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BACKGROUND: The synthetic antimicrobial peptide, PaDBS1R1, has been reported as a powerful anti-Klebsiella pneumoniae antimicrobial. However, there is only scarce knowledge about whether K. pneumoniae could develop resistance against PaDBS1R1 and which resistance mechanisms could be involved. OBJECTIVES: Identify via label-free shotgun proteomics the K. pneumoniae resistance mechanisms developed against PaDBS1R1. METHODS: An adaptive laboratory evolution experiment was performed to obtain a PaDBS1R1-resistant K. pneumoniae lineage. Antimicrobial susceptibility was determined through microdilution assay. Modifications in protein abundances between the resistant and sensitive lineages were measured via label-free quantitative shotgun proteomics. Enriched Gene Ontology terms and KEGG pathways were identified through over-representation analysis. Data are available via ProteomeXchange with identifier PXD033020. RESULTS: K. pneumoniae ATCC 13883 parental strain challenged with increased subinhibitory PaDBS1R1 concentrations allowed the PaDBS1R1-resistant K. pneumoniae lineage to emerge. Proteome comparisons between PaDBS1R1-resistant K. pneumoniae and PaDBS1R1-sensitive K. pneumoniae under PaDBS1R1-induced stress conditions enabled the identification and quantification of 1702 proteins, out of which 201 were differentially abundant proteins (DAPs). The profiled DAPs comprised 103 up-regulated proteins (adjusted P value < 0.05, fold change ≥ 2) and 98 down-regulated proteins (adjusted P value < 0.05, fold change ≤ 0.5). The enrichment analysis suggests that PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery could be relevant resistance mechanisms against PaDBS1R1. CONCLUSIONS: Based on experimental evolution and a label-free quantitative shotgun proteomic approach, we showed that K. pneumoniae developed resistance against PaDBS1R1, whereas PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery appear to be relevant resistance mechanisms against PaDBS1R1.
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Anti-Infecciosos , Infecções por Klebsiella , Humanos , Antibacterianos/farmacologia , Klebsiella pneumoniae/genética , Peptídeos Antimicrobianos , Proteômica , Lipopolissacarídeos , Anti-Infecciosos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Introduction: Although behavioral therapies can effectively treat skin picking disorder (SPD), there is no standardized treatment for improving SPD and its comorbidities and there is no group intervention option. This trial aimed to adapt the Rothbaum trichotillomania protocol to SPD (Study 1) and test its efficacy for treating SPD and comorbidities in individual and group formats (Study 2). Methods: The adapted protocol was applied to 16 SPD patients, who were allocated to group or individual treatment (Study 1). Afterwards, 54 patients were randomly allocated to treatment in an individual (n=27) or group format (n=27) (Study 2). In both studies, assessments of SPD severity, anxiety, depression, clinical status and skin lesion severity were performed at baseline and the endpoint. Results: The adapted protocol was feasible in both treatment modalities (Study 1) and led to high SPD remission rates (individual 63%; group 52%), with no significant difference between intervention types (p = 0.4) (Study 2). SPD, anxiety, and depression symptoms and objective patient lesion measures improved after treatment. There was large effect size for SPD symptom improvement in both treatment types (Cohen's d: group = 0.88; individual = 1.15) (Study 2). Conclusion: The adapted Rothbaum protocol was effective for SPD remission, comorbidities, and skin lesions, both in individual and group formats. Clinical trial registration: NCT03182478
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Humanos , Tricotilomania , Terapia Cognitivo-Comportamental , Transtornos de Ansiedade , ComorbidadeRESUMO
INTRODUCTION: Although behavioral therapies can effectively treat skin picking disorder (SPD), there is no standardized treatment for improving SPD and its comorbidities and there is no group intervention option. This trial aimed to adapt the Rothbaum trichotillomania protocol to SPD (Study 1) and test its efficacy for treating SPD and comorbidities in individual and group formats (Study 2). METHODS: The adapted protocol was applied to 16 SPD patients, who were allocated to group or individual treatment (Study 1). Afterwards, 54 patients were randomly allocated to treatment in an individual (n=27) or group format (n=27) (Study 2). In both studies, assessments of SPD severity, anxiety, depression, clinical status and skin lesion severity were performed at baseline and the endpoint. RESULTS: The adapted protocol was feasible in both treatment modalities (Study 1) and led to high SPD remission rates (individual 63%; group 52%), with no significant difference between intervention types (p = 0.4) (Study 2). SPD, anxiety, and depression symptoms and objective patient lesion measures improved after treatment. There was large effect size for SPD symptom improvement in both treatment types (Cohen's d: group = 0.88; individual = 1.15) (Study 2). CONCLUSION: The adapted Rothbaum protocol was effective for SPD remission, comorbidities, and skin lesions, both in individual and group formats. CLINICAL TRIAL REGISTRATION: NCT03182478.
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Terapia Cognitivo-Comportamental , Tricotilomania , Transtornos de Ansiedade , Comorbidade , HumanosRESUMO
OBJECTIVE: To describe the initial steps in the development and validation of a new self-reported instrument designed to assess daily rhythms of mood symptoms, namely, the Mood Rhythm Instrument. METHODS: A multidisciplinary group of experts took part in systematic meetings to plan the construction of the instrument. Clarity of items, their relevance to evaluation of mood states, and the consistency of findings in relation to the available evidence on the biological basis of mood disorders were investigated. The internal consistency of the questionnaire was evaluated through Cronbach's alpha. RESULTS: All of the items proposed in a first version were well rated in terms of clarity. The items more frequently rated as "rhythmic" were related to the somatic symptoms of mood. Their peaks in 24 hours were more frequent in the morning. The items associated with affective symptoms of mood were rated as less rhythmic, and their peak in 24 hours occurred more frequently in the afternoon and evening. Males and females behaved more similarly with respect to somatic than behavioral-affective items. The second version of the Mood Rhythm Instrument had a Cronbach's alpha of 0.73. CONCLUSION: The proposed Mood Rhythm Instrument may be able to detect individual rhythms of cognitive and behavioral measures associated with mood states. Validation in larger samples and against objective measures of rhythms, such as actigraphy, is warranted.
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Afeto/fisiologia , Transtornos do Humor/fisiopatologia , Periodicidade , Autorrelato , Inquéritos e Questionários , Adulto , Consenso , Autoavaliação Diagnóstica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Adulto JovemRESUMO
Objective: To describe the initial steps in the development and validation of a new self-reported instrument designed to assess daily rhythms of mood symptoms, namely, the Mood Rhythm Instrument. Methods: A multidisciplinary group of experts took part in systematic meetings to plan the construction of the instrument. Clarity of items, their relevance to evaluation of mood states, and the consistency of findings in relation to the available evidence on the biological basis of mood disorders were investigated. The internal consistency of the questionnaire was evaluated through Cronbach’s alpha. Results: All of the items proposed in a first version were well rated in terms of clarity. The items more frequently rated as “rhythmic” were related to the somatic symptoms of mood. Their peaks in 24 hours were more frequent in the morning. The items associated with affective symptoms of mood were rated as less rhythmic, and their peak in 24 hours occurred more frequently in the afternoon and evening. Males and females behaved more similarly with respect to somatic than behavioral-affective items. The second version of the Mood Rhythm Instrument had a Cronbach’s alpha of 0.73. Conclusion: The proposed Mood Rhythm Instrument may be able to detect individual rhythms of cognitive and behavioral measures associated with mood states. Validation in larger samples and against objective measures of rhythms, such as actigraphy, is warranted.