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1.
Brain ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489591

RESUMO

Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. Recent years altered this perception, as a growing number of leukodystrophies was described to have an onset at adult ages. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16 patients from eight families carrying one of four different stop-gain or frameshift dominant variants in the CST3 gene. Clinical and radiological features differ markedly from the previously described Icelandic Cerebral Amyloid Angiopathy that was found in patients carrying p.Leu68Asn substitution in CST3. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. In addition, in some cases acute onset clinical deterioration led to a prolonged episode with reduced consciousness and even early death. Radiologically, pathognomonic changes are found at typical predilection sites involving the deep cerebral white matter sparing a periventricular and directly subcortical rim, the middle blade of corpus callosum, posterior limb of the internal capsule, middle cerebellar peduncles, cerebral peduncles, and specifically the globus pallidus. Histopathologic characterization in two autopsy cases did not reveal angiopathy, but instead micro- to macrocystic degeneration of the white matter. Astrocytes were activated at early stages and later on displayed severe degeneration and loss. In addition, despite loss of myelin, elevated numbers of partly apoptotic oligodendrocytes were observed. A structural comparison of the variants in CST3 suggests that specific truncations of Cystatin C result in an abnormal function, possibly by rendering the protein more prone to aggregation. Future studies are required to confirm the assumed effect on the protein and to determine pathophysiologic downstream events at the cellular level.

2.
J Clin Oncol ; 42(14): 1665-1675, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38358946

RESUMO

PURPOSE: Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T. PATIENTS AND METHODS: This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti-B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133). Independent predictors of relapse/progression built a simple prediction model (Myeloma CAR-T Relapse [MyCARe] model) in the training cohort (Europe), which was externally validated (US cohort) and tested within patient- and treatment-specific subgroups. RESULTS: The overall response rate was 87% and comparable between both cohorts, and complete responses were seen in 48% (Europe) and 49% (the United States). The median time to relapse was 5 months, and early relapse <5 months from infusion showed poor survival across cohorts, with the 12-month overall survival of 30% (Europe) and 14% (the United States). The presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. Each factor received one point, forming the three-tiered MyCARe model: scores 0-1 (low risk), scores 2-3 (intermediate risk), and a score of 4 (high risk). The MyCARe model was significantly associated with distinct 5-month incidence of relapse/progression (P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. The model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups. CONCLUSION: Outcomes of patients with RRMM after CAR-T are comparable between Europe and the United States. The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups.


Assuntos
Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/imunologia , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Feminino , Idoso , Imunoterapia Adotiva/métodos , Antígeno de Maturação de Linfócitos B/imunologia , Estados Unidos , Adulto , Receptores de Antígenos Quiméricos/imunologia , Europa (Continente) , Resultado do Tratamento , Recidiva Local de Neoplasia/terapia
3.
Front Oncol ; 13: 1273478, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810988

RESUMO

Introduction: Small cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and their effect on brain metastases remain unclear. Methods: In this retrospective multicenter study, we analyzed r/r SCLC patients receiving second or further-line CPI versus chemotherapy between 2010 and 2020. We applied multivariable-adjusted Cox regression analysis to test for differences in 1-year mortality and real-world progression. We then used interaction analysis to evaluate whether brain metastases (BM) and/or cranial radiotherapy (CRT) modified the effect of CPI versus chemotherapy on overall survival. Results: Among 285 patients, 99 (35%) received CPI and 186 (65%) patients received chemotherapy. Most patients (93%) in the CPI group received nivolumab/ipilimumab. Chemotherapy patients were entirely CPI-naïve and only one CPI patient had received atezolizumab for first-line treatment. CPI was associated with a lower risk of 1-year mortality (adjusted Hazard Ratio [HRadj] 0.59, 95% CI 0.42 to 0.82, p=0.002). This benefit was modified by BM and CRT, indicating a pronounced effect in patients without BM (with CRT: HRadj 0.34, p=0.003; no CRT: HRadj 0.50, p=0.05), while there was no effect in patients with BM who received CRT (HRadj 0.85, p=0.59). Conclusion: CPI was associated with a lower risk of 1-year mortality compared to chemotherapy. However, the effect on OS was significantly modified by intracranial disease and radiotherapy, suggesting the benefit was driven by patients without BM.

5.
Front Neurol ; 14: 1163107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37292133

RESUMO

CSF1 receptor-related leukoencephalopathy is a rare genetic disorder presenting with severe, adult-onset white matter dementia as one of the leading symptoms. Within the central nervous system, the affected CSF1-receptor is expressed exclusively in microglia cells. Growing evidence implicates that replacing the defective microglia with healthy donor cells through hematopoietic stem cell transplant might halt disease progression. Early initiation of that treatment is crucial to limit persistent disability. However, which patients are suitable for this treatment is not clear, and imaging biomarkers that specifically depict lasting structural damage are lacking. In this study, we report on two patients with CSF1R-related leukoencephalopathy in whom allogenic hematopoietic stem cell transplant at advanced disease stages led to clinical stabilization. We compare their disease course with that of two patients admitted in the same timeframe to our hospital, considered too late for treatment, and place our cases in context with the respective literature. We propose that the rate of clinical progression might be a suitable stratification measure for treatment amenability in patients. Furthermore, for the first time we evaluate [18F] florbetaben, a PET tracer known to bind to intact myelin, as a novel MRI-adjunct tool to image white matter damage in CSF1R-related leukoencephalopathy. In conclusion, our data add evidence for allogenic hematopoietic stem cell transplant as a promising treatment in CSF1R-related leukoencephalopathy patients with slow to moderate disease progression.

6.
Brain Behav ; 13(3): e2878, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36748403

RESUMO

BACKGROUND: Up to 80% of women with X-linked adrenoleukodystrophy (X-ALD) develop symptoms of myelopathy and peripheral neuropathy during their lifetime. The study's objective was to compare symptomatic versus asymptomatic women with X-ALD regarding their physical and mental well-being and quality of life. METHODS: Data were obtained from a prospective, international, cross-sectional cohort study of women with X-ALD recruited both clinically and population based. Symptoms, quality of life, and physical and mental co-morbidities were assessed by questionnaires. Women were considered symptomatic if they reported any sign of myelopathy or peripheral neuropathy. Group differences between symptomatic versus asymptomatic women and between age groups were examined using χ2 tests for categorical and independent sample t tests or analysis of variance for continuous variables. RESULTS: Complete data were available from N = 180 women (mean age: 51.2 ± 13.6 years, range: 18-85), of whom 71.7% were classified as symptomatic, with prevalence increasing with age. Symptomatic versus asymptomatic women reported poorer physical and mental health, with 26.4% meeting the criteria for a clinical depression, 73.6% reporting chronic pain, 80.6% sleeping disturbances, 38.2% sexual dysfunction, and 47.3% restless legs syndrome. Large group differences were found on the physical health, but not on the mental health component of quality of life, where symptomatic women only differed when controlling for having a boy affected by X-ALD (small effect) and treatment frequency (medium effect). CONCLUSIONS: Symptomatic women with X-ALD present with physical and psychological co-morbidities significantly reducing individuals' quality of life. The findings emphasize the need to develop new multi-disciplinary treatment options tailored to women's specific needs.


Assuntos
Adrenoleucodistrofia , Doenças do Sistema Nervoso Periférico , Doenças da Medula Espinal , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adrenoleucodistrofia/epidemiologia , Estudos Prospectivos , Autorrelato , Qualidade de Vida , Estudos Transversais
7.
Brain Sci ; 12(12)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36552113

RESUMO

BACKGROUND: Although increased food cue reactivity is evidenced to be crucial to the development and maintenance of pediatric obesity, virtually nothing is known about the underlying neurophysiological aspects of food cue reactivity in children with obesity. Therefore, this study aimed at investigating neural characteristics in children with overweight or obesity using electroencephalography (EEG). METHODS: Electrophysiological brain activity was measured using EEG frequency band analysis in n = 9 children with overweight or obesity versus n = 16 children with normal weight (8-13 years) during the presentation of high- and low-calorie food pictures and images of appealing non-food stimuli. RESULTS: Children with overweight or obesity showed significantly increased relative central beta band activity induced by high-calorie foods and appealing non-food stimuli compared to children with normal weight. Beyond significant effects of the scalp region on EEG activity, non-significant effects of stimulus category or weight status were seen for theta and alpha frequency bands. CONCLUSIONS: This study demonstrated elevated beta band activity in children with overweight or obesity when viewing high-calorie food stimuli. Beta band activity may, thus, be a valuable target for neuromodulatory interventions in children with overweight or obesity.

8.
Adv Mater ; 34(3): e2106868, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34750901

RESUMO

Binary and ternary chalcogenides have recently attracted much attention due to their wide range of applications including phase-change memory materials, topological insulators, photonic switches, and thermoelectrics. These applications require a precise control of the number and mobility of charge carriers. Here, an unexpected charge-carrier transition in ternary compounds from the PbTe-Sb2 Te3 pseudo-binary line is reported. Upon thermal annealing, sputtered thin films of PbSb2 Te4 and Pb2 Sb2 Te5 undergo a transition in the temperature coefficient of resistance and in the type of the majority charge carriers from n-type to p-type. These transitions are observed upon increasing structural order within one crystallographic phase. To account for this striking observation, it is proposed that the Fermi energy shifts from the tail of the conduction band to the valence band because different levels of overall structural disorder lead to different predominant types of native point defects. This view is confirmed by an extensive computational study, revealing a transition from excess cations and SbPb for high levels of disorder to PbSb prevailing for low disorder. The findings will help fine-tune transport properties in certain chalcogenides via proper thermal treatment, with potential benefits for memories, thermoelectric material optimization, and neuromorphic devices.

9.
Front Psychol ; 12: 662125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366979

RESUMO

Instead of a full sentence like Bring me to the university (uttered by the passenger to a taxi driver) speakers often use fragments like To the university to get their message across. So far there is no comprehensive and empirically supported account of why and under which circumstances speakers sometimes prefer a fragment over the corresponding full sentence. We propose an information-theoretic account to model this choice: A speaker chooses the encoding that distributes information most uniformly across the utterance in order to make the most efficient use of the hearer's processing resources (Uniform Information Density, Levy and Jaeger, 2007). Since processing effort is related to the predictability of words (Hale, 2001) our account predicts two effects of word probability on omissions: First, omitting predictable words (which are more easily processed), avoids underutilizing processing resources. Second, inserting words before very unpredictable words distributes otherwise excessively high processing effort more uniformly. We test these predictions with a production study that supports both of these predictions. Our study makes two main contributions: First we develop an empirically motivated and supported account of fragment usage. Second, we extend previous evidence for information-theoretic processing constraints on language in two ways: We find predictability effects on omissions driven by extralinguistic context, whereas previous research mostly focused on effects of local linguistic context. Furthermore, we show that omissions of content words are also subject to information-theoretic well-formedness considerations. Previously, this has been shown mostly for the omission of function words.

10.
Front Psychol ; 12: 661087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122245

RESUMO

We investigate the underexplored question of when speakers make use of the omission phenomenon verb phrase ellipsis (VPE) in English given that the full form is also available to them. We base the interpretation of our results on the well-established information-theoretic Uniform Information Density (UID) hypothesis: Speakers tend to distribute processing effort uniformly across utterances and avoid regions of low information by omitting redundant material through, e.g., VPE. We investigate the length of the omittable VP and its predictability in context as sources of redundancy which lead to larger or deeper regions of low information and an increased pressure to use ellipsis. We use both naturalness rating and self-paced reading studies in order to link naturalness patterns to potential processing difficulties. For the length effects our rating and reading results support a UID account. Surprisingly, we do not find an effect of the context on the naturalness and the processing of VPE. We suggest that our manipulation might have been too weak or not effective to evidence such an effect.

11.
Ann Neurol ; 90(2): 266-273, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34105176

RESUMO

OBJECTIVE: X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder characterized by progressive demyelination ranging from mild myelopathic forms (adrenomyeloneuropathy [AMN]) to severe cerebral variants (adult cerebral adrenoleukodystrophy [ACALD]). The aim of this study was to compare cognitive function in adult-onset X-ALD phenotypes. METHODS: Cognitive function in various domains (intelligence, attention, memory, executive function, and processing speed) was assessed in 172 adults (117 with AMN, 30 with arrested ACALD, and 25 with acute ACALD) using comprehensive neuropsychological batteries. Phenotype differences were examined by analyses of variance. RESULTS: X-ALD phenotypes significantly differed in nonverbal intelligence, sustained attention, verbal encoding, nonverbal recognition, and processing speed (ps < 0.050). No group differences emerged regarding verbal intelligence, verbal retrieval and recognition, and executive function (ps > 0.050). Specifically, patients with acute ACALD showed severe cognitive deficits compared to AMN and normal data, with largest effects on processing speed. Contrary, cognition was overall intact in patients with AMN, independent of sex and corticospinal tract involvement, and those with arrested ACALD showed mild cognitive dysfunction, particularly in verbal encoding and processing speed. INTERPRETATION: Cerebral demyelination in patients with X-ALD causes white matter dementia, mainly characterized by an extreme slowdown in processing speed associated with deficits in attention and learning. Most patients with AMN show intact cognitive function. Future prospective, longitudinal studies with more sensitive imaging techniques are required to clarify whether early mild cognitive dysfunction found in some patients with AMN may be associated with subtle myelin abnormalities that do not yet appear as white matter lesions on cerebral MRI (cMRI) but have the potential to serve as early predictors of later cerebral progression. ANN NEUROL 2021;90:266-273.


Assuntos
Adrenoleucodistrofia/diagnóstico por imagem , Adrenoleucodistrofia/psicologia , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/psicologia , Cognição/fisiologia , Fenótipo , Adolescente , Adrenoleucodistrofia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto Jovem
12.
Gait Posture ; 85: 138-144, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33556782

RESUMO

BACKGROUND: Dual Task (DT) paradigms are frequently used by researchers and clinicians to examine the integrity of motor processes in many movement disorders. However, the mechanism of this interaction is not fully understood. Therefore, the aim of this study was to examine the within-stride interactions between cognitive and motor processes during dual task gait (DT). RESEARCH QUESTION: Do healthy young adults coordinate gait with secondary task processing? If so, is cognitive task processing capability associated with the coordination observed? METHODS: Nineteen healthy young adults walked for two minutes on a motorized treadmill whilst counting backwards in sevens from three-digit numbers. The coordination of calculation verbalizations with gait parameters were assessed across six phases of the gait cycle. Mid verbalization time points (VERMid) were used as points of high cognitive processing of the dual task and compared with the end of the verbalizations (VEREnd) as points of low cognitive processing. RESULTS: VERMid and VEREnd did not systematically occur in any phase of the gait cycle. However, 10/19 and 9/19 participants showed non-random distributions of verbalizations for VERMid and VEREnd time points respectively (p < 0.01), indicating that these walkers coordinated gait with the cognitive task. Analysis of subgroups of Verbalization Coordinators and Non-Coordinators showed slower verbalization response durations (VRD) for VERMid Coordinators compared to VERMid Non-Coordinators, indicating that VERMid Coordinators found the cognitive tasks more demanding. No differences were found in VRD for VEREnd Coordinators and VEREnd Non-Coordinators. SIGNIFICANCE: It was found that cognitive processing is coordinated with gait phases in some but not all healthy young adults during DT gait. When demands on cognitive processes are high, healthy young adults coordinate cognitive processing with phases of gait. Analysis of within-stride coordination may be of use for studying clinical conditions where gait and attentional cognition performance breaks down.


Assuntos
Atenção/fisiologia , Cognição/fisiologia , Marcha/fisiologia , Comportamento Multitarefa/fisiologia , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Teste de Esforço , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
PLoS One ; 16(2): e0246255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571248

RESUMO

We describe a novel approach to estimating the predictability of utterances given extralinguistic context in psycholinguistic research. Predictability effects on language production and comprehension are widely attested, but so far predictability has mostly been manipulated through local linguistic context, which is captured with n-gram language models. However, this method does not allow to investigate predictability effects driven by extralinguistic context. Modeling effects of extralinguistic context is particularly relevant to discourse-initial expressions, which can be predictable even if they lack linguistic context at all. We propose to use script knowledge as an approximation to extralinguistic context. Since the application of script knowledge involves the generation of prediction about upcoming events, we expect that scrips can be used to manipulate the likelihood of linguistic expressions referring to these events. Previous research has shown that script-based discourse expectations modulate the likelihood of linguistic expressions, but script knowledge has often been operationalized with stimuli which were based on researchers' intuitions and/or expensive production and norming studies. We propose to quantify the likelihood of an utterance based on the probability of the event to which it refers. This probability is calculated with event language models trained on a script knowledge corpus and modulated with probabilistic event chains extracted from the corpus. We use the DeScript corpus of script knowledge to obtain empirically founded estimates of the likelihood of an event to occur in context without having to resort to expensive pre-tests of the stimuli. We exemplify our method at a case study on the usage of nonsentential expressions (fragments), which shows that utterances that are predictable given script-based extralinguistic context are more likely to be reduced.


Assuntos
Processamento de Linguagem Natural , Humanos , Idioma , Modelos Teóricos , Probabilidade , Psicolinguística/métodos
14.
Adv Mater ; 33(9): e2006221, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33491816

RESUMO

Tailoring the degree of disorder in chalcogenide phase-change materials (PCMs) plays an essential role in nonvolatile memory devices and neuro-inspired computing. Upon rapid crystallization from the amorphous phase, the flagship Ge-Sb-Te PCMs form metastable rocksalt-like structures with an unconventionally high concentration of vacancies, which results in disordered crystals exhibiting Anderson-insulating transport behavior. Here, ab initio simulations and transport experiments are combined to extend these concepts to the parent compound of Ge-Sb-Te alloys, viz., binary Sb2 Te3 , in the metastable rocksalt-type modification. Then a systematic computational screening over a wide range of homologous, binary and ternary chalcogenides, elucidating the critical factors that affect the stability of the rocksalt structure is carried out. The findings vastly expand the family of disorder-controlled main-group chalcogenides toward many more compositions with a tunable bandgap size for demanding phase-change applications, as well as a varying strength of spin-orbit interaction for the exploration of potential topological Anderson insulators.

15.
AIP Adv ; 11(12): 125114, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35028193

RESUMO

Aerosol particles are one of the main routes of transmission of COVID-19. Mobile air purifiers are used to reduce the risk of infection indoors. We focus on an air purifier that generates a defined volumetric air flow through a highly efficient filter material. We investigate the transport of aerosol particles from an infected dummy equipped with an aerosol generator to receiving thermal dummies. For analysis, we use up to 12 particle sensors to monitor the particle concentration with high spatial resolution. Based on the measurement data, a computational fluid dynamics (CFD) model is set up and validated. The experimental and numerical methods are used to investigate how the risk of infection suggested by the particle exposure in an exemplary lecture hall can be reduced by a clever choice of orientation of the air purifier. It turns out that obstructing the outlet stream of the air purifier may be particularly advantageous. The particle concentration at the head height deviates by 13% for variations of the location and orientation. At an air change per hour of 5, the cumulated PM1 mass at the head level was reduced by 75%, independently of the location of the infected dummy, compared to the "natural decay" case, showing that filtration is an effective means of reducing aerosol particle concentrations. Finally, CFD simulation was used to monitor the particle fates. The steady simulation results fit quite well with the experimental findings and provide additional information about the particle path and for assessing the comfort level due to air flow.

16.
Respir Physiol Neurobiol ; 285: 103590, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33271307

RESUMO

Thirteen healthy male subjects (age 28 ±â€¯7 years) performed tests for critical power and W' determination and two square-wave high-intensity exercises until exhaustion either with prior very-heavy intensity cycling (EXP) or without (CON). Prior exercise bout induced a depletion of 60 % of W'. After 10 min of recovery, W' reconstitution was not fully achieved (∼ 92 %). Time to exhaustion and Δ blood lactate concentration were significantly lower in EXP compared to CON (595 ±â€¯118 s vs. 683 ±â€¯148 s; 3.5 ±â€¯1.2 mmol.L-1 vs. 8.8 ±â€¯2.3 mmol.L-1; p < 0.05, respectively). Oxygen uptake (VO2) and heart rate were significantly higher in EXP, during the first 150 s of exercise (p < 0.05). The carbon dioxide production kinetics was significantly slower in EXP (mean response time = 87.8 ±â€¯17.8 s vs. 73.7 ±â€¯16.6 s in CON; p < 0.05). Thus, prior exercise impairs high-intensity cycling performance which can partly be explained by physiological disturbances linked to W' depletion.


Assuntos
Ciclismo/fisiologia , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Adulto , Dióxido de Carbono/metabolismo , Frequência Cardíaca/fisiologia , Humanos , Ácido Láctico/sangue , Masculino , Adulto Jovem
18.
Front Psychiatry ; 11: 690, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765324

RESUMO

BACKGROUND: A growing body of research demonstrated impaired executive functions in individuals with severe obesity, including increased sensitivity to reward and impulsive decision making under risk conditions. For the assessment of decision making in patients with severe obesity, studies widely used the Iowa Gambling Task (IGT) or the Delay Discounting Task (DDT), which cover short-term or long-term consequences of decisions only. A further development originating from the field of addiction research is the Cards and Lottery Task (CLT), in which each decision made has conflicting immediate and long-term consequences at the same time. The present study aimed to validate the CLT in individuals with severe obesity. METHODS: Patients with severe obesity (N = 78, 67% women, 42.9 ± 10.4 years old, body mass index of 48.1 ± 8.3 kg/m2) were included. Convergent validity was evaluated using the computerized Delay Discounting Task and well-established self-report questionnaires assessing different aspects of impulsivity. For discriminant validity, CLT performance was compared between symptom groups characterized by high versus low impulsivity. The task's clinical validity was evaluated based on associations with general and eating disorder psychopathology, and body mass index. Test-retest reliability was determined by administering the CLT in n = 31 participants without weight-loss treatment one year later. The task's sensitivity to change due to weight loss was evaluated by retesting n = 32 patients one year after receiving obesity surgery. RESULTS: The number of advantageous decisions in the CLT was significantly positively associated with delay discounting and effortful control, and significantly negatively correlated with behavioral impulsivity. CLT performance differed significantly between individuals with and without symptoms of attention-deficit/hyperactivity disorder and between samples with severe obesity and healthy controls. Clinically, CLT performance was significantly associated with general, but not eating disorder psychopathology. The CLT showed moderate test-retest reliability after one year in weight-stable individuals and was sensitive to change in those undergoing obesity surgery. CONCLUSIONS: This study identified the CLT to be a highly promising, new complex measure of short- and long-term decision making with good reliability and validity in individuals with severe obesity. Future studies should assess its association with the IGT and predictive value for real-life health behavior.

19.
Biotechnol J ; 15(11): e2000091, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32735401

RESUMO

The current industrial production of polymer building blocks such as ε-caprolactone (ε-CL) and 6-hydroxyhexanoic acid (6HA) is a multi-step process associated with critical environmental issues such as the generation of toxic waste and high energy consumption. Consequently, there is a demand for more eco-efficient and sustainable production routes. This study deals with the generation of a platform organism that converts cyclohexane to such polymer building blocks without the formation of byproducts and under environmentally benign conditions. Based on kinetic and thermodynamic analyses of the individual enzymatic steps, a 4-step enzymatic cascade in Pseudomonas taiwanensis VLB120 is rationally engineered via stepwise biocatalyst improvement on the genetic level. It is found that the intermediate product cyclohexanol severely inhibits the cascade which could be optimized by enhancing the expression level of downstream enzymes. The integration of a lactonase enables exclusive 6HA formation without side products. The resulting biocatalyst shows a high activity of 44.8 ± 0.2 U gCDW -1 and fully converts 5 mm cyclohexane to 6HA within 3 h. This platform organism can now serve as a basis for the development of greener production processes for polycaprolactone and related polymers.


Assuntos
Cicloexanos , Pseudomonas , Biocatálise , Poliésteres , Pseudomonas/genética
20.
J Psychiatr Res ; 129: 214-221, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32781339

RESUMO

Research documented the effectiveness of obesity surgery (OS) for long-term weight loss and improvements in medical and psychosocial sequelae, and general cognitive functioning. However, there is only preliminary evidence for changes in attentional processing of food cues after OS. This study longitudinally investigated visual attention towards food cues from pre- to 1-year post-surgery. Using eye tracking (ET) and a Visual Search Task (VST), attentional processing of food versus non-food cues was assessed in n = 32 patients with OS and n = 31 matched controls without weight-loss treatment at baseline and 1-year follow-up. Associations with experimentally assessed impulsivity and eating disorder psychopathology and the predictive value of changes in visual attention towards food cues for weight loss and eating behaviors were determined. During ET, both groups showed significant gaze duration biases to non-food cues without differences and changes over time. No attentional biases over group and time were found by the VST. Correlations between attentional data and clinical variables were sparse and not robust over time. Changes in visual attention did not predict weight loss and eating disorder psychopathology after OS. The present study provides support for a top-down regulation of visual attention to non-food cues in individuals with severe obesity. No changes in attentional processing of food cues were detected 1-year post-surgery. Further studies are needed with comparable methodology and longer follow-ups to clarify the role of biased visual attention towards food cues for long-term weight outcomes and eating behaviors after OS.


Assuntos
Sinais (Psicologia) , Tecnologia de Rastreamento Ocular , Comportamento Alimentar , Alimentos , Humanos , Obesidade/cirurgia
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