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1.
J Exp Child Psychol ; 213: 105255, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34388641

RESUMO

Past research documents a bilingual advantage in the domain of executive functions (EFs). However, controversial debates have questioned the robustness of those behavioral differences. The current study aimed to better understand the underlying cognitive prerequisites in bilingual students as compared with monolingual students and focused on two processes: the role of verbal processes, on the one hand, and mental effort during task execution, on the other. The use of self-regulatory speech has been found to be related to performance in tasks requiring EFs. For bilinguals who have grown up with two language systems from an early age, those relations are not fully understood. Furthermore, results from neuroimaging studies have shown that bilinguals might exhibit less mental effort in EF tasks. We investigated both processes in German-speaking monolingual elementary school students (n = 33; Mage = 8.78 years) and German-Russian bilingual elementary school students (n = 34; Mage = 8.88 years) solving a planning task. Results showed that monolinguals were impaired by a verbal secondary task in comparison with a motor control condition, whereas bilinguals performed in both tasks at an equal level, indicating a differential role of self-regulatory speech in both language groups. Analyses of changes in pupil diameter revealed less mental effort during task execution for bilingual children as compared with monolingual children. The current study adds to the existing literature by supplying further evidence for cognitive differences between monolingual and bilingual children.


Assuntos
Multilinguismo , Criança , Cognição , Função Executiva , Humanos , Idioma , Federação Russa
2.
Psychol Res ; 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34932156

RESUMO

Previous studies in adults showed heterogeneous results regarding the associations of personality with intelligence and executive functions (EF). In children, there is a lack of studies investigating the relations between personality and EF. Therefore, the aim of our study was to examine the relations between the Big Five personality traits, EF, and intelligence in a sample of children (Experiment 1) and young adults (Experiment 2). A total of 155 children (Experiment 1, mean age = 9.54 years) and 91 young adults (Experiment 2, mean age = 23.49 years) participated in the two studies. In both studies, participants performed tasks measuring working memory (WM), inhibitory control, cognitive flexibility, and fluid intelligence and completed a personality questionnaire. In Experiment 1, we found a negative relation between neuroticism and intelligence. In Experiment 2, we found a positive relation between conscientiousness and intelligence and a positive relation between conscientiousness and cognitive flexibility. Our results suggest a complex interplay between personality factors, EF, and intelligence both in children as well as in young adults.

3.
Eur J Neurosci ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811827

RESUMO

Using digital technology for neuropsychological assessment is gaining popularity in both clinical and research settings. Digital neuropsychology offers many benefits over the traditional paper-pencil assessments; however, their comparability requires further validation. The aim of this study was to compare a digital, tablet-based Trail Making Test to the standard paper version. In a within-subject design, 108 healthy adults completed both digital and paper Trail Making Test in a counterbalanced order. Each participant also performed other tasks measuring core executive abilities (inhibition, working memory, flexibility) on the tablet. Our findings indicated that the Trail Making Test performance on the two different modalities correlated significantly. Furthermore, correlations of Trail Making Test performance with other cognitive tasks revealed that digital Trail Making Test is comparable to the paper version. However, the modality had a significant effect on Trail Making Test performance, i.e. participants were generally faster on the digital platform. Taken together, our findings suggest that with new normative data, traditional Trail Making Test can be adapted successfully to a digital platform.

4.
Nature ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814158

RESUMO

T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. We conducted a phase I open-label trial, recruiting 36 participants aged 18 to 80 years, who received one single subcutaneous CoVac-1 vaccination. The primary endpoint was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T-cell response was analysed as main secondary endpoint until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study subjects, while systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T-helper 1 CD4+ and CD8+ T cells. CoVac-1-induced interferon-γ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T- cell responses were unaffected by current SARS-CoV-2 variants of concern (VOC). Together, CoVac-1 showed a favourable safety profile and induced broad, potent and VOC-independent T- cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell/antibody deficiency.

5.
Front Psychol ; 12: 684117, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456798

RESUMO

The ability to differentiate between negative emotional states [negative emotion differentiation (NED)] has been conceptualized as a trait that facilitates effective emotion regulation and buffers stress reactivity. In the present research, we investigated the role of NED in within-person processes of daily affect regulation and coping during times of stress (the first COVID-19-related pandemic lockdown in April 2020). Using intensive longitudinal data, we analyzed whether daily stress had an indirect effect on sleep quality through calmness in the evening, and we tested whether NED moderated this within-person indirect effect by buffering the link between daily stress and calmness in the evening. A non-representative community sample (n = 313, 15-82 years old) participated in a 21-day ambulatory assessment with twice-daily surveys. The results of multilevel mediation models showed that higher daily stress was related to within-day change in calmness from morning to evening, resulting in less calmness in the evening within persons. Less calmness in the evening, in turn, was related to poorer nightly sleep quality within persons. As expected, higher NED predicted a less negative within-person link between daily stress and calmness in the evening, thereby attenuating the indirect effect of daily stress on nightly sleep quality through calmness. This effect held when we controlled for mean negative emotions and depression. The results provide support for a diathesis-stress model of NED, and hence, for NED as a protective factor that helps to explain why some individuals remain more resilient during times of stress than others.

6.
Anxiety Stress Coping ; : 1-19, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314262

RESUMO

BACKGROUND: Polyregulation-the concurrent or sequential use of multiple strategies to regulate affect or cope with stressors-is a frequent but understudied phenomenon. OBJECTIVES: We aimed to identify patterns of daily coping and individuals' coping repertoires (i.e., range of coping patterns employed across situations) during a COVID-19 pandemic lockdown. We investigated day-level covariates (appraisals, worrying, mood) of daily coping patterns and person-level covariates (psychopathology, average mood) of coping repertoires. Design: A non-representative community sample (n = 322, 15-82 years old) participated in a 21-day ambulatory assessment study. METHODS: We applied multilevel latent class analysis.. RESULTS: We identified seven daily coping patterns and ten classes of individuals differing in the size of their coping repertoire and their propensity for polyregulation. Daily coping patterns differed in daily perceived controllability and mood (but not in daily worrying or stress). At the person level, individuals with a higher level of average coronavirus-related worrying more frequently engaged in a high degree of polyregulation. The size of individuals' coping repertoire was unrelated to psychopathology and average mood. CONCLUSION: The findings provide insights into the composition of daily coping patterns and individuals' coping repertoires during crisis periods and contribute to a new polyregulation perspective on coping.

7.
ESC Heart Fail ; 8(4): 2502-2512, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34047078

RESUMO

AIMS: The Anxiety-CHF (Anxiety in patients with Chronic Heart Failure) study investigated heart-focused anxiety (HFA, with the dimensions fear, attention, and avoidance of physical activity), general anxiety, depression, and quality of life (QoL) in patients with heart failure. Psychological measures were assessed before and up to 2 years after the implantation of an implantable cardioverter defibrillator (ICD) with or without cardiac resynchronization therapy defibrillator (CRT-D). METHODS AND RESULTS: One hundred thirty-two patients were enrolled in this monocentric prospective study (44/88 CRT-D/ICD, mean age 61 ± 14 years, mean left ventricular ejection fraction 31 ± 9%, and 29% women). Psychological assessment was performed before device implantation as well as after 5, 12, and 24 months. After device implantation, mean total HFA, HFA-fear, HFA-attention, general anxiety, and QoL improved significantly. Depression and HFA-related avoidance of physical activity did not change. CRT-D patients compared with ICD recipients and women compared with men reported worse QoL at baseline. Younger patients (

Assuntos
Desfibriladores Implantáveis , Qualidade de Vida , Idoso , Ansiedade/epidemiologia , Ansiedade/etiologia , Depressão/epidemiologia , Depressão/etiologia , Medo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico , Função Ventricular Esquerda
8.
Mol Ther Oncolytics ; 20: 459-469, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33718594

RESUMO

Oncolytic viruses (OVs) have been shown to induce anti-cancer immunity and enhance cancer immunotherapies, such as immune checkpoint inhibitor therapies. OV therapies can be further improved by arming OVs with immunostimulatory molecules, including various cytokines or chemokines. Here, we have developed a novel adenovirus encoding two immunostimulatory molecules: cluster of differentiation 40 ligand (CD40L) and tumor necrosis factor receptor superfamily member 4 ligand (OX40L). This novel virus, designated VALO-D102, is designed to activate both innate and adaptive immune responses against tumors. CD40L affects the innate side by licensing antigen-presenting cells to drive CD8+ T cell responses, and OX40L increases clonal expansion and survival of CD8+ T cells and formation of a larger pool of memory T cells. VALO-D102 and its murine surrogate VALO-mD901, expressing murine OX40L and CD40L, were used in our previously developed PeptiCRAd cancer vaccine platform. Intratumoral administration of PeptiCRAd significantly increased tumor-specific T cell responses, reduced tumor growth, and induced systemic anti-cancer immunity in two mouse models of melanoma. In addition, PeptiCRAd therapy, in combination with anti-PD-1 immune checkpoint inhibitor therapy, significantly improved tumor growth control as compared to either monotherapy alone.

9.
Nat Immunol ; 22(1): 74-85, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32999467

RESUMO

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.


Assuntos
COVID-19/imunologia , Epitopos de Linfócito T/imunologia , Peptídeos/imunologia , SARS-CoV-2/imunologia , Linfócitos T/imunologia , Vacinas Virais/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Reações Cruzadas/imunologia , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Memória Imunológica/imunologia , SARS-CoV-2/fisiologia , Linfócitos T/metabolismo , Vacinas Virais/administração & dosagem
10.
J Affect Disord ; 276: 380-387, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871668

RESUMO

BACKGROUND: It has been shown that heart-focused anxiety raises the risk of adverse outcomes in patients with heart disease. Yet, there is a lack of studies investigating this association. We aim at identifying predictors of heart-focused anxiety in patients with stable heart failure to facilitate the identification of individuals with increased risk for adverse outcomes. METHODS: We assessed heart-focused anxiety and a set of psychological, demographic/lifestyle, and medical/laboratory variables in a sample of 107 patients with stable chronic heart failure to identify predictors of heart-focused anxiety. RESULTS: Heart-focused anxiety was best predicted by self-reported anxiety and quality of life. Moreover, the personality dimension conscientiousness as well as physical activity, and the laboratory value of renal function, the estimated glomerular filtration rate (eGFR), had predictive validity for heart-focused anxiety. LIMITATIONS: The present findings should be replicated in a longitudinal design with a less selective sample including more women and participants with more divers ethnical backgrounds. CONCLUSION: Heart-focused anxiety is predictable by psychological and lifestyle variables. eGFR, as a laboratory marker for renal function, showed also predictive validity. The awareness of such predictors may help detecting comorbid underlying heart-focused anxiety and thus identify patients with an increased need for psychological care.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Doença Crônica , Feminino , Taxa de Filtração Glomerular , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Humanos
11.
J Exp Child Psychol ; 197: 104866, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32531496

RESUMO

Previous studies demonstrated that dual-task impairments (i.e., dual-task costs) are higher in children than in young adults. However, these studies did not specify the mechanisms explaining higher dual-task costs and did not assess the specific task processes that particularly impair simultaneous task performance in children. We assessed sources of higher dual-task costs in children (n = 32) as compared with young adults (n = 32) by combining auditory (Task 1) and visual (Task 2) sensorimotor tasks into dual tasks of the psychological refractory period (PRP) type. Both tasks are separated by a varying stimulus onset asynchrony (SOA). In Visual Task 2, we manipulated task difficulty at the perceptual stage (contrast manipulation) and response selection stage (mapping manipulation) in order to identify age-related changes in capacity limitations during dual-task performance. The results showed that the response selection manipulation and SOA yielded additive effects in children and young adults, providing evidence for interference at response selection processes in both age groups. In contrast, the perceptual stage manipulation and SOA resulted in underadditive effects in young adults and additive effects in children. This age-related difference is consistent with the assumption that limitations in central processing are present in both age groups, whereas perceptual interference between tasks seems to be larger in children than in young adults.


Assuntos
Atenção , Desempenho Psicomotor , Tempo de Reação , Período Refratário Psicológico , Filtro Sensorial , Análise e Desempenho de Tarefas , Fatores Etários , Percepção Auditiva , Criança , Cognição , Feminino , Humanos , Masculino , Orientação , Período Refratário Psicológico/fisiologia , Percepção Visual , Adulto Jovem
12.
Cognition ; 203: 104329, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32526518

RESUMO

As children become older, they better maintain task-relevant information in preparation of upcoming cognitive demands. This is referred to as proactive control, which is a key component of cognitive control development. However, it is still uncertain whether children engage in proactive control consistently across different contexts and how proactive control relates to academic abilities. This study used two common tasks-the AX Continuous Performance Task (AX-CPT) and the Cued Task-Switching Paradigm (CTS)-to examine whether proactive control engagement in 102 children (age range: 6.91-10.91 years) converges between the two tasks and predicts academic abilities. Proactive control indices modestly correlated between tasks in higher but not lower working-memory children, suggesting that consistency in proactive control engagement across contexts is relatively low during childhood but increases with working memory capacity. Further, working memory (but not verbal speed) predicted proactive control engagement in both tasks. While proactive control as measured by each task predicted math and reading performance, only proactive control measured by CTS additionally predicted reasoning, suggesting that proactive control can be used as a proxy for academic achievements.


Assuntos
Sucesso Acadêmico , Criança , Cognição , Sinais (Psicologia) , Humanos , Memória de Curto Prazo , Testes Neuropsicológicos
13.
Clin Cancer Res ; 26(17): 4503-4510, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540851

RESUMO

PURPOSE: DNA mismatch repair (MMR) deficiency is a hallmark of Lynch syndrome, the most common inherited cancer syndrome. MMR-deficient cancer cells accumulate numerous insertion/deletion mutations at microsatellites. Mutations of coding microsatellites (cMS) lead to the generation of immunogenic frameshift peptide (FSP) neoantigens. As the evolution of MMR-deficient cancers is triggered by mutations inactivating defined cMS-containing tumor suppressor genes, distinct FSP neoantigens are shared by most MMR-deficient cancers. To evaluate safety and immunogenicity of an FSP-based vaccine, we performed a clinical phase I/IIa trial (Micoryx). PATIENTS AND METHODS: The trial comprised three cycles of four subcutaneous vaccinations (FSP neoantigens derived from mutant AIM2, HT001, TAF1B genes) mixed with Montanide ISA-51 VG over 6 months. Inclusion criteria were history of MMR-deficient colorectal cancer (UICC stage III or IV) and completion of chemotherapy. Phase I evaluated safety and toxicity as primary endpoint (six patients), phase IIa addressed cellular and humoral immune responses (16 patients). RESULTS: Vaccine-induced humoral and cellular immune responses were observed in all patients vaccinated per protocol. Three patients developed grade 2 local injection site reactions. No vaccination-induced severe adverse events occurred. One heavily pretreated patient with bulky metastases showed stable disease and stable CEA levels over 7 months. CONCLUSIONS: FSP neoantigen vaccination is systemically well tolerated and consistently induces humoral and cellular immune responses, thus representing a promising novel approach for treatment and even prevention of MMR-deficient cancer.


Assuntos
Antígenos de Neoplasias/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Neoplasias Colorretais/prevenção & controle , Reparo de Erro de Pareamento de DNA , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/efeitos adversos , Antígenos de Neoplasias/genética , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/imunologia , Proteínas de Ligação a DNA/genética , Feminino , Mutação da Fase de Leitura , Humanos , Injeções Subcutâneas , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas Pol1 do Complexo de Iniciação de Transcrição/genética , Proteínas/genética , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/efeitos adversos , Vacinas de Subunidades/genética
14.
GMS Infect Dis ; 8: Doc14, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32373439

RESUMO

This is the sixth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. The chapter deals with the antibacterial treatment of more severe infections of the ear, the nose, the throat and the maxillofacial region, including odontogenic and salivary gland infections.

15.
Assessment ; 27(5): 982-995, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-29993260

RESUMO

A recent review concluded that the Cognitive Failures Questionnaire is the most widely used instrument to assess cognitive failures. Our aims were to place cognitive failures self-reported with the Cognitive Failures Questionnaire into their nomological network by conceptually replicating known relations to the Big Five and by extending this knowledge through testing their relations with latent cognitive abilities (Study 1, N = 158, age 20-86 years) and theoretically relevant Big Five subfacets (Study 2, N = 176, age 19-39 years). Cognitive failures were unrelated to objective cognitive performance (processing speed, memory, and inhibition), but reliably related to the personality domains conscientiousness, neuroticism, and almost all their subfacets. Thus, self-reported cognitive failures do not qualify as a proxy for objective cognitive performance tasks. They are rather useful as illustration of behavioral manifestations related to personality domains.


Assuntos
Transtornos da Personalidade , Personalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição , Humanos , Memória , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
16.
Child Neuropsychol ; 26(3): 324-344, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31380706

RESUMO

There are several studies showing that executive functions such as working memory, inhibition, and cognitive flexibility are related to reading abilities. However, most of these studies did not simultaneously take different executive functions and intelligence into account. Therefore, the aim of our study was to investigate if working memory, inhibition, cognitive flexibility, and fluid intelligence uniquely contribute to reading. Furthermore, we tested the hypothesis that reading comprehension and reading speed are correlated but separable reading abilities with different relations to other cognitive functions. To test this assumption, we examined if executive functions and fluid intelligence unequally relate to reading comprehension and reading speed. A total of 186 school children (mean age = 9.31 years) participated in our study and performed a complex span task (working memory), task switching (cognitive flexibility), a stroop-like task (inhibition), raven matrices (fluid intelligence), a reading speed task and three reading comprehension tasks. Structural equation modeling (SEM) showed that working memory, inhibition, cognitive flexibility and fluid intelligence differently contributed to reading speed and reading comprehension. Working memory, inhibition and fluid intelligence were related to reading speed, indicating that a higher working memory capacity, better inhibitory abilities and higher fluid intelligence were associated with higher reading speed. Moreover, cognitive flexibility and fluid intelligence were related to reading comprehension, suggesting that higher cognitive flexibility and fluid intelligence were associated with better reading comprehension. Thus, our results point to differential contributions of executive functions to reading comprehension and reading speed.


Assuntos
Cognição/fisiologia , Compreensão/fisiologia , Testes de Inteligência/normas , Inteligência/fisiologia , Memória de Curto Prazo/fisiologia , Leitura , Criança , Feminino , Humanos , Masculino
17.
Dev Sci ; 23(4): e12866, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31132209

RESUMO

Several studies indicate that executive functions (EF), such as working memory (WM), inhibition or flexibility can be improved by training and that these training-related benefits in WM capacity generalize to reading and mathematical abilities. However, the results of these studies are inconsistent and most of them focused on WM training in children with learning difficulties. Evidence for typically developing children is rare and no study has investigated inhibition training or flexibility training. There is also a lack of studies taking motivational factors into account. Therefore, this study compared the effects of game-based and standard training regimens targeting WM, inhibition, or flexibility in children. One hundred and fifty-three typically developing elementary school students (mean age = 9.6 years, standard deviations  = 0.8) were investigated in an intervention design with a pretest, 21 sessions of training, a posttest and a follow-up after three months. They were randomized into one of six training groups or a control group. We found training gains in all training groups and higher self-reported motivation in the game-based as compared to the standard training groups. Furthermore, there was domain-specific transfer to untrained EF tasks across all training groups. We found greater performance improvements in reading ability (but not mathematics) in the game-based flexibility training group and the game-based inhibition training group as compared to the control group. Transfer effects were still significant at follow-up. In sum, our findings provide first evidence for a systematic comparison of training on different domains of EF and their differential effects on academic abilities.


Assuntos
Desempenho Acadêmico , Cognição , Função Executiva/fisiologia , Ensino/normas , Criança , Feminino , Humanos , Inibição Psicológica , Masculino , Matemática , Memória de Curto Prazo/fisiologia , Motivação , Leitura , Instituições Acadêmicas , Autorrelato
18.
J Exp Med ; 217(2)2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31704808

RESUMO

This report addresses whether small molecules can deplete FoxP3-expressing regulatory T (T reg) cells, thereby augmenting antitumor immunity. Imatinib, a tyrosine kinase inhibitor of oncogenic BCR-ABL protein expressed by chronic myelogenous leukemia (CML) cells, possesses off-targets including LCK expressed in T cells. We showed that imatinib-treated CML patients in complete molecular remission (CMR) exhibited selective depletion of effector T reg (eT reg) cells and significant increase in effector/memory CD8+ T cells while non-CMR patients did not. Imatinib at CML-therapeutic concentrations indeed induced apoptosis specifically in eT reg cells and expanded tumor antigen-specific CD8+ T cells in vitro in healthy individuals and melanoma patients, and suppressed colon tumor growth in vivo in mice. Mechanistically, because of FoxP3-dependent much lower expression of LCK and ZAP-70 in T reg cells compared with other T cells, imatinib inhibition of LCK further reduced their TCR signal intensity, rendering them selectively susceptible to signal-deprived apoptotis. Taken together, eT reg cell depletion by imatinib is instrumental in evoking effective immune responses to various cancers.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Imunidade/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Camundongos Transgênicos , Inibidores de Proteínas Quinases/farmacologia , Receptores de Antígenos de Linfócitos T/antagonistas & inibidores , Linfócitos T Reguladores/imunologia , Resultado do Tratamento
19.
J Pers Assess ; 102(2): 196-204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31625412

RESUMO

Anxiety symptoms and anxiety disorders are highly prevalent among older adults, and are associated with considerable distress, functional impairment, and burden. Also, there is growing need for brief instruments to measure anxiety symptoms in primary care and geriatric medical settings. Therefore, the current study focuses on the development and psychometric evaluation of a short-form of the Geriatric Anxiety Scale (GAS-G), a well-established anxiety instrument for use with older adults. Study 1 draws on the original data from the GAS-G validation study (N = 242) to develop the short-form (GAS-G-SF) and determines whether the results replicate with the short-form. Study 2 extends the validation of the GAS-G-SF to a clinical sample (N = 156; 62 patients with heart disease, 94 patients with Parkinson's disease). Overall, the GAS-G-SF showed promising psychometric properties in terms of internal consistency and validity. Also, the GAS-G-SF showed good discriminatory power based on receiver operating characteristic curve analysis in both studies. These results support the utility of the GAS-G-SF as a brief assessment measure for anxiety.


Assuntos
Ansiedade/diagnóstico , Avaliação Geriátrica/métodos , Inquéritos e Questionários/normas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Curva ROC , Reprodutibilidade dos Testes
20.
Psychol Res ; 84(8): 2354-2360, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31300875

RESUMO

Working memory (WM), a key feature of the cognitive system, allows for maintaining and processing information simultaneously and in a controlled manner. WM processing continuously develops across childhood, with significant increases both in verbal and visuospatial WM. Verbal and visuospatial WM may show different developmental trajectories, as verbal (but not visuospatial) WM relies on internal verbal rehearsal, which is less developed in younger children. We examined complex VWM and VSWM performance in 125 younger (age 4-6 years) and 101 older (age 8-10 years) children. Latent multi-group modeling showed that (1) older children performed better on both verbal and visuospatial WM span tasks than younger children, (2) both age groups performed better on verbal than visuospatial WM, and (3) a model with two factors representing verbal and visuospatial WM fit the data better than a one-factor model. Importantly, the correlation between the two factors was significantly higher in younger than in older children, suggesting an age-related differentiation of verbal and spatial WM processing in middle childhood. Age-related differentiation is an important characteristic of cognitive functioning and thus the findings contribute to our general understanding of WM processing.


Assuntos
Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Criança , Pré-Escolar , Compreensão , Feminino , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Reconhecimento Visual de Modelos/fisiologia
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