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1.
J Gambl Stud ; 40(1): 131-157, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37270469

RESUMO

Attempts to obtain rewards are not always successful. Despite investing much time, effort, or money, sometimes individuals may not obtain any reward. Other times they may obtain some reward, but the obtained reward may be smaller than their initial investment, such as partial wins in gambling. It remains unclear how such ambiguous outcomes are appraised. To address this question, we systematically varied the payoffs for different outcomes in a computerized scratch card task across three experiments. To test outcome appraisal, we used response vigor as a novel proxy. In the scratch card task, participants turned three cards one by one. Depending on the turned cards, they either received an amount that was higher than the wager (win), an amount lower than the wager (partial win), or nothing (loss). Overall, participants responded to partial wins more slowly than losses, but more quickly than wins. Partial wins were therefore appraised to be better than losses, but worse than wins. Importantly, further analyses showed that outcome appraisal was not based on the net win or loss amount. Instead, participants primarily used the configuration of turned cards as a cue for the relative rank of an outcome within a specific game. Outcome appraisals thus utilize simple heuristic rules, rely on salient information (such as outcome-related cues in gambling), and are specific to a local context. Together, these factors may contribute to the misperception of partial wins as real wins in gambling. Future work may examine how outcome appraisal may be modulated by the salience of certain information, and investigate the appraisal process in contexts beyond gambling.


Assuntos
Jogo de Azar , Humanos , Jogo de Azar/psicologia , Sinais (Psicologia) , Investimentos em Saúde , Recompensa
2.
J Health Monit ; 8(4): 17-23, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38384741

RESUMO

Background: Cancer predisposition syndromes (CPS) are rare diseases that are associated with an increased risk of cancer due to genetic alterations. At least 8 % of all cases of childhood cancer are attributable to CPS [1, 2]. The CPS registry was launched in 2017 to learn more about CPS and to improve the care to those afflicted by these diseases. Methods: This is an internationally networked registry with associated accompanying studies that investigate cancer risks and spectra, the possibilities of cancer prevention, early detection and therapy. Results: For several of these syndromes, new insights into the cancer risks and cancer types as well as factors modifying cancer risk have been gained. In addition, experimental, psycho-oncological, preclinical and clinical studies were initiated. Conclusions: The CPS registry is an example of how progress can be made within a short period of time to the benefit of individuals with rare diseases through systematic data collection and research.

3.
R Soc Open Sci ; 8(10): 210762, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34754496

RESUMO

Rapidly executing novel instructions is a critical ability. However, it remains unclear whether longer preparation of novel instructions improves performance, and if so, whether this link is modulated by performance benefits and costs of preparation. Regarding the first question, we reanalysed previous data on novel instruction implementation and ran Experiment 1. Experiment 1 consisted of multiple mini-blocks, in which participants prepared four novel stimulus-response (S-R) mappings in a self-paced instruction phase. After participants indicated they were ready, one of the four stimuli was presented and they responded. The reanalysis and Experiment 1 showed that longer preparation indeed led to better performance. To examine if preparation was modulated when the benefits of preparation were reduced, we presented the correct response with the stimulus on some trials in Experiments 2 and 3. Preparation was shorter when the probability that the correct response was presented with the stimulus increased. In Experiment 4, we manipulated the costs of preparation by changing the S-R mappings between the instruction and execution phases on some trials. This had only limited effects on preparation time. In conclusion, self-paced preparation of novel instructions comes with performance benefits and costs, and participants adjust their preparation strategy to the task context.

5.
Q J Exp Psychol (Hove) ; 74(2): 326-343, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32933423

RESUMO

In the target-distractor saccade task, a target and an irrelevant distractor are simultaneously presented and the task itself consists of a target-directed saccade. Findings usually show that as saccade latency increases, saccade trajectory deviation towards the distractor decreases. We presented this saccade task in two dual-task experiments to address the open question of whether performance of an auditory-manual task simply delays the temporal execution of a saccade, or whether it also interferes with the spatial planning of the saccade trajectory. We measured saccade latency, as a measure of a delay in execution, and saccade trajectory deviation, as a measure of the spatial planning. In Experiment 1, the auditory-manual task was a two-choice reaction time (two-CRT) task, and in Experiment 2, it was a go-no-go task. Performing the two tasks in close temporal succession shortly delayed the temporal execution of the saccade, but did not influence the spatial planning of the saccade trajectory. This result pattern was more pronounced when the auditory-manual task required the selection and execution of one of two possible manual responses (Experiment 1), less pronounced when the auditory-manual task required the decision to execute a button press (go condition, Experiment 2), and absent when the auditory-manual task required the decision to inhibit a button press (no-go condition, Experiment 2). Taken together, the manual response rather than the response selection process of the auditory-manual task led to a delay of saccade execution, but not to an impairment of the spatial planning of the saccade trajectory.


Assuntos
Atenção/fisiologia , Movimentos Sacádicos/fisiologia , Movimentos Oculares/fisiologia , Humanos , Estimulação Luminosa , Tempo de Reação/fisiologia
6.
Q J Exp Psychol (Hove) ; 73(10): 1564-1574, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32419615

RESUMO

Central and auditory attention are limited in capacity. In dual-tasks, central attention is required to select the appropriate response, but because central attention is limited in capacity, response selection can only be carried out for one task at a time. In auditory search tasks, search time to detect the target sound increases with the number of distractor sounds added to the auditory scene (set sizes), indicating that auditory attention is limited in capacity. Here, we investigated whether central and auditory attention relied on common or distinct capacity limitations using a dual-task paradigm. In two experiments, participants completed a visual choice discrimination task (task 1) together with an auditory search task (task 2), and the two tasks were separated by an experimentally modulated stimulus onset asynchrony (SOA). Analysing auditory search time as a function of SOA and set sizes (locus-of-slack method) revealed that the auditory search process in task 2 was performed after response selection in a visual two-choice discrimination task 1 (Experiment 1), but concurrently with response selection in a visual four-choice discrimination task 1 (Experiment 2). Hence, although response selection in the visual four-choice discrimination task demanded more central attention as compared with response selection in the two-choice discrimination task, the auditory search process was performed in parallel. Distribution analyses of inter-response time further indicated that parallel processing of response selection and auditory search was not influenced by response grouping. Taken together, the two experiments provided evidence that central and auditory attention relied on distinct capacity limitations.


Assuntos
Atenção , Percepção Auditiva , Discriminação Psicológica , Percepção Visual , Estimulação Acústica , Adolescente , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação , Adulto Jovem
7.
Atten Percept Psychophys ; 82(2): 715-728, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974939

RESUMO

Visual and central attention are limited in capacity. In conjunction search, visual attention is required to select the items and to bind their features (e.g., color, form, size), which results in a serial search process. In dual-tasks, central attention is required for response selection, but because central attention is limited in capacity, response selection can only be carried out for one task at a time. Here, we investigated whether visual and central attention rely on a common or on distinct capacity limitations. In two dual-task experiments, participants completed an auditory two-choice discrimination Task 1 and a conjunction search Task 2 that were presented with an experimentally modulated temporal interval between them (stimulus onset asynchrony [SOA]). In Experiment 1, Task 2 was a triple conjunction search task. Each item consisted of a conjunction of three features, so that target and distractors shared two features. In Experiment 2, Task 2 was a plus conjunction search task, in which target and distractors shared the same four features. The hypotheses for conjunction search time were derived from the locus-of-slack method. While plus conjunction search was performed after response selection in Task 1, a small part of triple conjunction search was still performed in parallel to response selection in Task 1. However, the between-experiment comparison was not significant, indicating that both search tasks may require central attention. Taken together, the present study provides evidence that visual and central attention share a common capacity limitation when conjunction search relies strongly on serial item selection.


Assuntos
Atenção/fisiologia , Percepção Auditiva/fisiologia , Discriminação Psicológica/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica , Adolescente , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologia , Análise e Desempenho de Tarefas , Adulto Jovem
8.
Psychol Belg ; 59(1): 321-337, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31497307

RESUMO

The present paper is the mission statement of the Control of Impulsive Action (Ctrl-ImpAct) Lab regarding Open Science. As early-career researchers (ECRs) in the lab, we first state our personal motivation to conduct research based on the principles of Open Science. We then describe how we incorporate four specific Open Science practices (i.e., Open Methodology, Open Data, Open Source, and Open Access) into our scientific workflow. In more detail, we explain how Open Science practices are embedded into the so-called 'co-pilot' system in our lab. The 'co-pilot' researcher is involved in all tasks of the 'pilot' researcher, that is designing a study, double-checking experimental and data analysis scripts, as well as writing the manuscript. The lab has set up this co-pilot system to increase transparency, reduce potential errors that could occur during the entire workflow, and to intensify collaborations between lab members. Finally, we discuss potential solutions for general problems that could arise when practicing Open Science.

9.
Psychol Res ; 83(3): 459-475, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28917014

RESUMO

Both response selection and visual attention are limited in capacity. According to the central bottleneck model, the response selection processes of two tasks in a dual-task situation are performed sequentially. In conjunction search, visual attention is required to select the items and to bind their features (e.g., color and form), which results in a serial search process. Search time increases as items are added to the search display (i.e., set size effect). When the search display is masked, visual attention deployment is restricted to a brief period of time and target detection decreases as a function of set size. Here, we investigated whether response selection and visual attention (i.e., feature binding) rely on a common or on distinct capacity limitations. In four dual-task experiments, participants completed an auditory Task 1 and a conjunction search Task 2 that were presented with an experimentally modulated temporal interval between them (Stimulus Onset Asynchrony, SOA). In Experiment 1, Task 1 was a two-choice discrimination task and the conjunction search display was not masked. In Experiment 2, the response selection difficulty in Task 1 was increased to a four-choice discrimination and the search task was the same as in Experiment 1. We applied the locus-of-slack method in both experiments to analyze conjunction search time, that is, we compared the set size effects across SOAs. Similar set size effects across SOAs (i.e., additive effects of SOA and set size) would indicate sequential processing of response selection and visual attention. However, a significantly smaller set size effect at short SOA compared to long SOA (i.e., underadditive interaction of SOA and set size) would indicate parallel processing of response selection and visual attention. In both experiments, we found underadditive interactions of SOA and set size. In Experiments 3 and 4, the conjunction search display in Task 2 was masked. Task 1 was the same as in Experiments 1 and 2, respectively. In both experiments, the d' analysis revealed that response selection did not affect target detection. Overall, Experiments 1-4 indicated that neither the response selection difficulty in the auditory Task 1 (i.e., two-choice vs. four-choice) nor the type of presentation of the search display in Task 2 (i.e., not masked vs. masked) impaired parallel processing of response selection and conjunction search. We concluded that in general, response selection and visual attention (i.e., feature binding) rely on distinct capacity limitations.


Assuntos
Atenção/fisiologia , Percepção Auditiva/fisiologia , Discriminação Psicológica/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Resolução de Problemas/fisiologia , Tempo de Reação/fisiologia , Estimulação Acústica , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
10.
Front Psychol ; 9: 991, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29971029

RESUMO

To evoke the impression of movement in the "immobile" image is one of the central motivations of the visual art, and the activating effect of images has been discussed in art psychology already some 100 years ago. However, this topic has up to now been largely neglected by the researchers in cognitive psychology and neuroscience. This study investigates - from an interdisciplinary perspective - the formation of lateralized instances of motion when an observer perceives movement in an image. A first step was to identify images that evoke a perception of movement in a certain direction and to give this a rating. Reaction times leading to the engagement of a joystick following the presentation of images are used to evidence the postulated movement occasioned by the perception of movement in an image. Where the required direction of joystick moves matched the expected perception of movement direction in the image, significantly shorter reaction times were recorded. The experiment was able to prove a "movement-image compatibility effect" in observers of images. Based on this, the paper revisits and brings up to date the theses on motor sensory response to images which were developed in art psychology at the beginning of the 20th century. It furthermore contributes an embodiment theory interpretation to the prevalent representational explanation of compatibility effects.

11.
Psychol Res ; 82(1): 40-53, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28856434

RESUMO

Dual tasks (DTs) are characterized by the requirement for additional mechanisms that coordinate the processing order of two temporally overlapping tasks. These mechanisms are indicated by two types of costs that occur when comparing DT blocks with fixed and random orders of the component tasks. On a block level, task-order control costs are reflected in increased reaction times (RTs) in random-order compared to fixed-order blocks, indicating global, monitoring-based, coordination mechanisms. On a trial level, within random-order blocks, order-switch costs are indicated by increased RTs on order switch compared to order repetition trials, reflecting memory-based mechanisms that guide task-order in DTs. To test the nature of these mechanisms in two experiments, participants performed DTs in fixed- and random-order blocks. In random-order blocks, participants were either instructed to respond to both tasks according to the order of task presentation (sequential-order instruction) or instructed to freely decide in which order to perform both tasks (free-order instruction). As a result of both experiments, we demonstrated that task-order control costs were reduced under the free-order compared to the sequential-order instruction, whereas order-switch costs were not affected by our instruction manipulation. This pattern of results suggests that the task-order control costs reflect global processes of task-order regulation such as engaging monitoring processes that are sensitive to changes in order instructions, while order-switch costs reflect rather local memory-based mechanisms that occur irrespective of any effort to coordinate task-order.


Assuntos
Comportamento de Escolha/classificação , Comportamento de Escolha/fisiologia , Comportamento Multitarefa/fisiologia , Desempenho Psicomotor/classificação , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Análise e Desempenho de Tarefas , Adulto , Tomada de Decisões , Feminino , Humanos , Individualidade , Israel , Masculino , Adulto Jovem
12.
Nat Commun ; 8(1): 218, 2017 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-28794406

RESUMO

Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.While micro-RNAs are known regulators of haematopoiesis and leukemogenesis, the role of long non-coding RNAs is less clear. Here the authors provide a non-coding RNA expression landscape of the human hematopoietic system, highlighting their role in the formation and maintenance of the human blood hierarchy.


Assuntos
Hematopoese , Leucemia/metabolismo , RNA não Traduzido/metabolismo , Linhagem da Célula , Perfilação da Expressão Gênica , Células HEK293 , Humanos , RNA Longo não Codificante/fisiologia
13.
Q J Exp Psychol (Hove) ; 70(12): 2460-2477, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27734768

RESUMO

Visual attention and response selection are limited in capacity. Here, we investigated whether visual attention requires the same bottleneck mechanism as response selection in a dual-task of the psychological refractory period (PRP) paradigm. The dual-task consisted of an auditory two-choice discrimination Task 1 and a conjunction search Task 2, which were presented at variable temporal intervals (stimulus onset asynchrony, SOA). In conjunction search, visual attention is required to select items and to bind their features resulting in a serial search process around the items in the search display (i.e., set size). We measured the reaction time of the visual search task (RT2) and the N2pc, an event-related potential (ERP), which reflects lateralized visual attention processes. If the response selection processes in Task 1 influence the visual attention processes in Task 2, N2pc latency and amplitude would be delayed and attenuated at short SOA compared to long SOA. The results, however, showed that latency and amplitude were independent of SOA, indicating that visual attention was concurrently deployed to response selection. Moreover, the RT2 analysis revealed an underadditive interaction of SOA and set size. We concluded that visual attention does not require the same bottleneck mechanism as response selection in dual-tasks.


Assuntos
Atenção/fisiologia , Percepção Auditiva/fisiologia , Comportamento de Escolha/fisiologia , Potenciais Evocados/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Estimulação Acústica , Adolescente , Adulto , Análise de Variância , Discriminação Psicológica/fisiologia , Eletroencefalografia , Movimentos Oculares/fisiologia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Fatores de Tempo , Adulto Jovem
14.
Scand J Gastroenterol ; 52(3): 276-283, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27826993

RESUMO

OBJECTIVE: The objective of this study was to evaluate the validity of the Heartburn Reflux Dyspepsia Questionnaire (HRDQ), a newly developed measure of gastro-oesophageal reflux disease (GORD) symptoms. Specifically, the HRDQ was developed for patients, who still experience symptoms with proton pump inhibitor (PPI) treatment. MATERIAL AND METHODS: The psychometric properties of HRDQ were evaluated based on data from two clinical trials of patients with GORD with a partial response to PPIs, one from the UK and one from Denmark and Germany. RESULTS: The HRDQ had good internal consistency (Cronbach's alpha range .83-.88) and test-retest reliability (intraclass correlation coefficient range .71-.90). Convergent and discriminant validity were supported by high correlations with ReQuest™ and ability to differentiate between groups based on ReQuest™ cut-off values. Responsiveness of HRDQ was demonstrated by moderate to high correlations with ReQuest™ change scores and time with symptoms. An HRDQ cut-off value of 0.70 for definition of 'bad day' was also evaluated. CONCLUSIONS: Based on existing evidence, the HRDQ is a valid and reliable measure of GORD symptoms that can be used as a study outcome in clinical trials.


Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/fisiopatologia , Azia/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Psicometria , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Dinamarca , Método Duplo-Cego , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Adulto Jovem
15.
Atten Percept Psychophys ; 77(4): 1052-69, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25810162

RESUMO

Visual attention and response selection are processes that are limited by capacity. The present study focuses on whether visual attention is subject to the response selection bottleneck. This was investigated by conducting 2 dual-task experiments of the psychological refractory period (PRP) type. A visual conjunction search task was chosen as Task 2 in these experiments. Conjunction search requires the binding of the stimulus' defining features. This binding is performed in a serial search process in displays of different amounts of stimuli until the presence or absence of the target is correctly indicated. In Experiment 1, the conjunction search was combined with a 2-choice tone discrimination Task 1, and in Experiment 2 with a 2-choice color discrimination Task 1. Detailed reaction time (RT) analyses revealed concurrent performance of visual search to both tone and color in Task 1's response selection. In conclusion, visual attention is not subject to the response selection bottleneck.


Assuntos
Atenção/fisiologia , Percepção Visual/fisiologia , Adulto , Análise de Variância , Comportamento de Escolha/fisiologia , Discriminação Psicológica/fisiologia , Feminino , Humanos , Masculino , Reconhecimento Visual de Modelos , Estimulação Luminosa , Discriminação da Altura Tonal/fisiologia , Desempenho Psicomotor/fisiologia , Período Refratário Psicológico/fisiologia , Adulto Jovem
16.
Scand J Gastroenterol ; 49(9): 1044-50, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24874283

RESUMO

OBJECTIVE: Both over-the-counter medicine, such as antacids or alginates, and proton pump inhibitors (PPI) are used for treating acid-related disorders. We sought to describe what characterizes users of these different medicines, including long-term PPI users within the general population. METHOD: A cross-sectional survey was conducted in an internet panel representative of the Danish adult population in 2012. Data queried included antacid/alginate and PPI use, reason for therapy, co-medication, and presence of upper gastrointestinal symptoms. Long-term PPI use was defined as using PPI ≥1/3 of the last year (∼120 days). Risk of long-term PPI use was estimated by logistic regression. RESULTS: A total of 18,223 people received the questionnaire, of which 52% (9390) responded. Antacid/alginate use was reported by 23%; 16% reported use of only antacid/alginate. PPI use was reported by 13.6%; 6.2% were defined as long-term PPI users. Antacid/alginate users were younger, used less co-medication, had most often started on therapy because of reflux symptoms, and had less often ongoing symptoms. Risk of long-term PPI use appeared to be increased in male gender, by renewing PPI prescription by phone/e-mail, using co-medication, and having started on PPI for several reasons. Combination of antacid/alginate and PPI was reported by approximately 50% of those on therapy with weekly or daily symptoms. CONCLUSION: 23% of Danish adults were using antacids or alginates and 14% were using PPI, of which one-half were on long-term therapy. Prescription renewal by phone or e-mail and use of other prescription medication were associated with long-term PPI use, indicating a behavioral pattern, in which unnecessary PPI therapy may be maintained.


Assuntos
Alginatos/uso terapêutico , Antiácidos/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Fatores Etários , Estudos Transversais , Dinamarca , Prescrições de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Inquéritos e Questionários , Fatores de Tempo
17.
Genes Dev ; 28(8): 858-74, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24736844

RESUMO

Although regulation of stem cell homeostasis by microRNAs (miRNAs) is well studied, it is unclear how individual miRNAs genomically encoded within an organized polycistron can interact to induce an integrated phenotype. miR-99a/100, let-7, and miR-125b paralogs are encoded in two tricistrons on human chromosomes 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Here, we show that miR-99a/100∼125b tricistrons are transcribed as a polycistronic message transactivated by the homeobox transcription factor HOXA10. Integrative analysis of global gene expression profiling, miRNA target prediction, and pathway architecture revealed that miR-99a/100, let-7, and miR-125b functionally converge at the combinatorial block of the transforming growth factor ß (TGFß) pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, down-regulation of tumor suppressor genes adenomatous polyposis coli (APC)/APC2 stabilizes active ß-catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFß signaling, the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo while favoring megakaryocytic differentiation. Hence, our study explains the high phylogenetic conservation of the miR-99a/100∼125b tricistrons controlling stem cell homeostasis, the deregulation of which contributes to the development of AMKL.


Assuntos
Células-Tronco Hematopoéticas/metabolismo , Homeostase/genética , MicroRNAs , Transdução de Sinais , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Wnt/metabolismo , Animais , Apoptose/genética , Regulação para Baixo , Eritropoese/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes APC/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Ligação Proteica , Trombopoese/genética , Proteínas Wnt/genética
19.
Best Pract Res Clin Gastroenterol ; 27(3): 443-54, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23998981

RESUMO

Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences. Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment.


Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Interações Medicamentosas , Fraturas Ósseas/induzido quimicamente , Humanos , Síndromes de Malabsorção/induzido quimicamente
20.
Hum Mutat ; 34(6): 905-14, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23463630

RESUMO

Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN). We screened CN (n = 395) or CyN (n = 92) patients for ELANE mutations and investigated the impact of mutations on mRNA expression, protein expression, and activity. We found 116 different mutations in 162 (41%) CN patients and 26 in 51 (55%) CyN patients, 69 of them were novel. CyN-associated mutations were predicted to be more benign than CN-associated mutations, but the mutation severity largely overlapped. The frequency of acquired CSF3R mutations, malignant transformation, and the need for hematopoietic stem cell transplantation was significantly higher in CN patients with ELANE mutation than in ELANE mutation negative patients. Cellular elastase activity was reduced in neutrophils from CN/CyN patients, irrespective of the mutation status. In CN, enzymatic activity was significantly lower in patients with ELANE mutations compared with those with wild-type ELANE. Despite differences in the spectrum of mutations in CN or CyN, type or localization of mutation only partially determine the clinical phenotype. Specific ELANE mutations have limited predictive value for leukemogenesis; the risk for leukemia was correlated with disease severity rather than with occurrence of an ELANE mutation.


Assuntos
Elastase de Leucócito/genética , Mutação , Neutropenia/congênito , Neutropenia/genética , Códon de Iniciação , Ativação Enzimática , Éxons , Expressão Gênica , Genótipo , Neoplasias Hematológicas/etiologia , Humanos , Elastase de Leucócito/metabolismo , Neutropenia/complicações , Neutropenia/metabolismo , Neutrófilos/metabolismo , Polimorfismo Genético , Regiões Promotoras Genéticas , Transporte Proteico , Sítios de Splice de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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