however, there is a need for larger studies that consider individual- and neighborhood-level measures of SES in racially diverse populations. In 825 participants from a multi-ethnic cohort, we investigated how SES shapes the gut microbiome. We determined the relationship of a range of individual- and neighborhood-level SES indicators with the gut microbiome. Individual education level and occupation were self-reported by questionnaire. Geocoding was applied to link participants' addresses with neighborhood census tract socioeconomic indicators, including average income and social deprivation in the census tract. Gut microbiome was measured using 16SV4 region rRNA gene sequencing of stool samples. We compared α-diversity, ß-diversity, and taxonomic and functional pathway abundance by SES. Lower SES was significantly associated with greater α-diversity and compositional differences among groups, as measured by ß-diversity. Several taxa related to low SES were identified, especially an increasing abundance of Prevotella copri and Catenibacterium sp000437715, and decreasing abundance of Dysosmobacter welbionis in terms of their high log-fold change differences. In addition, nativity and race/ethnicity have emerged as ecosocial factors that also influence the gut microbiota. Together, these results showed that lower SES was strongly associated with compositional and taxonomic measures of the gut microbiome, and may contribute to shaping the gut microbiota.


Assuntos
Etnicidade , Microbioma Gastrointestinal , Adulto , Humanos , Classe Social , Fatores Socioeconômicos , Renda
8.
Osteoporos Int ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472336

RESUMO

Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. PURPOSE: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. METHODS: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. RESULTS: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. CONCLUSION: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.

9.
iScience ; 27(4): 109414, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38532888

RESUMO

In pancreatic ductal adenocarcinoma (PDAC), no recurrent metastasis-specific mutation has been found, suggesting that epigenetic mechanisms, such as DNA methylation, are the major contributors of late-stage disease progression. Here, we performed the first whole-genome bisulfite sequencing (WGBS) on mouse and human PDAC organoid models to identify stage-specific and molecular subtype-specific DNA methylation signatures. With this approach, we identified thousands of differentially methylated regions (DMRs) that can distinguish between the stages and molecular subtypes of PDAC. Stage-specific DMRs are associated with genes related to nervous system development and cell-cell adhesions, and are enriched in promoters and bivalent enhancers. Subtype-specific DMRs showed hypermethylation of GATA6 foregut endoderm transcriptional networks in the squamous subtype and hypermethylation of EMT transcriptional networks in the progenitor subtype. These results indicate that aberrant DNA methylation contributes to both PDAC progression and subtype differentiation, resulting in significant and reoccurring DNA methylation patterns with diagnostic and prognostic potential.

10.
Sci Rep ; 14(1): 6854, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514828

RESUMO

The high risk of neurological disorders in postmenopausal women is an emerging medical issue. Based on the hypothesis of altered estrogen receptors (ERα and ß) after the decline of estrogen production, we investigated the changes in ERs expressions across brain regions and depressive/amnesic behaviors. C57BL/6J female mice were ovariectomized (OVX) to establish a menopausal condition. Along with behavior tests (anxiety, depression, and memory), the expression of ERs, microglial activity, and neuronal activity was measured in six brain regions (hippocampus, prefrontal cortex, striatum, raphe nucleus, amygdala, and hypothalamus) from 4 to 12 weeks after OVX. Mice exhibited anxiety- and depressive-like behaviors, as well as memory impairment. These behavioral alterations have been linked to a suppression in the expression of ERß. The decreased ERß expression coincided with microglial-derived neuroinflammation, as indicated by notable activations of Ionized calcium-binding adapter molecule 1 and Interleukin-1beta. Additionally, the activity of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus, decreased in a time-dependent manner from 4 to 12 weeks post-OVX. Our study provides evidence shedding light on the susceptibility to memory impairment and depression in women after menopause. This susceptibility is associated with the suppression of ERß and alteration of ERα in six brain regions.


Assuntos
Receptor beta de Estrogênio , Receptores de Estrogênio , Animais , Feminino , Humanos , Camundongos , Estradiol/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Estrogênios/metabolismo , Hipocampo/metabolismo , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Camundongos Endogâmicos C57BL , Ovariectomia , Receptores de Estrogênio/metabolismo
11.
Infect Chemother ; 56(1): 122-157, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38527781

RESUMO

"Long COVID" is a term used to describe a condition when the symptoms and signs associated with coronavirus disease 2019 (COVID-19) persist for more than three months among patients infected with COVID-19; this condition has been reported globally and poses a serious public health issue. Long COVID can manifest in various forms, highlighting the need for appropriate evaluation and management by experts from various fields. However, due to the lack of clear clinical definitions, knowledge of pathophysiology, diagnostic methods, and treatment protocols, it is necessary to develop the best standard clinical guidelines based on the scientific evidence reported to date. We developed this clinical guideline for diagnosing and treating long COVID by analyzing the latest research data collected from the start of the COVID-19 pandemic until June 2023, along with the consensus of expert opinions. This guideline provides recommendations for diagnosis and treatment that can be applied in clinical practice, based on a total of 32 key questions related to patients with long COVID. The evaluation of patients with long COVID should be comprehensive, including medical history, physical examination, blood tests, imaging studies, and functional tests. To reduce the risk of developing long COVID, vaccination and antiviral treatment during the acute phase are recommended. This guideline will be revised when there is a reasonable need for updates based on the availability of new knowledge on the diagnosis and treatment of long COVID.

12.
Sci Data ; 11(1): 262, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429291

RESUMO

This study discloses a dataset of electric vehicles' (EVs') charging transactions at a scale for multi-faceted analysis from both EV charger and user perspectives. The data comprises whole sessions that occurred during a charging operation company's annual commercial operation period, specifically including identifiers and charger location categories. For data acquisition, machine-to-machine wireless communication system with proper retransmission for interruption is utilised. The entire dataset is newly collected and is available with 72,856 sessions from 2,337 EV users and 2,119 chargers. The dataset can be used in a variety of ways for the functioning of power systems and markets, including EV charging service businesses, charger installation siting, demand transaction market design, and long-term investment planning of EV-related infrastructure.

13.
Adv Healthc Mater ; : e2303857, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38344923

RESUMO

Recently, mRNA-based therapeutics, including vaccines, have gained significant attention in the field of gene therapy for treating various diseases. Among the various mRNA delivery vehicles, lipid nanoparticles (LNPs) have emerged as promising vehicles for packaging and delivering mRNA with low immunogenicity. However, while mRNA delivery has several advantages, the delivery efficiency and stability of LNPs remain challenging for mRNA therapy. In this study, an ionizable helper cholesterol analog, 3ß[L-histidinamide-carbamoyl] cholesterol (Hchol) lipid is developed and incorporated into LNPs instead of cholesterol to enhance the LNP potency. The pKa values of the Hchol-LNPs are ≈6.03 and 6.61 in MC3- and SM102-based lipid formulations. Notably, the Hchol-LNPs significantly improve the delivery efficiency by enhancing the endosomal escape of mRNA. Additionally, the Hchol-LNPs are more effective in a red blood cell hemolysis at pH 5.5, indicating a synergistic effect of the protonated imidazole groups of Hchol and cholesterol on endosomal membrane destabilization. Furthermore, mRNA delivery is substantially enhanced in mice treated with Hchol-LNPs. Importantly, LNP-encapsulated SARS-CoV-2 spike mRNA vaccinations induce potent antigen-specific antibodies against SARS-CoV-2. Overall, incorporating Hchol into LNP formulations enables efficient endosomal escape and stability, leading to an mRNA delivery vehicle with a higher delivery efficiency.

14.
Mol Nutr Food Res ; 68(5): e2300611, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38319040

RESUMO

SCOPE: Rose petal extract (RPE) shows a significant antioxidant effect through its anthocyanin content. However, the mechanism underlying the anti-aging effects of orally administered RPE remains unclear. This study aims to describe the anti-aging effect and mechanism of action of orally administered RPE in ultraviolet (UV)B-induced skin aging. METHODS AND RESULTS: This study evaluates the protein expression of collagen type I alpha 1 (COL1A1) and matrix metalloproteinase 1 (MMP-1) and the mRNA expression of hyaluronic synthase 2 (HAS2) in human dermal fibroblasts. In addition, the hyaluronidase and collagenase inhibitory activities of RPE are confirmed. To evaluate the anti-aging effects of RPE, SKH-1 hairless mice are administered RPE daily for 12 weeks. Wrinkle formation, transepidermal water loss (TEWL), and skin moisture loss induced by UVB irradiation are suppressed in the dorsal skin of SKH-1 hairless mice orally administered RPE. Oral administration of RPE suppresses UVB irradiation-induced collagen disruption and reduction of hyaluronic acid. To find the bioactive compound in the RPE, serum protocatechuic acid (PCA), an anthocyanin metabolite, is analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CONCLUSION: Anthocyanins in RPE are metabolized to PCA in the body and circulated through the bloodstream to exhibit anti-aging effects on the skin.


Assuntos
Antocianinas , Envelhecimento da Pele , Animais , Camundongos , Humanos , Antocianinas/farmacologia , Camundongos Pelados , Cromatografia Líquida , Espectrometria de Massas em Tandem , Pele , Raios Ultravioleta/efeitos adversos , Extratos Vegetais/farmacologia
15.
Environ Res ; 249: 118437, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38346486

RESUMO

The widespread prevalence of micro and nanoplastics in the environment raises concerns about their potential impact on human health. Recent evidence demonstrates the presence of nanoplastics in human blood and tissues following ingestion and inhalation, yet the specific risks and mechanisms of nanoplastic toxicity remain inadequately understood. In this study, we aimed to explore the molecular mechanisms underlying the toxicity of nanoplastics at both systemic and molecular levels by analyzing the transcriptomic/metabolomic responses and signaling pathways in the intestines of mice after oral administration of nanoplastics. Transcriptome analysis in nanoplastic-administered mice revealed a notable upregulation of genes involved in pro-inflammatory immune responses. In addition, nanoplastics substantially reduced the expression of tight junction proteins, including occludin, zonula occluden-1, and tricellulin, which are crucial for maintaining gut barrier integrity and function. Importantly, nanoplastic administration increased gut permeability and exacerbated dextran sulfate sodium-induced colitis. Further investigation into the underlying molecular mechanisms highlighted significant activation of signaling transsducer and activator of transcription (STAT)1 and STAT6 by nanoplastic administration, which was in line with the elevation of interferon and JAK-STAT pathway signatures identified through transcriptome enrichment analysis. Additionally, the consumption of nanoplastics specifically induced nuclear factor kappa-B (NF-κB) and extracellular signal-regulated kinase (ERK)1/2 signaling pathways in the intestines. Collectively, this study identifies molecular mechanisms contributing to adverse effects mediated by nanoplastics in the intestine, providing novel insights into the pathophysiological consequences of nanoplastic exposure.


Assuntos
Fator de Transcrição STAT1 , Animais , Camundongos , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética , Transcriptoma/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator de Transcrição STAT6/metabolismo , Fator de Transcrição STAT6/genética , Camundongos Endogâmicos C57BL , Nanopartículas/toxicidade , Metabolômica , Masculino , Colite/induzido quimicamente , Colite/metabolismo
16.
bioRxiv ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38260600

RESUMO

Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive neuronal loss and pathological accumulation of the misfolded proteins amyloid-ß and tau1,2. Neuroinflammation mediated by microglia and brain-resident macrophages plays a crucial role in AD pathogenesis1-5, though the mechanisms by which age, genes, and other risk factors interact remain largely unknown. Somatic mutations accumulate with age and lead to clonal expansion of many cell types, contributing to cancer and many non-cancer diseases6,7. Here we studied somatic mutation in normal aged and AD brains by three orthogonal methods and in three independent AD cohorts. Analysis of bulk RNA sequencing data from 866 samples from different brain regions revealed significantly higher (~two-fold) overall burdens of somatic single-nucleotide variants (sSNVs) in AD brains compared to age-matched controls. Molecular-barcoded deep (>1000X) gene panel sequencing of 311 prefrontal cortex samples showed enrichment of sSNVs and somatic insertions and deletions (sIndels) in cancer driver genes in AD brain compared to control, with recurrent, and often multiple, mutations in genes implicated in clonal hematopoiesis (CH)8,9. Pathogenic sSNVs were enriched in CSF1R+ microglia of AD brains, and the high proportion of microglia (up to 40%) carrying some sSNVs in cancer driver genes suggests mutation-driven microglial clonal expansion (MiCE). Analysis of single-nucleus RNA sequencing (snRNAseq) from temporal neocortex of 62 additional AD cases and controls exhibited nominally increased mosaic chromosomal alterations (mCAs) associated with CH10,11. Microglia carrying mCA showed upregulated pro-inflammatory genes, resembling the transcriptomic features of disease-associated microglia (DAM) in AD. Our results suggest that somatic driver mutations in microglia are common with normal aging but further enriched in AD brain, driving MiCE with inflammatory and DAM signatures. Our findings provide the first insights into microglial clonal dynamics in AD and identify potential new approaches to AD diagnosis and therapy.

17.
NPJ Digit Med ; 7(1): 4, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38182738

RESUMO

Assessment of left ventricular diastolic function plays a major role in the diagnosis and prognosis of cardiac diseases, including heart failure with preserved ejection fraction. We aimed to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify echocardiographically determined diastolic dysfunction and increased filling pressure. We trained, validated, and tested an AI-enabled ECG in 98,736, 21,963, and 98,763 patients, respectively, who had an ECG and echocardiographic diastolic function assessment within 14 days with no exclusion criteria. It was also tested in 55,248 patients with indeterminate diastolic function by echocardiography. The model was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve, and its prognostic performance was compared to echocardiography. The AUC for detecting increased filling pressure was 0.911. The AUCs to identify diastolic dysfunction grades ≥1, ≥2, and 3 were 0.847, 0.911, and 0.943, respectively. During a median follow-up of 5.9 years, 20,223 (20.5%) died. Patients with increased filling pressure predicted by AI-ECG had higher mortality than those with normal filling pressure, after adjusting for age, sex, and comorbidities in the test group (hazard ratio (HR) 1.7, 95% CI 1.645-1.757) similar to echocardiography and in the indeterminate group (HR 1.34, 95% CI 1.298-1.383). An AI-enabled ECG identifies increased filling pressure and diastolic function grades with a good prognostic value similar to echocardiography. AI-ECG is a simple and promising tool to enhance the detection of diseases associated with diastolic dysfunction and increased diastolic filling pressure.

18.
PLoS One ; 19(1): e0291539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38277342

RESUMO

INTRODUCTION: Research indicates that sexual and gender minority youth [SGMY] may engage more with information communication technologies [ICTs] more than their non-SGMY counterparts Craig SL et al. 2020. While scholarship generally explores youth's use of ICTs, there are gaps in scholarship that connect SGMY, their ICT engagement and influences to mental health. This scoping review will synthesize the literature that connects these core concepts in order to better understand the influence ITCs have on the mental health of SGMY and to develop a more fulsome understanding of this emerging area of literature. METHODS AND ANALYSIS: Following the scoping review framework of Arksey and O'Malley, the search will be conducted in the PsycINFO [Ovid interface, 1980-], MEDLINE [Ovid interface, 1948-], CINAHL [EBSCO interface, 1937-], Sociological Abstracts [ProQuest interface, 1952-], Social Services Abstracts [ProQuest interface, 1979-], and Scopus. Descriptive summaries and thematic analysis will summarize the articles that meet the inclusion criteria using an extraction table. ETHICS AND DISSEMINATION: The review outlined in this paper provides an overview of information that exists on the technology use of SGMY, ICTs and the interconnection with mental health. Results will be disseminated through peer reviewed journals and national and international conferences. As information collected for this paper as is retrieved from publicly available sources, ethics approval is not required.


Assuntos
Saúde Mental , Minorias Sexuais e de Gênero , Adolescente , Humanos , Identidade de Gênero , Projetos de Pesquisa , Literatura de Revisão como Assunto , Comportamento Sexual , Serviço Social , Masculino , Feminino
19.
Cancer ; 130(7): 1092-1100, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38079517

RESUMO

BACKGROUND: Stomach cancer incidence presents significant racial/ethnic disparities among racial/ethnic minority groups in the United States, particularly among Asian and Hispanic immigrant populations. However, population-based evaluation of disparities by nativity has been scarce because of the lack of nativity-specific population denominators, especially for disaggregated Asian subgroups. Population-based stomach cancer incidence and tumor characteristics by detailed race/ethnicity and nativity were examined. METHODS: Annual age-adjusted incidence rates were calculated by race/ethnicity, sex, and nativity and tumor characteristics, such as stage and anatomic subsite, were evaluated using the 2011-2015 California Cancer Registry data. For Hispanic and Asian populations, nativity-specific population counts were estimated using the US Census and the American Community Survey Public Use Microdata Sample data. RESULTS: During 2011-2015 in California, 14,198 patients were diagnosed with stomach cancer. Annual age-adjusted incidence rates were higher among foreign-born individuals than their US-born counterparts. The difference was modest among Hispanics (∼1.3-fold) but larger (∼2- to 3-fold) among Chinese, Japanese, and Korean Americans. The highest incidence was observed for foreign-born Korean and Japanese Americans (33 and 33 per 100,000 for men; 15 and 12 per 100,000 for women, respectively). The proportion of localized stage disease was highest among foreign-born Korean Americans (44%); a similar proportion was observed among US-born Korean Americans, although numbers were limited. For other Asians and Hispanics, the localized stage proportion was generally lower among foreign-born than US-born individuals and lowest among foreign-born Japanese Americans (23%). CONCLUSIONS: Nativity-specific investigation with disaggregated racial/ethnic groups identified substantial stomach cancer disparities among foreign-born immigrant populations.


Assuntos
Asiático , Neoplasias Gástricas , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Etnicidade , Neoplasias Gástricas/epidemiologia , Grupos Minoritários , Hispânico ou Latino , California/epidemiologia
20.
Infect Control Hosp Epidemiol ; 45(2): 215-220, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37791517

RESUMO

OBJECTIVE: We investigated gender differences in psychosocial determinants that affect hand hygiene (HH) performance among physicians. DESIGN: The survey included a structured questionnaire with 7 parts: self-assessment of HH execution rate; knowledge, attitude, and behavior regarding HH; internal and emotional motivation for better HH; barriers to HH; need for external reminders; preference for alcohol gel; and embarrassment due to supervision. SETTING: The study was conducted across 4 academic referral hospitals in Korea. PARTICIPANTS: Physicians who worked at these hospitals were surveyed. METHODS: The survey questionnaire was sent to 994 physicians of the hospitals in July 2018 via email or paper. Differences in psychosocial determinants of HH among physicians were analyzed by gender using an independent t test or the Fisher exact test. RESULTS: Of the 994 physicians, 201 (20.2%) responded to the survey. Among them, 129 (63.5%) were men. Male physicians identified 4 barriers as significant: time wasted on HH (P = .034); HH is not a habit (P = .004); often forgetting about HH situations (P = .002); and no disadvantage when I do not perform HH (P = .005). Female physicians identified pain and dryness of the hands as a significant obstacle (P = .010), and they had a higher tendency to feel uncomfortable when a fellow employee performed inadequate HH (P = .098). Among the respondents, 26.6% identified diversifying the types of hand sanitizers as their first choice for overcoming barriers to improving HH, followed by providing reminders (15.6%) and soap and paper towels in each hospital room (13.0%). CONCLUSION: A significant difference in the barriers to HH existed between male and female physicians. Promoting HH activities could help increase HH compliance.


Assuntos
Infecção Hospitalar , Higiene das Mãos , Médicos , Humanos , Masculino , Feminino , Fatores Sexuais , Hospitais , Inquéritos e Questionários , Fidelidade a Diretrizes , Controle de Infecções , Desinfecção das Mãos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...