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Eutrophic shallow lakes are generally considered as a contributor to the emission of nitrous oxide (N2O), while regional and global estimates have remained imprecise. This due to a lack of data and insufficient understanding of the multiple contributing factors. This study characterized the spatiotemporal variability in N2O concentrations and N2O diffusive fluxes and the contributing factors in Lake Wuliangsuhai, a typical shallow eutrophic and seasonally frozen lake in Inner Mongolia with cold and arid climate. Dissolved N2O concentrations of the lake exhibited a range of 4.5 to 101.2 nmol/L, displaying significant spatiotemporal variations. The lowest and highest concentrations were measured in summer and winter, respectively. The spatial distribution of N2O flux was consistent with that of N2O concentrations. Additionally, the hotspots of N2O emissions were detected within close to the main inflow of lake. The wide spatial and temporal variation in N2O emissions indicate the complexity and its relative importance of factors influencing emissions. N2O emissions in different lake zones and seasons were regulated by diverse factors. Factors influencing the spatial and temporal distribution of N2O concentrations and fluxes were identified as WT, WD, DO, Chl-a, SD and COD. Interestingly, the same factor demonstrated opposing effects on N2O emission in various seasons or zones. This research improves our understanding of N2O emissions in shallow eutrophic lakes in cold and arid areas.
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Monitoreo del Ambiente , Lagos , Óxido Nitroso , Estaciones del Año , Óxido Nitroso/análisis , Lagos/química , China , Contaminantes Atmosféricos/análisis , Eutrofización , Análisis Espacio-Temporal , Contaminantes Químicos del Agua/análisisRESUMEN
CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors (IDLVs) induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors.
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BACKGROUND: T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses, but the functional role of Tfh cells in the pathogenesis of idiopathic membranous nephropathy (IMN) remains unclear. OBJECTIVES: This study aimed to establish a rat experimental membranous nephropathy model, investigate the phenotypic characteristics of Tfh cells, and analyze a clinically significant correlation between Tfh cells. MATERIAL AND METHODS: Passive Heymann nephritis (PHN) rats were induced by immunizing Sprague Dawley rats with anti-Fx1A serum. The frequency of Tfh and B cell subsets was analyzed with flow cytometry (FC). The serum concentration of interleukin-21 (IL-21), the relative mRNA expression levels of IL-21 and B cell lymphoma 6 (Bcl-6) in spleen mononuclear cells (MNCs), and the kidney infiltration of CD4+ T cells and IL-21 were assessed. The potential correlations among these measures were analyzed. RESULTS: In comparison with the control group, significantly increased percentages of Tfh cells, inducible T cell co-stimulator-positive (ICOS+) Tfh cells, and mRNA expression of Bcl-6 were detected in the spleen of PHN rats. Elevated IL-21 expression was detected in the serum and kidneys. Remarkably, the percentage of splenic ICOS+ Tfh cells was positively correlated with 24 h urine protein concentrations (r = 0.676, p = 0.011) in PHN rats. CONCLUSION: These data indicate that ICOS+ Tfh cells contribute to development of IMN, and they might be potential therapeutic targets for IMN.
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Modelos Animales de Enfermedad , Progresión de la Enfermedad , Glomerulonefritis Membranosa , Interleucinas , Proteínas Proto-Oncogénicas c-bcl-6 , Ratas Sprague-Dawley , Células T Auxiliares Foliculares , Animales , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/sangre , Células T Auxiliares Foliculares/inmunología , Células T Auxiliares Foliculares/metabolismo , Ratas , Interleucinas/sangre , Interleucinas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Masculino , Bazo/inmunología , Bazo/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismoRESUMEN
BACKGROUND: Dietary supplement (DS) use is common and increasing among older adults, though much data available on use frequencies are from surveys and performed cross-sectionally. This paper sought to assess the frequency and pattern of dietary supplement use among older adults over time. METHODS: A secondary analysis of data from the AAA LongROAD study, a longitudinal prospective cohort study of older adult drivers, using data from baseline and the first two years of follow up included a total of 2990 drivers aged 65-79 years recruited at five study sites across the US from July 2015 to March 2017. Participants underwent baseline and annual evaluations, which included a "brown bag" medication review. DS were identified and categorized according to type and key components. Prevalence and pattern of DS use over time and relationship to demographics were measured with frequency and Chi squared analyses. RESULTS: 84% of participants took at least one dietary supplement during the 2-year study period, and 55% of participants continually reported use. DS accounted for approximately 30% of the total pharmacologic-pill burden in all years. Participants who were White non-Hispanic, female, 75-79 years of age at baseline, and on more non-supplement medications took significantly more dietary supplements (P < 0.05). Vitamin D, multivitamins, calcium, and omega-3 formulations were the most common supplements, with stable use over time. Use of individual herbal supplements and cannabis products was uncommon (< 1% participants per year). CONCLUSIONS: DS use among older adults is common and relatively stable over time and contributes to polypharmacy. In clinical settings, providers should consider the influence of DS formulations on polypharmacy, and the associated cost, risk of medication interactions, and effect on medication compliance.
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Suplementos Dietéticos , Humanos , Anciano , Femenino , Masculino , Estudios Prospectivos , Estudios Longitudinales , Conducción de Automóvil , Estados UnidosRESUMEN
Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future.
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To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.
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BACKGROUND: Racial and ethnic minorities often receive care at different hospitals than non-Hispanic white patients, but how hospital characteristics influence the occurrence of disparities at the end of life is unknown. The aim of this study was to determine if disparities in end-of-life care were present among minoritized patients during terminal hospitalizations, and if these disparities varied with hospital characteristics. METHODS: We identified hospitalizations where a patient died in New York State, 2016-2018. Using multilevel logistic regression, we examined whether documented end-of-life care (do-not-resuscitate status (DNR), palliative care (PC) encounter) differed by race and ethnicity, and whether these disparities differed based on receiving care in hospitals with varying characteristics (Black or Hispanic-serving hospital; teaching status; bed size; and availability of specialty palliative care). RESULTS: We identified 143,713 terminal hospitalizations in 188 hospitals. Across all hospitals, only Black patients were less likely to have a PC encounter (adjusted odds ratio (aOR) 0.83 [0.80-0.87]) or DNR status (aOR 0.91 [0.87-0.95]) when compared with non-Hispanic White patients, while Hispanic patients were more likely to have DNR status (aOR 1.07 [1.01-1.13]). In non-teaching hospitals, all minoritized groups had decreased odds of PC (aOR 0.80 [0.76-0.85] for Black, aOR 0.91 [0.85-0.98] for Hispanic, aOR 0.93 [0.88-0.98] for Others), while in teaching hospitals, only Black patients had a decreased likelihood of a PC encounter (aOR 0.88 [0.82-0.93]). Also, Black patients in a Black-serving hospitals were less likely to have DNR status (aOR 0.80 [0.73-0.87]). Disparities did not differ based on whether specialty PC was available (p = 0.27 for PC encounter, p = 0.59 for DNR status). CONCLUSION: During terminal hospitalizations, Black patients were less likely than non-Hispanic White patients to have documented end-of-life care. This disparity appears to be more pronounced in non-teaching hospitals than in teaching hospitals.
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Disparidades en Atención de Salud , Hospitalización , Cuidados Paliativos , Órdenes de Resucitación , Cuidado Terminal , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/estadística & datos numéricos , Hispánicos o Latinos , Hospitalización/estadística & datos numéricos , New York , Cuidados Paliativos/estadística & datos numéricos , Cuidado Terminal/estadística & datos numéricos , Blanco , Negro o AfroamericanoRESUMEN
Objective: To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA). Methods: A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women. Result: A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-ß2 glycoprotein â antibodies (ß2GPâ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both ß2GPâ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both ß2GPâ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies. Conclusion: Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.
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Aborto Habitual , Autoanticuerpos , Inmunidad Humoral , Edad Materna , Humanos , Femenino , Adulto , Aborto Habitual/inmunología , Estudios Retrospectivos , Embarazo , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Persona de Mediana Edad , Síndrome Antifosfolípido/inmunología , China , Lupus Eritematoso Sistémico/inmunología , Síndrome de Sjögren/inmunología , Adulto Joven , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Artritis Reumatoide/inmunología , Enfermedades Indiferenciadas del Tejido Conectivo/inmunología , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Modelos LogísticosRESUMEN
N6-methyladenosine (m6A) methylation is one of the most predominant internal RNA modifications in eukaryotes and has become a hot spot in the field of epigenetics in recent years. Cardiovascular diseases (CVDs) are a leading cause of death globally. Emerging evidence demonstrates that RNA modifications, such as the m6A modification, are associated with the development and progression of many diseases, including CVDs. An increasing body of studies has indicated that programmed cell death (PCD) plays a vital role in CVDs. However, the molecular mechanisms underlying m6A modification and PCD in CVDs remain poorly understood. Herein, elaborating on the highly complex connections between the m6A mechanisms and different PCD signaling pathways and clarifying the exact molecular mechanism of m6A modification mediating PCD have significant meaning in developing new strategies for the prevention and therapy of CVDs. There is great potential for clinical application.
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Most studies investigate the cyclable capacity fading mechanism of Li-rich layered oxides (LLOs) from the microscopic structure level, lacking discussions about how the structure degradation influences the performance of the pouch cell precisely and quantitatively. Based on the analysis of the evolution of key parameters during the whole cycling period, a new transition-type fading mechanism is proposed. From the early-to-middle stage of the cycling period, polarization increases, most of which is interface-related, causing about 67% of the whole capacity loss. From the middle-to-late stage of the cycling period, active material losses turn out to be the dominating factor, inducing about 61% of the total capacity loss. Diffusion-related polarization, replacing the interface type, is responsible for most of the increased overpotential. Relative analysis confirms that during the early stage, the increase of the charge transfer resistance, induced by CEI (cathode electrolyte interface) growth and initial surface layered-structure degradation, is the main source of interface polarization. As the cycling evolves to the late stage, severe bulky structure degradation, including lattice-oxygen release, Li/Ni mixture and generation of a new spinel phase, turns out to be the major factor, causing further capacity fading.
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For perennial plants, newly emerged organs are fresh hot spots for environmental microbes to occupy and assemble to form mature microbial communities. In the microbial community, some commensal fungi can play important roles in microbial succession, thus significantly improving host plant growth and disease resistance. However, their participating patterns in microbial assembly and succession remain largely unknown. In this study, we profiled the fungal community and found a similar fungal succession pattern of spring-emerged leaves from March to October in two pomelo orchards. Specifically, the fungal species, tracked on the old leaves, dominated the spring leaves after emergence and then decreased in relative abundance. This reduction in priority effects on the spring leaves was then followed by an increase in the number of observed species, Shannon and phylogenetic diversity indices, and the pathogen-associated fungal groups. In addition, we found that the temporal fungal succession on the spring leaves highly correlated with the disease occurrence in the orchards and with the temperature and precipitation variation from spring to summer. Of the pathogen-associated fungal groups, an increase in the relative abundance of Mycosphaerellaceae, hosting the causal agent of citrus greasy spot, correlated with the occurrence of the disease, while the relative abundance of Diaporthaceae, hosting the causal agent of melanose, was extremely low during the fungal succession. These results confirm that the two kinds of pathogen-associated fungal groups share different lifestyles on citrus, and also suggest that the study of temporal fungal succession in microbial communities can add to our understanding of the epidemiology of potential plant pathogens.
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BACKGROUND: Diabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data. METHODS: Data for this study came from a multisite naturalistic driving study of drivers aged 65-79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM. RESULTS: Of the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53). CONCLUSION: Older adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.
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The most frequently reported adverse reaction to zoledronic acid is an acute phase reaction resembling influenza. While rarer adverse events such as osteonecrosis of the jaw and atypical femoral fractures have gained significant recognition, the ocular adverse effects, particularly scleritis, are not yet fully comprehended. Here, we present the case of a 75-year-old female patient with osteoporosis who developed bilateral redness and intense eye pain 48 h after receiving a 5 mg intravenous dose of zoledronic acid. Clinical presentation suggested bilateral conjunctivitis, but treatment with levofloxacin eye drops and acyclovir ophthalmic gel exacerbated the symptoms over 2 days, predominantly affecting the left eye. Ocular ultrasonography revealed thickening of the left eyeball wall with a "T" sign, while an orbital CT scan showed increased thickness of the left sclera. Treatment with methylprednisolone 80 mg intravenous infusion twice daily led to gradual symptom improvement and eventual resolution of inflammation. This report, based on a review of relevant literature, investigates the treatment and outcomes of zoledronic acid-induced scleritis, emphasizing the importance for clinicians to promptly identify and manage this rare and serious ocular adverse reaction.
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Background: Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation is a rare and serious adverse event. The aim of our study was to evaluate the risk factors and management of ERCP-related perforation, and to further determine the predictive factors associated with perforation outcome. Methods: A total of 27,018 ERCP procedures performed at the First Affiliated Hospital of Nanchang University (Nanchang, China) between January 2007 and March 2022 were included in the investigation of ERCP-related perforation. Medical records and endoscopic data were extracted to analyse the risk factors, management, and clinical outcome of ERCP-related perforation. Results: Seventy-six patients (0.28%) were identified as having experienced perforation following ERCP. Advanced age, Billroth II anatomy, precut sphincterotomy, and papillary balloon dilatation were significantly associated with ERCP-related perforation. Most patients with perforation (n = 65) were recognized immediately during ERCP whereas 11 were recognized later on. The delay in recognition primarily resulted from stent migration (n = 9). In addition, 12 patients experienced poor clinical outcome including death or hospice discharge (n = 3), ICU admission for >3 days (n = 6), and prolonged hospital stay for >1 month due to perforation (n = 3). Cancer and systemic inflammatory response syndrome (SIRS) are associated with a higher risk of poor outcome. Conclusions: Advanced age, Billroth II anatomy, precut sphincterotomy, and balloon dilation increase the risk of ERCP-related perforation whereas cancer and SIRS independently predicted poor clinical outcome.
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AIMS: Limited understanding exists regarding the neurobiological mechanisms underlying non-suicidal self-injury (NSSI) and suicide attempts (SA) in depressed adolescents. The maturation of brain network is crucial during adolescence, yet the abnormal alternations in depressed adolescents with NSSI or NSSI+SA remain poorly understood. METHODS: Resting-state functional magnetic resonance imaging data were collected from 114 depressed adolescents, classified into three groups: clinical control (non-self-harm), NSSI only, and NSSI+SA based on self-harm history. The alternations of resting-state functional connectivity (RSFC) were identified through support vector machine-based classification. RESULTS: Convergent alterations in NSSI and NSSI+SA predominantly centered on the inter-network RSFC between the Limbic network and the three core neurocognitive networks (SalVAttn, Control, and Default networks). Divergent alterations in the NSSI+SA group primarily focused on the Visual, Limbic, and Subcortical networks. Additionally, the severity of depressive symptoms only showed a significant correlation with altered RSFCs between Limbic and DorsAttn or Visual networks, strengthening the fact that increased depression severity alone does not fully explain observed FC alternations in the NSSI+SA group. CONCLUSION: Convergent alterations suggest a shared neurobiological mechanism along the self-destructiveness continuum. Divergent alterations may indicate biomarkers differentiating risk for SA, informing neurobiologically guided interventions.
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Encéfalo , Imagen por Resonancia Magnética , Conducta Autodestructiva , Intento de Suicidio , Humanos , Conducta Autodestructiva/psicología , Adolescente , Masculino , Femenino , Intento de Suicidio/psicología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Depresión/psicología , Depresión/fisiopatología , Depresión/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , NiñoRESUMEN
BACKGROUND: Polypharmacy (i.e., simultaneous use of two or more medications) poses a serious safety concern for older drivers. This study assesses the association between polypharmacy and hard braking events in older adult drivers. METHODS: Data for this study came from a naturalistic driving study of 2990 older adults. Information about medications was collected through the "brown-bag review" method. Primary vehicles of the study participants were instrumented with data recording devices for up to 44 months. Multivariable negative binomial model was used to estimate the adjusted incidence rate ratios (aIRRs) and 95 % confidence intervals (CIs) of hard-braking events (i.e., maneuvers with linear deceleration rates ≥0.4 g) associated with polypharmacy. RESULTS: Of the 2990 participants, 2872 (96.1 %) were eligible for this analysis. At the time of enrollment, 157 (5.5 %) drivers were taking fewer than two medications, 904 (31.5 %) were taking 2-5 medications, 895 (31.2 %) were taking 6-9 medications, 571 (19.9 %) were taking 10-13 medications, and 345 (12.0 %) were taking 14 or more medications. Compared to drivers using fewer than two medications, the risk of hard-braking events increased 8 % (aIRR 1.08, 95 % CI 1.04, 1.13) for users of 2-5 medications, 12 % (aIRR 1.12, 95 % CI 1.08, 1.16) for users of 6-9 medications, 19 % (aIRR 1.19, 95 % CI 1.15, 1.24) for users of 10-13 medications, and 34 % (aIRR 1.34, 95 % CI 1.29, 1.40) for users of 14 or more medications. CONCLUSIONS: Polypharmacy in older adult drivers is associated with significantly increased incidence of hard-braking events in a dose-response fashion. Effective interventions to reduce polypharmacy use may help improve driving safety in older adults.
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Conducción de Automóvil , Polifarmacia , Humanos , Femenino , Masculino , Anciano , Conducción de Automóvil/estadística & datos numéricos , Anciano de 80 o más Años , Accidentes de Tránsito/estadística & datos numéricos , Accidentes de Tránsito/prevención & control , Factores de RiesgoRESUMEN
This research is concentrated on investigating the role and mechanism of miR-652-3p in the protective effects of isoflurane (ISO) against myocardial ischemia-reperfusion (I/R) injury. H9c2 cells underwent pretreatment with varying concentrations of ISO, and subsequently, a hypoxia/reoxygenation (H/R) model was constructed. The levels of miR-652-3p, ISL LIM homeobox 1 (ISL1), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were evaluated through reverse transcription polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay was employed to investigate concentrations of myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI). Cell counting kit-8 was used to evaluate cell viability, while flow cytometry was utilized to measure apoptosis. Additionally, a dual luciferase reporter assay was conducted to validate the targeting relationship between ISL1 and miR-652-3p. Herein, we confirmed that the level of miR-652-3p was gradually increased with prolonged hypoxia; nevertheless, this increase was suppressed by ISO pretreatment (P < 0.05). Additionally, ISO pretreatment prevented the decrease in cell viability, increase in apoptosis, and overproduction of IL-6, TNF-α, CK-MB, and cTnI induced by H/R (P < 0.05). However, the inhibitory effects of ISO were counteracted by the increased levels of miR-652-3p (P < 0.05). ISL1 is a potential target of miR-652-3p. H/R induction suppressed ISL1 levels compared to the control, but ISO treatment increased its expression (P < 0.05). Overexpression of ISL1 inhibited the elimination of the protective effect of ISO on myocardial damage induced by the elevation of miR-652-3p (P < 0.05). The findings of this research confirm that miR-652-3p attenuated the protective effect of ISO on cardiomyocytes in myocardial ischemia by targeting ISL1.
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Apoptosis , Hipoxia de la Célula , Interleucina-6 , Isoflurano , Proteínas con Homeodominio LIM , MicroARNs , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Factores de Transcripción , MicroARNs/metabolismo , MicroARNs/genética , Isoflurano/farmacología , Proteínas con Homeodominio LIM/metabolismo , Proteínas con Homeodominio LIM/genética , Animales , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/enzimología , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/genética , Línea Celular , Apoptosis/efectos de los fármacos , Ratas , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Forma MB de la Creatina-Quinasa/metabolismo , Forma MB de la Creatina-Quinasa/sangre , Troponina I/metabolismo , CitoprotecciónRESUMEN
BACKGROUND: Recent studies report conflicting results regarding the relationship between labour epidural analgesia (LEA) in mothers and neurodevelopmental disorders in their offspring. We evaluated behavioural and neuropsychological test scores in children of mothers who used LEA. METHODS: Children enrolled in the Raine Study from Western Australia and delivered vaginally from a singleton pregnancy between 1989 and 1992 were evaluated. Children exposed to LEA were compared with unexposed children. The primary outcome was the parent-reported Child Behaviour Checklist (CBCL) reporting total, internalising, and externalising behavioural problem scores at age 10 yr. Score differences, an increased risk of clinical deficit, and a dose-response based on the duration of LEA exposure were assessed. Secondary outcomes included language, motor function, cognition, and autistic traits. RESULTS: Of 2180 children, 850 (39.0%) were exposed to LEA. After adjustment for covariates, exposed children had minimally increased CBCL total scores (+1.41 points; 95% confidence interval [CI] 0.09 to 2.73; P=0.037), but not internalising (+1.13 points; 95% CI -0.08 to 2.34; P=0.066) or externalising (+1.08 points; 95% CI -0.08 to 2.24; P=0.068) subscale subscores. Increased risk of clinical deficit was not observed for any CBCL score. For secondary outcomes, score differences were inconsistently observed in motor function and cognition. Increased exposure duration was not associated with worse scores in any outcomes. CONCLUSIONS: Although LEA exposure was associated with slightly higher total behavioural scores, there was no difference in subscores, increased risk of clinical deficits, or dose-response relationship. These results argue against LEA exposure being associated with consistent, clinically significant neurodevelopmental deficits in children.