RESUMO
BACKGROUND: Late-life depression (LLD) is characterized by a poor response to antidepressant medications and diminished cognitive performance, particularly in executive functioning. There is currently no accepted pharmacotherapy for LLD that effectively treats both mood and cognitive symptoms. This study investigated whether transdermal nicotine augmentation of standard antidepressant medications benefitted mood and cognitive symptoms in LLD. METHODS: Nonsmoking participants aged 60 years or older with unremitted LLD on stable SSRI or SNRI medications (N = 29) received transdermal nicotine patches up to a 21 mg daily dose over 12 weeks. Clinical measures assessed depression severity, secondary affective symptoms, and cognitive performance. Nicotine metabolite concentrations were obtained from blood samples. RESULTS: Depression severity significantly decreased over the trial, with a 76 % response rate and 59 % remission rate. Change in depression severity was positively associated with nicotine exposure. Participants also exhibited improvement in self-reported affective symptoms (apathy, insomnia, rumination, and generalized anxiety symptoms), negativity bias, and disability. Executive function test performance significantly improved, specifically in measures of cognitive control, as did subjective cognitive performance. Adverse events were generally mild, with 75 % of the sample tolerating the maximum dose. CONCLUSION: The current study extends our previous pilot open-label trial in LLD, supporting feasibility and tolerability of transdermal nicotine patches as antidepressant augmentation. Although preliminary, this open-label study supports the potential benefit of transdermal nicotine patches for both mood and cognitive symptoms of LLD. Further research, including definitive randomized, blinded trials, is warranted to confirm these findings and explore long-term risk and benefit. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT04433767).
Assuntos
Afeto , Antidepressivos , Função Executiva , Nicotina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração Cutânea , Afeto/efeitos dos fármacos , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Quimioterapia Combinada , Função Executiva/efeitos dos fármacos , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Nicotina/uso terapêutico , Dispositivos para o Abandono do Uso de Tabaco , Resultado do TratamentoRESUMO
OBJECTIVES: This study aimed to identify enablers and barriers to participation in MRI for clinical indications and scientific research, and to determine the perceptions of MRI performed during pregnancy. METHODS: We conducted a survey of 156 pregnant people in Newfoundland and Labrador including sociodemographic information, obstetrical history, MRI history, and willingness to participate in an MRI. Categorical variables were analyzed using a Fisher exact test and open-ended questions were analyzed using thematic analysis. RESULTS: In total, 80% of participants reported willingness to receive an MRI while pregnant for clinical indications compared to 24% for research. Only 10% reported prior knowledge about MRI during pregnancy and most participants (94%) wanted additional information from their physician before feeling comfortable with the procedure. Participants who knew someone with complications during pregnancy were more likely to be willing to participate in an MRI for research (uncorrected P < 0.05). Participants' positive perceptions towards MRI during pregnancy for clinical indications were that it was a necessary and useful procedure, while the negative perceptions identified MRI as unsafe. For research MRI, participants' positive perceptions included that it would add to the advancement of knowledge and the negative perceptions were that it was an unnecessary and risky procedure. CONCLUSIONS: Strategies are needed to improve patient knowledge about the benefits and safety of MRI during pregnancy. The present study suggests recruitment for research should incorporate education on safety concerns and relative risk, personal stories about the benefits of MRI in diagnosing pregnancy complications and should highlight the contribution to advancing scientific knowledge.
Assuntos
Imageamento por Ressonância Magnética , Médicos , Feminino , Gravidez , Humanos , Terra Nova e Labrador , Inquéritos e QuestionáriosRESUMO
When deciding what images we prefer, our brain must weigh many aesthetic variables, such as symmetry and complexity. To date, aesthetic research has mainly focused on investigating one variable at a time. In this article, we use symmetry and complexity to study the problem of multi aesthetic-variable interactions. For symmetry and complexity, there are two simple interaction hypotheses. The independence hypothesis proposes that the evaluation of aesthetic variables is mutually independent. Meanwhile, Birkhoff's aesthetic-measure hypothesis predicts that people prefer images high in symmetry and low in complexity, and dislike the opposite. To test these hypotheses, we generated images that systematically varied in levels of symmetry and complexity. We then compared the subjects' preference maps to identify regions of likes and dislikes. Unlike the predictions from these hypotheses, we found that most, but not all subjects, formed two distinct natural clusters, termed "islands," in terms of likes and dislikes. We also found that people with more art exposure were less likely to belong to an island. If someone did belong to an island, their gender influenced which cluster they belonged to. We discuss alternate hypotheses, possible mechanisms for the occurrence of islands, and their possible social implications.
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Encéfalo , Grupo Social , Humanos , Estética , EmoçõesRESUMO
Spinocerebellar ataxia type 1 (SCA1) is a dominant trinucleotide repeat neurodegenerative disease characterized by motor dysfunction, cognitive impairment, and premature death. Degeneration of cerebellar Purkinje cells is a frequent and prominent pathological feature of SCA1. We previously showed that transport of ATXN1 to Purkinje cell nuclei is required for pathology, where mutant ATXN1 alters transcription. To examine the role of ATXN1 nuclear localization broadly in SCA1-like disease pathogenesis, CRISPR-Cas9 was used to develop a mouse with an amino acid alteration (K772T) in the nuclear localization sequence of the expanded ATXN1 protein. Characterization of these mice indicates that proper nuclear localization of mutant ATXN1 contributes to many disease-like phenotypes including motor dysfunction, cognitive deficits, and premature lethality. RNA sequencing analysis of genes with expression corrected to WT levels in Atxn1175QK772T/2Q mice indicates that transcriptomic aspects of SCA1 pathogenesis differ between the cerebellum, brainstem, cerebral cortex, hippocampus, and striatum.
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Ataxina-1 , Ataxias Espinocerebelares , Transcriptoma , Animais , Camundongos , Ataxina-1/genética , Ataxina-1/metabolismo , Encéfalo/metabolismo , Cerebelo/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Fenótipo , Transporte Proteico/genética , Células de Purkinje/metabolismo , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/metabolismoRESUMO
Breakfast cereals are often consumed with dairy products or nondairy alternatives; however, the effect of the combination on blood glucose and food intake control is not well investigated. In a randomized, crossover study, 24 healthy women (age: 22.7 ± 2.5 years; body mass index: 22.1 ± 1.5 kg/m2) consumed, to satiation, 1 of 3 treatments: Greek yogurt with granola (150 kcal, 9.2 g protein, 2.6 g fat, 2.0 g dietary fibre, and 21.5 g available carbohydrate/100 g); cultured coconut product with granola (146 kcal, 3.2 g protein, 3.2 g fat, 5.6 g dietary fibre, and 21.9 g available carbohydrate/100 g); or water control. The data were analyzed with repeated-measures ANOVA. The 2 h blood glucose iAUC was 52% lower after the dairy compared with nondairy treatment (P < 0.0001). While there were no differences in food intake between the caloric treatments consumed to satiation, protein intake was 3 times higher and fibre intake was 4 times lower after the dairy compared with nondairy treatment. Both caloric treatments resulted in similar suppression of ad libitum food intake at 2 h (P < 0.003) and subjective appetite over 2 h (P < 0.0001) compared with water. The cumulative food intake over 2 h was lower after water (P < 0.05). The 1.8-fold increase in postprandial insulin after dairy compared with nondairy treatment may explain the reduction in blood glucose without an increase in subsequent energy intake. Novelty Blood glucose in young females is lower after a breakfast with granola in a high-protein cultured dairy than when in a high-fibre nondairy cultured product. Subjective appetite over 2 h and food intake 2 h later was similarly lower after both breakfasts but cumulative intake was higher compared with breakfast skipping.