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BACKGROUND: Despite expanded indications and demonstrated cardiovascular and renal benefits, prescribing rates of sodium-glucose cotransporter-2 (SGLT-2) inhibitors are low. OBJECTIVES: The study aimed to identify factors impacting prescriber decision-making when prescribing SGLT-2 inhibitors in the outpatient setting and identify differences across specialties in self-identified prescribing patterns. METHODS: An anonymous survey was administered electronically to prescribers in relevant specialties at a large community health system. Descriptive statistics were used to compile results, and subgroup comparisons were conducted utilizing Fisher's exact test. RESULTS: Fifty-one prescribers completed the survey, representing a 25.2% response rate. The highest reported prescribing rates were for type 2 diabetes (92%), and the lowest for HFpEF (20%) and ASCVD risk reduction (16%). Prescribers without clinic-embedded pharmacist were more likely to report cost and insurance had at least a moderate effect on prescribing compared to prescribers with clinic-embedded pharmacists (95.3% vs. 62.5%, P = 0.0228) and less likely to report hemoglobin A1c less than 6.5% to have at least a moderate effect on prescribing (20.9% vs. 62.5%, P = 0.0317). Compared to specialty providers, primary care prescribers were more likely to report hemoglobin A1c over 9% had at least a moderate effect on prescribing (92.0% vs. 42.9%, P = 0.0082) and less likely to note history of urinary tract infection (22.2% vs. 85.7%, P = 0.0028), history of mycotic infection (38.9% vs. 100%, P = 0.0036), and sex (male: 5.6% vs. 42.9%, P = 0.0242; female: 8.0% vs. 42.9%, P = 0.0447) had at least a moderate effect on prescribing. CONCLUSION: Prescribing hesitancies vary across specialty and when clinic-embedded pharmacists are present. Pharmacists may help improve SGLT-2 inhibitor prescribing rates and use of guideline-directed therapies. Pharmacists can target identified hesitancies through medication-access consultations, education regarding adverse effects, and expanded benefits of the class. Future studies should examine the impact of pharmacist intervention on SGLT-2 inhibitor prescribing rates.
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Diabetes Mellitus Tipo 2 , Padrões de Prática Médica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Masculino , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inquéritos e Questionários , Farmacêuticos/estatística & dados numéricos , Pacientes Ambulatoriais/estatística & dados numéricos , Prescrições de Medicamentos/estatística & dados numéricos , Pessoa de Meia-Idade , Padrões de Prática dos FarmacêuticosRESUMO
BACKGROUND: Despite expanded indications and demonstrated cardiovascular and renal benefits, prescribing rates of sodium-glucose cotransporter-2 (SGLT-2) inhibitors are low. OBJECTIVES: The study aimed to identify factors impacting prescriber decision-making when prescribing SGLT-2 inhibitors in the outpatient setting and identify differences across specialties in self-identified prescribing patterns. METHODS: An anonymous survey was administered electronically to prescribers in relevant specialties at a large community health system. Descriptive statistics were used to compile results, and subgroup comparisons were conducted utilizing Fisher's exact test. RESULTS: Fifty-one prescribers completed the survey, representing a 25.2% response rate. The highest reported prescribing rates were for type 2 diabetes (92%), and the lowest for HFpEF (20%) and ASCVD risk reduction (16%). Prescribers without clinic-embedded pharmacist were more likely to report cost and insurance had at least a moderate effect on prescribing compared to prescribers with clinic-embedded pharmacists (95.3% vs. 62.5%, P = 0.0228) and less likely to report hemoglobin A1c less than 6.5% to have at least a moderate effect on prescribing (20.9% vs. 62.5%, P = 0.0317). Compared to specialty providers, primary care prescribers were more likely to report hemoglobin A1c over 9% had at least a moderate effect on prescribing (92.0% vs. 42.9%, P = 0.0082) and less likely to note history of urinary tract infection (22.2% vs. 85.7%, P = 0.0028), history of mycotic infection (38.9% vs. 100%, P = 0.0036), and sex (male: 5.6% vs. 42.9%, P = 0.0242; female: 8.0% vs. 42.9%, P = 0.0447) had at least a moderate effect on prescribing. CONCLUSION: Prescribing hesitancies vary across specialty and when clinic-embedded pharmacists are present. Pharmacists may help improve SGLT-2 inhibitor prescribing rates and use of guideline-directed therapies. Pharmacists can target identified hesitancies through medication-access consultations, education regarding adverse effects, and expanded benefits of the class. Future studies should examine the impact of pharmacist intervention on SGLT-2 inhibitor prescribing rates.
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Auditory feedback is an important component of speech motor control, but its precise role in developing speech is less understood. The role of auditory feedback in development was probed by perturbing the speech of children 4-9 years old. The vowel sound /É/ was shifted to /æ/ in real time and presented to participants as their own auditory feedback. Analyses of the resultant formant magnitude changes in the participants' speech indicated that children compensated and adapted by adjusting their formants to oppose the perturbation. Older and younger children responded to perturbation differently in F1 and F2. The compensatory change in F1 was greater for younger children, whereas the increase in F2 was greater for older children. Adaptation aftereffects were observed in both groups. Exploratory directional analyses in the two-dimensional formant space indicated that older children responded more directly and less variably to the perturbation than younger children, shifting their vowels back toward the vowel sound /É/ to oppose the perturbation. Findings support the hypothesis that auditory feedback integration continues to develop between the ages of 4 and 9 years old such that the differences in the adaptive and compensatory responses arise between younger and older children despite receiving the same auditory feedback perturbation.
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Percepção da Fala , Adaptação Fisiológica , Adolescente , Criança , Pré-Escolar , Retroalimentação Sensorial , Humanos , Fonética , Fala , Acústica da Fala , Medida da Produção da FalaRESUMO
The aim of this study was to evaluate the quality of eggs from 2 selected commercial strains of laying hens and 2 unselected lines of chickens fed diets with different combinations of Ca and vitamin D and relate it to the profile of uterine proteins and ultrastructure of the shell. A group of 4 chickens was housed in each of 24 cages. The group consisted of one representative from each of the following breeds: Lohmann LSL- Lite, Lohmann Classic-Brown, Fayoumi, and Light Sussex. Six dietary combinations of Ca and vitamin D(3) (3.35%, 2,500 IU; 4.10%, 2,500 IU (control); 4.85%, 2,500 IU; 3.35%, 200 IU; 4.10%, 200 IU; and 4.85%, 200 IU) were randomly assigned to 4 replicate cages for 2 treatment periods (26-29 and 56-59 wk of age). Data were analyzed as a split-plot design with cage as the main plot and hen as the subplot. Egg quality traits were different (P < 0.0001) between commercial and heritage breeds. Lohmann Brown had stronger shells with higher specific gravity compared with other breeds. Both commercial and heritage birds responded to a drop in vitamin D3 level by marked reduction in shell thickness. The SDS-PAGE profiles of uterine fluid samples revealed a decrease (P < 0.05) in 200-, 150-, 116-, and ≤6.5-kDa proteins, whereas proteins with molecular weight (MW) of 80, 55, 52, 45, 42, and 28 kDa increased with bird age. A 36- and 52-kDa protein band was most intense for Fayoumi compared with other breeds. Ultrastructural characteristics showed flattened and deeply etched mammillary caps for Lohmann Brown and the presence of type A and type B bodies between mammillary cones in eggshells from Fayoumi and Lohmann Lite. The negative correlation between ultrastructural characteristics, which decrease with bird age, and the 116-kDa uterine protein band could provide insight into reduced eggshell quality as hens age.
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Proteínas Aviárias/metabolismo , Cálcio da Dieta/metabolismo , Galinhas/fisiologia , Colecalciferol/metabolismo , Casca de Ovo/ultraestrutura , Óvulo/fisiologia , Animais , Galinhas/genética , Dieta/veterinária , Casca de Ovo/crescimento & desenvolvimento , Eletroforese em Gel de Poliacrilamida/veterinária , Feminino , Microscopia Eletrônica de Varredura/veterinária , Óvulo/crescimento & desenvolvimento , Útero/metabolismoRESUMO
Attention allocation to positive and negative stimuli differs. For example, the flanker-interference asymmetry describes a pattern of results on flanker tasks using emotional stimuli, where a typical flanker-interference effect is observed for positive targets but not for negative targets. There are two dominant explanations for the flanker-interference asymmetry. According to the emotion-first explanation, negative targets are preferentially processed to facilitate the processing of potentially threatening stimuli. In contrast, feature-first explanations argue that the asymmetry results from differences in perceptual complexity between positive and negative stimuli. Three experiments used schematic emotional faces in a flanker task to directly compare these explanations. To manipulate the perceptual complexity of the stimuli, an enclosing circle was present on half of the trials. In all three experiments, reaction times showed the expected flanker-interference asymmetry, but the pattern was not influenced by the presence of the circle. However, event-related potentials showed that perceptual complexity influenced both the structural encoding and evaluative processing of the faces in the N170 and P3b time windows. These results suggest that both perceptual complexity and emotional valence play an important role in the processing of schematic emotional faces, but that emotional valence may have a stronger effect at evaluative stages of processing. Other findings show that the enclosing circle may alter the perceived emotional expression of neutral faces. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Atenção , Expressão Facial , Humanos , Emoções , Tempo de ReaçãoRESUMO
Educating parents about the newborn screening (NBS) process is critical in ensuring that families are aware of their child's NBS, which could contribute to better outcomes for the baby and experiences for the family. Successful education efforts result in expecting parents understanding the importance of NBS, feeling comfortable with the NBS process, and being aware of their choices after NBS is complete. Educating parents prenatally is challenging for many NBS programs for a variety of reasons. The COVID-19 pandemic added additional barriers to NBS programs' ability to educate parents prenatally about NBS. By initiating a department-wide partnership among other programs with a similar target audience, Michigan's NBS Program was able to host a virtual baby fair. Since the inaugural event, Michigan's NBS Program has hosted seven virtual fairs with 15 participating programs. A total of 692 participants registered for the baby fair and received a resource packet, over 157 participants joined one of the live presentations, and 211 have viewed the YouTube videos of recorded fairs. Virtual baby fairs are a cost-effective and convenient approach to education that could be implemented in any NBS program to educate parents prenatally about NBS.
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BACKGROUND: There is insufficient evidence of the effects of intermittent flushing with normal saline versus heparin to prevent occlusion or increased alteplase use in pediatric patients with central venous catheters. OBJECTIVES: The primary objective was to evaluate the effectiveness of a new standard flushing practice in the management of central venous access devices in pediatric patients with cancer. A secondary objective was to assess the cost of heparin flushing supplies to patients and financial impact. METHODS: New flushing guidelines included tunneled lines flushed with saline in the push-pause method twice daily in the inpatient setting. The outpatient setting required saline lock while receiving care and heparin lock on discharge. Alteplase usage was monitored for five months in all pediatric patients with cancer who had tunneled central lines. FINDINGS: There was no statistically significant difference in alteplase usage rate pre- to postimplementation. A formal flushing guideline was recommended using saline and lower heparin concentrations for tunneled catheters.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Neoplasias , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora , Cateteres Venosos Centrais/efeitos adversos , Criança , Heparina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Solução Salina/uso terapêutico , Cloreto de Sódio/uso terapêutico , Ativador de Plasminogênio TecidualRESUMO
INTRODUCTION: Second-language learning (SLL) depends on distinct functional-neuroanatomical systems including procedural and declarative long-term memory. Characteristic features of rapid eye movement (REM) and non-REM sleep such as rapid eye movements and sleep spindles are electrophysiological markers of cognitively complex procedural and declarative memory consolidation, respectively. In adults, grammatical learning depends at first on declarative memory ("early SLL") then shifts to procedural memory with experience ("late SLL"). However, it is unknown if the shift from declarative to procedural memory in early vs late SLL is supported by sleep. Here, we hypothesized that increases in sleep spindle characteristics would be associated with early SLL, whereas increases in REM activity (eg, density and EEG theta-band activity time-locked to rapid eye movements) would be associated with late SLL. METHODS: Eight Anglophone (English first language) participants completed four polysomnographic recordings throughout an intensive 6-week French immersion course. Sleep spindle data and electroencephalographic spectral power time-locked to rapid eye movements were extracted from parietal temporal electrodes. RESULTS: As predicted, improvements in French proficiency were associated with changes in spindles during early SLL. Furthermore, we observed increased event-related theta power time-locked to rapid eye movements during late SLL compared with early SLL. The increases in theta power were significantly correlated with improvements in French proficiency. DISCUSSION: This supports the notion that sleep spindles are involved in early SLL when grammar depends on declarative memory, whereas cortical theta activity time-locked to rapid eye movements is involved in late SLL when grammar depends on procedural memory.
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BACKGROUND: Viruses can fall prey to their defective interfering (DI) particles. When viruses are cultured by serial passage on susceptible host cells, the presence of virus-like DI particles can cause virus populations to rise and fall, reflecting predator-prey interactions between DI and virus particles. The levels of virus and DI particles in each population passage can be determined experimentally by plaque and yield-reduction assays, respectively. RESULTS: To better understand DI and virus particle interactions we measured vesicular stomatitis virus and DI particle production during serial-passage culture on BHK cells. When the multiplicity of infection (MOI, or ratio of infectious virus particles to cells) was fixed, virus yields followed a pattern of progressive decline, with higher MOI driving earlier and faster drops in virus level. These patterns of virus decline were consistent with predictions from a mathematical model based on single-passage behavior of cells co-infected with virus and DI particles. By contrast, the production of virus during fixed-volume passages exhibited irregular fluctuations that could not be described by either the steady-state or regular oscillatory dynamics of the model. However, these irregularities were, to a significant degree, reproduced when measured host-cell levels were incorporated into the model, revealing a high sensitivity of virus and DI particle populations to fluctuations in available cell resources. CONCLUSIONS: This study shows how the development of mathematical models, when guided by quantitative experiments, can provide new insight into the dynamic behavior of virus populations.
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Vírus Defeituosos/crescimento & desenvolvimento , Vesiculovirus/crescimento & desenvolvimento , Animais , Células Cultivadas , Cricetinae , Modelos Teóricos , Inoculações Seriadas , Carga Viral , Ensaio de Placa Viral , Cultura de VírusRESUMO
BACKGROUND: Sensor-guided compartmental pressure measurements are becoming increasingly utilized in total knee arthroplasty (TKA) to objectively confirm intraoperative knee balance. We aimed to determine agreement of pressure measurements between two observers when performing sensor-guided TKA with the use of computer-assisted surgery (CAS). METHODS: One-hundred and eighteen consecutive patients undergoing 130 TKAs were analysed. Femoral and tibial trial implants were inserted prior to performing knee balancing. We compared the reliability of sensor pressure compartmental measurements between two observers at 10, 45 and 90° of flexion using intraclass correlation coefficient (ICC) estimates and the 95% limits of agreement (Bland-Altman plots). RESULTS: The interobserver agreement between sensor pressure measurements was excellent at 10° of knee flexion, with ICCs of 0.93 and 0.91 in the medial and lateral compartments, respectively (P < 0.001). At 45°, medial and lateral compartment ICCs were 0.91 and 0.76, respectively (P < 0.001). At 90°, the ICC was 0.88 medially and 0.76 laterally (P < 0.001). Although the agreement decreased at higher knee flexion, it remained good to excellent. The 95% limits of agreement at each angle were all within 20 psi and 11 psi for the medial and lateral compartments, respectively. CONCLUSIONS: There was excellent interobserver agreement of sensor pressure measurements at 10° of knee flexion with computer-assisted TKA. Interobserver agreement decreased slightly as knee flexion angles increased, particularly in the lateral compartment. It is likely that interobserver agreement and hence reliability of sensor pressure measurements in TKA has some dependence on accurate angular positioning of the knee.
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Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Prótese do Joelho , Osteoartrite do Joelho/cirurgia , Amplitude de Movimento Articular/fisiologia , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Pressão , Curva ROC , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: The study objective was to investigate factors associated with resilience to rapid weight gain (RWG) among predominantly bottle-fed infants. METHODS: Data came from 1,353 mothers who participated in the Infant Feeding Practices Study 2. Mothers completed a prenatal questionnaire and monthly surveys of infant feeding and growth between birth and 12 months. Infants were classified as resilient if they were predominantly bottle fed but did not exhibit RWG between birth and the latter half of infancy (≥ +0.67 change in weight-for-age z score). RESULTS: Thirty-five percent of the sample (n = 467) was predominantly bottle fed but did not exhibit RWG ("Resilient"), 17% (n = 228) was predominantly bottle fed and exhibited RWG ("Not Resilient"), and 49% (n = 658) was not predominantly bottle fed ("Low Risk"). Significant predictors of resilience to RWG were greater gestational age (P = 0.042) and weight (P < 0.001) at birth, lower frequency of adding cereal to the bottle (P = 0.022), lower frequency of infant-led bottle-emptying (P = 0.047), and greater frequency of maternal encouragement of bottle-emptying (P = 0.002). CONCLUSIONS: Associations between bottle-feeding and RWG may be moderated by infant characteristics and maternal feeding practices. The present study highlighted several characteristics of predominantly bottle-fed infants who were resilient to RWG, but further research is needed to identify a broader array of key targets for future intervention efforts.
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Alimentação com Mamadeira/efeitos adversos , Aleitamento Materno/efeitos adversos , Comportamento Alimentar/psicologia , Aumento de Peso/fisiologia , Adulto , Alimentação com Mamadeira/métodos , Aleitamento Materno/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: In Michigan, pulse oximetry screening rates for critical congenital heart defects (CCHDs) are assessed for birthing hospitals but have not been assessed for the midwife-attended births that occur in the out-of-hospital birth community. This analysis was conducted to determine pulse oximetry screening rates among the midwife-attended out-of-hospital birth community in Michigan overall, and among midwives provided with loaned pulse oximeters from the Michigan Department of Health and Human Services (MDHHS). METHODS: Records for midwife-attended out-of-hospital births between April 1, 2014, and December 31, 2016, were linked via probabilistic matching with newborn screening records. Pulse oximetry screening rates were calculated for the midwife-attended out-of-hospital birth population overall, by midwife, and stratified by receipt of loaned pulse oximeters from MDHHS. Births from midwives who attended 5 or more nonhospital births during the study period were included in this analysis. RESULTS: Of the 3410 midwife-attended out-of-hospital births, 20.8% (n = 710) reported as having received a pulse oximetry screening for CCHDs. For births attended by midwives who received pulse oximeters from MDHHS, 50.5% had pulse oximetry screening results reported, compared with 12.7% among births attended by midwives without a loaned pulse oximeter. Of the 78 total midwives, 18% (n = 14) reported pulse oximetry screening results on more than half of the births they attended. Of the 14 midwives who received a pulse oximeter from MDHHS, 50.0% (n = 7) reported screening results for more than half of all births they attended. DISCUSSION: Our findings indicate that CCHD screening rates are low among midwife-attended out-of-hospital birth community. Screening rates were higher among midwives who received a pulse oximeter from MDHHS, but fewer than half of the attended births had a reported pulse oximetry screening. Further discussions with the midwife-attended out-of-hospital birth community to better understand screening barriers may be beneficial.
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Parto Domiciliar , Triagem Neonatal/métodos , Enfermeiros Obstétricos , Oximetria/estatística & dados numéricos , Padrões de Prática em Enfermagem/estatística & dados numéricos , Algoritmos , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Recém-Nascido , Masculino , Michigan , GravidezRESUMO
The current study sought to examine whether symptoms of posttraumatic stress disorder (PTSD), adolescent sexual assault (ASA), and drinking motivations (e.g., drinking to regulate emotional experiences) mediate the relationship between a history of childhood sexual abuse (CSA) and subsequent alcohol-related problems among college women. Participants were 579 female students at a Midwestern university. Participants were recruited as part of a larger longitudinal study that investigated risk and resiliency factors related to sexual revictimization. Using a serial mediation model, the current study found that the proposed constructs mediated the relationship between CSA and subsequent alcohol-related problems via two separate paths. In one path, CSA was associated with PTSD, which in turn predicted drinking to regulate emotional experiences, which then was related to alcohol-related problems in adulthood. In the second path, CSA was related to ASA, which in turn predicted drinking to regulate emotional experiences, which then was related to alcohol-related problems in adulthood. These results suggest that individuals with a history of CSA are more likely to experience both revictimization in adolescence and PTSD symptoms in adulthood, which may lead to alcohol-related problems via drinking to regulate emotional experiences. These findings suggest the importance of incorporating skills training in adaptive emotion regulation strategies into treatment for individuals with a history of CSA and ASA.
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Consumo de Bebidas Alcoólicas/psicologia , Transtornos Relacionados ao Uso de Álcool/psicologia , Abuso Sexual na Infância/psicologia , Vítimas de Crime/psicologia , Motivação , Transtornos de Estresse Pós-Traumáticos/psicologia , Estudantes/psicologia , Adolescente , Adulto , Criança , Feminino , Humanos , Acontecimentos que Mudam a Vida , Estudos Longitudinais , Resiliência Psicológica , Fatores de Risco , Comportamento Sexual/psicologia , Adulto JovemRESUMO
The inhalation anesthetic isoflurane is five times more soluble in lipid than in lean tissue. Using the meadow vole as a model, the authors sought to determine the effect of body composition on isoflurane induction and recovery times.
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Período de Recuperação da Anestesia , Anestesia por Inalação/veterinária , Arvicolinae/fisiologia , Composição Corporal/fisiologia , Isoflurano/farmacocinética , Análise de Variância , Animais , Arvicolinae/metabolismoRESUMO
A proteomic approach employing a two dimensional electrophoresis (2-DE) technique with SYPRO Ruby, a fluorescent stain with improved sensitivity and quantitative accuracy, was performed to separate the total proteins from apple fruit at different stages of ripening and senescence. After imaging and statistical analyses were performed on 2340 spots, a total of 316 spots, or approximately 13.5% of the total protein population, was found to be significantly changed in this study. Of the 316 proteins, 219 spots were only present at a specific ripening stage, while 97 spots were significantly different (p<0.05) throughout fruit ripening and in response to ethylene treatment. From 316 candidate spots, 221 proteins were further identified by liquid chromatography and mass spectrometry analysis with protein sequence and express sequence tag (EST) data searching. Analysis and identification of proteins revealed that apple fruit ripening is associated with increase of abundance of many proteins with functions such as ethylene production, antioxidation and redox, carbohydrate metabolism, oxidative stress, energy, and defense response. Ethylene treatment increased a group of unique proteins that were not present during normal fruit ripening and have not been previously reported. It also reduced some proteins involved in primary metabolism, including those of the last few steps of the glycolytic pathway. This study demonstrated the complexity and dynamic changes of protein profiles of apple fruit during ripening and in response to exogenous ethylene treatment. Identifying and tracking protein changes may allow us to better understand the mechanism of ripening in climacteric fruit. BIOLOGICAL SIGNIFICANCE: Postharvest physiology and biochemistry has been conducted on apple fruit for many years. Ethylene plays an important role in ripening and senescence in many climacteric fruit. However, little information is available at the proteome level to investigate fruit ripening and effect of ethylene treatment. The significance of this paper is that it is the first study employing 2-DE and fluorescent dye in the investigation of the apple fruit ripening and influence of ethylene treatment. It reveals some significant biological changes in association with these events and demonstrates significant changed proteins under these conditions. Therefore, our study links the biological events with proteomic information and provides detailed peptide information on all identified proteins. Through the function analysis, those significantly changed proteins are also analyzed. These findings from this paper provide not only proteome information on fruit ripening, but also pave the ground for further quantitative studies using SMR to investigate certain proteins and pathways under the hypothesis involved in fruit ripening. This article is part of a Special Issue entitled: Translational Plant Proteomics.
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Etilenos/farmacologia , Malus/fisiologia , Proteínas de Plantas/metabolismo , Cromatografia Líquida , Eletroforese em Gel Bidimensional , Etilenos/metabolismo , Corantes Fluorescentes , Frutas/química , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Malus/efeitos dos fármacos , Malus/genética , Espectrometria de Massas , Compostos Organometálicos , Proteínas de Plantas/análise , Proteômica/métodosRESUMO
Defective interfering particles (DIPs) are virus-like particles that arise during virus growth, fail to grow in the absence of virus, and replicate at the expense of virus during co-infections. The inhibitory effects of DIPs on virus growth are well established, but little is known about how DIPs influence their own growth. Here vesicular stomatitis virus (VSV) and its DIPs were used to co-infect BHK cells, and the effect of DIP dose on virus and DIP production was measured using a yield-reduction assay. The resulting dose-response data were used to fit and evaluate mathematical models that employed different assumptions. Our analysis supports a multiple-hit process where DIPs inhibit or promote virus and DIP production, depending on dose. Specifically, three regimes of co-infection were apparent: (i) low DIP - where both virus and DIPs are amplified, (ii) medium DIP - where amplification of both virus and DIPs is inhibited, and (iii) high DIP - with limited recovery of virus production and further inhibition of DIP growth. In addition, serial-passage infections enabled us to estimate the frequency of de novo DIP generation during virus amplification. Our combined experiments and models provide a means to understand better how DIPs quantitatively impact the growth of viruses and the spread of their infections.
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Vírus Defeituosos , Vírus da Estomatite Vesicular Indiana , Interferência Viral , Animais , Linhagem Celular , Cricetinae , Vírus Defeituosos/crescimento & desenvolvimento , Vírus Defeituosos/patogenicidade , Modelos Biológicos , Inoculações Seriadas , Vírus da Estomatite Vesicular Indiana/crescimento & desenvolvimento , Vírus da Estomatite Vesicular Indiana/patogenicidade , Ensaio de Placa Viral , Replicação ViralRESUMO
The aim of this study was to report concentrations of cerebrospinal fluid (CSF) baclofen in children undergoing chronic intrathecal baclofen (ITB) infusions. CSF baclofen concentrations were analyzed in 53 specimens obtained by intrathecal catheter aspiration from 43 participants (28 males, 15 females; range 3-44y, mean 16y [SD 8y 11mo]), with functioning baclofen pumps and catheters. Daily ITB doses ranged from 70 to 1395 microg per day (mean 607 microg per day [SD 363], median 575). Baclofen concentration was quantified by high-pressure liquid chromatography and confirmed by injection onto a gas chromatograph. CSF baclofen concentrations from children receiving either simple continuous or complex infusions ranged from 0.2 to 20.0 microg/ml (mean 4.64 microg/ml, median 3.3 microg/ml). CSF baclofen concentrations from children receiving simple continuous infusions ranged from 0.5 to 12.9 (mean 4.7 microg/ml, median 3.55 microg/ml). There was no correlation between ITB dosage and CSF baclofen concentration. We conclude that baclofen concentration can be measured to determine if baclofen is present in CSF. However, there appears to be no correlation between the ITB dose infused and the corresponding CSF baclofen level.