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1.
Proc Natl Acad Sci U S A ; 120(36): e2303758120, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37639582

RESUMO

In Arabidopsis thaliana, brassinosteroid (BR) signaling and stomatal development are connected through the SHAGGY/GSK3-like kinase BR INSENSITIVE2 (BIN2). BIN2 is a key negative regulator of BR signaling but it plays a dual role in stomatal development. BIN2 promotes or restricts stomatal asymmetric cell division (ACD) depending on its subcellular localization, which is regulated by the stomatal lineage-specific scaffold protein POLAR. BRs inactivate BIN2, but how they govern stomatal development remains unclear. Mapping the single-cell transcriptome of stomatal lineages after triggering BR signaling with either exogenous BRs or the specific BIN2 inhibitor, bikinin, revealed that the two modes of BR signaling activation generate spatiotemporally distinct transcriptional responses. We established that BIN2 is always sensitive to the inhibitor but, when in a complex with POLAR and its closest homolog POLAR-LIKE1, it becomes protected from BR-mediated inactivation. Subsequently, BR signaling in ACD precursors is attenuated, while it remains active in epidermal cells devoid of scaffolds and undergoing differentiation. Our study demonstrates how scaffold proteins contribute to cellular signal specificity of hormonal responses in plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Brassinosteroides , Divisão Celular Assimétrica , Quinase 3 da Glicogênio Sintase , Transdução de Sinais , Diferenciação Celular , Arabidopsis/genética , Proteínas Quinases/genética , Proteínas de Arabidopsis/genética
2.
Genome Res ; 32(11-12): 2003-2014, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36351769

RESUMO

Aging is associated with changes in a variety of biological processes at the transcriptomic level, including gene expression. Two types of aging occur during a lifetime: chronological and physiological aging. However, dissecting the difference between chronological and physiological ages at the transcriptomic level has been a challenge because of its complexity. We analyzed the transcriptomic features associated with physiological and chronological aging using Caenorhabditis elegans as a model. Many structural and functional transcript elements, such as noncoding RNAs and intron-derived transcripts, were up-regulated with chronological aging. In contrast, mRNAs with many biological functions, including RNA processing, were down-regulated with physiological aging. We also identified an age-dependent increase in the usage of distal 3' splice sites in mRNA transcripts as a biomarker of physiological aging. Our study provides crucial information for dissecting chronological and physiological aging at the transcriptomic level.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Perfilação da Expressão Gênica , Proteínas de Caenorhabditis elegans/genética , Transcriptoma
3.
Plant Cell Physiol ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38590034

RESUMO

Cellular responses to internal and external stimuli are orchestrated by intricate intracellular signaling pathways. To ensure an efficient and specific information flow, cells employ scaffold proteins as critical signaling organizers. With the ability to bind multiple signaling molecules, scaffold proteins can sequester signaling components within specific subcellular domains or modulate the efficiency of signal transduction. Scaffolds can also tune the output of signaling pathways by serving as regulatory targets. This review focuses on scaffold proteins associated with the plant GLYCOGEN SYNTHASE KINASE3-like kinase, BRASSINOSTEROID-INSENSITIVE2 (BIN2) that serve as a key negative regulator of brassinosteroid (BR) signaling. Here we summarize the current understanding of how scaffold proteins actively shape BR signaling outputs and crosstalk in plant cells via interactions with BIN2.

4.
Anal Chem ; 96(21): 8356-8364, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38753674

RESUMO

Lipids are essential for various cellular functions, including energy storage, membrane flexibility, and signaling molecule production. Maintaining proper lipid levels is important to prevent health problems such as cancer, neurodegenerative disorders, cardiovascular diseases, obesity, and diabetes. Monitoring cellular lipid droplets (LDs) in real-time with high resolution can provide insights into LD-related pathways and diseases owing to the dynamic nature of LDs. Fluorescence-based imaging is widely used for tracking LDs in live cells and animal models. However, the current fluorophores have limitations such as poor photostability and high background staining. Herein, we developed a novel fluorogenic probe based on a push-pull interaction combined with aggregation-induced emission enhancement (AIEE) for dynamic imaging of LDs. Probe 1 exhibits favorable membrane permeability and spectroscopic characteristics, allowing specific imaging of cellular LDs and time-lapse imaging of LD accumulation. This probe can also be used to examine LDs in fruit fly tissues in various metabolic states, serving as a highly versatile and specific tool for dynamic LD imaging in cellular and tissue environments.


Assuntos
Corantes Fluorescentes , Gotículas Lipídicas , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Animais , Humanos , Imagem Óptica , Compostos de Boro/química , Camundongos , Células HeLa , Drosophila melanogaster
5.
J Transl Med ; 22(1): 522, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822335

RESUMO

BACKGROUND: Dizziness and vertigo rank among the top 10 reasons for emergency and clinical referrals to neurologists. Chronic dizziness and imbalance not only reduce quality of life, but also increase mortality. While the Mediterranean diet has long been considered beneficial for human and planetary health, its effects on chronic dizziness or imbalance are understudied. We investigated the associations of adherence to the Mediterranean diet with chronic dizziness and imbalance. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey 2019-2021 and included 4,183 adults aged 40 years and older with complete information from diet, dizziness, and neurotology questionnaires. The alternate Mediterranean diet score (aMed) for nine food groups was calculated from 24-hour dietary recall data. Based on questionnaire responses, chronic dizziness was categorized as either isolated or chronic dizziness with imbalance, characterized by a cluster of difficulties maintaining a standing position, walking, or falling. RESULTS: In a multivariable-adjusted model, the prevalence of chronic imbalance was lower in the top aMed tertile than in the bottom tertile (OR 0.37; 95% CI, 0.18-0.74; p-trend = 0.01). Among the individual aMed components, the intake of whole grains and nuts exhibited an inverse relationship with chronic imbalance (OR 0.50; 95% CI, 0.27-0.93 for whole grains; OR 0.55; 95% CI, 0.31-1.01 for nuts). The aMed score was not associated with isolated chronic dizziness. CONCLUSIONS: Greater adherence to the Mediterranean diet may reduce chronic imbalance, particularly with an adequate intake of whole grains and nuts.


Assuntos
Dieta Mediterrânea , Tontura , Vida Independente , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doença Crônica , Adulto , República da Coreia/epidemiologia , Idoso , Inquéritos Nutricionais , Equilíbrio Postural , Cooperação do Paciente , Inquéritos e Questionários
6.
Int J Mol Sci ; 25(6)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38542192

RESUMO

Osteoarthritis is a widespread chronic degenerative disease marked by the deterioration of articular cartilage, modifications in subchondral bone, and a spectrum of symptoms, including pain, stiffness, and disability. Ultimately, this condition impairs the patient's quality of life. This study aimed to evaluate the therapeutic efficacy of standardized Boswellia serrata gum resin extract (BSRE) in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. A total of 60 rats were allocated into six groups: normal control group (NC), osteoarthritis control (injected with MIA, OC), O + B50 (injected with MIA and treated with 50 mg/kg body weight (BW) BSRE), O + B75 (injected with MIA and treated with 75 mg/kg BW BSRE), O + B100 (injected with MIA and treated with 100 mg/kg BW BSRE), and O + M (injected with MIA and treated with 150 mg/kg BW methyl sulfonyl methane). Several parameters, including knee joint swelling, histopathological changes, and the expression of collagen type II alpha 1 (COL2A1) and aggrecan, were comprehensively assessed. Concurrently, the serum levels and mRNA expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) were analyzed in both the serum and knee joint synovium. The results demonstrated that BSRE significantly mitigated knee joint swelling, cartilage destruction, and tissue deformation. Notably, BSRE administration markedly upregulated the expression of COL2A1 and aggrecan while concurrently reducing levels of nitric oxide, prostaglandin E2, leukotriene B4, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Furthermore, a substantial decrease was observed in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-6, TNF-α and MMP-3 and -13, thereby indicating promising therapeutic implications for osteoarthritis. In conclusion, BSRE exhibited anti-inflammatory properties and inhibited cartilage matrix degradation in a rat model of MIA-induced osteoarthritis, with the O + B100 group showing significant reductions in swelling and notable improvements in joint cartilage damage. These findings illuminate the preventive and therapeutic potential of BSRE for osteoarthritis treatment, emphasizing the criticality of exhaustive evaluation of novel compounds.


Assuntos
Boswellia , Cartilagem Articular , Osteoartrite , Ratos , Humanos , Animais , Boswellia/metabolismo , Agrecanas/metabolismo , Qualidade de Vida , Modelos Animais de Doenças , Osteoartrite/metabolismo , Inflamação/metabolismo , Articulação do Joelho/patologia , Ácido Iodoacético/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , RNA Mensageiro/metabolismo , Cartilagem Articular/metabolismo
7.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38892385

RESUMO

Aging leads to tissue and cellular changes, often driven by oxidative stress and inflammation, which contribute to age-related diseases. Our research focuses on harnessing the potent anti-inflammatory and antioxidant properties of Korean Ulmus macrocarpa Hance, a traditional herbal remedy, to address muscle loss and atrophy. We evaluated the effects of Ulmus extract on various parameters in a muscle atrophy model, including weight, exercise performance, grip strength, body composition, muscle mass, and fiber characteristics. Additionally, we conducted Western blot and RT-PCR analyses to examine muscle protein regulation, apoptosis factors, inflammation, and antioxidants. In a dexamethasone-induced muscle atrophy model, Ulmus extract administration promoted genes related to muscle formation while reducing those associated with muscle atrophy. It also mitigated inflammation and boosted muscle antioxidants, indicating a potential improvement in muscle atrophy. These findings highlight the promise of Ulmus extract for developing pharmaceuticals and supplements to combat muscle loss and atrophy, paving the way for clinical applications.


Assuntos
Extratos Vegetais , Sarcopenia , Ulmus , Ulmus/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Camundongos Endogâmicos C57BL , Masculino , Animais , Camundongos , Sarcopenia/tratamento farmacológico , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos
8.
Small ; 19(36): e2302334, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37127856

RESUMO

The surging demand for environmental-friendly and safe electrochemical energy storage systems has driven the development of aqueous zinc (Zn)-ion batteries (ZIBs). However, metallic Zn anodes suffer from severe dendrite growth and large volume change, resulting in a limited lifetime for aqueous ZIB applications. Here, it is shown that 3D mesoporous carbon (MC) with controlled carbon and defect configurations can function as a highly reversible and dendrite-free Zn host, enabling the stable operation of aqueous ZIBs. The MC host has a structure-controlled architecture that contains optimal sp2 -carbon and defect sites, which results in an improved initial nucleation energy barrier and promotes uniform Zn deposition. As a consequence, the MC host shows outstanding Zn plating/stripping performance over 1000 cycles at 2 mA cm-2 and over 250 cycles at 6 mA cm-2 in asymmetric cells. Density functional theory calculations further reveal the role of the defective sp2 -carbon surface in Zn adsorption energy. Moreover, a full cell based on Zn@MC900 anode and V2 O5 cathode exhibits remarkable rate performance and cycling stability over 3500 cycles. These results establish a structure-mechanism-performance relationship of the carbon host as a highly reversible Zn anode for the reliable operation of ZIBs.

9.
J Gen Intern Med ; 38(10): 2298-2307, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36757667

RESUMO

BACKGROUND: Non-arrivals to scheduled ambulatory visits are common and lead to a discontinuity of care, poor health outcomes, and increased subsequent healthcare utilization. Reducing non-arrivals is important given their association with poorer health outcomes and cost to health systems. OBJECTIVE: To develop and validate a prediction model for ambulatory non-arrivals. DESIGN: Retrospective cohort study. PATIENTS OR SUBJECTS: Patients at an integrated health system who had an outpatient visit scheduled from January 1, 2020, to February 28, 2022. MAIN MEASURES: Non-arrivals to scheduled appointments. KEY RESULTS: There were over 4.3 million ambulatory appointments from 1.2 million adult patients. Patients with appointment non-arrivals were more likely to be single, racial/ethnic minorities, and not having an established primary care provider compared to those who arrived at their appointments. A prediction model using the XGBoost machine learning algorithm had the highest AUC value (0.768 [0.767-0.770]). Using SHAP values, the most impactful features in the model include rescheduled appointments, lead time (number of days from scheduled to appointment date), appointment provider, number of days since last appointment with the same department, and a patient's prior appointment status within the same department. Scheduling visits close to an appointment date is predicted to be less likely to result in a non-arrival. Overall, the prediction model calibrated well for each department, especially over the operationally relevant probability range of 0 to 40%. Departments with fewer observations and lower non-arrival rates generally had a worse calibration. CONCLUSIONS: Using a machine learning algorithm, we developed a prediction model for non-arrivals to scheduled ambulatory appointments usable for all medical specialties. The proposed prediction model can be deployed within an electronic health system or integrated into other dashboards to reduce non-arrivals. Future work will focus on the implementation and application of the model to reduce non-arrivals.


Assuntos
Algoritmos , Agendamento de Consultas , Adulto , Humanos , Estudos Retrospectivos , Fatores de Tempo , Aprendizado de Máquina
10.
J Biomed Sci ; 30(1): 26, 2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37088847

RESUMO

BACKGROUND: Although mRNA dysregulation can induce changes in mesenchymal stem cell (MSC) homeostasis, the mechanisms by which post-transcriptional regulation influences MSC differentiation potential remain understudied. PUMILIO2 (PUM2) represses translation by binding target mRNAs in a sequence-specific manner. METHODS: In vitro osteogenic differentiation assays were conducted using human bone marrow-derived MSCs. Alkaline phosphatase and alizarin red S staining were used to evaluate the osteogenic potential of MSCs. A rat xenograft model featuring a calvarial defect to examine effects of MSC-driven bone regeneration. RNA-immunoprecipitation (RNA-IP) assay was used to determine the interaction between PUM2 protein and Distal-Less Homeobox 5 (DLX5) mRNA. Ovariectomized (OVX) mice were employed to evaluate the effect of gene therapy for postmenopausal osteoporosis. RESULTS: Here, we elucidated the molecular mechanism of PUM2 in MSC osteogenesis and evaluated the applicability of PUM2 knockdown (KD) as a potential cell-based or gene therapy. PUM2 level was downregulated during MSC osteogenic differentiation, and PUM2 KD enhanced MSC osteogenic potential. Following PUM2 KD, MSCs were transplanted onto calvarial defects in 12-week-old rats; after 8 weeks, transplanted MSCs promoted bone regeneration. PUM2 KD upregulated the expression of DLX5 mRNA and protein and the reporter activity of its 3'-untranslated region. RNA-IP revealed direct binding of PUM2 to DLX5 mRNA. We then evaluated the potential of adeno-associated virus serotype 9 (AAV9)-siPum2 as a gene therapy for osteoporosis in OVX mice. CONCLUSION: Our findings suggest a novel role for PUM2 in MSC osteogenesis and highlight the potential of PUM2 KD-MSCs in bone regeneration. Additionally, we showed that AAV9-siPum2 is a potential gene therapy for osteoporosis.


Assuntos
Células-Tronco Mesenquimais , Osteoporose , Humanos , Ratos , Camundongos , Animais , Osteogênese/genética , Regulação para Baixo , Diferenciação Celular , Regeneração Óssea/genética , RNA , RNA Mensageiro/metabolismo , Células Cultivadas , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
11.
BMC Med Inform Decis Mak ; 23(1): 260, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964232

RESUMO

BACKGROUND: Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model. METHODS: Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested is: Implementation of RN-led iCPR tools will reduce antibiotic prescribing across diverse primary care settings. Specifically, this study aims to: (1) determine the impact of iCPRs on rapid strep test and chest x-ray ordering and antibiotic prescribing rates when used by RNs; (2) examine resource use patterns and cost-effectiveness of RN visits across diverse clinical settings; (3) determine the impact of iCPR-guided care on patient satisfaction; and (4) ascertain the effect of the intervention on RN and physician burnout. DISCUSSION: This study represents an innovative approach to using an iCPR model led by RNs and specifically designed to address inappropriate antibiotic prescribing. This study has the potential to provide guidance on the effectiveness of delegating care of low-acuity patients with ARIs to RNs to increase use of iCPRs and reduce antibiotic overprescribing for ARIs in outpatient settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04255303, Registered February 5 2020, https://clinicaltrials.gov/ct2/show/NCT04255303 .


Assuntos
Sistemas de Apoio a Decisões Clínicas , Infecções Respiratórias , Humanos , Antibacterianos/uso terapêutico , Papel do Profissional de Enfermagem , Infecções Respiratórias/tratamento farmacológico , Registros Eletrônicos de Saúde , Padrões de Prática Médica , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Plant Cell ; 31(4): 791-808, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30814258

RESUMO

Brassinosteroid (BR) regulates a wide range of physiological responses through the activation of BRASSINAZOLE RESISTANT1 (BZR1), whose activity is tightly controlled by its phosphorylation status and degradation. Although BZR1 appears to be degraded in distinct ways in response to different hormonal or environmental cues, little is known about how BR signaling regulates its degradation. Here we show that the BR-regulated U-box protein PUB40 mediates the proteasomal degradation of BZR1 in a root-specific manner in Arabidopsis (Arabidopsis thaliana). BZR1 levels were strongly reduced by plant U-box40 (PUB40) overexpression, whereas the pub39 pub40 pub41 mutant accumulated much more BZR1 than wild type in roots. The bzr1-1D gain-of-function mutation reduced the interaction with PUB40, which suppressed PUB40-mediated BZR1 degradation in roots. The cell layer-specific expression of PUB40 in roots helps induce selective BZR1 accumulation in the epidermal layer. Both BR treatment and loss-of-function of PUB40 expanded BZR1 accumulation to most cell layers. In addition, BZR1 accumulation increased the resistance of pub39 pub40 pub41 to low inorganic phosphate availability, as observed in bzr1-1D BRASSINOSTEROID-INSENSITIVE2-induced phosphorylation of PUB40, which mainly occurs in roots, gives rise to BZR1 degradation through enhanced binding of PUB40 to BZR1 and PUB40's stability. Our results suggest a molecular mechanism of root-specific BZR1 degradation regulated by BR signaling.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Brassinosteroides/metabolismo , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
13.
J Thromb Thrombolysis ; 53(3): 683-689, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34480676

RESUMO

Mechanical fall is common among elders and has been associated with a lack of anticoagulant therapy among patients with atrial fibrillation (AF). However, anticoagulant therapy is recommended despite frequent fall due to an increased risk of a thromboembolic event. Using data from a large health system, we investigated the predictors of anticoagulation prescription on discharge in AF elderly patients after an in-hospital fall. In this retrospective analysis, we examined patients aged 60 years and older discharged from 2013 to 2018 with a diagnosis of AF and a secondary diagnosis of in-hospital fall. The primary outcome was the prescription of anticoagulation at discharge. We obtained patients' demographical (race, sex, and health insurance status) and clinical (management by a resident team, receipt of a head CT or a cardiology consultation, ambulation status and discharge location) data. We further categorized the type of anticoagulation prescribed as warfarin or novel oral anticoagulants (NOACs). We ran chi-square and Fischer's exact tests on all data and multivariable logistic regressions on those of patients with pre-existing AF to identify the predictors of anticoagulation prescription on discharge. In total, 67% of 235 patients were discharged on anticoagulation. Of patients admitted on anticoagulation, 91% were prescribed anticoagulation on discharge (p < 0.001), while only 40% of patients with new-onset AF were discharged on anticoagulation (p < 0.001). Patients over the age of 90, compared to those aged 60-89, with existing AF had lower odds (OR = 0.34 [95% CI 0.12-0.98]) of being prescribed anticoagulation on discharge. Among patients with preexisting AF, being admitted on anticoagulation increased the odds (OR = 39.8 [15.2-104.0]) of anticoagulation prescription on discharge. Asian patients with prior AF were less likely (OR = 0.12 [0.026-0.060]) to receive anticoagulation on discharge. Of patients with new AF, 81% were prescribed a NOAC as opposed to warfarin (p < 0.05). These results suggest that provider's decisions on anticoagulation initiation seem to be guided more by their concerns over bleeding complications than by the patient's risk for stroke. However, anchoring bias strongly influences anticoagulation prescription. It may benefit AF patients already on anticoagulation, but it may prevent anticoagulation prescription in patients with new AF and Asian patients.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Hospitais , Humanos , Pessoa de Meia-Idade , Prescrições , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico
14.
Aust N Z J Psychiatry ; 56(5): 542-550, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34231416

RESUMO

OBJECTIVE: To prevent copycat suicides following media reporting of celebrity suicides, the South Korean government enacted a 'suicide prevention law' in 2012 and revised the media guidelines for suicide reporting in 2013. This study examined how these two regulatory measures affected suicide trends among the general population in South Korea. METHODS: We analyzed the individual effect estimates for the general population within 30 days following the media report of 24 celebrity suicides using multivariate negative binomial regression. We performed a meta-analysis to compute the pooled rate ratios of the two regulations. We examined the trends in daily suicides by month during three time intervals before and after enactment using an autoregressive model and tested their significance using a piecewise linear regression. RESULTS: Total suicides increased by 6.27 daily during the 30-day period after celebrity suicides. Compared with the 30 days prior to the reports on the suicide of 24 celebrities, the number of suicidal deaths in the general population increased by 13% during the 30 days after the reports were announced (pooled rate ratio 1.13, 95% confidence interval: 0.06-0.18; p < 0.001). There was a significant downward trend in the average daily suicide deaths, and no significant increase in suicide rates, after the enactment of the suicide prevention law (p < 0.001) and revision of the media guidelines (p = 0.014). CONCLUSIONS: Suicide prevention and media guidelines were effective in reducing the effect of celebrity suicides. In addition to regulating media reporting of celebrity suicide, measures are needed to address viral republication on social media and to prevent suicide among entertainers.


Assuntos
Pessoas Famosas , Mídias Sociais , Prevenção do Suicídio , Governo , Humanos , Meios de Comunicação de Massa , República da Coreia/epidemiologia
16.
PLoS Pathog ; 15(4): e1007707, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30995283

RESUMO

Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo. However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of a subset of RSV cbDVG species. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus unable to produce a subset of cbDVGs due to mutations introduced in this sequence. The identified sequence was also found as a site for cbDVG generation during natural RSV infections, and common cbDVGs originated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome determine the location of cbDVG formation and, therefore, the generation of cbDVGs is not a stochastic process. These findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome.


Assuntos
Antivirais/metabolismo , Vírus Defeituosos/genética , Genoma Viral , RNA Viral/genética , Infecções por Vírus Respiratório Sincicial/genética , Vírus Sincicial Respiratório Humano/genética , Replicação Viral , Células A549 , Criança , Regulação Viral da Expressão Gênica , Células HeLa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Transcrição Gênica , Interferência Viral , Proteínas Virais
17.
Plant Cell ; 30(8): 1848-1863, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30065046

RESUMO

Crosstalk between signaling pathways is an important feature of complex regulatory networks. How signal crosstalk circuits are tailored to suit different needs of various cell types remains a mystery in biology. Brassinosteroid (BR) and abscisic acid (ABA) antagonistically regulate many aspects of plant growth and development through direct interactions between components of the two signaling pathways. Here, we show that BR and ABA synergistically regulate stomatal closure through crosstalk between the BR-activated kinase CDG1-LIKE1 (CDL1) and the OPEN STOMATA1 (OST1) of the ABA signaling pathway in Arabidopsis thaliana We demonstrate that the cdl1 mutant displayed reduced sensitivity to ABA in a stomatal closure assay, similar to the ost1 mutant. CDL1 and the BR receptor BR-INSENSITIVE1, but not other downstream components of the BR signaling pathway, were required for BR regulation of stomatal movement. Genetic and biochemical experiments demonstrated that CDL1 activates OST1 by phosphorylating it on residue Ser-7. BR increased phosphorylation of OST1, and the BR-induced OST1 activation was abolished in cdl1 mutants. Moreover, we found that ABA activates CDL1 in an OST1-dependent manner. Taken together, our findings illustrate a cell-type-specific BR signaling branch through which BR acts synergistically with ABA in regulating stomatal closure.


Assuntos
Ácido Abscísico/farmacologia , Brassinosteroides/farmacologia , Estômatos de Plantas/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
18.
J Gen Intern Med ; 36(5): 1214-1221, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33469750

RESUMO

BACKGROUND: Post-hospital discharge follow-up appointments are intended to evaluate patients' recovery following a hospitalization, but it is unclear how appointment statuses are associated with readmissions. OBJECTIVE: To examine the association between post-discharge ambulatory follow-up status, (1) having a scheduled appointment and (2) arriving to said appointment, and 30-day readmission. DESIGN AND SETTING: A retrospective cohort study of patients hospitalized at 12 hospitals in an Integrated Delivery Network and their ambulatory appointments in that same network. PATIENTS AND MAIN MEASURES: We included 50,772 patients who had an ambulatory appointment within 18 months of an inpatient admission in 2018. Primary outcome was readmission within 30 days post-discharge. KEY RESULTS: There were 32,108 (63.2%) patients with scheduled follow-up appointments and 18,664 (36.8%) patients with no follow-up; 28,313 (88.2%) patients arrived, 3149 (9.8%) missed, and 646 (2.0%) were readmitted prior to their scheduled appointments. Overall 30-day readmission rate was 7.3%; 6.0% [5.75-6.31] for those who arrived, 8.8% [8.44-9.25] for those without follow-up, and 10.3% [9.28-11.40] for those who missed a scheduled appointment (p < 0.001). After adjusting for covariates, patients who arrived at their appointment in the first week following discharge were significantly less likely to be readmitted than those not having any follow-up scheduled (medical adjusted hazard ratio (aHR) 0.57 [0.47-0.69], p < 0.001; surgical aHR 0.58 [0.44-0.75], p < 0.001) There was an increased risk at weeks 3 and 4 for medical patients who arrived at a follow-up compared to those with no follow-up scheduled (week 3 aHR 1.29 [1.10-1.51], p = 0.001; week 4 aHR 1.46 [1.26-1.70], p < 0.001). CONCLUSIONS: The benefit of patients arriving to their post-discharge appointments compared with patients who missed their follow-up visits or had no follow-up scheduled, is only significant during first week post-discharge, suggesting that coordination within 1 week of discharge is critical in reducing 30-day readmissions.


Assuntos
Alta do Paciente , Readmissão do Paciente , Assistência ao Convalescente , Agendamento de Consultas , Seguimentos , Humanos , Estudos Retrospectivos
19.
J Asthma ; 58(3): 405-412, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31749394

RESUMO

OBJECTIVES: In New York City, asthma prevalence is greater in Hispanics than non-Hispanics for both children (10.9% vs. 7.4%) and adults (9.0% vs. 6.3%). Disparities in asthma management among Hispanics are found to arise, in part, from a limited education about asthma. Using elements of Community Based Participatory Research (CBPR), we worked with the community to identify asthma priorities and misconceptions among Hispanics and used that information to develop a tailored asthma educational tool-the Asthma Training Modules (ATMs). METHODS: Over the past 3 years (2016, 2017, and 2018), we conducted educational asthma workshops to collect and analyze information to develop the ATMs and a summary of the ATMs in an Asthma Educational Card (AEC). We trained 6 Asthma-Community-Leaders using the ATMs, who assembled community members for teaching sessions using the AEC. Participants completed a pre-and-post asthma knowledge questionnaire. RESULTS: We identified asthma priorities and misconceptions themed on: culturally relevant resources for Hispanics, symptom and trigger recognition, and treatments. A total of 104 participants attended the teaching sessions led by Asthma-Community-Leaders and participants' mean knowledge score increased from 64% pre-teaching to 85% post-teaching, (p < 0.01). CONCLUSION: Our community-led education, which included a tailored asthma educational tool and trained Asthma-Community-Leaders, successfully improved asthma knowledge among Hispanics. Further studies are warranted to determine whether these results are reproducible among a larger cohort and what the comparative effectiveness of our intervention as compared to other education-based interventions.


Assuntos
Asma/etnologia , Educação em Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Hispânico ou Latino/educação , Participação da Comunidade , Pesquisa Participativa Baseada na Comunidade , Competência Cultural , Humanos , Cidade de Nova Iorque/epidemiologia , Fatores Socioeconômicos
20.
J Nerv Ment Dis ; 209(11): 820-828, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34238894

RESUMO

ABSTRACT: In this study, we defined obsessive thoughts (OT) as bothersome, unpleasant thoughts about oneself that keep entering the mind against one's will, and compulsive behavior (CB) as behavior that a person repeats against his or her wishes. The study included 12,532 adults selected randomly through a one-person-per-household method. Each subject selected underwent a face-to-face interview using the Korean version of the Composite International Diagnostic Interview with a questionnaire that examines lifetime suicide attempts (LSAs). Among the participants, 341 (2.74%) had OT and 639 (5.14%) had CB. The highest LSA rate was in subjects with both OT and CB, followed by those with either OT or CB; subjects with neither OT nor CB had the lowest LSA rate. In a multivariate logistic regression analysis of OT and CB, OT, ordering, and rituals of repeating words were significantly associated with LSAs. In subjects with OT and CB, those with MDD had a significantly higher risk of LSAs compared with those without, and MDD with both OT and CB showed odds of approximately 27-fold (adjusted odds ratio, 27.24; 13.29-55.82; p < 0.0001) compared with those without MDD, OT, or CB. OT and CB were associated with increased risk of LSAs, and comorbid MDD further increased LSAs.


Assuntos
Comportamento Compulsivo/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Comportamento Obsessivo/epidemiologia , Ideação Suicida , Tentativa de Suicídio/estatística & dados numéricos , Pensamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Pensamento/fisiologia , Adulto Jovem
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