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1.
Pest Manag Sci ; 80(3): 1446-1453, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37946692

RESUMO

BACKGROUND: Soil seedbanks have been recognized as one of the crucial components of agricultural ecosystems. However, studies on the shift in structure and biodiversity of soil seedbanks in herbicide-resistant crop systems are limited, and a functional trait perspective of the soil seedbank is often overlooked. RESULTS: A 6 years experiment was conducted to investigate the roles of region, crop system, and weed management strategy on species richness, functional trait diversity, and composition of the weed seedbank. Species richness was different across the interaction of region and crop system, while functional trait diversity only showed difference across regions. Species and functional trait compositions were affected by the interaction of region and crop system. Specifically, the compositional difference among crop systems was mainly determined by the significant heterogeneity of group dispersion. CONCLUSION: Growers and practitioners should consider weed functional traits in developing lasting agricultural management strategies. Long-term weed research should draw attention to the impact of transgenic crop systems and specific management tactics on weed dispersal, functional composition, and resistance evolution of weed species in such agroecosystems. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Herbicidas , Estados Unidos , Herbicidas/farmacologia , Controle de Plantas Daninhas , Banco de Sementes , Plantas Daninhas , Ecossistema , Produtos Agrícolas , Resistência a Herbicidas , Solo
2.
Sensors (Basel) ; 23(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38067672

RESUMO

In agricultural weed management, herbicides are indispensable, yet innovation in their modes of action (MOA)-the general mechanisms affecting plant processes-has slowed. A finer classification within MOA is the site of action (SOA), the specific biochemical pathway in plants targeted by herbicides. The primary objectives of this study were to evaluate the efficacy of hyperspectral imaging in the early detection of herbicide stress and to assess its potential in accelerating the herbicide development process by identifying unique herbicide sites of action (SOA). Employing a novel SOA classification method, eight herbicides with unique SOAs were examined via an automated, high-throughput imaging system equipped with a conveyor-based plant transportation at Purdue University. This is one of the earliest trials to test hyperspectral imaging on a large number of herbicides, and the study aimed to explore the earliest herbicide stress detection/classification date and accelerate the speed of herbicide development. The final models, trained on a dataset with nine treatments with 320 samples in two rounds, achieved an overall accuracy of 81.5% 1 day after treatment. With the high-precision models and rapid screening of numerous compounds in only 7 days, the study results suggest that hyperspectral technology combined with machine learning can contribute to the discovery of new herbicide MOA and help address the challenges associated with herbicide resistance. Although no public research to date has used hyperspectral technology to classify herbicide SOA, the successful evaluation of herbicide damage to crops provides hope to accelerate the progress of herbicide development.


Assuntos
Herbicidas , Humanos , Herbicidas/toxicidade , Imageamento Hiperespectral , Controle de Plantas Daninhas/métodos , Produtos Agrícolas , Resistência a Herbicidas
3.
PNAS Nexus ; 2(12): pgad338, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38059262

RESUMO

The rapid adoption of glyphosate-resistant crops at the end of the 20th century caused a simplification of weed management that relied heavily on glyphosate for weed control. However, the effectiveness of glyphosate has diminished. A greater understanding of trends related to glyphosate use will shed new light on weed adaptation to a product that transformed global agriculture. Objectives were to (1) quantify the change in weed control efficacy from postemergence (POST) glyphosate use on troublesome weeds in corn and soybean and (2) determine the extent to which glyphosate preceded by a preemergence (PRE) improved the efficacy and consistency of weed control compared to glyphosate alone. Herbicide evaluation trials from 24 institutions across the United States of America and Canada from 1996 to 2021 were compiled into a single database. Two subsets were created; one with glyphosate applied POST, and the other with a PRE herbicide followed by glyphosate applied POST. Within each subset, mean and variance of control ratings for seven problem weed species were regressed over time for nine US states and one Canadian province. Mean control with POST glyphosate alone decreased over time while variability in control increased. Glyphosate preceded by a labeled PRE herbicide showed little change in mean control or variability in control over time. These results illustrate the rapid adaptation of agronomically important weed species to the paradigm-shifting product glyphosate. Including more diversity in weed management systems is essential to slowing weed adaptation and prolonging the usefulness of existing and future technologies.

4.
PLoS One ; 18(12): e0286836, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38100475

RESUMO

BACKGROUND: Pediatric injuries are a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). It is important that injured children get quality care in order to improve their outcomes. Injured children are nearly always accompanied by family member caregivers invested in their outcome, and who will be responsible for their recovery and rehabilitation after discharge. OBJECTIVE: The purpose of this study was to identify family member caregiver perspectives on strengths and challenges in pediatric injury care throughout hospitalization at a tertiary hospital in Northern Tanzania. METHODS: This study was conducted at a zonal referral hospital in Northern Tanzania. Qualitative semi-structured in-depth interviews (IDIs) were conducted by trained interviewers who were fluent in English and Swahili in order to examine the strengths and challenges in pediatric injury care. IDIs were completed from November 2020 to October 2021 with 30 family member caregivers of admitted pediatric injured patients. De-identified transcripts were synthesized in memos and analyzed through a team-based, thematic approach informed by applied thematic analysis. RESULTS: Strengths and challenges were identified throughout the hospital experience, including emergency medicine department (EMD) care, inpatient wards care, and discharge. Across the three phases, strengths were identified such as how quickly patients were evaluated and treated, professionalism and communication between healthcare providers, attentive nursing care, frequent re-evaluation of a patient's condition, and open discussion with caregivers about readiness for discharge. Challenges identified related to lack of communication with caregivers, perceived inability of caregivers to ask questions, healthcare providers speaking in English during rounds with lack of interpretation into the caregivers' preferred language, and being sent home without instructions for rehabilitation, ongoing care, or guidance for follow-up. CONCLUSION: Caregiver perspectives highlighted strengths and challenges throughout the hospital experience that could lead to interventions to improve the care of pediatric injury patients in Northern Tanzania. These interventions include prioritizing communication with caregivers about patient status and care plan, ensuring all direct communication is in the caregivers' preferred language, and standardizing instructions regarding discharge and follow-up.


Assuntos
Cuidadores , Hospitalização , Humanos , Criança , Centros de Atenção Terciária , Tanzânia , Alta do Paciente , Pesquisa Qualitativa
5.
PLOS Glob Public Health ; 3(11): e0002599, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37983210

RESUMO

Pediatric injuries are a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). The recovery of injured children in LMICs is often impeded by barriers in accessing and receiving timely and quality care at healthcare facilities. The purpose of this study was to identify the barriers and the facilitators in pediatric injury care at Kilimanjaro Christian Medical Center (KCMC), a tertiary zonal referral hospital in Northern Tanzania. In this study, focus group discussions (FGDs) were conducted by trained interviewers who were fluent in English and Swahili in order to examine the barriers and facilitators in pediatric injury care. Five FGDs were completed from February 2021 to July 2021. Participants (n = 30) were healthcare providers from the emergency department, burn ward, surgical ward, and pediatric ward. De-identified transcripts were analyzed with team-based, applied thematic analysis using qualitative memo writing and consensus discussions. Our study found barriers that impeded pediatric injury care were: lack of pediatric-specific injury training and care guidelines, lack of appropriate pediatric-specific equipment, staffing shortages, lack of specialist care, and complexity of cases due to pre-hospital delays in patients presenting for care due to cultural and financial barriers. Facilitators that improved pediatric injury care were: team cooperation and commitment, strong priority and triage processes, benefits of a tertiary care facility, and flexibility of healthcare providers to provide specialized care if needed. The data highlights barriers and facilitators that could inform interventions to improve the care of pediatric injury patients in Northern Tanzania such as: increasing specialized provider training in pediatric injury management, the development of pediatric injury care guidelines, and improving access to pediatric-specific technologies and equipment.

6.
Plants (Basel) ; 12(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37176944

RESUMO

Weeds resistant to PPO-inhibiting herbicides threaten the profitability of crop producers relying on this chemistry. In Amaranthus palmeri, mutations at G210 (∆G210) and R128 (R128G/M) of the PPX2 gene were reported to confer PPO-inhibitor resistance. Here, A. palmeri samples from nine states in America, having survived a field application of a PPO-inhibitor, were genotyped to determine the prevalence of these mutations. Less than 5% of the 1828 A. palmeri plants screened contained the ∆G210 mutation. Of the plants lacking ∆G210, a R128 substitution was only found in a single plant. An A. palmeri population from Alabama without mutations at G210 or R128 had a resistance ratio of 3.1 to 3.5 for fomesafen. Of the candidate PPX2 mutations identified in this population, only V361A conferred resistance to lactofen and fomesafen in a transformed bacterial strain. This is the first report of the V361A substitution of PPX2 conferred PPO-inhibiting herbicide resistance in any plant species. Future molecular screens of PPO-inhibitor resistance in A. palmeri and other species should encompass the V361A mutation of PPX2 to avoid false-negative results.

7.
Nat Commun ; 13(1): 3140, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668129

RESUMO

Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4+ T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.


Assuntos
Pirimidinas , Sarcoidose , Citocinas/metabolismo , Humanos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia
8.
J Nucl Cardiol ; 29(5): 2171-2187, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34734365

RESUMO

Cardiac sarcoidosis (CS) is an inflammatory disease with high morbidity and mortality, with a pathognomonic feature of non-caseating granulomatous inflammation. While 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established modality to image inflammation and diagnose CS, there are limitations to its specificity and reproducibility. Imaging focused on the molecular processes of inflammation including the receptors and cellular microenvironments present in sarcoid granulomas provides opportunities to improve upon FDG-PET imaging for CS. This review will highlight the current limitations of FDG-PET imaging for CS while discussing emerging new nuclear imaging molecular targets for the imaging of cardiac sarcoidosis.


Assuntos
Cardiomiopatias , Miocardite , Sarcoidose , Cardiomiopatias/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Inflamação/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sarcoidose/diagnóstico por imagem
9.
PLOS Glob Public Health ; 2(8): e0000657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36962759

RESUMO

Pediatric injuries are a leading cause of morbidity and mortality in low-and middle-income countries. Timely presentation to care is key for favorable outcomes. The goal of this study was to identify and examine delays that children experience between injury and receiving definitive care at a zonal referral hospital in Northern Tanzania. Between November 2020 and October 2021, we enrolled 348 pediatric trauma patients, collecting quantitative data on referral and timing information. In-depth interviews (IDIs) to explain and explore delays to care were completed with a sub-set of 30 family members. Data were analyzed according to the Three Delays Model. 81.0% (n = 290) of pediatric injury patients sought care at an intermediary facility before reaching the referral hospital. Time from injury to presentation at the referral hospital was 10.2 hours [IQR 4.8, 26.5] if patients presented first to clinics, 8.0 hours [IQR 3.9, 40.0] if patients presented first to district/regional hospitals, and 1.4 hours [IQR 0.7, 3.5] if patients presented directly to the referral hospital. In-hospital mortality was 8.2% (n = 30); 86.7% (n = 26) of these children sought care at an intermediary facility prior to reaching the referral hospital. IDIs revealed themes related to each delay. For decision to seek care (Delay 1), delays included emergency recognition, applying first aid, and anticipated challenges. For reaching definitive care (Delay 2), delays included caregiver rationale for using intermediary facilities, the complex referral system, logistical challenges, and intermediary facility delays. For receiving definitive care (Delay 3), wait time and delays due to treatment cost existed at the referral hospital. Factors throughout the healthcare system contribute to delays in receipt of definitive care for pediatric injuries. To minimize delays and improve patient outcomes, interventions are needed to improve caregiver and healthcare worker education, streamline the current trauma healthcare system, and improve quality of care in the hospital setting.

10.
Int Heart J ; 62(5): 1096-1105, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544982

RESUMO

While cardiac imaging has improved the diagnosis and risk assessment for cardiac sarcoidosis (CS), treatment regimens have consisted of generalized heart failure therapies and non-specific anti-inflammatory regimens. The overall goal of this study was to perform high-sensitivity plasma profiling of specific inflammatory pathways in patients with sarcoidosis and with CS.Specific inflammatory/proteolytic cascades were upregulated in sarcoidosis patients, and certain profiles emerged for CS patients.Plasma samples were collected from patients with biopsy-confirmed sarcoidosis undergoing F-18 fluorodeoxyglucose positron emission tomography (n = 47) and compared to those of referent control subjects (n = 6). Using a high-sensitivity, automated multiplex array, cytokines, soluble cytokine receptor profiles (an index of cytokine activation), as well as matrix metalloproteinase (MMP), and endogenous MMP inhibitors (TIMPs) were examined.The plasma tumor necrosis factor (TNF) and soluble TNF receptors sCD30 and sTNFRI were increased using sarcoidosis, and sTNFRII increased in CS patients (n = 18). The soluble interleukin sIL-2R and vascular endothelial growth factor receptors (sVEGFR2 and sVEGFR3) increased to the greatest degree in CS patients. When computed as a function of referent control values, the majority of soluble cytokine receptors increased in both sarcoidosis and CS groups. Plasma MMP-9 levels increased in sarcoidosis but not in the CS subset. Plasma TIMP levels declined in both groups.The findings from this study were the identification of increased activation of a cluster of soluble cytokine receptors, which augment not only inflammatory cell maturation but also transmigration in patients with sarcoidosis and patients with cardiac involvement.


Assuntos
Citocinas/metabolismo , Cardiopatias/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Sarcoidose/diagnóstico , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos de Avaliação como Assunto , Feminino , Fluordesoxiglucose F18/administração & dosagem , Cardiopatias/sangue , Cardiopatias/complicações , Cardiopatias/patologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Inflamação/metabolismo , Masculino , Inibidores de Metaloproteinases de Matriz/metabolismo , Metaloproteinases da Matriz/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Receptores de Interleucina-2/metabolismo , Receptores do Fator de Necrose Tumoral/sangue , Medição de Risco , Sarcoidose/sangue , Sarcoidose/complicações , Sarcoidose/patologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Int J Cardiol Heart Vasc ; 34: 100782, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33997256

RESUMO

The treatment of active cardiac sarcoidosis (CS) usually involves immunosuppressive therapy, with the goal of preventing inflammation-induced scar formation. In most cases, steroids remain the first-line treatment for CS. However, given the side effect profile of their long-term use, steroid-sparing therapies are increasingly used. There are no published randomized trials of steroid-sparing agents in CS. We sought to do a systematic review to evaluate the current published data on the use of non-steroidal treatments in the management of CS. We searched the Cochrane Library, Ovid Medline, Ovid Embase, PubMed, and Web of Science Core Collection databases from inception of database to August 2020 to identify the effectiveness of biological or synthetic disease-modifying antirheumatic agents (s- and bDMARDs). Secondary objectives include safety profile as well as the change in the average corticosteroid dose after treatment initiation. Twenty-three studies were ultimately selected for inclusion which included a total of 480 cases of CS treated with a range of both s- and bDMARDs. In all included studies, sDMARDs and bDMARDs were studied in combination with steroids or as second or higher-line treatments after therapeutic failure or intolerance to corticosteroid use. Methotrexate (MTX) and infliximab (IFX) were the most common synthetic and biologic DMARDs studied respectively, reported in about 35% of the studies reviewed. The use of steroid-sparing agents was associated with a reduction in the maintenance steroid dose used. In conclusion, steroids will remain as the cornerstone of anti-inflammatory management in patients with CS until trials on the use and safety profile of other immunosuppressive agents are completed and published.

12.
Front Cardiovasc Med ; 8: 750573, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34988125

RESUMO

Infective endocarditis is a common and treatable condition that carries a high mortality rate. Currently the workup of infective endocarditis relies on the integration of clinical, microbiological and echocardiographic data through the use of the modified Duke criteria (MDC). However, in cases of prosthetic valve endocarditis (PVE) echocardiography can be normal or non-diagnostic in a high proportion of cases leading to decreased sensitivity for the MDC. Evolving multimodality imaging techniques including leukocyte scintigraphy (white blood cell imaging), 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), multidetector computed tomographic angiography (MDCTA), and cardiac magnetic resonance imaging (CMRI) may each augment the standard workup of PVE and increase diagnostic accuracy. While further studies are necessary to clarify the ideal role for each of these imaging techniques, nevertheless, these modalities hold promise in determining the diagnosis, prognosis, and care of PVE. We start by presenting a clinical vignette, then evidence supporting various modality strategies, balanced by limitations, and review of formal guidelines, when available. The article ends with the authors' summary of future directions and case conclusion.

13.
Lancet Psychiatry ; 8(1): 76-86, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33341172

RESUMO

A major barrier to improving care effectiveness for mental health is a lack of consensus on outcomes measurement. The International Consortium for Health Outcomes Measurement (ICHOM) has already developed a consensus-based standard set of outcomes for anxiety and depression in adults (including the Patient Health Questionnaire-9, the Generalised Anxiety Disorder 7-item Scale, and the WHO Disability Schedule). This Position Paper reports on recommendations specifically for anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder in children and young people aged between 6 and 24 years. An international ICHOM working group of 27 clinical, research, and lived experience experts formed a consensus through teleconferences, an exercise using an adapted Delphi technique (a method for reaching group consensus), and iterative anonymous voting, supported by sequential research inputs. A systematic scoping review identified 70 possible outcomes and 107 relevant measurement instruments. Measures were appraised for their feasibility in routine practice (ie, brevity, free availability, validation in children and young people, and language translation) and psychometric performance (ie, validity, reliability, and sensitivity to change). The final standard set recommends tracking symptoms, suicidal thoughts and behaviour, and functioning as a minimum through seven primarily patient-reported outcome measures: the Revised Children's Anxiety and Depression Scale, the Obsessive Compulsive Inventory for Children, the Children's Revised Impact of Events Scale, the Columbia Suicide Severity Rating Scale, the KIDSCREEN-10, the Children's Global Assessment Scale, and the Child Anxiety Life Interference Scale. The set's recommendations were validated through a feedback survey involving 487 participants across 45 countries. The set should be used alongside the anxiety and depression standard set for adults with clinicians selecting age-appropriate measures.


Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Transtorno Obsessivo-Compulsivo/diagnóstico , Psicometria/métodos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adolescente , Criança , Consenso , Humanos , Internacionalidade , Perfil de Impacto da Doença , Resultado do Tratamento , Adulto Jovem
14.
Molecules ; 25(16)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796576

RESUMO

Dicamba is a moderately volatile herbicide used for post-emergent control of broadleaf weeds in corn, soybean, and a number of other crops. With increased use of dicamba due to the release of dicamba-resistant cotton and soybean varieties, growing controversy over the effects of spray drift and volatilization on non-target crops has increased the need for quantifying dicamba collected from water and air sampling. Therefore, this study was designed to evaluate stable isotope-based direct quantification of dicamba from air and water samples using single-quadrupole liquid chromatography-mass spectrometry (LC-MS). The sample preparation protocols developed in this study utilize a simple solid-phase extraction (SPE) protocol for water samples and a single-step concentration protocol for air samples. The LC-MS detection method achieves sensitive detection of dicamba based on selected ion monitoring (SIM) of precursor and fragment ions and relies on the use of an isotopically labeled internal standard (IS) (D3-dicamba), which allows for calculating recoveries and quantification using a relative response factor (RRF). Analyte recoveries of 106-128% from water and 88-124% from air were attained, with limits of detection (LODs) of 0.1 ng mL-1 and 1 ng mL-1, respectively. The LC-MS detection method does not require sample pretreatment such as ion-pairing or derivatization to achieve sensitivity. Moreover, this study reveals matrix effects associated with sorbent resin used in air sample collection and demonstrates how the use of an isotopically labeled IS with RRF-based analysis can account for ion suppression. The LC-MS method is easily transferrable and offers a robust alternative to methods relying on more expensive tandem LC-MS/MS-based options.


Assuntos
Cromatografia Líquida/métodos , Dicamba/análise , Herbicidas/análise , Marcação por Isótopo/métodos , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Água/química , Ar , Dicamba/isolamento & purificação , Herbicidas/isolamento & purificação , Limite de Detecção
15.
J Biol Chem ; 295(16): 5496-5508, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32161116

RESUMO

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Leucemia Mieloide Aguda/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Ceramidas/metabolismo , Humanos , Células K562 , Células Tumorais Cultivadas
16.
J Exp Bot ; 71(12): 3701-3709, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32161961

RESUMO

The perception pathway for endogenous auxin has been well described, yet the mode of action of synthetic auxin herbicides, used for >70 years, remains uncharacterized. We utilized transcriptomics and targeted physiological studies to investigate the unknown rapid response to synthetic auxin herbicides in the globally problematic weed species Erigeron canadensis. Synthetic auxin herbicide application consistently and rapidly down-regulated the photosynthetic machinery. At the same time, there was considerable perturbation to the expression of many genes related to phytohormone metabolism and perception. In particular, auxin herbicide application enhanced the expression of the key abscisic acid biosynthetic gene, 9-cis-epoxycarotenoid deoxygenase (NCED). The increase in NCED expression following auxin herbicide application led to a rapid biosynthesis of abscisic acid (ABA). This increase in ABA levels was independent of a loss of cell turgor or an increase in ethylene levels, both proposed triggers for rapid ABA biosynthesis. The levels of ABA in the leaf after auxin herbicide application continued to increase as plants approached death, up to >3-fold higher than in the leaves of plants that were drought stressed. We propose a new model in which synthetic auxin herbicides trigger plant death by the whole-scale, rapid, down-regulation of photosynthetic processes and an increase in ABA levels through up-regulation of NCED expression, independent of ethylene levels or a loss of cell turgor.


Assuntos
Erigeron , Herbicidas , Ácido Abscísico , Regulação da Expressão Gênica de Plantas , Herbicidas/farmacologia , Ácidos Indolacéticos , Transcriptoma
17.
ACR Open Rheumatol ; 2(2): 106-109, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31916703

RESUMO

OBJECTIVE: Sarcoidosis is an idiopathic inflammatory disorder that is difficult to treat. There is accumulating evidence that constitutive activation of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling occurs in sarcoidosis and represents a target for treatment. Here we report the efficacy of tofacitinib, a Janus kinase (JAK) inhibitor, in a single patient with multiorgan sarcoidosis. METHODS: A patient with long-standing multiorgan sarcoidosis who was unresponsive to other commonly used therapies, including methotrexate, prednisone, and tumor necrosis factor α blockade, was treated with tofacitinib. RESULTS: Tofacitinib treatment resulted in clinical remission of cutaneous sarcoidosis lesions and resolution of positron emission tomography avid lesions in internal organs after 6 months. An evaluation of lesional tissue and blood before and during treatment showed resolution of granulomatous inflammation and normalization of disease biomarkers. CONCLUSION: This case illustrates the promise of JAK inhibition as a strategy to treat recalcitrant sarcoidosis and suggests that further study of JAK inhibitors in sarcoidosis is needed.

18.
Phys Med Rehabil Clin N Am ; 30(4): 697-707, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31563163

RESUMO

A profound need for rehabilitation services exists, especially in developing countries. This article highlights the role of the epidemiology of disability in addressing this critical need. The article concludes that national and global disability epidemiology statistics inform stakeholder development of rehabilitation policies and programs necessary to meet the global need for rehabilitation, directly supporting the World Health Organization Rehabilitation 2030: Call for Action and United Nations Sustainable Development Goal 3 to "ensure healthy lives and promote well-being for all at all ages."


Assuntos
Efeitos Psicossociais da Doença , Avaliação da Deficiência , Pessoas com Deficiência/classificação , Pessoas com Deficiência/reabilitação , Classificação Internacional de Funcionalidade, Incapacidade e Saúde , Organização Mundial da Saúde , Epidemiologia , Humanos
19.
J Vis Exp ; (149)2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31380828

RESUMO

Here, based on a clinician's point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in addition to a clinical, functional assessment methodology, including details for further encouragement of the development of non-drug surgical intervention strategies in knee osteoarthritis patients. However, we only present the effect of LBPP training in improvement of pain and knee function in one patient through three-dimensional gait analysis. The exact, long-term effects of this approach should be explored in future studies.


Assuntos
Teste de Esforço , Osteoartrite do Joelho/reabilitação , Caminhada/fisiologia , Fenômenos Biomecânicos , Feminino , Marcha , Humanos , Perna (Membro)/fisiologia , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Pressão
20.
Pest Manag Sci ; 75(12): 3235-3244, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30983048

RESUMO

BACKGROUND: Waterhemp (Amaranthus tuberculatus (Moq.) J. D. Sauer) is one of the most pernicious weeds in cropping systems of the USA due to its evolved resistance against several herbicide sites-of-action, including protoporphyrinogen oxidase inhibitors (PPO-R). Currently, the only source of PPO-R documented in waterhemp is ΔG210 of PPX2. Gene flow may not only lead to a transfer of herbicide-resistant alleles, but also produce a hybrid genotype more competitively fit than one or both parents. However, investigating gene flow of Amaranthus species has been of interest in the past two decades with limited evidence. RESULTS: Here, a high-throughput MiSeq amplicon sequencing method was used to investigate alterations of the PPX2 gene in 146 PPO-R waterhemp populations across five Midwest states of the USA. Five R128 codons of PPX2, novel to waterhemp, were found including AGG (R), GGA (G), GGG (G), AAA (K) and ATA (I). R128G, R128I, and R128K were found in 11, 3, and 2 populations, respectively. R128G and R128I, but not R128K, conferred fomesafen resistance in a bacterial system. Sequence alignment of the R128 region of PPX2 identified a tumble pigweed (Amaranthus albus)-type and Palmer amaranth (Amaranthus palmeri)-type PPX2 allele to be present and widespread in the surveyed waterhemp populations, thus providing strong evidence of gene flow between Amaranthus species. CONCLUSION: Using a next-generation sequencing method, we identified two PPO target-site mutations R128G/I novel to waterhemp and provided evidence of gene flow of Amaranthus species in a large group of screened waterhemp populations from five Midwest states of the USA. © 2019 Society of Chemical Industry.


Assuntos
Amaranthus/genética , Benzamidas/farmacologia , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Plantas Daninhas/genética , Protoporfirinogênio Oxidase/antagonistas & inibidores , Amaranthus/efeitos dos fármacos , Códon , Fluxo Gênico , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Hibridização Genética , Meio-Oeste dos Estados Unidos , Plantas Daninhas/efeitos dos fármacos
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