RESUMO
OBJECTIVE: Psychopathic traits are associated with abnormalities in fear processing. While traditional theories focus on a lack of fear, Hosker-Field et al. (2016) provided a new perspective. They suggested that individuals with elevated psychopathic traits may experience threatening situations with appreciation or positivity, resulting in reduced negative fear responses and heightened positive responses (fear enjoyment hypothesis, FEH). METHOD: Our study aimed to refine Hosker-Field et al.'s (2016) study design, addressing methodological limitations and improving the inconsistent operationalization of fear experience in the literature. In an online sample of 353 participants from the general population, we examined the relationship between the FEH and relevant psychopathic traits, specifically those derived from the PCL-R framework (i.e., SRP 4 Factor 1), and from a more trait-based approach to psychopathy with assumed links to fearlessness (i.e., TriPM Boldness). RESULTS: By employing linear mixed effect models, we extended Hosker-Field et al.'s correlational analysis and provided further evidence for the FEH, particularly in relation to psychopathic traits measured using the PCL-R framework. The results regarding Boldness, however, are somewhat inconclusive. CONCLUSION: The present study enhances existing research on fear deficits in psychopathy by assessing the subjective experience of individuals facing threat.
Assuntos
Medo , Felicidade , Humanos , Medo/fisiologia , Transtorno da Personalidade Antissocial , PrazerRESUMO
Epilepsy is a common neurological disorder which affects 50 million people worldwide. Patients with epilepsy may present cognitive deficits and psychological impairment. Currently, 30% of patients fail to respond to any available antiseizure drug, and a significant number of patients do not well tolerate the offered treatments. Then, it is necessary to find out alternatives for controlling epileptic seizures. Studies have shown that despite its neuroprotective effects, resveratrol shows poor anticonvulsant properties. Resveratrol analog, piceatannol, possesses higher biological activity than resveratrol and could be an alternative to control seizure. Thus, the present study investigated the effects of resveratrol and piceatannol in pentylenetetrazole-induced seizures in adult zebrafish (Danio rerio). Only the experimental positive control (diazepam) showed anticonvulsant effect in this study. In addition, no behavioral changes were observed 24 h after seizure occurrence. Finally, the expression of genes related to neuronal activity (c-fos), neurogenesis (p70S6Ka and p70S6Kb), inflammatory response (interleukin 1ß), and cell apoptosis (caspase-3) did not change by pentylenetetrazole-induced seizures. Therefore, we failed to observe any anticonvulsant and neuroprotective potential of resveratrol and piceatannol in adult zebrafish. However, resveratrol and piceatannol benefits in epilepsy are not discharged, and more studies are necessary.
Assuntos
Epilepsia , Fármacos Neuroprotetores , Animais , Anticonvulsivantes/efeitos adversos , Caspase 3 , Diazepam/uso terapêutico , Epilepsia/tratamento farmacológico , Interleucina-1beta , Fármacos Neuroprotetores/efeitos adversos , Pentilenotetrazol/toxicidade , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Estilbenos , Peixe-ZebraRESUMO
INTRODUCTION: Assessing vaccine serologic status presents opportunities to provide live vaccinations to kidney transplant candidates (KTC). This is especially important given the increased risk of infection while taking lifelong immunosuppression following transplant and the inability to routinely provide live vaccines to patients on immunosuppressive medications. In March 2019, the American Society of Transplantation Infectious Disease Community of Practice (AST-IDCOP) released updated guidelines for vaccination of KTC, which emphasize pretransplant viral serology screening and live vaccine administration prior to transplant. PRIMARY ENDPOINT: The primary endpoint of this study was to determine adherence to AST-IDCOP guidelines for live measles, mumps, and rubella (MMR) and VZV vaccination prior to transplant in KTC non-immune by serology. METHODS: This retrospective, descriptive study examined serologic status and rates of live vaccination in 672 patients listed for kidney transplant at our center between July 2014 and July 2019. Secondary endpoints included subgroup analysis of adherence to full AST-IDCOP vaccination recommendations and validation of CDC presumed immunity definitions for measles and VZV. RESULTS: Seventeen patients (2.7%) were nonimmune by serology for VZV, while 182 (27.1%) were nonimmune by serology to MMR. In a subgroup analysis of the seronegative KTC, none received VZV vaccination, and 6% received MMR vaccination prior to transplant or last follow-up. CONCLUSIONS: Overall, a large portion of KTC had immunity gaps that were not resolved before transplantation. These findings are limited due to the retrospective, single-center nature of this study and should be confirmed with larger, prospective assessments of serologic status and vaccine administration.
Assuntos
Doenças Transmissíveis , Transplante de Rim , Vacinação , Humanos , Anticorpos Antivirais , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Rubéola (Sarampo Alemão)/prevenção & controle , Vacinação/estatística & dados numéricos , Infecção pelo Vírus da Varicela-Zoster/prevenção & controle , Vacina contra Herpes ZosterRESUMO
Unspecific peroxygenases have attracted interest due to their ability to catalyze the oxygenation of various types of C-H bonds using only hydrogen peroxide as a cosubstrate. Due to the instability of these enzymes at even low hydrogen peroxide concentrations, careful fed-batch addition of the cosubstrate or ideally in situ production is required. While various approaches for hydrogen peroxide addition have been qualitatively assessed, only limited kinetic data concerning enzyme inactivation and peroxide accumulation has been reported so far. To obtain quantitative insights into the kinetics of such a process, a detailed data set for a peroxygenase-catalyzed benzylic hydroxylation coupled with electrochemical hydrogen peroxide production is presented. Based on this data set, we set out to model such an electroenzymatic process. For this, initial velocity data for the benzylic hydroxylation is collected and an extended Ping-Pong-Bi-Bi type rate equation is established, which sufficiently describes the enzyme kinetic. Moreover, we propose an empirical inactivation term based on the collected data set. Finally, we show that the full model does not only describe the process with sufficient accuracy, but can also be used predictively to control hydrogen peroxide feeding rates To limit the concentration of this critical cosubstrate in the system.
Assuntos
Agrocybe/enzimologia , Técnicas Eletroquímicas , Proteínas Fúngicas/química , Oxigenases de Função Mista/química , Modelos Químicos , CatáliseRESUMO
Epilepsy affects 50 million people around the world, and the patients experience cognitive, psychological and social consequences. Despite the considerable quantity of antiepileptic drugs available, 30% of patients still suffer in seizure. Therefore, the advance in therapeutic alternatives is mandatory. Resveratrol has been attracting the attention of many researchers because of its pharmacological potential. However, despite its neuroprotective and anti-epileptic effects, clinical resveratrol use is impaired by its low bioavailability. Here, we applied the supercritical fluid micronization technology (SEDS) to overcome this deficit, and investigated the anticonvulsant potential of micronized resveratrol in a PTZ-induced seizure model in adult zebrafish (Danio rerio). SEDS permits obtaining significantly reduced particle size with a fine size distribution in comparison with the starting material. It can improve the pharmacotherapeutic efficacy. Our data showed that micronized resveratrol decreased the occurrence of the tonic-clonic seizure stage and slowed the development of the seizures in a similar manner of diazepam. Non-processed resveratrol was not able to protect the animals. Furthermore, diazepam decreased the locomotion and exploratory behavior. Differently from diazepam, the micronized resveratrol did not induce behavioral adverse events. In addition, our data showed that the PTZ-induced seizures increased the c-fos transcript levels following the neural excitability. However, the increase in c-fos levels was prevented by micronized resveratrol. In conclusion, our results demonstrate that the micronized resveratrol shows anticonvulsant effect, like the classical antiepileptic drug diazepam in a PTZ-induced seizure model. Excitingly, different from diazepam, micronized resveratrol did not provoke behavioral adverse events.
Assuntos
Anticonvulsivantes/uso terapêutico , Resveratrol/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/química , Diazepam/uso terapêutico , Feminino , Locomoção/efeitos dos fármacos , Masculino , Tamanho da Partícula , Pentilenotetrazol , Proteínas Proto-Oncogênicas c-fos/metabolismo , Resveratrol/química , Convulsões/induzido quimicamente , Peixe-ZebraRESUMO
Epilepsy affects around 50 million people worldwide, and an important number of patients (30%) fail to respond to any available antiepileptic drug. Previous studies have shown that luteolin presents a promising potential as an anticonvulsant. On the other hand, different studies showed that luteolin does not promote anticonvulsant effects. Therefore, there is a lack of consensus about the use of luteolin for seizure control. Luteolin low bioavailability could be a limiting factor to obtain better results. Attractively, micronization technology has been applied to improve flavonoids bioavailability. Thus, the present study aimed to investigate the effects of luteolin on its raw form and micronized luteolin in a PTZ-induced seizure model in adult zebrafish (Danio rerio). Our results demonstrate that luteolin and micronized luteolin did not block PTZ-induced seizures in adult zebrafish. Also, luteolin and micronized luteolin did not provoke behavioral changes. Finally, our results show that 24 h after seizure occurrence, no changes were detected for p70S6Kb, interleukin 1ß, and caspase-3 transcript levels. Altogether, we failed to observe an anticonvulsant potential of luteolin in adult zebrafish, even in its micronized form. However, we recommend new studies to investigate luteolin benefits in epilepsy.
Assuntos
Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/síntese química , Luteolina/administração & dosagem , Luteolina/síntese química , Convulsões/tratamento farmacológico , Fatores Etários , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Tamanho da Partícula , Pentilenotetrazol/toxicidade , Convulsões/induzido quimicamente , Peixe-ZebraRESUMO
Psychopathic traits have been linked to anomalies in experiencing fear and anxiety. It remains unclear, however, to what extent fear and anxiety levels are useful parameters to effectively distinguish between subtypes of psychopathy. Therefore, we aimed to elucidate whether different psychopathic phenotypes (primary and secondary psychopathy) can be delineated based on fear/anxiety levels. To investigate associations between psychopathic traits and conscious experiences of fear and/or anxiety a systematic qualitative review of studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventeen studies were included in the review. We found some evidence for attenuated fear/anxiety levels in primary psychopathy. In secondary psychopathy, the experience of fear/anxiety seemed rather intact. Moreover, primary psychopathy might be associated with a more positive appraisal of the conscious feeling of fear. We reason that consciously experienced fear and anxiety are distinctly related to primary and secondary psychopathy. Due to a lack of consistent and comprehensive operationalizations of fear and anxiety, however, conclusions about their potential to differentiate psychopathic subtypes should be drawn with caution.
Assuntos
Ansiedade , Medo , Ansiedade/diagnóstico , HumanosRESUMO
The metabolic flexibility of the opportunistic fungal pathogen Candida albicans is important for colonisation and infection of different host niches. Complex regulatory networks, in which protein kinases play central roles, link metabolism and other virulence-associated traits, such as filamentous growth and stress resistance, and thereby control commensalism and pathogenicity. By screening a protein kinase deletion mutant library that was generated in the present work using an improved SAT1 flipper cassette, we found that the previously uncharacterised kinase Sak1 is a key upstream activator of the protein kinase Snf1, a highly conserved regulator of nutrient stress responses that is essential for viability in C. albicans. The sak1Δ mutants failed to grow on many alternative carbon sources and were hypersensitive to cell wall/membrane stress. These phenotypes were mirrored in mutants lacking other subunits of the SNF1 complex and partially compensated by a hyperactive form of Snf1. Transcriptional profiling of sak1Δ mutants showed that Sak1 ensures basal expression of glyoxylate cycle and gluconeogenesis genes even in glucose-rich media and thereby contributes to the metabolic plasticity of C. albicans. In a mouse model of gastrointestinal colonisation, sak1Δ mutants were rapidly outcompeted by wild-type cells, demonstrating that Sak1 is essential for the in vivo fitness of C. albicans.
Assuntos
Candida albicans/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Candida albicans/genética , Carbono/metabolismo , Feminino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Biblioteca Gênica , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais , VirulênciaRESUMO
The pathogenic yeast Candida albicans can develop resistance to azole antifungal drugs by overexpressing ERG11, which encodes the drug target, or the multidrug efflux pumps MDR1 and CDR1/CDR2. The constitutive upregulation of these genes is usually caused by gain-of-function mutations in the zinc cluster transcription factors Upc2, Mrr1, and Tac1, respectively. These transcription factors are also required for the induction of their target genes in drug-susceptible strains in the presence of specific stimuli. By swapping the DNA-binding domains of Mrr1, Tac1, and Upc2 we investigated if the hybrid transcription factors could activate their new target genes in response to the same signals. When Tac1 was targeted to the MDR1 and ERG11 promoters, the expression of these genes became inducible by fluphenazine. Similarly, MDR1 and CDR2 were strongly upregulated by fluconazole when Upc2 was fused to the DNA-binding domains of Mrr1 and Tac1, respectively. In contrast, Mrr1 was unable to promote gene expression in response to benomyl when it was targeted to the CDR2 and ERG11 promoters instead of the MDR1 promoter. These results suggest that Tac1 and Upc2 themselves are activated by the inducers fluphenazine and fluconazole, respectively, whereas benomyl does not activate Mrr1 itself but a coregulatory factor that is present at the promoters of Mrr1 target genes. Strains in which the expression levels of Mrr1 and Tac1 target genes were controlled by Upc2 exhibited increased fluconazole resistance, demonstrating that the ability to efficiently upregulate the expression of efflux pumps in the presence of the drug results in enhanced intrinsic fluconazole resistance.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Fatores de Transcrição/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Sítios de Ligação , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/farmacologia , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Regiões Promotoras Genéticas , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Transcrição/metabolismo , Zinco/metabolismoRESUMO
BACKGROUND: Patients with chronic kidney disease (CKD) exhibit a high prevalence of neuropsychiatric alterations, including depression and behavioural changes. CKD is also associated with decreased physical activity not fully explained by co-morbidities. In patients without CKD, the brain-derived neurotropic factor (BDNF) as well as the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) had been suspected to be involved in major depression. The aim of our study was to examine the role of ADMA and BDNF in the behaviour of haemodialysis patients (CKD5D) as well as in a rat model of 5/6 nephrectomy and chronic ADMA infusion alone. METHODS: Eleven (5F/6M) CKD5D patients underwent Beck Depression Inventory (BDI) testing along with analysis of ADMA and BDNF. Male Sprague-Dawley rats were randomly assigned to four groups: (i) saline infusion; (ii) ADMA (250 µg/kg/day) infusion via osmotic mini pumps; (iii) 5/6 nephrectomy; (iv) untreated controls. After 28 days, the animals underwent behavioural tests measuring anxiety, locomotion and investigative behaviour. Animals were sacrificed, blood samples were drawn and analysed and hippocampal immunohistology for BDNF was performed. RESULTS: In CKD5D patients, decreased BDNF levels correlated with higher scores of depression (Pearson r = -0.8156, P = 0.002). ADMA infusion led to a significant decrease of BDNF while the decrease of BDNF in 5/6 nephrectomy was not significant. However, an attenuated hippocampal BDNF expression could be detected in 5/6 nephrecomized animals. Decreased spontaneous locomotor activity was shown in ADMA-infused rats [15.9 (13.5-26.1) lines crossed/min] and 5/6 nephrectomy [14.6 (6.1-20.2) lines crossed/min] when compared with controls [32.5 (15.3-42.4) lines crossed/min]. Anxiety-like behaviour tested by hole investigation time was significantly more pronounced in 5/6 nephrectomy [24 (6-44) s] when compared with ADMA infusion [64 (28-93) s] and controls [33 (26-65) s]. CONCLUSIONS: Progressive renal failure in rats is accompanied by a marked increase of ADMA and a decrease in BDNF. 5/6 nephrectomy leads to significantly decreased exploratory behaviour and locomotion. Both behaviours could be reproduced by ADMA infusion alone. Indicators of anxiety were more pronounced in ADMA-infused animals when compared with 5/6 nephrectomized rats. Furthermore, an inverse relationship of BDNF and BDI in 11 CKD5D patients was shown.
Assuntos
Arginina/análogos & derivados , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Depressão/sangue , Transtorno Depressivo Maior/sangue , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/metabolismo , Insuficiência Renal Crônica/complicações , Animais , Arginina/fisiologia , Estudos de Coortes , Estudos Transversais , Depressão/etiologia , Depressão/psicologia , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/psicologia , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Nefrectomia , Comportamento Problema , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/psicologiaRESUMO
BACKGROUND: Cognitive function declines in parallel to the decrease in glomerular filtration rate, best epitomized by the markedly reduced cerebral performance in patients undergoing maintenance haemodialysis [chronic kidney disease stage 5 dialysis (CKD5D)]. Aside from structural permanent damage, there seems to be a reversible part of low cognitive performance. The potential effect of a single dialysis session on cognitive function remains still elusive. The aim of the study was to assess cognitive function using a widespread test battery and avoiding excluding effects of circadian variations. METHODS: Twenty-eight medically stable CKD5D patients (age: 54.9 ± 13.2 years, dialysis vintage: 46.2 ± 51.0 month) at two tertiary care centres with outpatient dialysis units were enrolled. Cognitive testing was always performed twice within 24 h, 1 h prior to haemodialysis (T1pre-dialysis) as well as 19 h after the end of dialysis (T2post-dialysis) including assessment of memory, attention and concentration, executive functioning, word fluency and psychomotor speed by using a well-validated neuropsychological test battery. Patients were randomized into two groups. One group was examined before (T1pre-dialysis) and after (T2post-dialysis) Dialysis Session 1. The other group was first examined the day after Dialysis Session 1 (T2post-dialysis) and then before Dialysis Session 2 (T1pre-dialysis) in order to exclude potential learning effects. Twenty age-matched subjects with normal excretory renal function were used for comparison. RESULTS: Neuropsychological testing found that the CKD5D performed significantly worse on measures of alertness, attention, working memory, logical and visual memory, word fluency and executive functions compared with non-CKD subjects. No differences in short-term memory, selective attention, as well as problem-solving and planning were found between CKD5D patients and non-CKD subjects. A single haemodialysis session led to a significant improvement in logical (Rivermead Behaviour Memory Test story: P < 0.001) and visual memories [Rey-Osterrieth Complex Figure Test (RCFT) memory quotient: P < 0.001], psychomotor speed [Trail Making Test (TMT) B: P = 0.020], activity planning (executive functions) (RCFT copy/points deduction: P < 0.001) and concentration (TMT A: P < 0.001). CONCLUSION: Our data demonstrate improvements in memory functions, executive functions and psychomotor abilities after a single dialysis session, pointing to a reversible component of low cognitive performance in CKD5D.
Assuntos
Transtornos Cognitivos/fisiopatologia , Cognição/fisiologia , Diálise Renal , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Insuficiência Renal Crônica/classificaçãoRESUMO
Two decades ago, the introduction of functional near-infrared spectroscopy (fNIRS) into the field of neuroscience created new opportunities for investigating neural processes within the human cerebral cortex. Since then, fNIRS has been increasingly used to conduct functional activation studies in different neuropsychiatric disorders, most prominently schizophrenic illnesses, affective disorders and developmental syndromes, such as attention-deficit/hyperactivity disorder as well as normal and pathological aging. This review article provides a comprehensive overview of state of the art fNIRS research in psychiatry covering a wide range of applications, including studies on the phenomenological characterization of psychiatric disorders, descriptions of life-time developmental aspects, treatment effects, and genetic influences on neuroimaging data. Finally, methodological shortcomings as well as current research perspectives and promising future applications of fNIRS in psychiatry are discussed. We conclude that fNIRS is a valid addition to the range of neuroscientific methods available to assess neural mechanisms underlying neuropsychiatric disorders. Future research should particularly focus on expanding the presently used activation paradigms and cortical regions of interest, while additionally fostering technical and methodological advances particularly concerning the identification and removal of extracranial influences on fNIRS data as well as systematic artifact correction. Eventually, fNIRS might be a useful tool in practical psychiatric settings involving both diagnostics and the complementary treatment of psychological disorders using, for example, neurofeedback applications.
Assuntos
Neuroimagem Funcional/métodos , Transtornos Mentais/patologia , Transtornos Mentais/psicologia , Psiquiatria/instrumentação , Psiquiatria/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Encéfalo/fisiologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Humanos , Transtornos Mentais/terapia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/patologia , Transtornos Psicóticos/terapiaRESUMO
The ability to recognize and adequately interpret emotional states in others plays a fundamental role in regulating social interaction. Body language presents an essential element of nonverbal communication which is often perceived prior to mimic expression. However, the neural networks that underlie the processing of emotionally expressive body movement and body posture are poorly understood. 33 healthy subjects have been investigated using the optically based imaging method functional near-infrared spectroscopy (fNIRS) during the performance of a newly developed emotion discrimination paradigm consisting of faceless avatars expressing fearful, angry, sad, happy or neutral gait patterns. Participants were instructed to judge (a) the presented emotional state (emotion task) and (b) the observed walking speed of the respective avatar (speed task). We measured increases in cortical oxygenated haemoglobin (O2HB) in response to visual stimulation during emotion discrimination. These O2HB concentration changes were enhanced for negative emotions in contrast to neutral gait sequences in right occipito-temporal and left temporal and temporo-parietal brain regions. Moreover, fearful and angry bodies elicited higher activation increases during the emotion task compared to the speed task. Haemodynamic responses were correlated with a number of behavioural measures, whereby a positive relationship between emotion regulation strategy preference and O2HB concentration increases after sad walks was mediated by the ability to accurately categorize sad walks. Our results support the idea of a distributed brain network involved in the recognition of bodily emotion expression that comprises visual association areas as well as body/movement perception specific cortical regions that are also sensitive to emotion. This network is activated less when the emotion is not intentionally processed (i.e. during the speed task). Furthermore, activity of this perceptive network is, mediated by the ability to correctly recognize emotions, indirectly connected to active emotion regulation processes. We conclude that a full understanding of emotion perception and its neural substrate requires the investigation of dynamic representations and means of expression other than the face.
Assuntos
Emoções/fisiologia , Neuroimagem Funcional/métodos , Marcha/fisiologia , Percepção Social , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Caminhada/psicologia , Adolescente , Adulto , Algoritmos , Análise de Variância , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Circulação Cerebrovascular/fisiologia , Interpretação Estatística de Dados , Discriminação Psicológica , Feminino , Hemodinâmica/fisiologia , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Adulto JovemRESUMO
The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain-of-function mutations in the transcription factors Mrr1, Tac1 and Upc2, which result in constitutive overexpression of multidrug efflux pumps and ergosterol biosynthesis genes respectively. It is not known how the permanently changed gene expression program in resistant strains affects their fitness in the absence of drug selection pressure. We have systematically investigated the effects of activating mutations in Mrr1, Tac1 and Upc2, individually and in all possible combinations, on the degree of fluconazole resistance and on the fitness of C. albicans in an isogenic strain background. All combinations of different resistance mechanisms resulted in a stepwise increase in drug resistance, culminating in 500-fold increased fluconazole resistance in strains possessing mutations in the three transcription factors and an additional resistance mutation in the drug target enzyme Erg11. The acquisition of resistance mutations was associated with reduced fitness under non-selective conditions in vitro as well as in vivo during colonization of a mammalian host. Therefore, without compensatory mutations, the inability to appropriately regulate gene expression results in a loss of competitive fitness of drug-resistant C. albicans strains.
Assuntos
Antifúngicos/farmacologia , Candida albicans/genética , Farmacorresistência Fúngica , Fluconazol/farmacologia , Proteínas Fúngicas/genética , Mutação , Fatores de Transcrição/genética , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Candidíase/microbiologia , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores de Transcrição/metabolismoRESUMO
Atypical antipsychotic agents are a frequently and effectively used treatment in schizophrenia and psychotic disorders. Other than conventional antipsychotics, which mainly exert their pharmacological effect in subcortical dopaminergic systems, atypical antipsychotics additionally affect partly serotonergically innervated structures within prefrontal areas, such as the anterior cingulate cortex (ACC). However, only few controlled, randomized studies have so far investigated direct and indirect effects of atypical antipsychotics on the ACC and, up until now, no clinical investigation has exclusively addressed the specific effects of quetiapine on ACC function. The present study assessed ACC function in 18 quetiapine-medicated patients and 13 flupentixol-treated patients suffering from schizophrenia by means of the error-related negativity (ERN), a neurophysiological marker of ACC function, in a pre-post design. Between-group comparisons revealed different effects of quetiapine and flupentixol on ACC function despite similar improvement in psychopathology, cognitive performance and quality of life. Whereas atypical treatment was associated with an increase in amplitudes over time, there were prolonged ERN peak latencies in patients treated with the typical agent. Moreover, treatment effects depended on baseline prefrontal cortex function in both groups. We conclude that both flupentixol and quetiapine improve prefrontal function especially in patients with weak initial ACC function which might be due to their shared affinity for serotonin receptors in frontal brain regions. However, since this affinity is more pronounced for quetiapine, patients treated with quetiapine seemed to profit more evidently concerning their prefrontal cortex function compared to patients of the flupentixol group, who exhibited a compensatory prolongation of processes.
Assuntos
Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Potenciais Evocados/efeitos dos fármacos , Flupentixol/uso terapêutico , Giro do Cíngulo/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Cognição/efeitos dos fármacos , Eletroencefalografia , Feminino , Alemanha , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiopatologia , Estudos Prospectivos , Qualidade de Vida , Fumarato de Quetiapina , Tempo de Reação , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Management of a chronic medical condition is a complex process and requires coordinated action between healthcare providers and patients. This process is further complicated by the fact that an increasing number of patients suffer from multiple chronic conditions. Self-management involves active participation of the patients in the everyday care of the symptoms of their illness(es) and medical treatments, as well as maintaining general health and prevention of progression of medical conditions. Managing the psychosocial consequences of illness is also an important component of self-management. Data have demonstrated that enhancing self-management improves quality of life, coping, symptom management, disability, and reduces healthcare expenditures and service utilization. To foster self-management, potential barriers to implementation as well as facilitators and supports for this approach must be acknowledged. In this article, we review various aspects of self-management in chronic illness, focusing on chronic kidney disease. Better understanding of these concepts will facilitate patient-provider collaboration, improve patient care with increased patient and staff satisfaction, and may ultimately result in better clinical outcomes and enhanced quality of life for both the patients and their families.
Assuntos
Falência Renal Crônica/terapia , Autocuidado , Adaptação Psicológica , Doença Crônica/terapia , Comportamento Cooperativo , Tomada de Decisões , Gerenciamento Clínico , HumanosRESUMO
Objective: To evaluate the effect of parenteral amino acid application in hospitalized hypoalbuminemic dogs. Materials and methods: Medical records of client-owned hypoalbuminemic dogs (albumin ≤ 25 g/L) were analyzed. Dogs receiving amino acids for only 1-2 days, receiving transfusions or surgery, or <6 months of age were excluded. Dogs were grouped as those receiving intravenous amino acids (AA, 80 dogs) over 3 days and longer, and those without additional amino acid treatment (CON, 78 dogs). Duration of hospitalization, albumin, and total protein concentrations were compared between groups by Mann-Whitney U test. Course of albumin and total protein concentration was evaluated by Friedman test and Dunn's multiple comparison test. Significance was set to p ≤ 0.05. Results: Dogs in group AA received 10% amino acid solution intravenously over median 4 days (3-11 days). No significant differences regarding survival and adverse effects were observed between groups. Dogs of group AA had significantly longer duration of hospitalization (median 8 days; 3-33 days) compared to group CON dogs (median 6 days, 3-24 days; p < 0.001). Initial albumin concentration was lower in group AA compared to CON (p < 0.001). This difference was no longer present on day 2 (p = 0.134). Conclusions and clinical relevance: Intravenous application of 10% amino acid solution in hypoalbuminemic dogs can improve albumin concentration after 2 days, but does not influence outcome.
RESUMO
The Trifurcated Model of Narcissism (TriMN) has received growing attention in the scientific study of narcissistic traits, as it provides a clear and clinically useful distinction of the three core elements of narcissistic personalities: agentic extraversion (AE), narcissistic antagonism (NA), and narcissistic neuroticism (NN). So far, the Five-Factor Narcissism Inventory (FFNI) and its abbreviations-for example, the recently introduced brief form (FFNI-BF)-represent the only measures that allow for a direct and simultaneous assessment of these traits. Distinct parts of the TriMN have also been measured by other narcissism scales, however, including the Narcissistic Admiration and Rivalry Questionnaire (NARQ) or the Hypersensitive Narcissism Scale (HSNS). It remains unclear to what extent trait estimates provided by these alternative measures overlap and under which circumstances they can be used interchangeably. Here, we present a model-driven combination of NARQ and HSNS items that may serve as a valuable, economic tool to assess the three narcissism dimensions. In two studies (accumulated N = 2,266, 1,673 female, 580 male, 13 diverse), we show that the NARQ/HSNS and the FFNI-BF access virtually the same presentations of AE, NA, and NN, whereby the combined NARQ/HSNS outperforms the FFNI-BF in terms of structure, theory-consistent relations among (latent) narcissistic traits, and predictive validity with respect to personality pathology. Our research provides new insights on the assessment of narcissistic traits according to the increasingly popular TriMN and can inform future research on its dimensions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Assuntos
Narcisismo , Personalidade , Humanos , Masculino , Feminino , Transtornos da Personalidade/diagnóstico , Inquéritos e Questionários , NeuroticismoRESUMO
The increase in proinflammatory cytokine expression causes behavioral changes consistent with sickness behavior, and this led to the suggestion that depression might be a psychoneuroimmunological phenomenon. Here, we evaluated the effects of the pretreatment with fluoxetine (10 mg/kg, i.p.) and curcumin (0.5 mg/kg, i.p.) on the immune response elicited by the inoculation of an Aeromonas hydrophila bacterin in zebrafish. Non-pretreated but A. hydrophila-inoculated and sham-inoculated groups of fish served as controls. The social preference, locomotor, exploratory activities, and cerebral expression of il1b, il6, tnfa, and bdnf mRNA were compared among the groups. Behavioral changes characteristic of sickness behavior and a significant increase in the expression of il1b and il6 cytokines were found in fish from the immunostimulated group. The behavioral alterations caused by the inflammatory process were different between males and females, which was coincident with the increased expression of cerebral BDNF. Fluoxetine and curcumin prevented the sickness behavior induced by A. hydrophila and the increased expression of proinflammatory cytokines. Our results point to the potential of zebrafish as a translational model in studies related to neuroinflammation and demonstrate for the first time the effects of fluoxetine and curcumin on zebrafish sickness behavior.
Assuntos
Curcumina , Fluoxetina , Masculino , Animais , Feminino , Fluoxetina/farmacologia , Citocinas/metabolismo , Peixe-Zebra/metabolismo , Curcumina/farmacologia , Fator Neurotrófico Derivado do Encéfalo , Interação Social , Interleucina-6RESUMO
BACKGROUND: One hallmark of uremia is the impairment of neuro-cognitive function. Anecdotal clinical description from the early days of chronic dialysis therapy impressively illustrates the improvement of those functions by chronic hemodialysis treatment. Fortunately, today, uremia is only rarely observed in industrialized countries as many patients seek medical/nephrological attention prior to the occurrence of deadly complications of uremia. CASE PRESENTATION: We report a rare case of severe uremia and describe the day to day improvement in neuro-cognitive function by dialysis using state of the arte test battery--starting at a serum creatinine of 2443 µmol/l. CONCLUSIONS: Especially executive functions, which are assumed to be localized in the frontal cerebral regions, are impaired in severe uremia and improve remarkably with the correction of severe uremia, i.e., initiation of dialysis.