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1.
BMC Genomics ; 17: 383, 2016 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-27207143

RESUMO

BACKGROUND: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant pigs can result in congenital infection and ultimately fetal death. Little is known about immune responses to infection at the maternal-fetal interface and in the fetus itself, or the molecular events behind virus transmission and disease progression in the fetus. To investigate these processes, RNA-sequencing of two sites, uterine endothelium with adherent placental tissue and fetal thymus, was performed 21 days post-challenge on four groups of fetuses selected from a large PRRSV challenge experiment of pregnant gilts: control (CON), uninfected (UNINF), infected (INF), and meconium-stained (MEC) (n = 12/group). Transcriptional analyses consisted of multiple contrasts between groups using two approaches: differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). Biological functions, pathways, and regulators enriched for differentially expressed genes or module members were identified through functional annotation analyses. Expression data were validated by reverse transcription quantitative polymerase chain reaction (RTqPCR) carried out for 16 genes of interest. RESULTS: The immune response to infection in endometrium was mainly adaptive in nature, with the most upregulated genes functioning in either humoral or cell-mediated immunity. In contrast, the expression profile of infected fetal thymus revealed a predominantly innate immune response to infection, featuring the upregulation of genes regulated by type I interferon and pro-inflammatory cytokines. Fetal infection was associated with an increase in viral load coupled with a reduction in T cell signaling in the endometrium that could be due to PRRSV-controlled apoptosis of uninfected bystander cells. There was also evidence for a reduction in TWIST1 activity, a transcription factor involved in placental implantation and maturation, which could facilitate virus transmission or fetal pathology through dysregulation of placental function. Finally, results suggested that events within the fetus could also drive fetal pathology. Thymus samples of meconium-stained fetuses exhibited an increase in the expression of pro-inflammatory cytokine and granulocyte genes previously implicated in swine infectious disease pathology. CONCLUSIONS: This study identified major differences in the response to PRRSV infection in the uterine endometrium and fetus at the gene expression level, and provides insight into the molecular basis of virus transmission and disease progression.


Assuntos
Feto/metabolismo , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno/genética , Placenta/metabolismo , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína , Transcriptoma , Animais , Análise por Conglomerados , Endométrio/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Especificidade de Órgãos/genética , Gravidez , Reprodutibilidade dos Testes , Transdução de Sinais , Suínos , Carga Viral
2.
Vet Res ; 46: 107, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26407558

RESUMO

Minimal research has focused on understanding mechanisms underlying porcine reproductive and respiratory syndrome virus (PRRSV) induced reproductive failure. We have completed a large-scale project investigating phenotypic and genotypic predictors of reproductive PRRS severity in which numerous clinical, pathological, immunologic and viral responses were characterized in dams and fetuses. The goal was to determine which phenotypic responses were associated with fetal viral load and death after experimental infection of pregnant gilts with type 2 PRRSV, thereby elucidating mechanisms of reproductive PRRS in third trimester pregnant gilts. The presence of fetal infection and increasing RNA concentration at the maternal-fetal interface were strong predictors of the probability of fetal death, while PRRSV RNA concentration in dam sera and systemic tissues were not associated with the odds of fetal death. Fetal infection and death clustered, indicating that the status of adjacent fetuses is crucial for lateral transmission and fetal outcome. Several systemic immune responses of gilts were associated with fetal outcome and viral load: interferon-α contributed to the probability of fetal death, but absolute numbers of T helper cells in early infection, absolute numbers of myeloid cells over time and interleukin 12 levels appeared protective. These results suggest specific immune responses may either contribute to, or protect against, transplacental virus transmission. The WUR10000125 SNP on chromosome 4, associated with PRRS resilience in nursery pigs, was not associated with reproductive outcome. Whereas past research suggested that fetal death results from events occurring at the maternal-fetal interface, we conclude that viral replication within fetuses and spread of PRRSV to adjacent fetuses are pivotal events in the pathogenesis of reproductive PRRS.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Complicações Infecciosas na Gravidez/veterinária , Timo/virologia , Carga Viral/veterinária , Animais , Feminino , Feto/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , RNA Viral/análise , Suínos
3.
Sci Adv ; 9(5): eadd2143, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36724230

RESUMO

Volatiles expelled from subducted plates promote melting of the overlying warm mantle, feeding arc volcanism. However, debates continue over the factors controlling melt generation and transport, and how these determine the placement of volcanoes. To broaden our synoptic view of these fundamental mantle wedge processes, we image seismic attenuation beneath the Lesser Antilles arc, an end-member system that slowly subducts old, tectonized lithosphere. Punctuated anomalies with high ratios of bulk-to-shear attenuation (Qκ-1/Qµ-1 > 0.6) and VP/VS (>1.83) lie 40 km above the slab, representing expelled fluids that are retained in a cold boundary layer, transporting fluids toward the back-arc. The strongest attenuation (1000/QS ~ 20), characterizing melt in warm mantle, lies beneath the back-arc, revealing how back-arc mantle feeds arc volcanoes. Melt ponds under the upper plate and percolates toward the arc along structures from earlier back-arc spreading, demonstrating how slab dehydration, upper-plate properties, past tectonics, and resulting melt pathways collectively condition volcanism.

4.
J Youth Adolesc ; 40(9): 1192-202, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20821257

RESUMO

While many adolescents and young adults experiment with substances (e.g., alcohol, cigarette smoking, marijuana), recent research suggests that rural youth and young adults may be more at risk for substance use than their urban counterparts. This study was designed to examine the longitudinal relationships between rural adolescents' prosocial behaviors and substance use in young adulthood. Furthermore, we examined the potential mediating effects of adolescent substance use, academic investment, and delinquency. Rural youth (N = 531; 263 girls) were surveyed in grades 10-12 (Time 1; M age = 16.17; SD = .91) and again in early adulthood (Time 2). Measures of prosocial behaviors, substance use, academic investment, and deviant activities were assessed at Time 1. At Time 2, measures of marijuana use, cigarette smoking, and getting drunk were administered. Overall, the findings showed that rural adolescents who frequently exhibit prosocial behaviors are less likely to engage in substance use in young adulthood than those who exhibit relatively low levels of prosocial behaviors. These findings indicate that prosocial behaviors may have positive health consequences, establishing behavioral trajectories that lead to lower levels of risky health behaviors in adulthood in rural populations.


Assuntos
Comportamento do Adolescente , População Rural/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Intoxicação Alcoólica/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Masculino , Assunção de Riscos , Adulto Jovem
5.
Nat Commun ; 12(1): 4211, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244511

RESUMO

The margins of the Caribbean and associated hazards and resources have been shaped by a poorly understood history of subduction. Using new data, we improve teleseismic P-wave imaging of the eastern Caribbean upper mantle and compare identified subducted-plate fragments with trench locations predicted from plate reconstruction. This shows that material at 700-1200 km depth below South America derives from 90-115 Myr old westward subduction, initiated prior to Caribbean Large-Igneous-Province volcanism. At shallower depths, an accumulation of subducted material is attributed to Great Arc of the Caribbean subduction as it evolved over the past 70 Ma. We interpret gaps in these subducted-plate anomalies as: a plate window and tear along the subducted Proto-Caribbean ridge; tearing along subducted fracture zones, and subduction of a volatile-rich boundary between Proto-Caribbean and Atlantic domains. Phases of back-arc spreading and arc jumps correlate with changes in age, and hence buoyancy, of the subducting plate.

6.
BMC Genomics ; 11: 455, 2010 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-20670446

RESUMO

BACKGROUND: Haemophilus parasuis is the causative agent of Glässer's disease in pigs. Currently, little is known about the molecular mechanisms that contribute to disease susceptibility. This study used a porcine oligonucleotide microarray to identify genes that were differentially expressed (DE) in the lungs of colostrum-deprived animals previously characterized as being either 'Fully Resistant' (FR) or 'Susceptible' to infection by H. parasuis in a bacterial challenge experiment. RESULTS: Gene expression profiles of 'FR' and 'Susceptible' animals were obtained by the identification of genes that were differentially expressed between each of these groups and mock-inoculated 'Control' animals. At 24 hours post-inoculation, a total of 21 and 58 DE genes were identified in 'FR' and 'Susceptible' animals respectively. At 72 hours, the numbers of genes were 20 and 347 respectively. 'FR' animals at 24 hours exhibited an increased expression of genes encoding extracellular matrix and TGF-beta signalling components, possibly indicative of tissue repair following the successful early resolution of infection. The gene expression profile of 'FR' animals at 72 hours supported the hypothesis that higher levels of antibacterial activity were responsible for the 'FR' phenotype, possibly due to an increase in natural immunoglobulin A and decrease in signalling by the immunoregulatory transcription factor peroxisome proliferator-activated receptor gamma (PPAR-gamma). The expression profile of 'Susceptible' animals at both time-points was characterized by an imbalance in signalling between pro and anti-inflammatory cytokines and an increased expression of genes involved in biological processes associated with inflammation. These include the pro-inflammatory cytokine genes resistin (RETN) and interleukin 1-beta (IL1B). At 72 hours, a reduction in the expression of genes involved in antigen presentation by both MHC class I and II molecules was observed, which could have contributed to the inability of 'Susceptible' animals to clear infection. CONCLUSIONS: This study is the first to have identified discrete sets of DE genes in pigs of differing susceptibility to H. parasuis infection. Consequently, several candidate genes and pathways for disease resistance or susceptibility phenotypes have been identified. In addition, the findings have shed light on the molecular pathology associated with Glässer's disease.


Assuntos
Predisposição Genética para Doença , Infecções por Haemophilus/genética , Haemophilus parasuis/fisiologia , Pneumopatias/genética , Suínos/genética , Animais , Perfilação da Expressão Gênica
7.
Behav Pharmacol ; 21(4): 323-31, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20505511

RESUMO

Place conditioning is widely used to study the conditioned rewarding effects of drugs. In the standard version, one reward (cocaine) is compared with no reward (saline). A modified variant of this task, 'reference-conditioning' procedure, compares two potentially rewarding stimuli (high vs. low cocaine dose). There has been little research on the utility of this procedure. Experiment 1 used the standard protocol with saline administered before confinement to the reference compartment of a place conditioning chamber. On alternate days, saline, 2.5, 5, 7.5, 10, or 20 mg/kg cocaine was administered before confinement to the opposite compartment. In experiments 2 and 3, reference-compartment saline was replaced with 5 and 7.5 mg/kg cocaine, respectively. Relative to saline, 7.5-20 mg/kg cocaine had comparable conditioned rewarding effects (i.e. similar increase in time in paired compartment). When cocaine replaced saline, there was competition at doses lower than 7.5 mg/kg. Rats that received 7.5 versus 2.5 mg/kg spent similar time in each compartment, indicating competition. Competition was not seen with 5 versus 20 mg/kg; preference was for the 20 mg/kg compartment. Experiment 4 showed that the competition at 2.5 mg/kg was not due to reward sensitization. The reference-conditioning procedure has increased the sensitivity for measuring associatively motivated choice behavior.


Assuntos
Comportamento de Escolha/efeitos dos fármacos , Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , Motivação , Animais , Cocaína/administração & dosagem , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Masculino , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Recompensa
8.
Addict Biol ; 14(2): 165-73, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19076926

RESUMO

Bupropion can serve as a discriminative stimulus (S(D)) in an operant drug discrimination task, and a variety of stimulants substitute for the bupropion S(D). There are no reports, however, of bupropion functioning as a Pavlovian occasion setter (i.e. feature positive modulator). The present experiment seeks to fill this gap in the literature by training bupropion in rats as a feature positive modulator that disambiguates when a light will be paired with sucrose. Specifically, on bupropion (10 mg/kg intraperitoneal) sessions, offset of 15-second cue lights were followed by brief delivery of liquid sucrose; saline sessions were similar except no sucrose was available. Rats readily acquired the discrimination with more conditioned responding to the light on bupropion sessions. Bupropion is approved for use as a smoking cessation aid, and more recently has drawn attention as a potential pharmacotherapy for cocaine and methamphetamine abuse. Accordingly, after discrimination training, we tested the ability of cocaine (1-10 mg/kg), methamphetamine (0.1 to 1 mg/kg) and nicotine (0.00625 to 0.2 mg/kg) to substitute for the bupropion feature. Nicotine (0.05 mg/kg) and methamphetamine (0.3 mg/kg) substituted fully for bupropion; cocaine did not substitute. These results extend previous research on shared stimulus properties between bupropion and other stimulants to a Pavlovian occasion setting function. Further, this is the first report of nicotine and methamphetamine substitution for bupropion. The overlap in stimulus properties might explain the effectiveness of bupropion as a smoking cessation aid and highlight the possible utility of bupropion for treatment of stimulant use disorder.


Assuntos
Bupropiona/farmacologia , Cocaína/farmacologia , Condicionamento Clássico , Aprendizagem por Discriminação/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Metanfetamina/farmacologia , Nicotina/farmacologia , Bupropiona/administração & dosagem , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Humanos , Metanfetamina/administração & dosagem , Nicotina/administração & dosagem , Peritônio
9.
Vaccine ; 37(13): 1743-1755, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30808565

RESUMO

We investigated gene expression patterns in whole blood and fecal microbiota profile as potential predictors of immune response to vaccination, using healthy M. hyopneumoniae infection free piglets (n = 120). Eighty piglets received a dose of prophylactic antibiotics during the first two days of life, whereas the remaining 40 did not. Blood samples for RNA-Seq analysis were collected on experimental Day 0 (D0; 28 days of age) just prior to vaccination, D2, and D6 post-vaccination. A booster vaccine was given at D24. Fecal samples for microbial 16SrRNA sequencing were collected at 7 days of age, and at D0 and D35 post-vaccination. Pigs were ranked based on the levels of M. hyopneumoniae-specific antibodies in serum samples collected at D35, and groups of 'high' (HR) and 'low' (LR) responder pigs (n = 15 each) were selected. Prophylactic antibiotics did not influence antibody titer levels and differential expression analysis did not reveal differences between HR and LR at any time-point (FDR > 0.05); however, based on functional annotation with Ingenuity Pathway Analysis, D2 post-vaccination, HR pigs were enriched for biological terms relating to increased activation of immune cells. In contrast, the immune activation decreased in HR, 6 days post-vaccination. No significant differences were observed prior to vaccination (D0). Two days post-vaccination, multivariate analysis revealed that ADAM8, PROSER3, B4GALNT1, MAP7D1, SPP1, HTRA4, and ENO3 genes were the most promising potential biomarkers. At D0, OTUs annotated to Prevotella, CF21, Bacteroidales and S24-7 were more abundant in HR, whereas Fibrobacter, Paraprevotella, Anaerovibrio, [Prevotella], YRC22, and Helicobacter positively correlated with the antibody titer as well as MYL1, SPP1, and ENO3 genes. Our study integrates gene differential expression and gut microbiota to predict vaccine response in pigs. The results indicate that post-vaccination gene-expression and early-life gut microbiota profile could potentially predict vaccine response in pigs, and inform a direction for future research.


Assuntos
Vacinas Bacterianas/imunologia , Fezes/microbiologia , Microbioma Gastrointestinal , Perfilação da Expressão Gênica , Mycoplasma hyopneumoniae/imunologia , Pneumonia Suína Micoplasmática/prevenção & controle , Transcriptoma , Animais , Vacinas Bacterianas/administração & dosagem , Suínos , Vacinação
10.
Pharmacol Biochem Behav ; 88(3): 256-64, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17888504

RESUMO

The rewarding effects of nicotine contribute to the chronic use of tobacco products. The place conditioning task, a widely used pre-clinical model to study drug reward, has lead to mixed results in rats when nicotine was administered subcutaneously or intraperitoneally; intravenously administered nicotine has not been examined. Further, much of the research demonstrating a nicotine-conditioned place preference in rats has used a biased design making these results susceptible to non-reward interpretations. The present study assessed whether intravenous (IV) nicotine would condition a place preference in an unbiased design and evaluated important behavioral parameters: nicotine dose, number of conditioning trials, and infusion-to-placement interval. In adult male Sprague Dawley rats, IV nicotine (0.03 mg/kg) conditioned a place preference after 8 conditioning trials. This conditioned preference was observed whether nicotine was infused 10 min before or immediately after placement in the paired environment for 10 min; infusing nicotine immediately after removal from the paired environment did not condition a preference after 4 or 8 conditioning trials. Four conditioning trials were not sufficient to condition a preference regardless of the temporal relation between the paired environment and 0.03 mg/kg nicotine. A 0.01 mg/kg dose of nicotine did not condition a place preference after 4 or 8 trials when infused immediately upon placement in the paired environment. Intravenous nicotine (0.03 mg/kg) has rewarding effects in an unbiased design suggesting that the place conditioning protocol used in the present study might be an especially useful model for studying the processes underlying the conditioned rewarding effects of nicotine.


Assuntos
Condicionamento Operante/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Animais , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Injeções Intravenosas , Masculino , Atividade Motora/efeitos dos fármacos , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Tabagismo/psicologia
11.
Physiol Behav ; 90(5): 790-6, 2007 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-17300819

RESUMO

Bupropion is marketed as an antidepressant, Wellbutrin and smoking cessation aid, Zyban. Although the therapeutic neurological mechanisms of bupropion have not been fully elucidated, bupropion shares some behavioral similarities with classic psychomotor stimulants. The present study sought to further investigate these psychomotor stimulant effects of bupropion by assessing whether repeated administration of bupropion in a distinct environment produced conditioned hyperactivity. Paired rats received 10 daily i.p. injections of bupropion (2.5-30 mg/kg) before placement in locomotor chambers for 30 min. Bupropion (10-30 mg/kg) produced acute locomotor hyperactivity compared to Unpaired controls. After repeated administration, there was no progressive increase or decrease in bupropion-induced activity. In a subsequent drug-free session conditioned hyperactivity was observed at 5-30 mg/kg doses. In a follow-up experiment, we examined whether responsiveness to novelty predicted the subsequent unconditioned and conditioned locomotor effect of bupropion. Reactivity to inescapable novelty, novel environment approach, and novel-object interaction were measured before locomotor conditioning with 30 mg/kg bupropion. We replicated the previous experiment, but scores on the novelty screens did not predict locomotor response to bupropion. This study extends the literature by demonstrating that environmental cues repeatedly paired with the stimulant effects of bupropion come to evoke elevated activity in the absence of drug (i.e., conditioned hyperactivity). This finding is consistent with the literature suggesting that bupropion shares many behavioral similarities with other psychomotor stimulants which also produce conditioned hyperactivity. However, a predictive relation between reactivity to forced novelty and the subsequent locomotor effect of bupropion may not be one of these similarities.


Assuntos
Aprendizagem por Associação/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Bupropiona/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Hipercinese/induzido quimicamente , Análise de Variância , Animais , Antidepressivos de Segunda Geração/farmacologia , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
12.
J Genet Psychol ; 168(2): 147-76, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17936970

RESUMO

In the present study, the authors examined the relations among parenting styles, parental practices, sympathy, and prosocial behaviors in adolescents. The participants were 233 adolescents (M age = 16.7 years; 69% girls; mostly White) from public high schools in the Midwestern region of the United States who completed measures of prosocial behaviors, parenting styles, parenting practices, and sympathy. Overall, the authors found evidence that parenting practices were significantly associated with adolescents' prosocial behaviors. However, the associations between parenting practices and prosocial behaviors occurred mostly through the indirect relations with sympathy. The relations among parenting practices, sympathy, and prosocial behaviors varied as a function of the specific parenting practice and the specific prosocial behavior. Implications for future research on the study of prosocial development and parenting among adolescents are discussed.


Assuntos
Empatia , Desenvolvimento Moral , Poder Familiar/psicologia , Psicologia do Adolescente , Comportamento Social , Adolescente , Altruísmo , Feminino , Humanos , Masculino , Inventário de Personalidade , Fatores Sexuais , Meio Social , Socialização
14.
Vet Microbiol ; 209: 114-123, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28292546

RESUMO

A large challenge experiment using North American porcine reproductive and respiratory virus (PRRSV-2) provided new insights into the pathophysiology of reproductive PRRS. Deep phenotyping of dams and fetuses identified maternal and fetal predictors of PRRS severity and resilience. PRRSV infection resulted in dramatic decreases in all leukocyte subsets by 2days post inoculation. Apoptosis in the interface region was positively related to endometrial vasculitis, viral load in endometrium and fetal thymus, and odds of meconium staining. Viral load at the maternal-fetal interface was a strong predictor of viral load in fetal thymus and odds of fetal death. However, interferon-alpha suppression, a consequence of PRRSV infection, was protective against fetal death. Although the prevalence of fetal lesions was low, their presence in fetal organs and umbilical cord was strongly associated with fetal compromise. Fetal death and viral load clustered in litters suggesting inter-fetal transmission starting from a limited number of index fetuses. Factors associated with index fetal infection are unclear, but large fetuses appear at greater risk. Disease progression in fetuses was associated with an up-regulation of genes associated with inflammation, innate immunity, and cell death signaling, and down-regulation of genes associated with cell cycle and lymphocyte quality. A number of maternal transcriptomic responses were associated with PRRS resilience including higher basal gene expression correlated with platelet function, interferon and pro-inflammatory responses. Twenty-one genomic regions across 10 chromosomes were associated with important traits including fetal viral load, fetal death and viability suggesting that selection for reproductive PRRS resilience may be possible.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/fisiopatologia , Animais , Genoma/genética , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/mortalidade , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Seleção Genética , Suínos/genética
15.
Clin Transl Allergy ; 7: 24, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28794855

RESUMO

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effectiveness, safety and cost-effectiveness of AIT for ARC. METHODS: We undertook a systematic overview, which involved searching nine international biomedical databases from inception to October 31, 2015. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews. Data were descriptively synthesized. RESULTS: Our searches yielded a total of 5932 potentially eligible studies, from which 17 systematic reviews met our inclusion criteria. Eight of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare for both SCIT and SLIT. Two systematic reviews reported some evidence of potential cost savings associated with use of SCIT and SLIT. CONCLUSIONS: We found moderate-to-strong evidence that SCIT and SLIT can, in appropriately selected patients, reduce symptoms and medication requirements in patients with ARC with reassuring safety data. This evidence does however need to be interpreted with caution, particularly given the heterogeneity in the populations, allergens and protocols studied. There is a lack of data on the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. We are now systematically reviewing all the primary studies, including recent evidence that has not been incorporated into the published systematic reviews.

18.
Psychopharmacology (Berl) ; 184(3-4): 470-81, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16047193

RESUMO

RATIONALE: Pavlovian feature negative discriminations have been widely used to understand inhibitory conditioning processes using exteroceptive stimuli. Comparatively little is known about inhibitory conditioning processes using a drug state as a negative feature. A negative feature signals that presentation of a conditional stimulus (CS) will not be paired with an unconditioned stimulus. OBJECTIVES: The present research examined whether nicotine served as a negative feature and started characterizing its properties. METHODS AND RESULTS: In acquisition, rats received intermixed saline and nicotine (0.4 mg/kg, base) sessions. On saline sessions, a 15-s light CS was paired with 4-s access to sucrose; the CS was presented on nicotine sessions, but sucrose was withheld. The discrimination was acquired with more goal tracking during the CS on saline sessions. Nicotine's inhibition of this conditioned response (CR) was sensitive to nicotine dose (ED50=0.225) and injection to testing interval (CR returned at 200 min). Mecamylamine pretreatment, but not hexamethonium, produced a loss of inhibitory control by nicotine suggesting a role for central nicotinic acetylcholine receptors. Amphetamine, bupropion, arecoline, and chlordiazepoxide, but not caffeine, substituted for the nicotine feature. However, in locomotor tests, amphetamine and bupropion increased activity; arecoline and chlordiazepoxide decreased activity. For this reason, the motor effects of these ligands could not be dissociated from substitution via shared stimulus properties. CONCLUSIONS: This feature negative task provides a preclinical model for studying how drug states inhibit responding, although identifying the process(es) mediating CR inhibition will require further research.


Assuntos
Condicionamento Clássico/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Nicotina/farmacologia , Reforço Psicológico , Anfetamina/farmacologia , Animais , Arecolina/farmacologia , Aprendizagem por Associação/efeitos dos fármacos , Bupropiona/farmacologia , Cafeína/farmacologia , Clordiazepóxido/farmacologia , Aprendizagem por Discriminação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Hexametônio/farmacologia , Masculino , Mecamilamina/farmacologia , Atividade Motora/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/efeitos dos fármacos , Sacarose/administração & dosagem
19.
PLoS One ; 11(4): e0153615, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27093427

RESUMO

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant females causes fetal death and increased piglet mortality, but there is substantial variation in the extent of reproductive pathology between individual dams. This study used RNA-sequencing to characterize the whole blood transcriptional response to type 2 PRRSV in pregnant gilts during the first week of infection (at 0, 2, and 6 days post-inoculation), and attempted to identify gene expression signatures associated with a low or high level of fetal mortality rates (LFM and HFM; n = 8/group) at necropsy, 21 days post-inoculation. The initial response to infection measured at 2 days post-inoculation saw an upregulation of genes involved in innate immunity, such as interferon-stimulated antiviral genes and inflammatory markers, and apoptosis. A concomitant decrease in expression of protein synthesis and T lymphocyte markers was observed. By day 6 the pattern had reversed, with a drop in innate immune signaling and an increase in the expression of genes involved in cell division and T cell signaling. Differentially expressed genes (DEGs) associated with extremes of litter mortality rate were identified at all three time-points. Among the 15 DEGs upregulated in LFM gilts on all three days were several genes involved in platelet function, including integrins ITGA2B and ITGB3, and the chemokine PF4 (CXCL4). LFM gilts exhibited a higher baseline expression of interferon-stimulated and pro-inflammatory genes prior to infection, and of T cell markers two days post-infection, indicative of a more rapid progression of the immune response to PRRSV. This study has increased our knowledge of the early response to PRRSV in the blood of pregnant gilts, and could ultimately lead to the development of a biomarker panel that can be used to predict PRRSV-associated reproductive pathology.


Assuntos
Células Sanguíneas/virologia , Expressão Gênica/genética , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/mortalidade , Reprodução/genética , Suínos/virologia , Animais , Células Sanguíneas/imunologia , Feminino , Morte Fetal , Mortalidade Fetal , Imunidade Inata/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Gravidez , Complicações Infecciosas na Gravidez/genética , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/mortalidade , Reprodução/imunologia , Suínos/imunologia , Linfócitos T/imunologia
20.
Pharmacy (Basel) ; 4(1)2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28970385

RESUMO

This paper looks at the opinions of 241 European academics (who provide pharmacy education), and of 258 European community pharmacists (who apply it), on competences for pharmacy practice. A proposal for competences was generated by a panel of experts using Delphi methodology. Once finalized, the proposal was then submitted to a large, European-wide community of academics and practicing pharmacists in an additional Delphi round. Academics and community pharmacy practitioners recognized the importance of the notion of patient care competences, underlining the nature of the pharmacist as a specialist of medicines. The survey revealed certain discrepancies. Academics placed substantial emphasis on research, pharmaceutical technology, regulatory aspects of quality, etc., but these were ranked much lower by community pharmacists who concentrated more on patient care competences. In a sub-analysis of the data, we evaluated how perceptions may have changed since the 1980s and the introduction of the notions of competence and pharmaceutical care. This was done by splitting both groups into respondents < 40 and > 40 years old. Results for the subgroups were essentially statistically the same but with some different qualitative tendencies. The results are discussed in the light of the different conceptions of the professional identity of the pharmacist.

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