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1.
J Exp Bot ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38812358

RESUMO

Plants, being sessile organisms, constantly need to respond to environmental stresses, often leading to the accumulation of reactive oxygen species (ROS). While ROS can be harmful, they also act as messengers guiding plant growth and stress responses. Because chloroplasts are sensitive to environmental changes and are both a source and target of ROS during stress conditions, they are important in conveying environmental changes to the nucleus, where acclimation responses are coordinated to maintain organellar and overall cellular homeostasis. ANAC102 has previously been established as a regulator of ß-cyclocitral-mediated chloroplast-to-nucleus signaling, protecting plants against photooxidative stress. However, debates persist about where ANAC102 is located - in chloroplasts or in the nucleus. Our study, utilizing the genomic ANAC102 sequence driven by its native promoter, establishes ANAC102 primarily as a nuclear protein, lacking a complete N-terminal chloroplast-targeting peptide. Moreover, our research reveals the sensitivity of plants overexpressing ANAC102 to severe superoxide-induced chloroplast oxidative stress. Transcriptome analysis unraveled ANAC102's dual role in negatively and positively regulating genome-wide transcriptional responses to chloroplast oxidative stress. Through the integration of published data and our own study, we constructed a comprehensive transcriptional network, which suggests that ANAC102 exerts direct and indirect control over transcriptional responses through downstream transcription factor networks, providing deeper insights into the ANAC102-mediated regulatory landscape during oxidative stress.

2.
Reprod Biomed Online ; 48(5): 103752, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38489925

RESUMO

Telemedicine is being applied in assisted reproduction technology (ART) to provide remote consultations, monitoring and support for patients. This study aimed to evaluate the potential advantages of telemedicine in ART treatment in the form of virtual consultations. Studies in which patients were using telemedicine during ART treatment were identified from four scientific databases (PudMed, EMBASE, Scopus, Web of Science). The success of fertility treatments was compared between telemedicine and in-office care, and patient satisfaction with ART through telemedicine was assessed. Eleven studies, comprising 4697 patients, were identified. Quality assessment (Joanna Briggs Institute Critical Appraisal and revised Cochrane risk-of-bias tools) revealed an acceptable risk of bias for both randomized controlled trials and observational studies. Using a fixed-effects model, telemedicine was comparable to in-person care regarding the pregnancy rate achieved (odds ratio 1.02, 95% confidence intervals 0.83-1.26, P = 0.83). A Q-test suggested that all the included studies were homogeneous. Patients who received telemedicine during fertility treatment reported a high level of satisfaction (91%, 95% confidence intervals 80-96%). Egger's test confirmed that no publication bias was found. Telemedicine could serve as a complementary tool during fertility treatment to facilitate patients' satisfaction and overcome some practical problems without compromising treatment outcomes. Future studies should continue exploring the potential applications of telemedicine in assisted reproduction.


Assuntos
Satisfação do Paciente , Técnicas de Reprodução Assistida , Telemedicina , Humanos , Feminino , Gravidez , Taxa de Gravidez
3.
Ann Vasc Surg ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39067852

RESUMO

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a complex disease with environmental and genetic risk factors. Polygenic risk scores (PRS) based on disease-specific risk-associated single nucleotide variants (SNVs) have demonstrated effectiveness in stratifying individual-level disease risk for cardiovascular diseases. This prospective cohort study assessed associations of PRS of AAA (PRSAAA) with risk of incident AAA, analyzed the effectiveness of a combined clinical-genetic risk model, and explored the clinical utility of the model in identifying high-risk individuals for AAA screening. METHODS: PRSAAA was calculated using 911,440 SNVs and PRSCAD was calculated using 2,324,683 SNVs derived from mixed ancestry genome wide association studies. The UK Biobank was used as the study cohort. All individuals with complete genetic data available and no diagnosis of AAA at time of recruitment were included in the analysis and followed prospectively to assess for incident AAA. A PRS informed clinical model, Prob-AAA, was developed using clinically significant variables and PRSAAA. RESULTS: 481,105 individuals were included in the analysis with 2,668 incident AAA cases. Incident AAA increased from 0.30% to 0.93% between the lowest and highest decile of PRSAAA; similarly, severe AAA, requiring surgery and/or presenting with rupture, increased from 23% to 39% of incident AAA cases across deciles. PRSAAA was a predictor of incident AAA diagnosis (HR 2.06 [1.70 - 2.48]) independent of other clinical risk factors including male sex, older age, and smoking history. Prob-AAA was an independent predictor of incident AAA (HR 1.92 [1.69 - 2.20]), and identified 9.6% of cases of incident AAA compared to only 4.2% by PRSAAA. Current screening guidelines captured 5.7% of the overall cohort, with an incident AAA rate of approximately 3.2%. Amongst males not included by current guidelines, Prob-AAA identified an additional cohort, approximately 2% of the overall cohort, with a similar rate of incident AAA. CONCLUSIONS: Prob-AAA, a PRS informed clinical model for AAA, improved upon the predictive power of current, clinical risk factor informed, screening guidelines for AAA.

4.
Plant Cell ; 32(4): 1063-1080, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32034035

RESUMO

Reactive oxygen species (ROS) are important messengers in eukaryotic organisms, and their production is tightly controlled. Active extracellular ROS production by NADPH oxidases in plants is triggered by receptor-like protein kinase-dependent signaling networks. Here, we show that CYSTEINE-RICH RLK2 (CRK2) kinase activity is required for plant growth and CRK2 exists in a preformed complex with the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) in Arabidopsis (Arabidopsis thaliana). Functional CRK2 is required for the full elicitor-induced ROS burst, and consequently the crk2 mutant is impaired in defense against the bacterial pathogen Pseudomonas syringae pv tomato DC3000. Our work demonstrates that CRK2 regulates plant innate immunity. We identified in vitro CRK2-dependent phosphorylation sites in the C-terminal region of RBOHD. Phosphorylation of S703 RBOHD is enhanced upon flg22 treatment, and substitution of S703 with Ala reduced ROS production in Arabidopsis. Phylogenetic analysis suggests that phospho-sites in the C-terminal region of RBOHD are conserved throughout the plant lineage and between animals and plants. We propose that regulation of NADPH oxidase activity by phosphorylation of the C-terminal region might be an ancient mechanism and that CRK2 is an important element in regulating microbe-associated molecular pattern-triggered ROS production.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , NADPH Oxidases/química , NADPH Oxidases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Arabidopsis/efeitos dos fármacos , Arabidopsis/microbiologia , Proteínas de Arabidopsis/química , Sequência Conservada , Citosol/efeitos dos fármacos , Citosol/metabolismo , Resistência à Doença , Flagelina/farmacologia , Células HEK293 , Humanos , Modelos Biológicos , Moléculas com Motivos Associados a Patógenos/metabolismo , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Desenvolvimento Vegetal/efeitos dos fármacos , Doenças das Plantas/microbiologia , Ligação Proteica/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/química , Pseudomonas syringae/patogenicidade , Pseudomonas syringae/fisiologia , Virulência/efeitos dos fármacos
5.
Chemistry ; 29(49): e202301640, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37310277

RESUMO

The formal synthesis of (±)-salvinorin A is presented. Our approach utilizes two distinct gold(I) catalytic processes. The combination of a gold(I)-catalyzed reaction with an intermolecular Diels-Alder reaction followed by a gold(I)-catalyzed photoredox reaction generated in eight steps the framework of the natural product with high diastereoselectivity.

6.
Langmuir ; 39(48): 17551-17559, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37987777

RESUMO

To improve the rate of DWC, numerous studies have adjusted the distribution of drops through biphilic surface patterning and wettability gradients to control the nucleation and drop shedding rates on the condensing surface, yet the connection between drop shedding mechanisms and surface wettability patterning remains unclear. Moreover, wettability patterning places geometric bounds on the governing forces (i.e., gravity, capillary, and inertia), which drive the droplet shedding mechanisms. Thus, the subsequent influence of droplet distribution along the DWC regions on the shedding mechanisms may not be known a priori. In this study, the area fraction, ADWC, of the DWC and also the DWC region width, LN, were varied between 10 and 50% and 0.5-1.5 mm, respectively, to probe the dominant droplet shedding mechanisms on a high wettability contrast surface (i.e., the contact angle on the DWC was 159 ± 3.4° and the hysteresis 9 ± 3.6°, whereas the FWC was nearly perfectly wetting). Humid air was introduced inside a custom-built chamber with the upright steady-state condensation imaged by both real-time and high-speed imaging techniques. We found that the droplet shedding mechanisms changed with increasing LN where the sliding drop radii are reduced with LN while the jumping drop radii remained unchanged with LN. The maximum drop size for shedding also decreased by 13%, which we attribute to the secondary droplet inertia, which helps gravity overcome the capillary retention force. Lastly, although many studies have probed DWC enhancements via surface wettability patterning, an optimal combination of ADWC and LN provided in this study significantly aids in the improvement of future DWC-based condensers and water collector applications.

7.
Crit Care ; 27(1): 257, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393330

RESUMO

BACKGROUND: Interpreting point-of-care lung ultrasound (LUS) images from intensive care unit (ICU) patients can be challenging, especially in low- and middle- income countries (LMICs) where there is limited training available. Despite recent advances in the use of Artificial Intelligence (AI) to automate many ultrasound imaging analysis tasks, no AI-enabled LUS solutions have been proven to be clinically useful in ICUs, and specifically in LMICs. Therefore, we developed an AI solution that assists LUS practitioners and assessed its usefulness in  a low resource ICU. METHODS: This was a three-phase prospective study. In the first phase, the performance of four different clinical user groups in interpreting LUS clips was assessed. In the second phase, the performance of 57 non-expert clinicians with and without the aid of a bespoke AI tool for LUS interpretation was assessed in retrospective offline clips. In the third phase, we conducted a prospective study in the ICU where 14 clinicians were asked to carry out LUS examinations in 7 patients with and without our AI tool and we interviewed the clinicians regarding the usability of the AI tool. RESULTS: The average accuracy of beginners' LUS interpretation was 68.7% [95% CI 66.8-70.7%] compared to 72.2% [95% CI 70.0-75.6%] in intermediate, and 73.4% [95% CI 62.2-87.8%] in advanced users. Experts had an average accuracy of 95.0% [95% CI 88.2-100.0%], which was significantly better than beginners, intermediate and advanced users (p < 0.001). When supported by our AI tool for interpreting retrospectively acquired clips, the non-expert clinicians improved their performance from an average of 68.9% [95% CI 65.6-73.9%] to 82.9% [95% CI 79.1-86.7%], (p < 0.001). In prospective real-time testing, non-expert clinicians improved their baseline performance from 68.1% [95% CI 57.9-78.2%] to 93.4% [95% CI 89.0-97.8%], (p < 0.001) when using our AI tool. The time-to-interpret clips improved from a median of 12.1 s (IQR 8.5-20.6) to 5.0 s (IQR 3.5-8.8), (p < 0.001) and clinicians' median confidence level improved from 3 out of 4 to 4 out of 4 when using our AI tool. CONCLUSIONS: AI-assisted LUS can help non-expert clinicians in an LMIC ICU improve their performance in interpreting LUS features more accurately, more quickly and more confidently.


Assuntos
Inteligência Artificial , Unidades de Terapia Intensiva , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Ultrassonografia
8.
Molecules ; 28(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36903577

RESUMO

This work reports the use of mesoporous silica rods as templates for the step-wise preparation of multifunctional Fe3O4 NPs filled polydopamine hollow rods (Fe3O4@PDA HR). The capacity of as-synthesized Fe3O4@PDA HR as a new drug carrier platform was assessed by its loading and the triggered release of fosfomycin under various stimulations. It was found that the release of fosfomycin was pH dependent with ~89% of fosfomycin being released in pH 5 after 24 h, which was 2-fold higher than that in pH 7. The magnetic properties of Fe3O4 NPs and the photothermal properties of PDA enabled the triggered release of fosfomycin upon the exposure to rotational magnetic field, or NIR laser irradiation. Additionally, the capability of using multifunctional Fe3O4@PDA HR to eliminate preformed bacterial biofilm was demonstrated. Upon exposure to the rotational magnetic field, the biomass of a preformed biofilm was significantly reduced by 65.3% after a 20 min treatment with Fe3O4@PDA HR. Again, due to the excellent photothermal properties of PDA, a dramatic biomass decline (72.5%) was achieved after 10 min of laser exposure. This study offers an alternative approach of using drug carrier platform as a physical mean to kill pathogenic bacteria along with its traditional use for drug delivery.


Assuntos
Fosfomicina , Nanopartículas Multifuncionais , Nanopartículas , Portadores de Fármacos/química , Antibacterianos , Nanopartículas/química
9.
Contemp Oncol (Pozn) ; 27(2): 71-79, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37794989

RESUMO

Introduction: This study aimed to evaluate the treatment outcomes of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy alone or in combination with locoregional brain therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC) patients with brain metastases. Material and methods: A retrospective study involving 72 advanced EGFR-mutant NSCLC patients with brain metastases at the Vietnam National Cancer Hospital were conducted. Patients were divided into 2 groups: EGFR-TKI (erlotinib) monotherapy and EGFR-TKI combined with locoregional therapy (γ knife surgery - GKS or whole-brain radiation therapy). Evaluation criteria included clinical and laboratory characteristics, central nervous system (CNS) progression time, progression-free survival (PFS), overall survival (OS), T790M mutation rate, and adverse events. Results: Epidermal growth factor receptor tyrosine kinase inhibitor monotherapy patients had better performance status (PS), fewer CNS symptoms, and significantly fewer brain metastases (p < 0.05). Median PFS and OS were 11 and 25 months, respectively, in both groups. Patients with PS 0-1 had longer median PFS (15 months) than those with PS 2 (7 months) (p = 0.039). Exon 19 deletion patients in both groups had longer median OS (26 months) than those with L858R exon 21 (15 months) (p = 0.023). Patients with T790M mutation who received osimertinib after progression had longer median OS (41 months vs. 23 months, p = 0.0001). Median time to CNS progression was 13.9 months (48 patients). Longer time to CNS progression correlated with longer OS (R2 = 0.89). Conclusions: Epidermal growth factor receptor tyrosine kinase inhibitor therapy, with or without locoregional therapy, is effective for advanced EGFR-mutant NSCLC patients with brain metastases. Exon 19 deletion patients had better prognosis.

10.
Langmuir ; 38(3): 1243-1251, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35025520

RESUMO

While drop oscillation dynamics has been widely studied for many decades, the influence of a moving contact line on the oscillation modes of drops remains underexplored. Herein, we report the oscillation dynamics of drops on thin liquid films with different viscosities where lower viscosities provide a slipping surface and higher viscosities immobilize the contact line. A gently deposited drop onto an oil film undergoes shape oscillations due to capillarity, where the frequency, amplitude, and apparent contact angle are tracked via a high-speed camera. This study demonstrates that restraining the mobility of the drop contact line by increasing the viscosity of a thin oil film underneath the drop increases the extent of the drop oscillation time as well as affecting the natural frequency of the drop oscillation. The drop oscillation time was defined by the time at which the changes in the drop height dropped to values less than 1% of the equilibrium height. The experimental results for the first longitudinal mode oscillation frequencies as a function of the equilibrium contact angles for the pinning and slipping contact lines were in good agreement with previously reported numerical simulations and model predictions.

11.
BMC Infect Dis ; 22(1): 722, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057771

RESUMO

BACKGROUND: Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue. METHODS: We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes. RESULTS: The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use. CONCLUSIONS: The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children.


Assuntos
Escores de Disfunção Orgânica , Dengue Grave , Humanos , Unidades de Terapia Intensiva , Insuficiência de Múltiplos Órgãos , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Centros de Atenção Terciária
12.
Anaerobe ; 77: 102514, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35007729

RESUMO

Even one case of foodborne botulism constitutes a public health emergency. We report a series of cases with delayed treatment due to delayed diagnosis. Clostridium botulinum type A(B) was isolated from vegetarian home-canned pate, but not from stool samples. These are the first recorded cases of foodborne botulism in Hanoi.


Assuntos
Botulismo , Clostridium botulinum tipo A , Clostridium botulinum , Humanos , Botulismo/diagnóstico , Vietnã , Microbiologia de Alimentos , Vegetarianos
13.
Sensors (Basel) ; 22(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35408216

RESUMO

A compact flexible multi-frequency antenna for smart portable and flexible devices is presented. The antenna consists of a coplanar waveguide-fed slotted circular patch connected to a rectangular secondary resonator (stub). A thin low-loss substrate is used for flexibility, and a rectangular stub in the feedline is deployed to attain wide operational bandwidth. A rectangular slot is etched in the middle of the circular patch, and a p-i-n diode is placed at its center. The frequency reconfigurability is achieved through switching the diode that distributes the current by changing the antenna's electrical length. For the ON state, the antenna operates in the UWB region for -10 dB impedance bandwidth from 2.76 to 8.21 GHz. For the OFF state of the diode, the antenna operates at the ISM band (2.45/5.8 GHz), WLAN band (5.2 GHz), and lower X-band (8 GHz) with a minimum gain of 2.49 dBi and a maximum gain of 5.8 dBi at the 8 GHz band. Moreover, the antenna retains its performance in various bending conditions. The proposed antenna is suitable for modern miniaturized wireless electronic devices such as wearables, health monitoring sensors, mobile Internet devices, and laptops that operate at multiple frequency bands.

14.
Nano Lett ; 21(19): 8495-8502, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34596406

RESUMO

Understanding the kinetic selectivity of carbon nanotube growth at the scale of individual nanotubes is essential for the development of high chiral selectivity growth methods. Here we demonstrate that homodyne polarization microscopy can be used for high-throughput imaging of long individual carbon nanotubes under real growth conditions (at ambient pressure, on a substrate) and with subsecond time resolution. Our in situ observations on hundreds of individual nanotubes reveal that about half of them grow at a constant rate all along their lifetime while the other half exhibits stochastic changes in growth rates and/or switches between growth, pause, and shrinkage. Statistical analysis shows that the growth rate of a given nanotube essentially varies between two values, with a similar average ratio (∼1.7) regardless of whether the rate change is accompanied by a change in chirality. These switches indicate that the nanotube edge or the catalyst nanoparticle fluctuates between different configurations during growth.


Assuntos
Nanotubos de Carbono , Catálise , Cinética , Microscopia de Polarização , Nanotecnologia
15.
Angew Chem Int Ed Engl ; 61(1): e202110575, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34714952

RESUMO

A one-pot cascade sequence to generate synthetically challenging polycyclic scaffolds is reported utilizing a novel Lewis acid gold catalyst for the key cyclization step, enabling the divergent synthesis of both 6,6,5-tricyclic and 6,6,6,5-tetracyclic cores through both ligand and reaction condition control. We have combined the intrinsic complexity and stereoselectivity of cycloadditions with the electronic and steric properties of gold complexes to selectively generate complex polycyclic scaffolds in a single operation.

16.
J Antimicrob Chemother ; 76(5): 1117-1129, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33491090

RESUMO

Antimicrobial resistance (AMR) is a major global issue and antimicrobial stewardship is central to tackling its emergence. The burden of AMR disproportionately impacts low- and middle-income countries (LMICs), where capacity for surveillance and management of resistant pathogens is least developed. Poorly regulated antibiotic consumption in the community is a major driver of AMR, especially in LMICs, yet community-based interventions are neglected in stewardship research, which is often undertaken in high-income settings and/or in hospitals. We reviewed the evidence available to researchers and policymakers testing or implementing community-based antimicrobial stewardship strategies in LMICs. We critically appraise that evidence, deliver recommendations and identify outstanding areas of research need. We find that multifaceted, education-focused interventions are likely most effective in our setting. We also confirm that the quality and quantity of community-based stewardship intervention research is limited, with research on microbiological, clinical and economic sustainability most urgently needed.


Assuntos
Gestão de Antimicrobianos , Antibacterianos/uso terapêutico , Países em Desenvolvimento , Hospitais , Pobreza
17.
Langmuir ; 37(33): 10135-10142, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34379973

RESUMO

For drops to contact various surfaces, the removal of the interstitial fluid is the prerequisite to contact. While the conventional understanding is for drops to irreversibly spread on a film made of the same substance, we describe the dynamics of drops initiating contact yet carrying enough momentum to completely lift off of the substrate which we label as contact bouncing. We report new experimental results of the dynamics between drops impacting thin films described by the ratio of the liquid film hL to the drop with diameter D0 for the range of 0.004 < hL/D0 < 0.08. Using high-speed interferometry, we visualize the interfacial gas layer spatiotemporal signatures across the various film thicknesses and Weber numbers. We find that while increasing the deformability of the thin films enhances the gas entrainment phenomenon at early times, it also increases the rate of the gas purging rate, increasing the chance of contact just prior to the gas film retraction and drop lift off sequence. Drops which contact the liquid film during the retraction stage are able to bounce with <5% volume loss.

18.
Am J Emerg Med ; 42: 143-149, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32107132

RESUMO

OBJECTIVES: Immediate ischemic stroke treatment improves outcomes and early alteplase administration is recommended for patients within window. We implemented stroke guidelines through a neuro-resuscitation initiative (NRI) and hypothesized that the intervention would decrease times to assessment and treatment. METHODS: We analyzed quality assurance data for EMS and triage patients arriving to our academic emergency department with suspected ischemic stroke to compare outcomes 12 months before to 6 months after initiative implementation at an academic certified primary stroke center in the U.S. Southwest. We examined four time-based outcomes: neurology at bedside, CT head without contrast, CT head angiogram, and alteplase administration. We summarized times with median and IQR values and compared pre and post times to event (in minutes) with Wilcoxon rank sum tests and Kaplan-Meier survival curves. RESULTS: We identified 203 EMS (83 pre, 120 post) and 66 (11 pre, 55 post) triage Stroke Alert patients. We observed decreased times for all outcomes in both the EMS and triage samples; however, only those in the EMS sample were significant. In the EMS sample, neurology at bedside median times decreased from 20 min to 2 min (p < 0.001); median minutes to CT head without contrast decreased from 16 min to 9 min (p < 0.001); median minutes to CT head angiogram decreased from 71 min to 21 min (p = 0.007); and, median minutes to alteplase decreased from 72 min to 49.5 min (p = 0.04). CONCLUSIONS: An academic ED led stroke care initiative streamlined evaluation and care with significantly shortened times to all four events.


Assuntos
Serviço Hospitalar de Emergência/normas , Fibrinolíticos/uso terapêutico , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Angiografia Cerebral , Feminino , Fidelidade a Diretrizes , Humanos , AVC Isquêmico/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde , Terapia Trombolítica , Tomografia Computadorizada por Raios X , Triagem
19.
PLoS Genet ; 14(10): e1007676, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30365533

RESUMO

Morphogen gradients provide concentration-dependent positional information along polarity axes. Although the dynamics of the establishment of these gradients is well described, precision and noise in the downstream activation processes remain elusive. A simple paradigm to address these questions is the Bicoid morphogen gradient that elicits a rapid step-like transcriptional response in young fruit fly embryos. Focusing on the expression of the major Bicoid target, hunchback (hb), at the onset of zygotic transcription, we used the MS2-MCP approach which combines fluorescent labeling of nascent mRNA with live imaging at high spatial and temporal resolution. Removing 36 putative Zelda binding sites unexpectedly present in the original MS2 reporter, we show that the 750 bp of the hb promoter are sufficient to recapitulate endogenous expression at the onset of zygotic transcription. After each mitosis, in the anterior, expression is turned on to rapidly reach a plateau with all nuclei expressing the reporter. Consistent with a Bicoid dose-dependent activation process, the time period required to reach the plateau increases with the distance to the anterior pole. Despite the challenge imposed by frequent mitoses and high nuclei-to-nuclei variability in transcription kinetics, it only takes 3 minutes at each interphase for the MS2 reporter loci to distinguish subtle differences in Bicoid concentration and establish a steadily positioned and steep (Hill coefficient ~ 7) expression boundary. Modeling based on the cooperativity between the 6 known Bicoid binding sites in the hb promoter region, assuming rate limiting concentrations of the Bicoid transcription factor at the boundary, is able to capture the observed dynamics of pattern establishment but not the steepness of the boundary. This suggests that a simple model based only on the cooperative binding of Bicoid is not sufficient to describe the spatiotemporal dynamics of early hb expression.


Assuntos
Drosophila melanogaster/embriologia , Proteínas de Homeodomínio/fisiologia , Morfogênese/fisiologia , Transativadores/fisiologia , Animais , Sítios de Ligação/genética , Padronização Corporal/genética , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Homeodomínio/genética , Imagem Óptica/métodos , Regiões Promotoras Genéticas/genética , Transativadores/genética , Fatores de Transcrição/genética , Zigoto/metabolismo
20.
Plant Physiol ; 180(4): 2004-2021, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31118265

RESUMO

High salinity is an increasingly prevalent source of stress to which plants must adapt. The receptor-like protein kinases, including members of the Cys-rich receptor-like kinase (CRK) subfamily, are a highly expanded family of transmembrane proteins in plants that are largely responsible for communication between cells and the extracellular environment. Various CRKs have been implicated in biotic and abiotic stress responses; however, their functions on a cellular level remain largely uncharacterized. Here we have shown that CRK2 enhances salt tolerance at the germination stage in Arabidopsis (Arabidopsis thaliana) and also modulates root length. We established that functional CRK2 is required for salt-induced callose deposition. In doing so, we revealed a role for callose deposition in response to increased salinity and demonstrated its importance for salt tolerance during germination. Using fluorescently tagged proteins, we observed specific changes in the subcellular localization of CRK2 in response to various stress treatments. Many of CRK2's cellular functions were dependent on phospholipase D activity, as were the subcellular localization changes. Thus, we propose that CRK2 acts downstream of phospholipase D during salt stress, promoting callose deposition and regulating plasmodesmal permeability, and that CRK2 adopts specific stress-dependent subcellular localization patterns that allow it to carry out its functions.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Germinação/efeitos dos fármacos , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Tolerância ao Sal , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologia
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