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1.
J Exp Psychol Learn Mem Cogn ; 50(2): 212-229, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37668566

RESUMO

Eye-tracking methodologies have revealed that eye movements and pupil dilations are influenced by our previous experiences. Dynamic fluctuations in pupil size during learning reflect in part the formation of memories for learned information, while viewing behavior during memory testing is influenced by memory retrieval and drawn to previously learned associations. However, no study to date has linked fluctuations in pupil dilation at encoding to the magnitude of viewing behavior at test. The current investigation involved monitoring eye movements both in single item recognition and relational recognition tasks. In the item task, all faces were presented with the same background scene and memory for faces was subsequently tested, whereas in the relational task each face was presented with its own unique background scene and memory for the face-scene association was subsequently tested. Pupil size changes during encoding predicted the magnitude of preferential viewing during test, as well as future recognition accuracy. These effects emerged only in the relational task, but not in the item task, and were replicated in an additional experiment in which stimulus luminance was more tightly controlled. A follow-up experiment and additional analyses ruled out differences in orienting instructions or number of fixations to the encoding display as explanations of the observed effects. The results shed light on the links between pupil dilation, memory encoding, and eye movement patterns during recognition and suggest that trial-level fluctuations in pupil dilation during encoding reflect relational binding of items to their context rather than general memory formation or strength. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Memória , Pupila , Humanos , Reconhecimento Psicológico , Movimentos Oculares , Transtornos da Memória
2.
J Cogn Neurosci ; 36(1): 1-23, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902591

RESUMO

Predicting upcoming words during language comprehension not only affects processing in the moment but also has consequences for memory, although the source of these memory effects (e.g., whether driven by lingering pre-activations, re-analysis following prediction violations, or other mechanisms) remains underspecified. Here, we investigated downstream impacts of prediction on memory in two experiments. First, we recorded EEG as participants read strongly and weakly constraining sentences with expected, unexpected but plausible, or semantically anomalous endings ("He made a holster for his gun / father / train") and were tested on their recognition memory for the sentence endings. Participants showed similar rates of false alarms for predicted but never presented sentence endings whether the prediction violation was plausible or anomalous, suggesting that these arise from pre-activation of the expected words during reading. During sentence reading, especially in strongly constraining sentences, plausible prediction violations elicited an anterior positivity; anomalous endings instead elicited a posterior positivity, whose amplitude was predictive of later memory for those anomalous words. ERP patterns at the time of recognition differentiated plausible and anomalous sentence endings: Words that had been plausible prediction violations elicited enhanced late positive complex amplitudes, suggesting greater episodic recollection, whereas anomalous sentence endings elicited greater N1 amplitudes, suggesting attentional tagging. In a follow-up behavioral study, a separate group of participants read the same sentence stimuli and were tested for sentence-level recall. We found that recall of full sentences was impaired when sentences ended with a prediction violation. Taken together, the results suggest that prediction violations draw attention and affect encoding of the violating word, in a manner that depends on plausibility, and that this, in turn, may impair future memory of the gist of the sentence.


Assuntos
Idioma , Semântica , Masculino , Humanos , Rememoração Mental , Reconhecimento Psicológico/fisiologia , Linguística , Leitura , Eletroencefalografia , Potenciais Evocados/fisiologia , Compreensão/fisiologia
3.
Medicina (Kaunas) ; 59(8)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37629671

RESUMO

Background and Objectives: Trigger points (TrPs) are prevalent in patients with migraine headaches. Needling interventions targeting TrPs in migraine patients may reduce the intensity and frequency of headaches, yet systematic reviews reveal a lack of robust evidence. Intramuscular electrical stimulation (IMES) is a modality that delivers electrical current into muscles and TrPs, with recent studies suggesting it may amplify the therapeutic effects of dry needling peripherally and centrally. This could be advantageous for patients with migraine and symptomatic TrPs. Materials and Methods: This study will implement a multiple baseline single-case experimental design (SCED). In a clinical setting, a SCED study lends itself to conducting research with only a few patients that each serve as their own controls. In this SCED study, four participants with chronic migraine will be enrolled in a non-concurrent manner and randomized to one of four baseline measurement periods (4, 5, 6 or 7 weeks), leading to four potentially different start dates for each participant in the intervention phase. During the intervention phase, patients will receive five sessions of dry needling with IMES, one session per week for five weeks. The primary outcome measure will be headache frequency, i.e., the reduction in the number of headache days over a one-month period using electronic headache diary data from the Migraine Buddy smartphone application. Secondary outcome measures will be changes in mean migraine pain intensity using a numeric pain rating scale (NPRS), migraine disability using the Migraine Disability Assessment Test (MIDAS), the Headache Impact Test (HIT-6), and changes in selected cervical musculoskeletal impairments including pressure pain thresholds (PPTs) over TrPs, the craniocervical flexion test (CCFT), and cervical active range of motion (AROM). Primary and secondary outcome measures will be analyzed separately using both visual and statistical analyses. Results: Actively recruiting participants. This project was approved by the Mass General Brigham Institutional Review Board (protocol #2023P000931) and is registered with ClinicalTrials.gov (NCT05893914). Conclusions: This study will seek to determine the effects of a five-week intervention period of IMES to TrPs in the posterior cervical muscles of subjects with chronic migraine.


Assuntos
Transtornos de Enxaqueca , Projetos de Pesquisa , Humanos , Projetos Piloto , Pontos-Gatilho , Transtornos de Enxaqueca/terapia , Cefaleia , Estimulação Elétrica , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Front Immunol ; 14: 1012799, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36756111

RESUMO

Introduction: Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects. Methods: To measure the spatiotemporal kinetics of local andabscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and contralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry. Results: Unilateral histotripsy triggered abscopal tumor growth inhibition. Within the ablation zone, early high mobility group box protein 1 (HMGB1) release and necroptosis were accompanied by immunogenic cell death transcriptional responses in tumor cells and innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Delayed CD8+ T cell intratumoral infiltration was spatiotemporally aligned with cancer cell features of ferroptosis; this effect was enhanced by CTLA-4 blockade and recapitulated in vitro when tumor-draining lymph node CD8+ T cells were co-cultured with tumor cells. Inoculation with cell-free tumor fractions generated by histotripsy but not radiation or freeze/thaw conferred partial protection from tumor challenge. Discussion: We propose that histotripsy may evoke local necroptotic immunogenic cell death, priming systemic adaptive immune responses and abscopal ferroptotic cancer cell death.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Camundongos Endogâmicos C57BL , Morte Celular , Carcinoma Hepatocelular/terapia , Imunidade
5.
Psychophysiology ; 60(8): e14269, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36762757

RESUMO

When reading, comprehenders construct a message-level representation and integrate new information as it becomes available. Such compositional processing may differ for idioms, where the meanings of the individual words do not always relate to the figurative meaning. Here, we examined how predictability and idiom decomposability contribute to compositional processing. Participants' EEG was recorded while they read sentences containing idioms that varied in decomposability and phrase-final word cloze probability, or their literal match (break the ice/slip on the ice) with little context prior to the phrase, along with adjective insertion conditions (break the freezing ice/slip on the freezing ice). Cloze probability modulated N400 amplitudes to critical words for both idiomatic and literal phrases, whereas P600 amplitudes only elicited by idiomatic phrases were also modulated. Phrases with adjective insertions reduced acceptability judgments, particularly for idioms, and led to N400 amplitude differences compared to critical words, but only for idioms. N400 differences were also found between idiomatic and literal contexts at the point of adjective insertion. Additionally, both cloze probability and decomposability modulated gamma band activity, with greater gamma activity for more predictable and less decomposable idioms, but at different times and with different scalp topographies, suggesting dissociable components of processing. These results support a hybrid model of processing in which multiple linguistic factors determine the type of processing engaged by the brain to comprehend non-literal language. When prior context is minimal, compositional processing may still be engaged when reading idioms.


Assuntos
Compreensão , Eletroencefalografia , Humanos , Masculino , Feminino , Gelo , Potenciais Evocados , Idioma , Semântica
6.
J Neurosci ; 43(11): 1963-1975, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36810228

RESUMO

Humans have the ability to intentionally forget information via different strategies, included suppression of encoding (directed forgetting) and mental replacement of the item to encode (thought substitution). These strategies may rely on different neural mechanisms; namely, encoding suppression may induce prefrontally mediated inhibition, whereas thought substitution is potentially accomplished through modulating contextual representations. Yet, few studies have directly related inhibitory processing to encoding suppression, or tested its involvement in thought substitution. Here, we directly tested whether encoding suppression recruits inhibitory mechanisms with a cross-task design, relating the behavioral and neural data from male and female participants in a Stop Signal task (a task specifically testing inhibitory processing) to a directed forgetting task with both encoding suppression (Forget) and thought substitution (Imagine) cues. Behaviorally, Stop Signal task performance (stop signal reaction times) was related to the magnitude of encoding suppression, but not thought substitution. Two complementary neural analyses corroborated the behavioral result. Namely, brain-behavior analysis demonstrated that the magnitude of right-frontal beta activity following stop signals was related to stop signal reaction times and successful encoding suppression, but not thought substitution; and classifiers trained to discriminate successful and unsuccessful stopping in the Stop Signal task could also classify successful and unsuccessful forgetting following Forget cues, but not Imagine cues. Importantly, inhibitory neural mechanisms were engaged following Forget cues at a later time than motor stopping. These findings not only support an inhibitory account of directed forgetting, and that thought substitution engages separate mechanisms, but also potentially identify a specific time in which inhibition occurs when suppressing encoding.SIGNIFICANCE STATEMENT Forgetting often seems like an unintended experience, but forgetting can be intentional, and can be accomplished with multiple strategies. These strategies, including encoding suppression and thought substitution, may rely on different neural mechanisms. Here, we test the hypothesis that encoding suppression engages domain-general prefrontally driven inhibitory control mechanisms, while thought substitution does not. Using cross-task analyses, we provide evidence that encoding suppression engages the same inhibitory mechanisms used for stopping motor actions, but these mechanisms are not engaged by thought substitution. These findings not only support the notion that mnemonic encoding processes can be directly inhibited, but also have broad relevance, as certain populations with disrupted inhibitory processing may be more successful accomplishing intentional forgetting through thought substitution strategies.


Assuntos
Encéfalo , Memória , Humanos , Masculino , Feminino , Memória/fisiologia , Encéfalo/fisiologia , Sinais (Psicologia) , Tempo de Reação/fisiologia , Inibição Psicológica , Rememoração Mental/fisiologia
7.
Med Health Care Philos ; 25(3): 541-544, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35581459

RESUMO

In this article, we argue that physicians have normative authority over patients. First we elaborate on the nature of normative authority. We then examine and critique Arthur Isak Applbaum's view that physicians lack authority over patients. Our argument appeals to four cases that demonstrate physicians' authority.


Assuntos
Médicos , Dissidências e Disputas , Humanos
8.
AMA J Ethics ; 23(11): E864-868, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34874255

RESUMO

Health professionals seeking religious exemption from caring for some patients or providing some interventions receive robust legal protection. Similarly, religiously affiliated organizations have great latitude in deciding which services to offer. These protections could soon become stronger, as the US Supreme Court considers 2 cases that revisit constraints on exemption claims established in Employment Division, Department of Human Resources of Oregon v Smith (1990). This article contends that overturning this case's precedent might result in clinicians claiming more religious exemptions, which, barring acts of US Congress, would erode the rule of law and increase risk of harm to patients.


Assuntos
Emprego , Humanos , Estados Unidos
9.
Netw Neurosci ; 5(3): 734-756, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746625

RESUMO

Metamemory involves the ability to correctly judge the accuracy of our memories. The retrieval of memories can be improved using transcranial electrical stimulation (tES) during sleep, but evidence for improvements to metamemory sensitivity is limited. Applying tES can enhance sleep-dependent memory consolidation, which along with metamemory requires the coordination of activity across distributed neural systems, suggesting that examining functional connectivity is important for understanding these processes. Nevertheless, little research has examined how functional connectivity modulations relate to overnight changes in metamemory sensitivity. Here, we developed a closed-loop short-duration tES method, time-locked to up-states of ongoing slow-wave oscillations, to cue specific memory replays in humans. We measured electroencephalographic (EEG) coherence changes following stimulation pulses, and characterized network alterations with graph theoretic metrics. Using machine learning techniques, we show that pulsed tES elicited network changes in multiple frequency bands, including increased connectivity in the theta band and increased efficiency in the spindle band. Additionally, stimulation-induced changes in beta-band path length were predictive of overnight changes in metamemory sensitivity. These findings add new insights into the growing literature investigating increases in memory performance through brain stimulation during sleep, and highlight the importance of examining functional connectivity to explain its effects.

10.
Cortex ; 142: 317-331, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34343901

RESUMO

Psychological and neuroscientific experiments have established that people can intentionally forget information via different strategies: direct suppression and thought substitution. However, few studies have directly compared the effectiveness of these strategies in forgetting specific items, and it remains an open question if the neural mechanisms supporting these strategies differ. Here, we developed a novel item-method directed forgetting paradigm with Remember, Forget, and Imagine cues, and recorded EEG to directly compare these strategies. Behaviorally, Forget and Imagine cues produced similar forgetting compared to Remember cues, but through separable neural processes; Forget cues elicited frontal oscillatory power changes that were predictive of future forgetting, whereas item-cue representational similarity was predictive of later accuracy for Imagine cues. These results suggest that both strategies can lead to intentional forgetting, but directed forgetting may rely on frontally-mediated suppression, while thought substitution may lead to contextual shifting, impairing successful retrieval.


Assuntos
Sinais (Psicologia) , Rememoração Mental , Humanos , Projetos de Pesquisa
11.
Cereb Cortex ; 31(9): 4300-4313, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-33895819

RESUMO

Predicting upcoming events is a critical function of the brain, and language provides a fertile testing ground for studying prediction, as comprehenders use context to predict features of upcoming words. Many aspects of the mechanisms of prediction remain elusive, partly due to a lack of methodological tools to probe prediction formation in the moment. To elucidate what features are neurally preactivated and when, we used representational similarity analysis on previously collected sentence reading data. We compared EEG activity patterns elicited by expected and unexpected sentence final words to patterns from the preceding words of the sentence, in both strongly and weakly constraining sentences. Pattern similarity with the final word was increased in an early time window following the presentation of the pre-final word, and this increase was modulated by both expectancy and constraint. This was not seen at earlier words, suggesting that predictions were precisely timed. Additionally, pre-final word activity-the predicted representation-had negative similarity with later final word activity, but only for strongly expected words. These findings shed light on the mechanisms of prediction in the brain: rapid preactivation occurs following certain cues, but the predicted features may receive reduced processing upon confirmation.


Assuntos
Antecipação Psicológica/fisiologia , Encéfalo/fisiologia , Compreensão/fisiologia , Eletroencefalografia/métodos , Idioma , Estimulação Luminosa/métodos , Adolescente , Adulto , Feminino , Previsões , Humanos , Masculino , Adulto Jovem
12.
Brain Res ; 1764: 147466, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33861998

RESUMO

Although we often seem to successfully comprehend language in the face of distraction, few studies have examined the role of sustained attention in critical components of sentence processing, such as integrating information over a sentence and revising predictions when unexpected information is encountered. The current study investigated the impact of attention on sentence processing using a novel dual-task paradigm. Participants read weakly and strongly constraining sentences with expected or unexpected endings while also tracking the motion of dots in the background, and their EEG was recorded. Under full attention, the amplitude of the N400 component of the ERP, a measure of semantic access, was reduced (facilitated) in a graded fashion by contextual strength and fit. This context-based facilitation was attenuated when attention was divided, suggesting that sustained attention is important for building up message-level representations. In contrast, the post-N400 frontal positivity that has been observed to prediction violations and associated with revision processes was unaffected by dividing attention. However, under divided attention, participants also elicited posteriorly-distributed effects to these violations. Thus, predictive processes seem to be engaged even when attention is divided, but additional resources may then be required to process unexpected information.


Assuntos
Atenção/fisiologia , Compreensão/fisiologia , Idioma , Adolescente , Adulto , Eletroencefalografia , Potenciais Evocados , Feminino , Lobo Frontal/fisiologia , Humanos , Masculino , Desempenho Psicomotor , Tempo de Reação , Adulto Jovem
13.
Sci Eng Ethics ; 26(6): 3217-3227, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32960411

RESUMO

The increasing accuracy of algorithms to predict values and preferences raises the possibility that artificial intelligence technology will be able to serve as a surrogate decision-maker for incapacitated patients. Following Camillo Lamanna and Lauren Byrne, we call this technology the autonomy algorithm (AA). Such an algorithm would mine medical research, health records, and social media data to predict patient treatment preferences. The possibility of developing the AA raises the ethical question of whether the AA or a relative ought to serve as surrogate decision-maker in cases where the patient has not issued a medical power of attorney. We argue that in such cases, and against the standard practice of vesting familial surrogates with decision making authority, the AA should have sole decision-making authority. This is because the AA will likely be better at predicting what treatment option the patient would have chosen. It would also be better at avoiding bias and, therefore, choosing in a more patient-centered manner. Furthermore, we argue that these considerations override any moral weight of the patient's special relationship with their relatives.


Assuntos
Inteligência Artificial , Tomada de Decisões , Humanos , Princípios Morais , Preferência do Paciente
14.
Contemp Clin Trials Commun ; 17: 100549, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32154432

RESUMO

Previous observational studies have shown that the endocrine disrupting chemical bisphenol A (BPA) is associated with type 2 diabetes, but few studies have examined direct effects of BPA on human health. The purpose of this study is to determine whether orally administered BPA at the US Environmental Protection Agency (EPA) safe dose of 50 µg/kg body weight has an adverse effect on hepatic glucose production and skeletal muscle insulin sensitivity. Forty, non-habitually active, healthy adults of normal weight will be enrolled. Participants will begin with a 2-day baseline energy balance diet low in bisphenols in which urine and blood will be collected, and standard tests performed to assess the primary outcome measures of hepatic glucose production (via [6,6-2H] glucose infusion) and skeletal muscle insulin sensitivity (via euglycemic hyperinsulinemic clamp technique). Secondary outcome measures are fasting hormones/endocrine factors (insulin, glucose, C-peptide, Pro-insulin, adiponectin, 17-beta-estradiol, free fatty acids) related to the pathogenesis of type 2 diabetes. Participants will then be randomly assigned to a 4-day energy balance diet plus oral administration of BPA at 50 µg/kg body weight (Diet + BPA) or 4-day energy balance diet plus oral administration of placebo (Diet + No BPA); all outcome measures will be reassessed after 4 days. Findings from this study will provide a framework for other studies in this area, and provide much needed experimental evidence using gold standard measures as to whether oral BPA administration over several days poses any risk of type 2 diabetes.

15.
Orthop J Sports Med ; 8(2): 2325967119900958, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118081

RESUMO

BACKGROUND: Approximately 47 million people in the United States have been diagnosed with arthritis. Autologous platelet-rich plasma (PRP) injections have been documented to alleviate symptoms related to knee osteoarthritis (OA) in randomized controlled trials, systematic reviews, and meta-analyses. Autologous bone marrow aspirate concentrate (BMC) injections have also emerged as a treatment option for knee OA, with a limited clinical evidence base. PURPOSE: To compare the efficacy of BMC to PRP for the treatment of knee OA regarding pain and function at multiple time points up to 12 months after an injection. We hypothesized that BMC will be more effective in improving outcomes in patients with knee OA. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 90 participants aged between 18 and 80 years with symptomatic knee OA (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaires before and 1, 3, 6, 9, and 12 months after a single intra-articular injection of leukocyte-rich PRP or BMC. RESULTS: There were no statistically significant differences in baseline IKDC or WOMAC scores between the 2 groups. All IKDC and WOMAC scores for both the PRP and BMC groups significantly improved from baseline to 1 month after the injection (P < .001). These improvements were sustained for 12 months after the injection, with no difference between PRP and BMC at any time point. CONCLUSION: Both PRP and BMC were effective in improving patient-reported outcomes in patients with mild to moderate knee OA for at least 12 months; neither treatment provided a superior clinical benefit. Autologous PRP and BMC showed promising clinical potential as therapeutic agents for the treatment of OA, and while PRP has strong clinical evidence to support its efficacy, BMC has limited support. This study did not prove BMC to be superior to PRP, providing guidance to clinicians treating OA. It is possible that the results were affected by patients knowing that there was no control group. REGISTRATION: NCT03289416 (ClinicalTrials.gov identifier).

16.
J Immunother Cancer ; 8(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31940590

RESUMO

BACKGROUND: Developing the ability to use tumor-directed therapies to trigger potentially therapeutic immune responses against cancer antigens remains a high priority for cancer immunotherapy. We hypothesized that histotripsy, a novel non-invasive, non-thermal ablation modality that uses ultrasound-generated acoustic cavitation to disrupt tissues, could engender adaptive immune responses to tumor antigens. METHODS: Immunocompetent C57BL/6 mice inoculated with flank melanoma or hepatocellular carcinoma tumors were treated with histotripsy, thermal ablation, radiation therapy, or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) blockade checkpoint inhibition. Lymphocyte responses were measured using flow cytometric and immunohistochemical analyses. The impact of histotripsy on abscopal immune responses was assessed in mice bearing bilateral tumors, or unilateral tumors with pulmonary tumors established via tail vein injection. RESULTS: Histotripsy ablation of subcutaneous murine melanoma tumors stimulated potent local intratumoral infiltration of innate and adaptive immune cell populations. The magnitude of this immunostimulation was stronger than that seen with tumor irradiation or thermal ablation. Histotripsy also promoted abscopal immune responses at untreated tumor sites and inhibited growth of pulmonary metastases. Histotripsy was capable of releasing tumor antigens with retained immunogenicity, and this immunostimulatory effect was associated with calreticulin translocation to the cellular membrane and local and systemic release of high mobility group box protein 1. Histotripsy ablation potentiated the efficacy of checkpoint inhibition immunotherapy in murine models of melanoma and hepatocellular carcinoma. CONCLUSIONS: These preclinical observations suggest that non-invasive histotripsy ablation can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy.


Assuntos
Técnicas de Ablação/métodos , Antineoplásicos Imunológicos/farmacologia , Antígeno CTLA-4/antagonistas & inibidores , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Neoplasias Hepáticas Experimentais/terapia , Melanoma Experimental/terapia , Animais , Terapia Combinada , Neoplasias Hepáticas Experimentais/imunologia , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL
17.
BME Front ; 20202020.
Artigo em Inglês | MEDLINE | ID: mdl-34327513

RESUMO

OBJECTIVE AND IMPACT STATEMENT: This is the first longitudinal study investigating the effects of histotripsy on local tumor progression in an in vivo orthotopic, immunocompetent rat hepatocellular carcinoma (HCC) model. INTRODUCTION: Histotripsy is the first noninvasive, nonionizing, nonthermal, mechanical ablation technique using ultrasound to generate acoustic cavitation to liquefy the target tissue into acellular debris with millimeter accuracy. Previously, histotripsy has demonstrated in vivo ablation of noncancerous liver tissue. METHODS: N1-S1 HCC tumors were generated in the livers of immunocompetent rats (n = 6, control; n = 15, treatment). Real-time ultrasound-guided histotripsy was applied to ablate either 100% tumor volume + up to 2mm margin (n = 9, complete treatment) or 50-75% tumor volume (n = 6, partial treatment) by delivering 1-2 cycle histotripsy pulses at 100 Hz PRF (pulse repetition frequency) with p - ≥30MPa using a custom 1MHz transducer. Rats were monitored weekly using MRI (magnetic resonance imaging) for 3 months or until tumors reached ~25mm. RESULTS: MRI revealed effective post-histotripsy reduction of tumor burden with near-complete resorption of the ablated tumor in 14/15 (93.3%) treated rats. Histopathology showed <5mm shrunken, non-tumoral, fibrous tissue at the treatment site at 3 months. Rats with increased tumor burden (3/6 control and 1 partial treatment) were euthanized early by 2-4 weeks. In 3 other controls, histology revealed fibrous tissue at original tumor site at 3 months. There was no evidence of histotripsy-induced off-target tissue injury. CONCLUSION: Complete and partial histotripsy ablation resulted in effective tumor removal for 14/15 rats, with no evidence of local tumor progression or recurrence.

18.
Front Hum Neurosci ; 13: 339, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680902

RESUMO

It is well-established that aging impairs memory for associations more than it does memory for single items. Aging also impacts processes involved in online language comprehension, including the ability to form integrated, message-level representations. These changes in comprehension processes could impact older adults' associative memory performance, perhaps by reducing or altering the effectiveness of encoding strategies that encourage semantic integration. The present study examined age differences in the use of a strategy termed conceptual combination, which involves integrating two words (e.g., "winter" and "salad") into a single concept ("a salad for winter"). We recorded ERPs while participants studied unrelated noun pairs using a strategy that either did or did not encourage conceptual combination. We also varied the concreteness of the first noun in each pair in order to measure compositional concreteness effects, or ERP differences at the second noun due to the concreteness of the first noun. At the first nouns, older adults showed word-level concreteness effects that were similar to those of younger adults. However, compositional concreteness effects were diminished in older adults, consistent with reduced semantic integration. Older adults' associative memory performance was better for word pairs studied during the conceptual combination task versus the non-combinatory encoding task; however, the magnitude of the age-related associative memory deficit did not differ between tasks. Finally, analyses of both memory accuracy and trial-by-trial ratings of perceived combination success suggested that older adults had disproportionate difficulty applying the conceptual combination strategy to word pairs that began with abstract nouns. Overall, these results indicate that changes to integrative language processing that occur with age are not independent of - and may sometimes exacerbate - age-related memory decline.

20.
Front Hum Neurosci ; 13: 291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555111

RESUMO

When people process language, they can use context to predict upcoming information, influencing processing and comprehension as seen in both behavioral and neural measures. Although numerous studies have shown immediate facilitative effects of confirmed predictions, the downstream consequences of prediction have been less explored. In the current study, we examined those consequences by probing participants' recognition memory for words after they read sets of sentences. Participants read strongly and weakly constraining sentences with expected or unexpected endings ("I added my name to the list/basket"), and later were tested on their memory for the sentence endings while EEG was recorded. Critically, the memory test contained words that were predictable ("list") but were never read (participants saw "basket"). Behaviorally, participants showed successful discrimination between old and new items, but false alarmed to the expected-item lures more often than to new items, showing that predicted words or concepts can linger, even when predictions are disconfirmed. Although false alarm rates did not differ by constraint, event-related potentials (ERPs) differed between false alarms to strongly and weakly predictable words. Additionally, previously unexpected (compared to previously expected) endings that appeared on the memory test elicited larger N1 and LPC amplitudes, suggesting greater attention and episodic recollection. In contrast, highly predictable sentence endings that had been read elicited reduced LPC amplitudes during the memory test. Thus, prediction can facilitate processing in the moment, but can also lead to false memory and reduced recollection for predictable information.

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