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One of the very fundamental attributes for telencephalic neural computation in mammals involves network activities oscillating beyond the initial trigger. The continuing and automated processing of transient inputs shall constitute the basis of cognition and intelligence but may lead to neuropsychiatric disorders such as epileptic seizures if carried so far as to engross part of or the whole telencephalic system. From a conventional view of the basic design of the telencephalic local circuitry, the GABAergic interneurons (INs) and glutamatergic pyramidal neurons (PNs) make negative feedback loops which would regulate the neural activities back to the original state. The drive for the most intriguing self-perpetuating telencephalic activities, then, has not been posed and characterized. We found activity-dependent deployment and delineated functional consequences of the electrical synapses directly linking INs and PNs in the amygdala, a prototypical telencephalic circuitry. These electrical synapses endow INs dual (a faster excitatory and a slower inhibitory) actions on PNs, providing a network-intrinsic excitatory drive that fuels the IN-PN interconnected circuitries and enables persistent oscillations with preservation of GABAergic negative feedback. Moreover, the entities of electrical synapses between INs and PNs are engaged in and disengaged from functioning in a highly dynamic way according to neural activities, which then determine the spatiotemporal scale of recruited oscillating networks. This study uncovers a special wide-range and context-dependent plasticity for wiring/rewiring of brain networks. Epileptogenesis or a wide spectrum of clinical disorders may ensue, however, from different scales of pathological extension of this unique form of telencephalic plasticity.
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Sinapsis Eléctricas , Epilepsia , Animales , Humanos , Sinapsis/fisiología , Interneuronas/fisiología , Encéfalo , Epilepsia/patología , Convulsiones/patología , MamíferosRESUMEN
Many organs of Drosophila show stereotypical left-right (LR) asymmetry; however, the underlying mechanisms remain elusive. Here, we have identified an evolutionarily conserved ubiquitin-binding protein, AWP1/Doctor No (Drn), as a factor required for LR asymmetry in the embryonic anterior gut. We found that drn is essential in the circular visceral muscle cells of the midgut for JAK/STAT signaling, which contributes to the first known cue for anterior gut lateralization via LR asymmetric nuclear rearrangement. Embryos homozygous for drn and lacking its maternal contribution showed phenotypes similar to those with depleted JAK/STAT signaling, suggesting that Drn is a general component of JAK/STAT signaling. Absence of Drn resulted in specific accumulation of Domeless (Dome), the receptor for ligands in the JAK/STAT signaling pathway, in intracellular compartments, including ubiquitylated cargos. Dome colocalized with Drn in wild-type Drosophila. These results suggest that Drn is required for the endocytic trafficking of Dome, which is a crucial step for activation of JAK/STAT signaling and the subsequent degradation of Dome. The roles of AWP1/Drn in activating JAK/STAT signaling and in LR asymmetric development may be conserved in various organisms.
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Proteínas de Drosophila , Drosophila , Animales , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Transducción de Señal/fisiología , Endocitosis/genética , Quinasas Janus/genética , Quinasas Janus/metabolismo , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismoRESUMEN
With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.
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Bacterias , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Humanos , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Animales , Antibacterianos/farmacología , Farmacorresistencia Microbiana , Farmacorresistencia Bacteriana , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiologíaRESUMEN
Mitochondrial dynamics regulate the quality and morphology of mitochondria. Calcium (Ca2+) plays an important role in regulating mitochondrial function. Here, we investigated the effects of optogenetically engineered Ca2+ signaling on mitochondrial dynamics. More specifically, customized illumination conditions could trigger unique Ca2+ oscillation waves to trigger specific signaling pathways. In this study, we found that modulating Ca2+ oscillations by increasing the light frequency, intensity and exposure time could drive mitochondria toward the fission state, mitochondrial dysfunction, autophagy and cell death. Moreover, illumination triggered phosphorylation at the Ser616 residue but not the Ser637 residue of the mitochondrial fission protein, dynamin-related protein 1 (DRP1, encoded by DNM1L), via the activation of Ca2+-dependent kinases CaMKII, ERK and CDK1. However, optogenetically engineered Ca2+ signaling did not activate calcineurin phosphatase to dephosphorylate DRP1 at Ser637. In addition, light illumination had no effect on the expression levels of the mitochondrial fusion proteins mitofusin 1 (MFN1) and 2 (MFN2). Overall, this study provides an effective and innovative approach to altering Ca2+ signaling for controlling mitochondrial fission with a more precise resolution than pharmacological approaches in the temporal dimension.
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Calcio , Dinámicas Mitocondriales , Dinámicas Mitocondriales/fisiología , Calcio/metabolismo , Dinaminas/genética , Dinaminas/metabolismo , Mitocondrias/metabolismo , Fosforilación , Muerte Celular , Proteínas Mitocondriales/metabolismoRESUMEN
We investigated a fatal case of primary amoebic meningoencephalitis from an indoor surfing center in Taiwan. The case was detected through encephalitis syndromic surveillance. Of 56 environmental specimens, 1 was positive for Naegleria fowleri ameba. This report emphasizes the risk for N. fowleri infection from inadequately disinfected recreational waters, even indoors.
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Infecciones Protozoarias del Sistema Nervioso Central , Naegleria fowleri , Humanos , Naegleria fowleri/aislamiento & purificación , Naegleria fowleri/genética , Taiwán/epidemiología , Infecciones Protozoarias del Sistema Nervioso Central/parasitología , Infecciones Protozoarias del Sistema Nervioso Central/diagnóstico , Infecciones Protozoarias del Sistema Nervioso Central/epidemiología , Resultado Fatal , Masculino , Meningoencefalitis/parasitología , Meningoencefalitis/diagnóstico , Amebiasis/diagnóstico , Amebiasis/parasitología , AdultoRESUMEN
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.
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COVID-19/diagnóstico , COVID-19/genética , Secuenciación del Exoma , Exoma/genética , Predisposición Genética a la Enfermedad , Hospitalización/estadística & datos numéricos , COVID-19/inmunología , COVID-19/terapia , Femenino , Humanos , Interferones/genética , Masculino , Pronóstico , SARS-CoV-2 , Tamaño de la MuestraRESUMEN
Electron-induced dissociation of a fluorocarbon adsorbate CF3 (ad) at 4.6 K is shown by Scanning Tunnelling Microscopy (STM) to form directed energetic F-atom 'projectiles' on Cu(110). The outcome of a collision between these directed projectiles and stationary co-adsorbed allyl 'target' molecules was found through STM to give rotational excitation of the target allyl, clockwise or anti-clockwise, depending on the chosen collision geometry. Molecular dynamics computation linked the collisional excitation of the allyl target to an 'abortive chemical reaction', in which the approach of the F-projectile stretched an H-C bond lifting the allyl above the surface, facilitating isomerization from 'Across' to 'Along' a Cu row.
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BACKGROUND: The potential health effects of taxing sugar-sweetened beverages (SSBs) has been insufficiently examined in Asian contexts. This study aimed to assess the impact of SSB taxation on the prevalence of obesity/overweight and type 2 diabetes mellitus (T2DM) in Hong Kong using a willingness-to-pay (WTP) survey and simulation analysis. METHODS: A random telephone survey was conducted with 1000 adults from May to June 2020. We used a contingent valuation approach to assess individuals' WTP for SSBs under four tax payment scenarios (5%, 10%, 40%, and 50% of the current market price). Based on the WTP, a simulation analysis was conducted to project changes in SSB purchase and associated reductions in the prevalence of obesity/overweight and T2DM over a 10-year simulation period. FINDINGS: When 5% and 10% taxation rates were introduced, approximately one-third of the population were unwilling to maintain their SSB purchase. Our simulation demonstrated a gradual decline in the prevalence of obesity/overweight and diabetes with a more pronounced decrease when higher taxation rates were introduced. 10% taxation resulted in a mean reduction of 1532.7 cases of overweight/obesity per 100 thousand population at the sixth year, while T2DM prevalence decreased by 267.1 (0.3%). CONCLUSIONS: This study underscores the effects of an SSB tax on purchase behaviors and health outcomes in an affluent Asia setting, with a more pronounced influence on adult population. These findings are expected to inform policymakers in making decisions regarding an effective and equitable tax rate on SSBs.
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Diabetes Mellitus Tipo 2 , Obesidad , Sobrepeso , Bebidas Azucaradas , Impuestos , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Bebidas Azucaradas/economía , Bebidas Azucaradas/estadística & datos numéricos , Masculino , Femenino , Obesidad/epidemiología , Adulto , Sobrepeso/epidemiología , Persona de Mediana Edad , Hong Kong/epidemiología , Prevalencia , Encuestas y CuestionariosRESUMEN
PURPOSE: The introduction of bolt-on dimensions in EQ-5D instruments is growing common, but most bolt-on studies have targeted the diseased population and obtained bolt-on from other existing Health-related Quality of Life (HRQoL) instruments. As the qualitative approach offers important evidence to support the consistency and design of the potential bolt-on items, this paper studies the Hong Kong SAR community's perception of the current EQ-5D-5 L instrument and identifies potential bolt-on via a qualitative approach. METHODS: A representative sample mix was recruited based on the age group, gender, and education level composition of the Hong Kong SAR community by quota sampling. Semi-structured interviews were conducted and the interviews were transcribed and coded to identify emergent and recurrent themes. RESULTS: Thirty interviews were conducted and the majority of the interviewees considered the EQ-5D-5 L insufficiently comprehensive to illustrate their HRQoL. While some key HRQoL aspects included in the EQ-5D matched with the community's HRQoL perception, respondents showed concern about the potential overlap of the existing HRQoL dimension, the optimal number or attributes, and the appropriateness of the EQ-VAS. Among the potential bolt-on dimensions that emerged, 'Sleep', 'Interpersonal Relationship', and 'Satisfaction' were the key potential bolt-on dimensions identified and emphasized in the interviews. CONCLUSIONS: The qualitative findings of the study illustrate the possible gap between EQ-5D-5 L measurements and community HRQoL perception, while the findings support the development of EQ-5D bolt-on dimensions in the target community with content and face validity.
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Entrevistas como Asunto , Investigación Cualitativa , Calidad de Vida , Humanos , Masculino , Femenino , Hong Kong , Calidad de Vida/psicología , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Anciano , Psicometría , Estado de Salud , Adulto JovenRESUMEN
Proteolysis targeting chimeras (PROTACs) have emerged as revolutionary anticancer therapeutics that degrade disease-causing proteins. However, the anticancer performance of PROTACs is often impaired by their insufficient bioavailability, unsatisfactory tumor specificity and ability to induce acquired drug resistance. Herein, we propose a polymer-conjugated PROTAC prodrug platform for the tumor-targeted delivery of the most prevalent von Hippel-Lindau (VHL)- and cereblon (CRBN)-based PROTACs, as well as for the precise codelivery of a degrader and conventional small-molecule drugs. The self-assembling PROTAC prodrug nanoparticles (NPs) can specifically target and be activated inside tumor cells to release the free PROTAC for precise protein degradation. The PROTAC prodrug NPs caused more efficient regression of MDA-MB-231 breast tumors in a mouse model by degrading bromodomain-containing protein 4 (BRD4) or cyclin-dependent kinase 9 (CDK9) with decreased systemic toxicity. In addition, we demonstrated that the PROTAC prodrug NPs can serve as a versatile platform for the codelivery of a PROTAC and chemotherapeutics for enhanced anticancer efficiency and combination benefits. This study paves the way for utilizing tumor-targeted protein degradation for precise anticancer therapy and the effective combination treatment of complex diseases.
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Nanopartículas , Profármacos , Proteolisis , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéutico , Humanos , Animales , Proteolisis/efectos de los fármacos , Nanopartículas/química , Línea Celular Tumoral , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Femenino , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Proteínas de Ciclo Celular/metabolismo , Ratones , Quinasa 9 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 9 Dependiente de la Ciclina/metabolismo , Factores de Transcripción/metabolismo , Ratones Desnudos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Ratones Endogámicos BALB C , Sistemas de Liberación de Medicamentos , Proteínas que Contienen Bromodominio , Ubiquitina-Proteína LigasasRESUMEN
Shorebirds (order Charadriiformes) are among the world's most threatened avian taxa. Within the East Asian-Australasian Flyway (EAAF), a major threat to shorebirds' survival may be the gauntlet of pollution along the flyway. Metals, persistent organic pollutants (POPs), and per-/polyfluoroalkyl substances (PFASs) persist in the environment to the detriment of wildlife. In this study, we analysed element and PFAS concentrations in blood from 142 individuals across six species of Arctic-breeding migratory shorebirds with contrasting population trends, to discern species- and site-specific pollution differences, and determine how pollution correlated with population trends of EAAF shorebirds. Potential within-year pollution variations were investigated by blood-sampling birds at two sites, representing different points in the birds' annual migrations: staging in Taiwan on southward migrations and at non-breeding grounds in Western Australia (WA). Species' pollutant concentrations were compared to established population trends. Concentrations of potentially toxic elements were low in most individuals regardless of species. PFASs (range: <0.001-141 ng/g), Hg (<0.001-9910 ng/g) and Pb (<0.01-1210 ng/g) were higher in Taiwan than in WA (PFAS Taiwan median: 14.5 ng/g, WA median: 3.45 ng/g; Hg Taiwan: 338 ng/g, WA: 23.4 ng/g; Pb Taiwan: 36.8 ng/g, WA: 2.26 ng/g). Meanwhile As (range <0.001-8840 ng/g) and Se (290-47600 ng/g) were higher in WA than Taiwan (As Taiwan median: 500 ng/g, WA median: 1660 ng/g; Se Taiwan: 5490 ng/g, Se WA: 23700 ng/g). Nevertheless, pollutant concentrations in a subset of individuals may exceed sublethal effect thresholds (As, Se and PFASs). Finally, we found no consistent differences in pollution among species and demonstrated no correlation between pollution and population trends, suggesting pollution is likely not a major driver for population declines of EAAF shorebirds. However, ongoing and locally heavy environmental degradation and exposure to other contaminants not investigated here, such as POPs, warrants continued consideration when managing EAAF shorebird populations.
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Contaminantes Ambientales , Fluorocarburos , Mercurio , Humanos , Animales , Contaminantes Ambientales/análisis , Plomo , Aves , Mercurio/análisis , Fluorocarburos/análisisRESUMEN
BACKGROUND: Discharging older adult patients from the hospital poses risks due to their vulnerable conditions, complex instructions and limited health literacy. Insufficient information about medication side effects adds to patient concerns. To address this, a post-discharge information summary system was developed. While it has shown positive impacts, concerns exist regarding implementation fidelity. OBJECTIVE: This study employed a theory-driven approach to understand health providers' perspectives on effective implementation. METHOD: Individual semi-structured interviews were conducted via telephone with nurses, doctors and pharmacists from local public hospitals. All interviews were audio-recorded and transcribed verbatim. Theoretical Domains Framework (TDF) was applied for direct content analysis. Belief statements were generated by thematic synthesis under each of the TDF domains. RESULTS: A total of 98 participants were interviewed. Out of the 49 belief statements covering eight TDF domains, 19 were determined to be highly relevant to the implementation of the post-discharge information summary system. These TDF domains include knowledge, skills, social/professional role and identity, beliefs about consequences, intentions, memory, attention and decision processes, environmental context and resources and social influences. CONCLUSION: Our study contributes to the understanding of determinants in implementing discharge interventions for older adult patients' self-care. Our findings can inform tailored strategies for frontline staff, including aligning programme rationale with stakeholders, promoting staff engagement through co-creation, reinforcing positive programme outcomes and creating default settings. Future research should employ rigorous quantitative designs to examine the actual impact and relationships among these determinants.
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Alta del Paciente , Investigación Cualitativa , Automanejo , Humanos , Femenino , Masculino , Anciano , Conocimientos, Actitudes y Práctica en Salud , Entrevistas como Asunto , Actitud del Personal de Salud , Persona de Mediana Edad , Educación del Paciente como AsuntoRESUMEN
AIM: To reveal the cellular composition and molecular environment of the periodontal and peri-implant inflammatory infiltrates through a single-cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri-implant/periodontal tissue immunity. MATERIALS AND METHODS: High-throughput single-cell transcriptomic profiling of peri-implant tissues from patients with peri-implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri-implantitis and periodontitis. RESULTS: Based on our single-cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri-implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation-promoting fibroblasts as well as a predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction in peri-implantitis. CONCLUSIONS: Our study indicated that the predominance of CXCL8+ fibroblast-CXCR2+ neutrophil interaction might underline the enhanced host response in peri-implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri-implantitis.
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Implantes Dentales , Periimplantitis , Periodontitis , Humanos , Neutrófilos , Inflamación , Periodontitis/patología , FibroblastosRESUMEN
BACKGROUND: Diabetes is an important factor in the development of penile inflammation. We studied whether type 2 diabetes (DM), with/without hypertension and hyperlipidemia increased the risk of circumcision among men aged between 30 and 69 using a population-based dataset in Taiwan during a 5-year follow-up period. METHODS: The research data in this study were obtained from Taiwan's National Health Insurance Research Database between 1997 and 2010. We identified 23,197 patients who had a new diagnosis of DM and randomly matched 115,985 subjects as controls. We observed whether circumcision was the treatment after a new DM diagnosis. The initial step involved analyzing the data using Poisson regression analysis. To address potential confounding factors, this study employed propensity score matching based on three variables. Additionally, a Cox regression with a Gamma frailty was utilized to compare outcomes between different groups. RESULTS: Poisson regression analysis showed that DM (RR = 1.75, 95CI = 0.10 ~ 1.22), but not hypertension (RR = 1.14, 95CI=-0.44 ~ 0.70), hyperlipidemia (RR = 0.94, 95CI=-0.66 ~ 0.53), or age (RR = 0.83, 95CI=-0.43 ~ 0.62), had an impact on circumcision treatment. Cox regression with a frailty model found that DM was a risk factor associated with circumcision (HR = 2.31, 95% CI = 1.74 ~ 3.06, p-value < 0.01), whereas no significant difference was noted between circumcision and hypertension (HR = 1.10, 95% CI = 0.80 ~ 1.51), hyperlipidemia (HR = 1.05, 95% CI = 0.79 ~ 1.40), or age (HR = 1.00, 95% CI = 0.99 ~ 1.02). CONCLUSIONS: Type 2 diabetes mellitus, but not hypertension, hyperlipidemia or age increases the risk of circumcision in men aged between 30 and 69 years.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Fragilidad , Hiperlipidemias , Hipertensión , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios de Seguimiento , Taiwán/epidemiología , Fragilidad/complicaciones , Factores de Riesgo , Hipertensión/complicaciones , Hiperlipidemias/epidemiología , Hiperlipidemias/complicaciones , Incidencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Older adult patients are particularly vulnerable to medication-related issues during the discharge process. To enhance medication discharge education and patient experience, a written medication reminder, incorporating crucial medication side effects and warning signs, was implemented in medicine wards. This study aimed to examine the influence of this reminder on patient experience and medication-taking behaviors among older adults in public healthcare settings. METHODS: Two separate rounds of cross-sectional surveys were conducted before and after the program implementation among different discharged patients in each round. The study enrolled older adult patients aged ≥ 65 or their caregivers discharged from the medical wards of four pilot public hospitals in Hong Kong. A structured questionnaire was administered via telephone within 14 days of the patient's discharge. The survey assessed patients' experience with the provided medication information during discharge, including the clarity, adequacy, and usefulness of the information, as well as their overall experience with inpatient services. The self-reported medication-taken behaviors, including adherence and side-effect encounters, were also measured. RESULTS: A total of 1,265 responses were collected before the implementation of the medication reminder, and 1,426 responses were obtained after the implementation. Pre/post-implementation survey comparison showed significant improvement in patient experience regarding the clarity of the provided medication information (7.93 ± 1.84 vs. 8.18 ± 1.69, P = 0.002), adequacy (7.92 ± 1.93 vs. 8.15 ± 1.76, P = 0.014), and usefulness (8.06 ± 1.80 vs. 8.26 ± 1.70, P = 0.017), significantly positive experience on the overall discharge information (ß coefficient, 0.43 [95%CI, 0.30 to 0.56]) and inpatient service (ß coefficient, 0.47 [95%CI, 0.32 to 0.61]). In addition, the side effects encounters were significantly lower in the post-implementation survey group (11.6% vs. 9.0%, P = 0.04) and no statistical difference was found in self-reported medication adherence between the two groups. CONCLUSIONS: The provision of written medication reminders on key medication risks effectively improved older adult patients' experience and reduced side effects without any unintended negative consequences. The findings can serve as a reference for similar settings seeking to enhance post-discharge care among older adult patients. Future studies could investigate the influence in other specialties and age groups and include clinical outcomes to test the program's effectiveness.
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Cumplimiento de la Medicación , Alta del Paciente , Sistemas Recordatorios , Humanos , Estudios Transversales , Masculino , Anciano , Femenino , Anciano de 80 o más Años , Cumplimiento de la Medicación/psicología , Encuestas y Cuestionarios , Hong Kong/epidemiologíaRESUMEN
The niobium-92-zirconium-92 (92Nb-92Zr) decay system with a half-life of 37 Ma has great potential to date the evolution of planetary materials in the early Solar System. Moreover, the initial abundance of the p-process isotope 92Nb in the Solar System is important for quantifying the contribution of p-process nucleosynthesis in astrophysical models. Current estimates of the initial 92Nb/93Nb ratios have large uncertainties compromising the use of the 92Nb-92Zr cosmochronometer and leaving nucleosynthetic models poorly constrained. Here, the initial 92Nb abundance is determined to high precision by combining the 92Nb-92Zr systematics of cogenetic rutiles and zircons from mesosiderites with U-Pb dating of the same zircons. The mineral pair indicates that the 92Nb/93Nb ratio of the Solar System started with (1.66 ± 0.10) × 10-5, and their 92Zr/90Zr ratios can be explained by a three-stage Nb-Zr evolution on the mesosiderite parent body. Because of the improvement by a factor of 6 of the precision of the initial Solar System 92Nb/93Nb, we can show that the presence of 92Nb in the early Solar System provides further evidence that both type Ia supernovae and core-collapse supernovae contributed to the light p-process nuclei.
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This study aimed to evaluate the potential prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid carcinoma (PTC). Based on The TCGA database, lncRNAs and ferroptosis-related genes with differential expression levels in PTC tumors vs. normal tissues were screened. After the co-expression network construction, ferroptosis-related lncRNAs (FRLs) were screened. Kaplan-Meier analysis was conducted to compare the survival performance of patients with PTC in the high- and low-risk groups. Furthermore, a nomogram was created to enhance PTC prognosis. CIBERSORT was used to investigate the infiltration of various immune cells in high- and low-risk groups. In total, 10 lncRNA pairs with differential expression levels were obtained. There were significant differences in the histological subtype and pathological stage between the high- and low-risk groups, and age (P = 7.39E-13) and FRLM model status (P = 1.09E-04) were identified as independent prognostic factors. Subsequently, the nomogram survival model showed that the predicted one-, three-, and five-year survival rates were similar to the actual one- (c-index = 0.8475), three- (c-index = 0.7964), and five-year (c-index = 0.7555) survival rates. Subjects in the low-risk group had significantly more CD4 + memory T cells and resting myeloid dendritic cells, and subjects in the high-risk group had more plasma B cells and monocytes. The risk assessment model constructed using FRLs showed good predictive value for the prognosis of patients with PTC.
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BACKGROUND: Electronic mental health literacy (eMHL) is critical for accessing and effectively using digital mental health resources. However, there is a paucity of research on how eMHL varies across age groups. OBJECTIVE: This study aimed to investigate differences in eMHL among young, middle-aged, and older adults; provide insights into the needs, behaviors, and attitudes of different age groups in relation to digital mental health resources; and ultimately, inform the improvement of mental health services. METHODS: A qualitative investigation was conducted to examine the differences in eMHL across different age demographics in the Chinese population in 2023. The study sample comprised 3 distinct age groups: 18-34 years, 35-64 years, and 65 years and older. Participants were recruited through purposive sampling to ensure a diverse representation of the population. Data were collected through semistructured one-on-one interviews, which allowed for in-depth exploration of individual experiences and perceptions. The gathered data were subsequently subjected to rigorous thematic analysis to enable the identification and interpretation of recurring patterns and themes. RESULTS: The principal outcomes derived from these interviews were synthesized into 5 distinct dimensions: emotional needs, use of digital mental health resources, assessment of digital mental health information, engagement with social media to regulate emotions, and coping strategies. These dimensions were uniformly observed across the 3 age groups. CONCLUSIONS: We identified differences in knowledge, skills, and attitudes regarding the use of web-based information for managing mental health problems between the 3 age groups. The findings highlight the importance of age-specific strategies for improving eMHL.
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Alfabetización en Salud , Salud Mental , Investigación Cualitativa , Humanos , Adulto , Persona de Mediana Edad , Femenino , Masculino , Anciano , Adolescente , Adulto Joven , Factores de Edad , ChinaRESUMEN
Two new nervogenic acid derivatives liparisnervosides Q (1) and R (5), as well as five known nervogenic acid derivatives (2-4, 6, 7) and four phenanthrenes (8-11) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray) Lindl.. Their structures were detremined using extensive spectroscopic techniques, including 1D, 2D NMR, and HR-ESI-MS, and acid hydrolysis. Furthermore, their antimicrobial and immunosuppressive activities were evaluated. Nervosine VII (3) exhibited antimicrobial activity against Staphylococcus aureus with an MIC of 62.5â µg/mL and inhibited the proliferation of human T cells with an IC50 value of 9.67±0.96â µM. These findings contribute to our understanding of the potential pharmacological properties of these compounds.
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Proliferación Celular , Inmunosupresores , Pruebas de Sensibilidad Microbiana , Fenantrenos , Staphylococcus aureus , Humanos , Inmunosupresores/farmacología , Inmunosupresores/química , Inmunosupresores/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fenantrenos/farmacología , Fenantrenos/química , Fenantrenos/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Linfocitos T/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND: Drug-induced sleep endoscopy (DISE) is used for evaluating upper airway anatomy and determining airway obstruction patterns. It is typically performed with the patient in the supine position. Airway collapse severity is influenced by body position and level of consciousness; the resultant dynamic changes may vary across patients. In this study, we evaluated the severity of upper airway collapse through awake endoscopy and DISE and identified factors affecting the pattern of airway collapse severity. METHODS: This study included 66 patients with obstructive sleep apnea. The patients underwent type 1 polysomnography, tongue strength assessment, awake endoscopy in the sitting and supine positions, and DISE. Group-based trajectory modeling was performed to identify patients with different collapse severity patterns in different body positions and at different levels of consciousness. RESULTS: Patient with similar severity trajectory were assigned to the same group. Two different severity trajectories (group 1 and group 2) were identified at the tongue base level. Tongue depression strength varied significantly between groups 1 and 2 (47.00 vs. 35.00 kPa; P = .047). During awake endoscopy, collapse severity was significantly higher in group 2 than in group 1. Group 1 had lower rapid eye movement/nonrapid eye movement apnea-hypopnea index ratios and higher tongue depression strength than did group 2. CONCLUSION: In patients with obstructive sleep apnea, tongue strength may vary depending on body position. Our results should be interpreted with caution because of the limited sample size. Future studies should investigate the effect of oropharyngeal rehabilitation on tongue strength and collapse severity.