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1.
Plant Cell Environ ; 46(10): 3040-3058, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36213953

RESUMO

Plant disease limits crop production, and host genetic resistance is a major means of control. Plant pathogenic Ralstonia causes bacterial wilt disease and is best controlled with resistant varieties. Tomato wilt resistance is multigenic, yet the mechanisms of resistance remain largely unknown. We combined metaRNAseq analysis and functional experiments to identify core Ralstonia-responsive genes and the corresponding biological mechanisms in wilt-resistant and wilt-susceptible tomatoes. While trade-offs between growth and defence are common in plants, wilt-resistant plants activated both defence responses and growth processes. Measurements of innate immunity and growth, including reactive oxygen species production and root system growth, respectively, validated that resistant plants executed defence-related processes at the same time they increased root growth. In contrast, in wilt-susceptible plants roots senesced and root surface area declined following Ralstonia inoculation. Wilt-resistant plants repressed genes predicted to negatively regulate water stress tolerance, while susceptible plants repressed genes predicted to promote water stress tolerance. Our results suggest that wilt-resistant plants can simultaneously promote growth and defence by investing in resources that act in both processes. Infected susceptible plants activate defences, but fail to grow and so succumb to Ralstonia, likely because they cannot tolerate the water stress induced by vascular wilt.


Assuntos
Doenças das Plantas , Solanum lycopersicum , Desidratação , Genes de Plantas , Doenças das Plantas/microbiologia , Solanum lycopersicum/genética , Solanum lycopersicum/microbiologia
2.
Environ Res ; 237(Pt 2): 117018, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37657605

RESUMO

Distribution patterns of 10 phthalic acid diesters (PAEs) and four cyclic volatile methylsiloxanes (cVMSs) were investigated in fine particulate matter (PM0.1 and PM0.5) collected from Bac Ninh, an industrial province in Vietnam during September-October in 2021. Total concentrations of PAEs found in PM0.1 and PM0.5 were in the ranges of 1.76-372 (median: 34.0 ng/m3) and 2.23-895 ng/m3 (median: 15.4 ng/m3), respectively. Among PAEs, di-n-butyl phthalate (DBP) was the most abundant compound found in PM0.1, whereas, di-2-(ethyl)hexyl phthalate (DEHP) was measured at the highest concentration in PM0.5. Total concentrations of cVMSs measured in PM0.1 and PM0.5 were in the ranges of method quantification limit (MQL)-203 (median: 2.10 ng/m3) and MQL-537 ng/m3 (median: 0.389 ng/m3), respectively. Among cVMSs, decamethylcyclopentasiloxane (D5) was found at the highest concentration in both PM0.1 and PM0.5 fractions of particulate matter. The concentration ratios between PAEs and cVMSs in PM0.1/PM0.5 were greater than 1 (except di-n-octyl phthalate: DnOP), suggesting that these chemicals tend to sorb to PM0.1 more preferentially than PM0.5. Among sampling locations, high concentrations of PAEs and cVMSs were found at traffic intersections (Que Vo district) and a craft village (Tu Son city). Relatively stronger correlations existed between cVMSs pairs in PM0.1 and PM0.5 (correlation coefficient: 0.73-1) than those of PAEs (-0.83-0.90). The human exposure doses to PAEs and cVMSs through inhalation of particulate matter were estimated based on the measured concentrations in PM0.1 and PM0.5 fractions. The estimated exposure doses of PAEs and cVMSs for infants (7.1 ng/kg-bw/d and 2.5 ng/kg-bw/d) were higher than those for adults (2.6 ng/kg-bw/d and 0.9 ng/kg-bw/d).

3.
J Med Internet Res ; 25: e48730, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37728990

RESUMO

BACKGROUND: Over the past 2 years, the COVID-19 pandemic has placed enormous pressure on the health care industry. There has been an increase in demand and, at the same time, a shortage of supplies. This has shown that supply chain management in the health care industry cannot be taken for granted. Furthermore, the health care industry is also facing other major challenges, such as the current labor market shortage. In the literature, the Internet of Things (IoT) is highlighted as an effective tool to build a more resilient and efficient supply chain that can manage these challenges. Although using IoT in supply chain management has been extensively examined in other types of supply chains, its use in the health care supply chain has largely been overlooked. Given that the health care supply chain, compared to others, is more complex and is under growing pressure, a more in-depth understanding of the opportunities brought by IoT is necessary. OBJECTIVE: This study aims to address this research gap by identifying and ranking the drivers of and barriers to implementing IoT in the health care supply chain. METHODS: We conducted a 2-stage study. In the first, exploratory stage, a total of 12 semistructured interviews were conducted to identify drivers and barriers. In the second, confirmatory stage, a total of 26 health care supply chain professionals were asked in a survey to rank the drivers and barriers. RESULTS: The results show that there are multiple financial, operational, strategy-related, and supply chain-related drivers for implementing IoT. Similarly, there are various financial, strategy-related, supply chain-related, technology-related, and user-related barriers. The findings also show that supply chain-related drivers (eg, increased transparency, traceability, and collaboration with suppliers) are the strongest drivers, while financial barriers (eg, high implementation costs and difficulties in building a business case) are the biggest barriers to overcome. CONCLUSIONS: The findings of this study add to the limited literature regarding IoT in the health care supply chain by empirically identifying the most important drivers and barriers to IoT implementation. The ranking of drivers and barriers provides guidance for practitioners and health care provider leaders intending to implement IoT in the health care supply chain.


Assuntos
COVID-19 , Internet das Coisas , Humanos , Pandemias , Comércio , Lacunas de Evidências
4.
Environ Geochem Health ; 45(5): 1711-1722, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35622306

RESUMO

Comprehensive studies on emerging contaminants like volatile methyl siloxanes in settled dust from different micro-environments are still limited. In this study, concentrations and distribution of cyclic volatile methyl siloxanes (CVMSs) including D3, D4, D5, and D6 were examined in indoor dust samples collected from various micro-environments in northern and central Vietnam. Concentrations of total CVMSs in the dust samples ranged from 86.0 to 5890 (median 755) ng/g and decreased in the order: waste processing workshops (median 1560; range 329-5890) > common houses (650; 115-1680) > university classrooms (480; 86.0-1540) > vehicle repair shops (295; 126-1950) ng/g. This observation suggests that informal waste processing activities are sources of CVMSs. Among the studied CVMSs, D5 was the most predominant compound (41 ± 14%), followed by D6 (26 ± 13%), D4 (23 ± 12%), and D3 (11 ± 11%). Moderate positive correlations between D3/D4, D4/D5, and D5/D6 were found. Median daily intake doses of D3, D4, D5, and D6 through dust ingestion were 0.016, 0.051, 0.11, and 0.054 ng/kg/d, respectively, which were comparable to water consumption and markedly lower than the air inhalation pathway.


Assuntos
Poluição do Ar em Ambientes Fechados , Monitoramento Ambiental , Siloxanas , Humanos , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Poeira/análise , Siloxanas/análise , Vietnã , Poluentes Atmosféricos
5.
J Exp Bot ; 73(16): 5758-5772, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35596672

RESUMO

Utilizing beneficial microbes for crop improvement is one strategy to achieve sustainable agriculture. However, identifying microbial isolates that promote crop growth is challenging, in part because using bacterial taxonomy to predict an isolate's effect on plant growth may not be reliable. The overall aim of this work was to determine whether in vitro functional traits of bacteria were predictive of their in planta impact. We isolated 183 bacterial endophytes from field-grown roots of two tomato species, Solanum lycopersicum and S. pimpinellifolium. Sixty isolates were screened for six in vitro functional traits: auxin production, siderophore production, phosphate solubilization, antagonism to a soilborne pathogen, and the presence of two antimicrobial metabolite synthesis genes. Hierarchical clustering of the isolates based on the in vitro functional traits identified several groups of isolates sharing similar traits. We called these groups 'functional groups'. To understand how in vitro functional traits of bacteria relate to their impact on plants, we inoculated three isolates from each of the functional groups on tomato seedlings. Isolates within the same functional group promoted plant growth at similar levels, regardless of their host origin or taxonomy. Together, our results demonstrate the importance of examining root endophyte functions for improving crop production.


Assuntos
Endófitos , Solanum lycopersicum , Bactérias/metabolismo , Ácidos Indolacéticos/metabolismo , Solanum lycopersicum/metabolismo , Desenvolvimento Vegetal , Raízes de Plantas/metabolismo
6.
Environ Res ; 209: 112843, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35101399

RESUMO

Pollution status and distribution characteristics of ten typical phthalic acid esters (PAEs) were investigated in 36 sediment samples collected from three rivers in Northern Vietnam from June to October 2020. The total concentrations of PAEs in sediment samples collected from the To Lich River (n = 9), the Nhue River (n = 12), and the Day River (n = 15) were in ranges of 11,000-125,000 ng/g-dwt (mean/median: 50,000/42,200 ng/g-dwt), 2140-89,900 ng/g-dwt (mean/median: 29,300/20,700 ng/g-dwt), and 1140-43,100 ng/g-dwt (mean/median: 13,800/10,400 ng/g-dwt), respectively. Among ten PAEs studied, di-(2-ethylhexyl) phthalate (DEHP) was found at the highest levels in all samples meanwhile dimethyl phthalate (DMP), diethyl phthalate (DEP), and dipropyl phthalate (DPP) were detected at low frequency and concentration. Significant correlations have existed between the median-chain (C4-C7) PAE pairs in sediment samples. Due to the high accumulation in the sediments, the median-chain PAEs had a higher ecological risk than the short-chain (C1-C3) PAEs. These contaminants may present a longstanding influence on organisms and ecosystems.


Assuntos
Ácidos Ftálicos , Poluentes Químicos da Água , China , Dibutilftalato , Ecossistema , Ésteres , Sedimentos Geológicos , Medição de Risco , Rios , Vietnã , Poluentes Químicos da Água/análise
7.
Environ Res ; 197: 111158, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33887272

RESUMO

Comprehensive and updated information about polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) in surface sediments from Hanoi, the capital city of Vietnam, is rather scarce. In this study, concentrations and profiles of 209 PCBs, 41 polybrominated diphenyl ethers (PBDEs), 2,2',4,4',5,5'-hexabromobiphenyl (BB-153), hexabromocyclododecane (HBCD), pentabromoethylbenzene (PBEB), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and decabromodiphenyl ethane (DBDPE) were determined in sediment samples collected from the Red River and some inner-city rivers of Hanoi. Concentrations (ng/g dry weight, median and range) of pollutants decreased in the order: DBDPE (28; not detected ND - 59) ≈ PCBs (27; 1.7-50) > PBDEs (23; 0.20-61) > HBCD (1.2; ND - 5.2) > BTBPE (0.46; ND - 3.6) > BB-153 (0.004; ND - 0.014) > PBEB (ND). Pollutant levels in the inner-city river sediments were about one to two orders of magnitude higher than those measured in the Red River main stream sediments. Tri-to hexa-CBs are major homologs but detailed profiles vary between individual samples, reflecting source and/or seasonal variations. CB-11 and CB-209 were found at higher proportions in sediments than in technical PCB mixtures, suggesting their novel sources from pigments. Deca-BDE and DBDPE are the most predominant BFRs with an increasing trend predicted for DBDPE. A preliminary ecological risk assessment was conducted for these pollutants in sediments. Total PCBs and deca-BDE in a few inner-city river sediments may exhibit adverse effects on benthic organisms, but no serious risk was estimated in general.


Assuntos
Retardadores de Chama , Bifenilos Policlorados , Monitoramento Ambiental , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Vietnã
8.
MMWR Morb Mortal Wkly Rep ; 69(3): 67-71, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31971935

RESUMO

Zika virus infection during pregnancy can cause congenital brain and eye abnormalities and is associated with neurodevelopmental abnormalities (1-3). In areas of the United States that experienced local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy increased in the second half of 2016 compared with the first half (4). To update the previous report, CDC analyzed population-based surveillance data from 22 states and territories to estimate the prevalence of birth defects potentially related to Zika virus infection, regardless of laboratory evidence of or exposure to Zika virus, among pregnancies completed during January 1, 2016-June 30, 2017. Jurisdictions were categorized as those 1) with widespread local transmission of Zika virus; 2) with limited local transmission of Zika virus; and 3) without local transmission of Zika virus. Among 2,004,630 live births, 3,359 infants and fetuses with birth defects potentially related to Zika virus infection during pregnancy were identified (1.7 per 1,000 live births, 95% confidence interval [CI] = 1.6-1.7). In areas with widespread local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy was significantly higher during the quarters comprising July 2016-March 2017 (July-September 2016 = 3.0; October-December 2016 = 4.0; and January-March 2017 = 5.6 per 1,000 live births) compared with the reference period (January-March 2016) (1.3 per 1,000). These findings suggest a fourfold increase (prevalence ratio [PR] = 4.1, 95% CI = 2.1-8.4) in birth defects potentially related to Zika virus in widespread local transmission areas during January-March 2017 compared with that during January-March 2016, with the highest prevalence (7.0 per 1,000 live births) in February 2017. Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance.


Assuntos
Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/virologia , Vigilância da População , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Prevalência , Porto Rico/epidemiologia , Estados Unidos/epidemiologia , Ilhas Virgens Americanas/epidemiologia
9.
MMWR Morb Mortal Wkly Rep ; 69(1): 1-5, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31917782

RESUMO

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.


Assuntos
Infecções por HIV/diagnóstico , Defeitos do Tubo Neural/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estados Unidos/epidemiologia , Adulto Jovem
10.
MMWR Morb Mortal Wkly Rep ; 68(2): 31-36, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30653484

RESUMO

Prevalence of gastroschisis, a serious birth defect of the abdominal wall resulting in some of the abdominal contents extending outside the body at birth, has been increasing worldwide (1,2). Gastroschisis requires surgical repair after birth and is associated with digestive and feeding complications during infancy, which can affect development. Recent data from 14 U.S. states indicated an increasing prevalence of gastroschisis from 1995 to 2012 (1). Young maternal age has been strongly associated with gastroschisis, but research suggests that risk factors such as smoking, genitourinary infections, and prescription opioid use also might be associated (3-5). Data from 20 population-based state surveillance programs were pooled and analyzed to assess age-specific gastroschisis prevalence during two 5-year periods, 2006-2010 and 2011-2015, and an ecologic approach was used to compare annual gastroschisis prevalence by annual opioid prescription rate categories. Gastroschisis prevalence increased only slightly (10%) from 2006-2010 to 2011-2015 (prevalence ratio = 1.1, 95% confidence interval [CI] = 1.0-1.1), with the highest prevalence among mothers aged <20 years. During 2006-2015, the prevalence of gastroschisis was 1.6 times higher in counties with high opioid prescription rates (5.1 per 10,000 live births; CI = 4.9-5.3) and 1.4 times higher where opioid prescription rates were medium (4.6 per 10,000 live births; CI = 4.4-4.8) compared with areas with low prescription rates (3.2 per 10,000 live births; CI = 3.1-3.4). Public health research is needed to understand factors contributing to the association between young maternal age and gastroschisis and assess the effect of prescription opioid use during pregnancy on this pregnancy outcome.


Assuntos
Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Fenômenos Ecológicos e Ambientais , Gastrosquise/epidemiologia , Adulto , Distribuição por Idade , Analgésicos Opioides/efeitos adversos , Etnicidade/estatística & dados numéricos , Feminino , Gastrosquise/etnologia , Humanos , Recém-Nascido , Mães/estatística & dados numéricos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Prevalência , Grupos Raciais/estatística & dados numéricos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
11.
J Vasc Interv Radiol ; 30(11): 1719-1724, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587943

RESUMO

PURPOSE: To evaluate if sedation with propofol during catheter-directed thrombolysis (CDT) in patients with acute submassive pulmonary embolism (PE) affects survival. MATERIALS AND METHODS: This single-institution, retrospective study identified 136 patients from 2011-2017 who underwent CDT for acute submassive PE. Patients were grouped based on procedural sedation-propofol versus fentanyl and/or midazolam. Groups were compared for differences in baseline characteristics. Primary endpoint was in-hospital mortality. Logistic regression analysis was performed to evaluate for independent variables predictive of mortality. Propensity-matched analysis was also performed. RESULTS: Propofol was given to 18% (n = 25) of patients, and fentanyl and/or midazolam was given to 82% (n = 111) of patients. Mortality was 28% (n = 7) in the propofol group versus 3% (n = 3) in the fentanyl/midazolam group (P = .0003). Patients receiving propofol had 10.4 times the risk of cardiopulmonary arrest or dying during hospitalization compared with patients receiving fentanyl and/or midazolam (95% confidence interval, 2.9-37.3, P = .0003). The number needed to harm was 4 (95% confidence interval, 2.8-6.8). Logistic regression model analysis including Pulmonary Embolism Severity Index score, right-to-left ventricle diameter ratio and age was not predictive of mortality (P = .19). Adding type of sedation made the model predictive of mortality (P < .001). Propensity-matched analysis controlling for baseline differences in age, adjunctive maneuvers, American Society of Anesthesiologists class, and intubation before the procedure revealed that statistical significance between groups remained (P = .01). CONCLUSIONS: Sedation with propofol during CDT for acute submassive PE is associated with increased mortality and should be used with caution.


Assuntos
Anestésicos Intravenosos/efeitos adversos , Fibrinolíticos/efeitos adversos , Mortalidade Hospitalar , Hipnóticos e Sedativos/efeitos adversos , Propofol/efeitos adversos , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica/mortalidade , Ativador de Plasminogênio Tecidual/efeitos adversos , Doença Aguda , Adulto , Idoso , Anestésicos Intravenosos/administração & dosagem , Feminino , Fentanila/efeitos adversos , Fibrinolíticos/administração & dosagem , Florida , Hemodinâmica/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Midazolam/efeitos adversos , Pessoa de Meia-Idade , Propofol/administração & dosagem , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
12.
Mol Cell Proteomics ; 16(4): 642-662, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28188227

RESUMO

HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large scale quantitative mass spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats. Heterozygous deletion of Erap1, which reduced the Erap1 level to less than half, had no qualitative or quantitative effects on the B27 peptidome. Homozygous deletion of Erap1 affected approximately one-third of the B27 peptidome but left most of the B27 peptidome unchanged, suggesting the possibility that some of the HLA-B27 immunopeptidome is not processed in the presence of Erap1. Deletion of Erap1 was permissive for the AS-like phenotype, increased mean peptide length and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser, or Lys. The presence of Erap1 increased the frequency of C-terminal Lys and Arg, of Glu and Asp at intermediate residues, and of N-terminal Gly. Several peptides of potential interest in AS pathogenesis, previously identified in human cell lines, were isolated. However, rats susceptible to arthritis had B27 peptidomes similar to those of non-susceptible rats, and no peptides were found to be uniquely associated with arthritis. Whether specific B27-bound peptides are required for AS pathogenesis remains to be determined. Data are available via ProteomeXchange with identifier PXD005502.


Assuntos
Aminopeptidases/genética , Deleção de Genes , Antígeno HLA-B27/metabolismo , Peptídeos/análise , Proteômica/métodos , Espondilite Anquilosante/genética , Animais , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Antígeno HLA-B27/genética , Humanos , Masculino , Espectrometria de Massas , Mapas de Interação de Proteínas , Ratos , Ratos Transgênicos , Espondilite Anquilosante/metabolismo
13.
Proc Natl Acad Sci U S A ; 112(7): 2245-50, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25646452

RESUMO

Blue light activation of the photoreceptor CRYPTOCHROME (CRY) evokes rapid depolarization and increased action potential firing in a subset of circadian and arousal neurons in Drosophila melanogaster. Here we show that acute arousal behavioral responses to blue light significantly differ in mutants lacking CRY, as well as mutants with disrupted opsin-based phototransduction. Light-activated CRY couples to membrane depolarization via a well conserved redox sensor of the voltage-gated potassium (K(+)) channel ß-subunit (Kvß) Hyperkinetic (Hk). The neuronal light response is almost completely absent in hk(-/-) mutants, but is functionally rescued by genetically targeted neuronal expression of WT Hk, but not by Hk point mutations that disable Hk redox sensor function. Multiple K(+) channel α-subunits that coassemble with Hk, including Shaker, Ether-a-go-go, and Ether-a-go-go-related gene, are ion conducting channels for CRY/Hk-coupled light response. Light activation of CRY is transduced to membrane depolarization, increased firing rate, and acute behavioral responses by the Kvß subunit redox sensor.


Assuntos
Criptocromos/fisiologia , Transdução de Sinal Luminoso , Canais de Potássio/fisiologia , Animais , Drosophila , Oxirredução
14.
Anal Chem ; 89(17): 9491-9501, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28795574

RESUMO

Thirty-five melamine-formaldehyde (MF) monolithic materials with bimodal pore distributions were synthesized in fused silica capillaries by catalyst-free polycondensation, starting with an aqueous MF precondensate, using acetonitrile as the macroporogen and a variety of aliphatic polyethers and triblock copolymeric surfactants as porogens and mesoporogens, respectively. By varying the prepolymer composition and the type and molecular weight of the polymeric porogen components, a library of porous monolithic materials was produced, covering a range of meso- and macroporous properties. A multivariate evaluation revealed that the amount of surfactant was the strongest contributor to specific surface area and pore volume and to the inversely related mesopore size, whereas the macropore dimensions were controlled mainly by the amount of aliphatic polyether porogen. One of these capillary monoliths, chosen based on the combination of meso- and macropores providing optimal percolative flow and accessible surface area, was synthesized in the presence of N-Fmoc and O-Et protected phosphoserine and phosphotyrosine to prepare molecularly imprinted monoliths with surface layers selective for phosphopeptides. These imprinted monoliths were characterized alongside nonimprinted monoliths by a variety of techniques and finally evaluated by liquid chromatography-mass spectrometry in the capillary format to assess their abilities to trap and release phosphorylated amino acids and peptides from partly aqueous media. Selective enrichment of phosphorylated targets was demonstrated, suggesting that these materials could be useful as trapping media in affinity-based phosphoproteomics.


Assuntos
Impressão Molecular/métodos , Fosfopeptídeos/química , Triazinas/química , Celiprolol , Modelos Moleculares , Estrutura Molecular , Transição de Fase , Conformação Proteica
15.
Pediatr Crit Care Med ; 18(9): e388-e394, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28640009

RESUMO

OBJECTIVES: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault. DESIGN: Retrospective, two-center, cohort study from 2003 to 2016. SETTING: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals. PATIENTS: Children from 1 to 21 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Identify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 µg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R = 0.083). CONCLUSIONS: Augmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.


Assuntos
Antibacterianos/farmacocinética , Estado Terminal , Modelos Teóricos , Vancomicina/farmacocinética , Adolescente , Biomarcadores/metabolismo , Criança , Pré-Escolar , Creatinina/metabolismo , Cuidados Críticos , Monitoramento de Medicamentos , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Modelos Lineares , Masculino , Taxa de Depuração Metabólica , Estudos Retrospectivos , Adulto Jovem
16.
Matern Child Health J ; 21(10): 1949-1960, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28710700

RESUMO

Introduction A practice-based care coordination (CC) model was developed by Louisiana's Title V Children's Special Health Services (CSHS) program to meet the overwhelming needs of the New Orleans post-Katrina population. The pilot clinic demonstrated an improvement in medical home (MH) capacity over the course of 3 months. The purpose of the current study is to evaluate the replicability of the model and sustainability of MH improvement over at least 2 years, while identifying factors that may modify the effect of the intervention. Methods The CSHS CC model utilizing a practice based care coordinator was implemented in 15 academic primary care pediatric clinics. Increase in MH capacity was determined using the MH Index-Short Version (MHI-SV) tool. Results The analysis of the MHI-SV scores for the ten clinics with >2 years of data demonstrated a significant improvement with each of the ten MHI-SV indicators. The mean clinic MHI-SV score improved from 19.70 to 34.15 on a scale of 10-50. Characteristics associated with the greatest MHI score improvement were rural geographic location, having an electronic health record, and using social workers or nurses as care coordinators. Characteristics associated with lower MHI scores were physician or care coordinator turnover and using stand-alone databases rather than tracking CC activities within the central patient record. Conclusion This study provides a flexible framework for implementing CC services in pediatric, family medicine, and medicine-pediatric practices, and demonstrates the value of CC as a driver for improvement in medical home capacity.


Assuntos
Serviços de Saúde da Criança/organização & administração , Crianças com Deficiência , Avaliação de Resultados em Cuidados de Saúde , Equipe de Assistência ao Paciente , Assistência Centrada no Paciente/métodos , Pré-Escolar , Feminino , Humanos , Masculino , Modelos Organizacionais , Nova Orleans , Atenção Primária à Saúde/organização & administração , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade
17.
Curr Opin Rheumatol ; 27(4): 357-63, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26002027

RESUMO

PURPOSE OF REVIEW: To review the recent developments in our understanding of endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) function in relation to its role in major histocompatibility complex (MHC) class I peptide presentation and human leukocyte antigen (HLA) class I-associated diseases. RECENT FINDINGS: ERAP1 polymorphisms exhibiting loss-of-function have been associated with protection from AS. The aminopeptidase function of ERAP1 optimizes peptides for binding and presentation by MHC class I. Most of the studies have revealed reduced MHC class I expression in situations of reduced ERAP1 function. Under these circumstances, the presented peptides are often N-terminally extended, and cell surface complexes are unstable and fall apart more readily. In contrast, peptides presented by HLA-B*27 : 05 when ERAP1 is silenced are frequently extended on the C-terminus. Recent work has emphasized on the importance of assessing the function of allotypes encoded by ERAP1 haplotypes, rather than effects of single amino acid substitutions. The allotypes found in a series of AS patients were poorer at restoring HLA-B27 expression than allotypes found in unaffected controls, which may seem contrary to the genetic data linking loss-of-function to protection. SUMMARY: More work is needed to understand how ERAP1 variants associated with risk and protection influence the quality and quantity of peptides available for binding to HLA class I molecules in the ER. Moreover, we need to determine allele-specific effects of ERAP1 variants in the context of HLA-B*51 and HLA-Cw*6, which are associated with Behçet's disease and psoriasis, respectively.


Assuntos
Aminopeptidases/genética , Doenças Reumáticas/genética , Aminopeptidases/fisiologia , Predisposição Genética para Doença , Antígeno HLA-B27/imunologia , Haplótipos , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Antígenos de Histocompatibilidade Menor , Polimorfismo de Nucleotídeo Único , Doenças Reumáticas/imunologia
18.
J Surg Res ; 197(1): 162-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25891677

RESUMO

BACKGROUND: Although it is assumed that obese patients are naturally protected against anterior abdominal stab wounds, the relationship has never been formally studied. We sought to examine the impact of body mass index (BMI) on severity of sustained injury, need for operation, and patient outcomes. MATERIALS AND METHODS: We conducted a review of all patients presenting with abdominal stab wounds at an urban level I trauma center from January 2000-December 2012. Patients were divided into groups based on their BMI (<18.5, 18.5-29.9, 30-35, and >35). Data abstracted included baseline demographics, physiologic data, and characterization of whether the stab wound had violated the peritoneum, caused intra-abdominal injury, or required an operation that was therapeutic. The one-sided Cochran-Armitage trend test was used for significance testing of the protective effect. RESULTS: Of 281 patients with abdominal stab wounds, 249 had complete data for evaluation. Chest and abdomen abbreviated injury scale trends decreased with increasing BMI, as did overall injury severity score, the percent of patients severely injured (injury severity score ≥ 25), and length of intensive care unit stay. Rates of peritoneal violation (100%, 84%, 77%, and 74%; P = 0.077), visceral injury (83%, 56%, 50%, and 30%; P = 0.022), and injury requiring a therapeutic operation (67%, 45%, 40%, and 20%; P = 0.034) all decreased with increasing BMI. Patients in the thinnest group required an operation three times more often than those in the most obese. CONCLUSIONS: Increased BMI protects patients with abdominal stab wounds and is associated with lower incidence of severe injury and need for operation. Heavier patients may be more suitable to observation and serial examinations, whereas very thin patients are more likely to require an operation and be critically injured.


Assuntos
Traumatismos Abdominais/cirurgia , Índice de Massa Corporal , Escala de Gravidade do Ferimento , Obesidade , Ferimentos Perfurantes/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Arch Environ Contam Toxicol ; 68(3): 489-99, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25702083

RESUMO

Phthalate diesters are used as plasticizers in a wide range of consumer products. Because phthalates have been shown in laboratory animal studies to be toxic, human exposure to these chemicals is a matter of concern. Nevertheless, little is known about inhalation exposure to phthalates in the United States. In this study, occurrence of nine phthalates was determined in 60 indoor air samples collected in 2014 in Albany, New York, USA. Airborne particulate and vapor phase samples were collected from various sampling locations by use of a low-volume air sampler. The median concentrations of nine phthalates in air samples collected from homes, offices, laboratories, schools, salons (hair and nail salons), and public places were 732, 143, 170, 371, 2600, and 354 ng/m(3), respectively. Diethyl phthalate (DEP) was found at the highest concentrations, which ranged from 4.83 to 2250 ng/m(3) (median 152) followed by di-n-butyl phthalate, which ranged from 4.05 to 1170 ng/m(3) (median 63.3). The median inhalation exposure dose to phthalates was estimated at 0.845, 0.423, 0.203, 0.089, and 0.070 µg/kg-bw/d for infants, toddlers, children, teenagers, and adults, respectively. Inhalation is an important pathway of human exposure to DEP.


Assuntos
Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Poeira/análise , Exposição Ambiental/estatística & dados numéricos , Ácidos Ftálicos/análise , Habitação/estatística & dados numéricos , Humanos , New York , Plastificantes/análise
20.
J La State Med Soc ; 166(3): 109-18, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25075727

RESUMO

OBJECTIVES: The medical home is associated with key healthcare services. We assessed its association with the pediatric developmental screening among United States (US) children less than or equal to five years. METHODS: The 2007 national survey of children's health data was analyzed using state clusters, and pediatric developmental screening probability was modeled as a function of the medical home. RESULTS: Only 19.5% of US children received pediatric developmental screening, and crosstabs showed a null medical home association. Based on medical home status, adjusted state models showed much variation in pediatric developmental screening odds. A random intercept and slope model had the best fit. The medical home increased pediatric developmental screening odds by 24% (1.10, 1.38). CONCLUSIONS: The pediatric developmental screening rate and the medical home association are partially influenced by an individual's state. A multilevel model including state level predictors will help illuminate factors that promote healthcare service acquisition. This knowledge will enhance policy development in public and private sector health programs.


Assuntos
Desenvolvimento Infantil , Saúde da Criança , Programas Nacionais de Saúde , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estados Unidos
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