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INTRODUCTION: Dysfunctions in the oxytocin system have been reported in patients with borderline personality disorder (BPD). Deficits could be related to interpersonal hypersensitivity, which has been previously associated with failures in social cognition (SC) in this disorder, especially in Theory of Mind (ToM) skills. The aim of this work is to study the links between the oxytocin system and SC impairments in patients with BPD. METHOD: Plasma oxytocin levels (OXT) and protein expression of oxytocin receptors in blood mononuclear cells (OXTR) were examined in 33 patients with a diagnosis of BPD (age: M 28.85, DT = 8.83). Social cognition was assessed using the Movie for the Assessment of Social Cognition (MASC). Statistical associations between biochemical factors and different response errors in MASC were analyzed through generalized linear regression controlling for relevant clinical factors. RESULTS: Generalized linear regression showed a significant relationship between lower OXTR and overmentalization in BPD patients (OR = 0.90). CONCLUSIONS: This work supports the relationship between alterations in the oxytocin system and ToM impairments observed in BPD patients, enhancing the search for endophenotypes related to the phenotypic features of the disorder to improve current clinical knowledge and address more specific therapeutic targets.
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Transtorno da Personalidade Borderline , Ocitocina , Receptores de Ocitocina , Cognição Social , Teoria da Mente , Humanos , Transtorno da Personalidade Borderline/sangue , Transtorno da Personalidade Borderline/fisiopatologia , Ocitocina/sangue , Ocitocina/metabolismo , Adulto , Feminino , Receptores de Ocitocina/metabolismo , Masculino , Teoria da Mente/fisiologia , Adulto JovemRESUMO
INTRODUCTION: This work aims to demonstrate, through the International Affective Picture System (IAPS) responses, an altered emotional pattern in borderline personality disorder (BPD) patients and to find a specific emotional response pattern by understanding their relationship with traumatic experiences and attachment bonds towards their primary caregivers. METHOD: A total of 50 BPD patients and 39 control patients were evaluated using the IAPS, and its assessment was carried out through the Self-Assessment Manikin (SAM). Paternal and maternal attachment bonds as well as traumatic experiences in BPD patients were evaluated. Statistical associations were analysed in the different variables. RESULTS: Significant differences between BPD and control patients were found in all emotional response components for pleasant, unpleasant and neutral images (p < .01), with one exception, the arousal in pleasant images. Patients' experience of traumatic experiences was positively related to scores on the happiness component of pleasant imagery (p = .057) and on the arousal component of unpleasant imagery (p = .058). Poorer maternal bonding in BPD patients was significantly related to lower scores on happiness (p < .01) and dominance (p < .05) components of pleasant imagery and all emotional response components for unpleasant imagery (p < .01). CONCLUSIONS: The results of the study confirm an impaired emotional response pattern in patients with borderline personality disorder (BPD), showing an emotional response to pleasant images similar to that of depression, while the pattern found to unpleasant images could be related to the complex trauma observed in these patients, which includes PTSD experiences such as sexual abuse and attachment trauma experiences.
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Transtorno da Personalidade Borderline , Masculino , Humanos , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/psicologia , Emoções/fisiologia , Nível de Alerta/fisiologia , Autoavaliação (Psicologia) , FelicidadeRESUMO
High comorbidity between borderline personality disorder (BPD) and eating disorders (ED) shows the necessity of developing transdiagnostic models, where impulsivity could play a relevant role in the manifestations of self-injurious behaviour.
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Transtorno da Personalidade Borderline , Transtornos da Alimentação e da Ingestão de Alimentos , Comportamento Autodestrutivo , Humanos , Comportamento Autodestrutivo/complicações , Comportamento Autodestrutivo/diagnóstico , Comportamento Impulsivo , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/epidemiologia , Transtorno da Personalidade Borderline/diagnóstico , Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/complicaçõesRESUMO
BACKGROUND: Some studies suggest that inflammatory signaling dysregulation may contribute to eating disorder (ED) pathophysiology. However, little is known about the influence of inflammatory response on altered processes seen among patients with ED, such as emotional processing and reactivity. OBJECTIVES: The objectives were: (a) to investigate the systemic inflammatory response in ED women; and (b) to analyze the role of inflammatory markers in emotional reactivity. METHOD: Concentrations of several intercellular and intracellular inflammatory mediators (cytokines, prostaglandin by-products and enzymes, TBARS, and MAPK proteins) were quantified in plasma and PBMCs from 68 women with an ED (m = 22.01 years, SD = 9.15) and 35 healthy controls (m = 18.54 years, SD = 4.21). Moreover, emotional reactivity to affective pictures (those without either food or thinness content) was studied using the adult (>18 years old) sample (n = 41). RESULTS: Between-group differences were revealed for most markers (TNF-α, PGE2 , COX2, and ratio of activated MAPK proteins), pointing to increased inflammatory response in patients (p < .01). Women with ED showed heightened emotional reactivity, regardless of picture valence. Principal components derived from inflammatory markers showed an explanatory loading on patient's emotional reaction, in terms of valence and arousal. CONCLUSION: This study corroborates the altered systemic inflammatory response in patients with ED. The inflammatory dysregulation may contribute to ED phenotype, as seen by its relationship with heightened emotional reactivity, even though the inflammatory markers were not evaluated throughout the emotional reactivity protocol.
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Nível de Alerta , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Emoções , Feminino , HumanosRESUMO
INTRODUCTION: Neurocognitive impairment is considered an essential symptom of schizophrenia, particularly in its early stages. Nonetheless, the neuropsychological features of borderline personality disorder (BPD) could cast doubt on the specificity of neurocognitive dysfunctions. The aim of this study is to determine whether neurocognitive deficits are specific to schizophrenia-spectrum conditions as compared to a similarly severe psychiatric illness like BPD. METHOD: A battery of neuropsychological tests was used to assess the abilities for attention, verbal memory and executive functions in a group of 34 borderline personality disorder (BPD) patients, 24 patients with first episode of a schizophrenia-spectrum disorder (FEP) and a group of 19 controls. RESULTS: ANOVA for multiple measures with subsequent post-hoc tests demonstrated significant effect sizes between controls and patients for all cognitive domains. However, the effect sizes of comparisons between both groups of patients were not significant. CONCLUSIONS: Results show significant neuropsychological impairment in both disorders when compared with normal controls, but no specific pattern of neurocognitive deficits for schizophrenia-spectrum disorders was found.
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Transtorno da Personalidade Borderline/diagnóstico , Esquizofrenia/diagnóstico , Adolescente , Adulto , Atenção , Transtorno da Personalidade Borderline/fisiopatologia , Transtorno da Personalidade Borderline/psicologia , Estudos de Casos e Controles , Diagnóstico Diferencial , Função Executiva , Feminino , Humanos , Masculino , Memória , Testes Neuropsicológicos , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto JovemRESUMO
Hyperprolactinemia is an underappreciated/unknown adverse effects of antipsychotics. The consequences of hyperprolactinemia compromise therapeutic adherence and can be serious. We present the consensus recommendations made by a group of experts regarding the management of antipsychotic-induced hyperprolactinemia. The current consensus was developed in 3 phases: 1, review of the scientific literature; 2, subsequent round table discussion to attempt to reach a consensus among the experts; and 3, review by all of the authors of the final conclusions until reaching a complete consensus. We include recommendations on the appropriate time to act after hyperprolactinemia detection and discuss the evidence on available options: decreasing the dose of the antipsychotic drug, switching antipsychotics, adding aripiprazole, adding dopaminergic agonists, and other type of treatment. The consensus also included recommendations for some specific populations such as patients with a first psychotic episode and the pediatric-youth population, bipolar disorder, personality disorders and the elderly population.
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Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Hiperprolactinemia/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Consenso , Humanos , Doença Iatrogênica/prevenção & controleRESUMO
Horizontal gene transfer is common among viruses, while they also have highly compact genomes and tend to lose artificial genomic insertions rapidly. Understanding the stability of genomic insertions in viral genomes is therefore relevant for explaining and predicting their evolutionary patterns. Here, we revisit a large body of experimental research on a plant RNA virus, tobacco etch potyvirus (TEV), to identify the patterns underlying the stability of a range of homologous and heterologous insertions in the viral genome. We obtained a wide range of estimates for the recombination rate-the rate at which deletions removing the insertion occur-and these appeared to be independent of the type of insertion and its location. Of the factors we considered, recombination rate was the best predictor of insertion stability, although we could not identify the specific sequence characteristics that would help predict insertion instability. We also considered experimentally the possibility that functional insertions lead to higher mutational robustness through increased redundancy. However, our observations suggest that both functional and non-functional increases in genome size decreased the mutational robustness. Our results therefore demonstrate the importance of recombination rates for predicting the long-term stability and evolution of viral RNA genomes and suggest that there are unexpected drawbacks to increases in genome size for mutational robustness.
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Elementos de DNA Transponíveis/genética , Genoma Viral , Potyvirus/genética , Vírus de RNA/genética , Transferência Genética Horizontal , Mutagênese , Recombinação Genética , Deleção de SequênciaRESUMO
Transcription factors (TFs) regulate gene expression through binding to cis-regulatory specific sequences in the promoters of their target genes. In contrast to the genetic code, the transcriptional regulatory code is far from being deciphered and is determined by sequence specificity of TFs, combinatorial cooperation between TFs and chromatin competence. Here we addressed one of these determinants by characterizing the target sequence specificity of 63 plant TFs representing 25 families, using protein-binding microarrays. Remarkably, almost half of these TFs recognized secondary motifs, which in some cases were completely unrelated to the primary element. Analyses of coregulated genes and transcriptomic data from TFs mutants showed the functional significance of over 80% of all identified sequences and of at least one target sequence per TF. Moreover, combining the target sequence information with coexpression analysis we could predict the function of a TF as activator or repressor through a particular DNA sequence. Our data support the correlation between cis-regulatory elements and the sequence determined in vitro using the protein-binding microarray and provides a framework to explore regulatory networks in plants.
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Arabidopsis/metabolismo , DNA de Plantas/metabolismo , Genes de Plantas , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Sítios de Ligação , DNA de Plantas/químicaRESUMO
Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (â¢) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc.
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Antioxidantes/farmacologia , Carnitina/farmacologia , Túbulos Renais Proximais/patologia , Leptina/toxicidade , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Western Blotting , Células Cultivadas , Ativação Enzimática , Humanos , Rim , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , NADPH Oxidases/genética , Substâncias Protetoras/farmacologia , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxidos/metabolismoRESUMO
BACKGROUND: Follow-up studies revealed that subjects with borderline personality disorder (BPD) present high rates of clinical remission, although psychosocial functioning often remains impaired. The aim of this study is to evaluate the efficacy of a cognitive rehabilitation intervention versus a psychoeducational program on psychosocial functioning in subjects with BPD. METHODS: A multicenter, randomized, and positive-controlled clinical trial was conducted. Seventy outpatients with BPD were randomized to cognitive rehabilitation or psychoeducational group interventions. Participants were evaluated after completion of the intervention period (16 weeks) and after the follow-up period (6 months). Psychosocial functioning, clinical and neuropsychological outcomes were evaluated. RESULTS: No main effects of group or group x time were observed on functionality but a significant effect of time was found. Post-hoc analyses showed that only cognitive rehabilitation increased psychosocial functioning significantly at endpoint. Psychoeducation showed a significant enhancement of depressive symptoms. CONCLUSIONS: Cognitive rehabilitation and psychoeducational interventions appeared to show good efficacy in improving disabilities in daily life in subjects with BPD. These interventions are easily implemented in mental health settings and have the advantage of improving general functioning and clinical symptoms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02033044. Registered 9 January 2014.
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Transtorno da Personalidade Borderline/reabilitação , Terapia Cognitivo-Comportamental/métodos , Adulto , Assistência Ambulatorial , Transtorno da Personalidade Borderline/psicologia , Depressão/reabilitação , Função Executiva/fisiologia , Feminino , Seguimentos , Humanos , Relações Interpessoais , Masculino , Memória/fisiologia , Educação de Pacientes como Assunto/métodos , Resultado do TratamentoRESUMO
BACKGROUND: This study is done to compare the effect of adjunctive therapy with pregabalin versus usual care (UC) on health-care costs and clinical and patients consequences in generalized anxiety disorder (GAD) subjects with partial response (PR) to a previous selective serotonin reuptake inhibitor (SSRI) course in medical practice in Spain. METHODS: Post hoc analysis of patients with PR to SSRI monotherapy enrolled in a prospective 6-month naturalistic study was done. PR was defined as a Clinical Global Impression (CGI) scale score ≥3 and insufficient response with persistence of anxiety symptoms ≥16 in the Hamilton Anxiety Rating Scale (HAM-A). Two groups were analyzed: 1) adjunctive therapy (AT) with pregabalin (150-600 mg/day) to existing therapy and 2) UC (switching to a different SSRI or adding another anxiolytic different than pregabalin). Costs included GAD-related health-care resources utilization. Consequences were a combination of psychiatrist-based measurements [HAM-A, CGI, and Montgomery-Asberg Depression Rating Scale (MADRS)] and patient-reported outcomes [Medical Outcomes Study Sleep (MOS-sleep) scale, disability (World Health Organization Disability Assessment Schedule II (WHO-DAS II) and quality-of-life (Euro Qol-5D (EQ-5D)]. Changes in both health-care costs and scale scores were compared separately at end-of-trial visit by a general linear model with covariates. RESULTS: Four hundred eighty-six newly prescribed pregabalin and 239 UC GAD patients [mean (SD) HAM-A 26.7 (6.9) and CGI 4.1 (0.5)] were analyzed. Adding pregabalin was associated with significantly higher mean (95% CI) score reductions vs. UC in HAM-A [-14.9 (-15.6; -14.2) vs. -11.2 (-12.2; -10.2), p < 0.001] and MADRS [-11.6 (-12.2; -10.9) vs. -7.8 (-8.7; -6.8), p < 0.001]. Changes in all patient-reported outcomes favored significantly patients receiving pregabalin, including quality-of-life gain; 26.4 (24.7; 28.1) vs. 19.4 (17.1; 21.6) in the EQ-VAS, p < 0.001. Health-care costs were significantly reduced in both cohorts yielding similar 6-month costs; 1,565 (1,426; 1,703) pregabalin and 1,406 (1,200; 1,611) UC, p = 0.777. The effect of sex on costs and consequences were negligible. CONCLUSION: In medical practice, GAD patients with PR to SSRI experienced greater consequence improvements with adjunctive therapy with pregabalin versus UC, without increasing health-care cost. The effect of pregabalin was independent of patient gender.
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The outcome of a viral infection depends on a complex interplay between the host physiology and the virus, mediated through numerous protein-protein interactions. In a previous study, we used high-throughput yeast two-hybrid (HT-Y2H) to identify proteins in Arabidopsis thaliana that bind to the proteins encoded by the turnip mosaic virus (TuMV) genome. Furthermore, after experimental evolution of TuMV lineages in plants with mutations in defense-related or proviral genes, most mutations observed in the evolved viruses affected the VPg cistron. Among these mutations, D113G was a convergent mutation selected in many lineages across different plant genotypes, including cpr5-2 with constitutive expression of systemic acquired resistance. In contrast, mutation R118H specifically emerged in the jin1 mutant with affected jasmonate signaling. Using the HT-Y2H system, we analyzed the impact of these two mutations on VPg's interaction with plant proteins. Interestingly, both mutations severely compromised the interaction of VPg with the translation initiation factor eIF(iso)4E, a crucial interactor for potyvirus infection. Moreover, mutation D113G, but not R118H, adversely affected the interaction with RHD1, a zinc-finger homeodomain transcription factor involved in regulating DNA demethylation. Our results suggest that RHD1 enhances plant tolerance to TuMV infection. We also discuss our findings in a broad virus evolution context.
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Interpersonal difficulties in borderline personality disorder (BDP) have been suggested to be related to impairments in Social Cognition (SC), mainly due to deficits in Theory of Mind (ToM). However, literature is scarce and ambiguous. This work aims to study the SC impairments in BPD patients, by the specific assessment of ToM deficits, and to investigate the relationship between these SC impairments and clinical variables. 82 BPD patients with BPD and 47 control subjects were assessed with the Movie for the Assessment of Social Cognition (MASC). Clinical variables of severity, chronicity, functionality and anxious-depressive symptomatology were recorded. BPD patients had fewer correct mentalization responses and more overmentalization, undermentalization, and absence of mentalization errors than controls. Chronicity was negatively correlated with overmentalization and positively correlated with undermentalization and absence of mentalization errors. Functionality was indirectly correlated with absence of mentalization. These results confirm previous reports of alterations in SC in BPD patients. Furthermore, this study shows that SC impairments in patients with BPD are dependent on characteristics such as chronicity or degree of functionality. The different ToM profiles in patients with BPD indicate the necessity of developing variants of mentalization therapy depending on the deficits of each patient.
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Transtorno da Personalidade Borderline , Teoria da Mente , Humanos , Cognição Social , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/terapia , Relevância Clínica , Ansiedade , Teoria da Mente/fisiologia , CogniçãoRESUMO
PURPOSE: To model the cost-effectiveness (CEA) of the use of pregabalin versus usual care (UC) in outpatients with refractory generalised anxiety disorder (GAD) treated in daily practice in mental health settings in Spain. METHODS: This CEA model used data extracted from a 6-month prospective non-interventional trial: the Amplification of Definition of ANxiety (ADAN) study, which was conducted to determine the cost-of-illness in GAD subjects. Refractory subjects were those who reported persistent symptoms of anxiety and showed suboptimal response in the Hamilton-anxiety scale (HAM-A ≥ 16) after a standard dose regimen of anxiolytics other than pregabalin, alone or in combination, over 6 months. The pregabalin arm was documented with data extracted from patients who received pregabalin in the study for the first time, added or replacing the existing therapy. In the UC arm, treatment might include one or more of the following: a serotonin selective reuptake inhibitor, a serotonin-norepinephrine reuptake inhibitor, other anti-depressants, a benzodiazepine or an anti-epileptic drug other than pregabalin. The time horizon of the modelling was 6 months in the base-case scenario, and the National Health System perspective was chosen to calculate costs. Effectiveness was expressed as quality-adjusted life years (QALYs) gained, which were derived using the EQ-5D questionnaire, at baseline and end-of-trial visits. Results of the CEA model was expressed as an incremental cost-effectiveness ratio (ICER) per QALY gained. Probabilistic sensitivity analysis using bootstrapping techniques was also carried out to obtain the cost-effectiveness plane and the corresponding acceptability curve. RESULTS: Data from a total of 429 subjects per arm (mean HAM-A score 25.7) meeting eligible criteria for inclusion in CEA modelling were extracted from the original trial. Compared with UC, pregabalin (average dose 218 mg/day) was associated with significantly higher QALY gain; 0.1209 ± 0.1030 versus 0.0994 ± 0.0979 (P = 0.003), but increased healthcare costs as well;
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Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Recursos em Saúde/estatística & dados numéricos , Ácido gama-Aminobutírico/análogos & derivados , Ansiolíticos/economia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/economia , Estudos de Casos e Controles , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Pregabalina , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Espanha , Inquéritos e Questionários , Resultado do Tratamento , Ácido gama-Aminobutírico/economia , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
OBJECTIVE: To compare the relative healthcare costs, from the perspective of the Spanish National Healthcare System (NHS), of initiating treatment with either pregabalin, or SSRI/SNRI, as add-on therapies, in patients with generalized anxiety disorder (GAD), who are resistant to benzodiazepine-based therapy (BR). METHODS: BR out-patients with GAD (DSM-IV) who were included in a 6-month, prospective, multicentre, observational cohort study were selected for this post-hoc economic analysis. BR was defined as insufficient response, with persistence of symptoms of anxiety (HAM-Anxiety scale≥16), after a 6-month course of benzodiazepines. Patients had not been previously exposed to pregabalin or SSRI/SNRI. Healthcare resource utilization (drugs, medical visits, hospitalizations, etc.) associated with GAD was collected at baseline and end-of-trial visits. Related costs were estimated at each visit and adjusted changes were compared using ANCOVA. RESULTS: A total of 128 patients with refractory GAD were treated with pregabalin and 126 SSRI/SNRI. Compared with SSRI/SNRI, pregabalin was associated with significantly lower percentage of benzodiazepines users; 57.0% vs 87.3%, p<0.001, and greater reduction in medical visits; -15.1 vs -13.0, p=0.029. Mean total healthcare resource utilization costs decreased significantly in the pregabalin cohort only; -289 (p=0.003), although six months costs were not significantly different in both groups; 977 vs 822, respectively. CONCLUSION: Initiating treatment with pregabalin was associated with significant reduction in medical visits and total health care resource costs of GAD compared to SSRI/ SNRI in BR patients in the Spanish NHS setting. Compared with SSRI/SNRI, pregabalin therapy was accompanied by significantly less percentage of patients on concomitant benzodiazepines therapy.
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Inibidores da Captação Adrenérgica/economia , Inibidores da Captação Adrenérgica/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/economia , Custos de Cuidados de Saúde , Inibidores Seletivos de Recaptação de Serotonina/economia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Ácido gama-Aminobutírico/análogos & derivados , Adulto , Benzodiazepinas/uso terapêutico , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pregabalina , Estudos Prospectivos , Espanha , Ácido gama-Aminobutírico/economia , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
Viruses are obligate intracellular parasites that have co-evolved with their hosts to establish an intricate network of protein-protein interactions. Here, we followed a high-throughput yeast two-hybrid screening to identify 378 novel protein-protein interactions between turnip mosaic virus (TuMV) and its natural host Arabidopsis thaliana. We identified the RNA-dependent RNA polymerase NIb as the viral protein with the largest number of contacts, including key salicylic acid-dependent transcription regulators. We verified a subset of 25 interactions in planta by bimolecular fluorescence complementation assays. We then constructed and analyzed a network comprising 399 TuMV-A. thaliana interactions together with intravirus and intrahost connections. In particular, we found that the host proteins targeted by TuMV are enriched in different aspects of plant responses to infections, are more connected and have an increased capacity to spread information throughout the cell proteome, display higher expression levels, and have been subject to stronger purifying selection than expected by chance. The proviral or antiviral role of ten host proteins was validated by characterizing the infection dynamics in the corresponding mutant plants, supporting a proviral role for the transcriptional regulator TGA1. Comparison with similar studies with animal viruses, highlights shared fundamental features in their mode of action.
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Arabidopsis , Potyvirus , Arabidopsis/genética , Interações Hospedeiro-Patógeno/genética , Potyvirus/genética , ProteomaRESUMO
OBJECTIVE: To elucidate the consequences of broadening DSM-IV criteria for generalized anxiety disorder (GAD), we examined prospectively the evolution of GAD symptoms in two groups of patients; one group diagnosed according to DSM-IV criteria and the other, according to broader criteria. METHOD: Multicentre, prospective and observational study conducted on outpatient psychiatric clinics. Patients were selected from October 2007 to January 2009 and diagnosed with GAD according to DSM-IV criteria (DSM-IV group) or broader criteria. Broader criteria were considered 1-month of excessive or non-excessive worry and only 2 of the associated symptoms listed on DSM-IV for GAD diagnosis. Socio-demographic data, medical history and functional outcome measures were collected three times during a 6-month period. RESULTS: 3,549 patients were systematically recruited; 1,815 patients in DSM-IV group (DG) and 1,264 in broad group (BG); 453 patients did not fulfil inclusion criteria and were excluded. Most patients (87.9% in DG, 82.0% in BG) were currently following pharmacological therapies (mainly benzodiazepines) to manage their anxiety symptoms. The changes observed during the study were: 49.0% and 58.0%, respectively of patients without anxiety symptoms as per HAM-A scale at the 6 month visit (p=0.261) and 59.7% and 67.7%, respectively (p=0.103) of responder rates (> 50% reduction of baseline scoring). CONCLUSION: Broadening of GAD criteria does not seem to affect psychiatric care results in subjects with GAD, is able to identify the core symptoms of the disease according to the DSM-IV criteria and could lead to an earlier diagnosis.
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BACKGROUND: Lung ultrasound (LUS) and procalcitonin (PCT) are independently used to improve accuracy when diagnosing lung infections. The aim of the study was to evaluate the accuracy of a new algorithm combining LUS and PCT for the diagnosis of bacterial pneumonia. METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children <18 years old with suspected pneumonia admitted to pediatric intensive care unit were included, and randomized into experimental group (EG) or control group (CG) if LUS or chest X-Ray (CXR) were done as the first pulmonary image, respectively. PCT was determined. In patients with bacterial pneumonia, sensitivity, specificity, and predictive values of LUS, CXR, and of both combined with PCT were analyzed and compared. Concordance between the final diagnosis and the diagnosis concluded through the imaging test was assessed. RESULTS: A total of 194 children, with a median age of 134 (interquartile range [IQR]: 39-554) days, were enrolled, 96 randomized into the EG and 98 into the CG. Bacterial pneumonia was diagnosed in 97 patients. Sensitivity and specificity for bacterial pneumonia diagnosis were 78% (95% confidence interval [CI]: 70-85) and 98% (95% CI: 93-99) for LUS, 85% (95% CI: 78-90) and 53% (95% CI: 43-62) for CXR, 90% (95% CI: 83-94) and 85% (95% CI: 76-91) when combining LUS and PCT, and 95% (95% CI: 90-98) and 41% (95% CI: 31-52) when combining CXR and PCT. The positive predictive value for LUS and PCT was 88% (95% C:I 79%-93%) versus 68% (95% CI: 60-75) for CXR and PCT. The concordance between the final diagnosis and LUS had a kappa value of 0.69 (95% CI: 0.62-0.75) versus 0.34 (95% CI: 0.21-0.45) for CXR, (p < 0.001). CONCLUSIONS: The combination of LUS and PCT presented a better accuracy for bacterial pneumonia diagnosis than combining CXR and PCT. Therefore, its implementation could be a reliable tool for pneumonia diagnosis in critically ill children.
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Pneumonia Bacteriana , Pneumonia , Adolescente , Algoritmos , Criança , Estado Terminal , Humanos , Pulmão/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Pneumonia Bacteriana/diagnóstico por imagem , Pró-Calcitonina , Estudos Prospectivos , Ultrassonografia/métodosRESUMO
It is assumed that host genetic variability for susceptibility to infection conditions virus evolution. Differences in host susceptibility can drive a virus to diversify into strains that track different defense alleles (e.g. antigenic diversity) or to infect only the most susceptible genotypes. Here, we have studied how variability in host defenses determines the evolutionary fate of a plant RNA virus. We performed evolution experiments with Turnip mosaic potyvirus in Arabidopsis thaliana mutants that had disruptions in infection-response signaling pathways or in genes whose products are essential for potyvirus infection. Plant genotypes were classified into five phenogroups according to their response to infection. We found that evolution proceeded faster in more restrictive hosts than in more permissive ones. Most of the phenotypic differences shown by the ancestral virus across host genotypes were removed after evolution, suggesting the combined action of selection and chance. When all evolved viral lineages were tested in all plant genotypes used in the experiments, we found compelling evidences that the most restrictive plant genotypes selected for more generalist viruses, while more permissive genotypes selected for more specialist viruses. Sequencing the genomes of the evolved viral lineages, we found that selection targeted the multifunctional genome-linked protein VPg in most host genotypes. Overall, this work illustrates how different host defenses modulate the rates and extent of virus evolution.
RESUMO
The attempts to clarify the origin of eating disorders (ED) have not been completely successful and their etiopathogenesis remains unknown. Current research shows an activation of the immune response in neuropsychiatric diseases, including ED. We aimed to investigate immune response parameters in patients with ED and to identify psychological factors influencing the inflammatory response. The relationship between inflammation markers and impulsivity and affective symptomatology was explored as well. Thirty-four adult female patients with current diagnosis of ED, none of them under psychopharmacological treatment (excluding benzodiazepines), were included in this study. Patients were compared with a healthy control group of fifteen adult females. The levels of inflammatory markers and indicators of oxidative/nitrosative stress were evaluated in plasma and/or in peripheral blood mononuclear cells (PBMCs). Subjects were assessed by means of different ED evaluation tools. Additionally, the Barratt Impulsiveness Scale, the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were also employed. Patients with ED shown increased plasma levels of the pro-inflammatory nuclear factor kappa B (NFκB) and the cytokine tumor necrosis factor-alpha (TNF-α), among other factors and an increment in the oxidative/nitrosative stress as well as increased glucocorticoid receptor (GR) expression levels in their PBMCs. Moreover, the inflammatory prostaglandin E2 (PGE2) correlated with impulsiveness and the anti-inflammatory prostaglandin J2 (15d-PGJ2) correlated with depressive symptomatology. Our results point towards a relationship between the immune response and impulsiveness and between the immune response and depressive symptomatology in female adult patients with ED.