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BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.
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Neoplasias da Mama , Criocirurgia , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estudos ProspectivosRESUMO
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.
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Neoplasias da Mama , Neoplasias Ovarianas , Neoplasias Pancreáticas , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Humanos , Masculino , Mutação , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genéticaRESUMO
Emotional eating (EE) has been proposed as a key weight loss barrier. However, most investigations of EE rely on retrospective self-reports, which may have poor construct validity. This study evaluated concordance between a common self-report EE measure and a novel method for assessing momentary EE using ecological momentary assessment (EMA). We further assessed the utility of both measures for predicting both BMI and weight outcomes. Participants with overweight or obesity enrolled in a weight loss trial (N = 163) completed a self-report measure of EE and underwent an EMA protocol that assessed momentary emotions and eating behaviors. Momentary EE was derived from EMA data using generalized linear mixed-effects models. Linear regression models examined associations between both EE measures and concurrent BMI as well as weight losses over 30 months. Retrospectively self-reported EE and momentary EE were negatively correlated with one another (r = -0.27). Higher momentary EE and higher retrospectively reported EE both predicted higher concurrent BMI, and higher retrospectively reported EE predicted poorer weight loss outcomes at all time points (p < 0.05). By contrast, higher momentary EE predicted improved weight outcomes at 1-year and 2-year follow-up (p < 0.05). Our findings extend prior research suggesting that retrospective self-report EE measures capture a different construct than intended and suggest that momentary EE could predict improved weight loss outcomes.
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Emoções , Comportamento Alimentar , Avaliação Momentânea Ecológica , Humanos , Sobrepeso , Estudos RetrospectivosRESUMO
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.
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Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Biomarcadores Tumorais , Feminino , Estudos de Associação Genética , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Humanos , Síndromes Neoplásicas Hereditárias/terapia , Penetrância , Neoplasias PancreáticasRESUMO
OBJECTIVE: Self-compassion meditation, which involves compassion toward the self in moments of suffering, shows promise for improving pain-related functioning, but its underlying mechanisms are unknown. This longitudinal, exploratory pilot study investigated the effects of a brief (eight contact hours, two weeks of home practice) self-compassion training on pain-related brain processing in chronic low back pain (cLBP). METHODS: We evaluated functional magnetic resonance imaging (fMRI) response to evoked pressure pain and its anticipation during a self-compassionate state and compared altered brain responses following training with changes on self-reported measures of self-compassion (Self-Compassion Scale [SCS]), interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness [MAIA]), and clinical pain intensity. RESULTS: In a sample of participants with cLBP (N = 20 total, N = 14 with complete longitudinal data) who underwent self-compassion training, we observed reduced clinical pain intensity and disability (P < 0.01) and increased trait self-compassion and interoceptive awareness (all P < 0.05) following training. Evoked pressure pain response in the right temporo-parietal junction (TPJ) was reduced following training, and decreases were associated with reduced clinical pain intensity. Further, increased fMRI responses to pain anticipation were observed in the right dorsolateral prefrontal cortex (dlPFC) and ventral posterior cingulate cortex (vPCC), and these increases were associated with mean post-training changes in SCS scores and scores from the body listening subscale of the MAIA. DISCUSSION: These findings, though exploratory and lacking comparison with a control condition, suggest that self-compassion training supports regulation of pain through the involvement of self-referential (vPCC), salience-processing (TPJ), and emotion regulatory (dlPFC) brain areas. The results also suggest that self-compassion could be an important target in the psychotherapeutic treatment of cLBP, although further studies using controlled experimental designs are needed to determine the specificity of these effects.
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Dor Crônica , Dor Lombar , Meditação , Dor Crônica/terapia , Empatia , Humanos , Dor Lombar/terapia , Imageamento por Ressonância Magnética , Projetos PilotoRESUMO
OBJECTIVE: Fibromyalgia (FM) is characterized by pervasive pain-related symptomatology and high levels of negative affect. Mind-body treatments such as cognitive behavioral therapy (CBT) appear to foster improvement in FM via reductions in pain-related catastrophizing, a set of negative, pain-amplifying cognitive and emotional processes. However, the neural underpinnings of CBT's catastrophizing-reducing effects remain uncertain. This randomized controlled mechanistic trial was designed to assess CBT's effects on pain catastrophizing and its underlying brain circuitry. METHODS: Of 114 enrolled participants, 98 underwent a baseline neuroimaging assessment and were randomized to 8 weeks of individual CBT or a matched FM education control (EDU) condition. RESULTS: Compared with EDU, CBT produced larger decreases in pain catastrophizing post treatment (P < 0.05) and larger reductions in pain interference and symptom impact. Decreases in pain catastrophizing played a significant role in mediating those functional improvements in the CBT group. At baseline, brain functional connectivity between the ventral posterior cingulate cortex (vPCC), a key node of the default mode network (DMN), and somatomotor and salience network regions was increased during catastrophizing thoughts. Following CBT, vPCC connectivity to somatomotor and salience network areas was reduced. CONCLUSION: Our results suggest clinically important and CBT-specific associations between somatosensory/motor- and salience-processing brain regions and the DMN in chronic pain. These patterns of connectivity may contribute to individual differences (and treatment-related changes) in somatic self-awareness. CBT appears to provide clinical benefits at least partially by reducing pain-related catastrophizing and producing adaptive alterations in DMN functional connectivity.
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Dor Crônica , Terapia Cognitivo-Comportamental , Fibromialgia , Humanos , Fibromialgia/diagnóstico por imagem , Fibromialgia/terapia , Dor Crônica/diagnóstico por imagem , Dor Crônica/terapia , Dor Crônica/psicologia , Terapia Cognitivo-Comportamental/métodos , Encéfalo/diagnóstico por imagem , NeuroimagemRESUMO
Automated digital interventions for weight loss represent a highly scalable and potentially cost-effective approach to treat obesity. However, current understanding of the active components of automated digital interventions is limited, hindering efforts to improve efficacy. Thus, the current systematic review and meta-analysis (preregistration: PROSPERO 2021-CRD42021238878) examined relationships between utilisation of behaviour change techniques (BCTs) and the efficacy of automated digital interventions for producing weight loss. Electronic database searches (December 2020 to March 2021) were used to identify trials of automated digital interventions reporting weight loss as an outcome. BCT clusters were coded using Michie's 93-item BCT taxonomy. Mixed-effects meta-regression was used to examine moderating effects of BCT clusters and techniques on both within-group and between-group measures of weight change. One hundred and eight conditions across sixty-six trials met inclusion criteria (13,672 participants). Random-effects meta-analysis revealed a small mean post-intervention weight loss of -1.37â kg (95% CI, -1.75 to -1.00) relative to control groups. Interventions utilised a median of five BCT clusters, with goal-setting, feedback and providing instruction on behaviour being most common. Use of Reward and Threat techniques, and specifically social incentive/reward BCTs, was associated with a higher between-group difference in efficacy, although results were not robust to sensitivity analyses.
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Terapia Comportamental , Obesidade , Humanos , Terapia Comportamental/métodos , Obesidade/prevenção & controleRESUMO
OBJECTIVE: Binge-eating disorder (BED) is highly comorbid with obesity. Weight loss may benefit individuals with BED; however, these individuals are often excluded from behavioral weight loss interventions (BWLIs), and findings from BWLIs including participants with and without BED are mixed. To the authors' knowledge, this study represents the first meta-analysis of weight loss outcomes of individuals with and without BED in BWLIs, while adjusting for weight-influencing variables. Treatment dropout rates were also examined. METHODS: Electronic search engines and grey literature search methods were used to identify manuscripts published through December 2022 related to BWLIs and BED. Thirty manuscripts (BED n = 1519; 25 non-BED n = 6345) were included. RESULTS: A meta-regression found that individuals with BED lost less weight compared with individuals without BED (~1.4 kg; ~2.9 kg among studies without meal replacements), but they still lost ~8.1 kg at post-treatment. A random-effects model showed that BED diagnosis increased odds of treatment dropout by 50%. CONCLUSIONS: BWLIs produced robust weight loss in those with BED, but those with BED lost less weight and had higher risk of dropout compared with those without. Future research should aim to close the gap in weight loss outcomes and retention between those with and without BED.
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Transtorno da Compulsão Alimentar , Humanos , Transtorno da Compulsão Alimentar/terapia , Transtorno da Compulsão Alimentar/diagnóstico , Resultado do Tratamento , Redução de Peso , Obesidade/terapia , Terapia ComportamentalRESUMO
Gold standard behavioral weight loss (BWL) is limited by the availability of expert clinicians and high cost of delivery. The artificial intelligence (AI) technique of reinforcement learning (RL) is an optimization solution that tracks outcomes associated with specific actions and, over time, learns which actions yield a desired outcome. RL is increasingly utilized to optimize medical treatments (e.g., chemotherapy dosages), and has very recently started to be utilized by behavioral treatments. For example, we previously demonstrated that RL successfully optimized BWL by dynamically choosing between treatments of varying cost/intensity each week for each participant based on automatic monitoring of digital data (e.g., weight change). In that preliminary work, participants randomized to the AI condition required one-third the amount of coaching contact as those randomized to the gold standard condition but had nearly identical weight losses. The current protocol extends our pilot work and will be the first full-scale randomized controlled trial of a RL system for weight control. The primary aim is to evaluate the hypothesis that a RL-based 12-month BWL program will produce non-inferior weight losses to standard BWL treatment, but at lower costs. Secondary aims include testing mechanistic targets (calorie intake, physical activity) and predictors (depression, binge eating). As such, adults with overweight/obesity (N = 336) will be randomized to either a gold standard condition (12 months of weekly BWL groups) or AI-optimized weekly interventions that represent a combination of expert-led group, expert-led call, paraprofessional-led call, and automated message). Participants will be assessed at 0, 1, 6 and 12 months.
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Inteligência Artificial , Obesidade , Adulto , Humanos , Análise Custo-Benefício , Obesidade/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Redução de Peso , Dieta , TelemedicinaRESUMO
OBJECTIVE: Automated digital interventions (ADIs) represent a potentially promising approach to enhance the outcomes of human coach-delivered weight loss interventions. However, the extent to which ADIs provide additive benefit is unclear. This study represents the first systematic review and meta-analysis of the effectiveness of ADIs for improving the outcomes of human coach-delivered weight loss treatment. METHOD: Electronic database searches were used to identify trials that compared differences in weight change between (a) weight loss interventions that were delivered exclusively by coaches and (b) interventions supplementing this same human coaching with an ADI. Subgroup and moderator analyses examined the influence of intervention duration, duration of human coach contact, presence of tailored coaching, modality of the ADI and demographic variables on ADI effectiveness outcomes. RESULTS: Thirteen studies met inclusion criteria (1,471 participants). Random-effects meta-analysis revealed a mean difference in weight change between conditions of 2.18 kg at postintervention, representing a medium effect size of .54 (95% CI [.13, .95]). Subgroup analyses suggested that lower duration of coach contact was associated with improved additive effectiveness of ADIs. No other subgroup differences were found. Publication bias appeared to be a potential concern, though high levels of heterogeneity and a small number of included studies likely limited the ability to infer its presence. CONCLUSIONS: Results support the use of ADIs to augment coach-delivered behavioral weight loss treatment, and also suggest that ADIs have the greatest impact when coaching is relatively low in frequency or duration. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Terapia Comportamental , Redução de Peso , HumanosRESUMO
A major contributor to the obesity epidemic is the overconsumption of high-calorie foods, which is partly governed by inhibitory control, that is, the ability to override pre-prepotent impulses and drives. Computerized inhibitory control trainings (ICTs) have demonstrated qualified success at affecting real-world health behaviors, and at improving weight loss, particularly when repeated frequently over an extended duration. It has been proposed that gamification (i.e., incorporating game-like elements such as a storyline, sounds, graphics, and rewards) might enhance participant interest and thus training compliance. Previous findings from a mostly female sample did support this hypothesis; however, it might be expected that the effects of gamification differ by gender such that men, who appear more motivated by gaming elements, stand to benefit more from gamification. The present study evaluated whether gender moderated the effect of a gamified ICT on weight loss. Seventy-six overweight individuals received a no-sugar-added dietary prescription and were randomized to 42 daily and 2 weekly ICTs focused on sweet foods that were either gamified or nongamified. Results supported the hypothesis that gamification elements had a positive effect on weight loss for men and not women (p = .03). However, mechanistic hypotheses for the moderating effect (in terms of enjoyment, compliance, and improvements in inhibitory control) were generally not supported (p's > .20). These results suggest that gamification of ICTs may boost weight loss outcomes for men and not women, but further research is needed to determine the specific mechanisms driving this effect and to arrive at gamification elements that enhance effects for both men and women.
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Comportamentos Relacionados com a Saúde , Redução de Peso , Dieta , Feminino , Humanos , Masculino , Recompensa , Fatores SexuaisRESUMO
Behavioral weight loss treatment (BT) for individuals with overweight and obesity is effective but leaves room for improvement. Mindfulness and acceptance-based treatments may bolster weight loss outcomes; yet, little is known about the efficacy of the individual components or the combinations of components that are most effective in producing weight loss above and beyond standard BT strategies for weight loss. This protocol manuscript describes the use of a multiphase optimization strategy to evaluate the independent and combinatory efficacy of three mindfulness and acceptance-based components (mindful awareness, willingness, values). Using a 2 × 2 × 2 factorial design, participants (N = 288) will be randomized to one of eight conditions, each representing a combination of core MABT strategies in addition to foundational BT strategies. Assessments occur at baseline, mid-treatment (week 24 through 26), post-treatment, and at 6, 12, and 24-month follow-up. The primary aim is to elucidate the independent efficacy of each MABT component on weight loss above gold-standard BT. The secondary aims are to evaluate the independent effect of these components on calorie intake, physical activity, and overall quality of life; evaluate target engagement (i.e., the degree to which each treatment component affects proposed mechanisms of action); and evaluate the potential moderating effect of susceptibility to internal and external food cues on outcomes. The exploratory aim is to quantify any component interaction effects (which may be synergistic, fully additive, or partially additive).
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Atenção Plena , Redução de Peso , Humanos , Obesidade/terapia , Sobrepeso/terapia , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Individuals receiving behavioral weight loss treatment frequently fail to adhere to prescribed dietary and self-monitoring instructions, resulting in weight loss clinicians often needing to assess and intervene in these important weight control behaviors. A significant obstacle to improving adherence is that clinicians and clients sometimes disagree on the degree to which clients are actually adherent. However, prior research has not examined how clinicians and clients differ in their perceptions of client adherence to weight control behaviors, nor the implications for treatment outcomes. PURPOSE: In the context of a 6-month weight-loss treatment, we examined differences between participants and clinicians when rating adherence to weight control behaviors (dietary self-monitoring; limiting calorie intake) and evaluated the hypothesis that rating one's own adherence more highly than one's clinician would predict less weight loss during treatment. METHODS: Using clinician and participant-reported measures of self-monitoring and calorie intake adherence, each assessed using a single item with a 7- or 8-point scale, we characterized discrepancies between participant and clinician adherence and examined associations with percent weight change over 6 months using linear mixed-effects models. RESULTS: Results indicated that ratings of adherence were higher when reported by participants and supported the hypothesis that participants who provided higher adherence ratings relative to their clinicians lost less weight during treatment (p < 0.001). CONCLUSIONS: These findings suggest that participants in weight loss treatment frequently appraise their own adherence more highly than their clinicians and that participants who do so to a greater degree tend to lose less weight.
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Terapia Comportamental , Redução de Peso , Dieta , Comportamentos Relacionados com a Saúde , HumanosRESUMO
BACKGROUND: Fibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood. METHODS: We applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro-metabolite (e.g. combined glutamate and glutamine, Glx; myo-inositol, mIno; and combined (total) N-acetylaspartate and N-acetylaspartylglutamate, tNAA) levels and multidimensional clinical/behavioural variables (e.g. pain catastrophizing, clinical pain severity and evoked pain sensitivity) in women with fibromyalgia (N = 87). RESULTS: Pain catastrophizing scores were positively correlated with Glx and tNAA levels in insular cortex, and negatively correlated with mIno levels in posterior cingulate cortex (PCC). Clinical pain severity was positively correlated with Glx levels in insula and PCC, and with tNAA levels in anterior midcingulate cortex (aMCC), but negatively correlated with mIno levels in aMCC and thalamus. Evoked pain sensitivity was negatively correlated with levels of tNAA in insular cortex, MCC, PCC and thalamus. CONCLUSIONS: These findings support single voxel placement targeting nociceptive processing areas in prior 1 H-MRS studies, but also highlight other areas not as commonly targeted, such as PCC, as important for chronic pain pathophysiology. Identifying target brain regions linked to multidimensional symptoms of fibromyalgia (e.g. negative cognitive/affective response to pain, clinical pain, evoked pain sensitivity) may aid the development of neuromodulatory and individualized therapies. Furthermore, efficient multi-region sampling with 3D MRSI could reduce the burden of lengthy scan time for clinical research applications of molecular brain-based mechanisms supporting multidimensional aspects of fibromyalgia. SIGNIFICANCE: This large N study linked brain metabolites and pain features in fibromyalgia patients, with a better spatial resolution and brain coverage, to understand a molecular mechanism underlying pain catastrophizing and other aspects of pain transmission. Metabolite levels in self-referential cognitive processing area as well as pain-processing regions were associated with pain outcomes. These results could help the understanding of its pathophysiology and treatment strategies for clinicians.
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Dor Crônica , Fibromialgia , Encéfalo/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Feminino , Fibromialgia/diagnóstico por imagem , Ácido Glutâmico , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância MagnéticaRESUMO
Chronic pain negatively affects psychological functioning including self-perception. Self-compassion may improve self-related functioning in patients with chronic pain but understanding of the neural mechanisms is limited. In this study, twenty patients with chronic low back pain read negative self-related situations and were instructed to be either self-reassuring or self-critical while undergoing fMRI. Patients rated their feelings of self-reassurance and self-criticism during each condition, and brain responses were contrasted with neutral instructions. Trait self-compassion measures (SCS) were also acquired. Brain activations during self-criticism and self-reassurance were localized to prefrontal, self- and emotion-processing areas, such as medial prefrontal cortex, dorsolateral prefrontal cortex (dlPFC), dorsal anterior cingulate cortex and posterior cingulate cortex. Self-reassurance resulted in more widespread and stronger activations relative to self-criticism. Patients then completed a brief self-compassion training (8 contact hours, 2 weeks home practice). Exploratory pre-post comparisons in thirteen patients found that feelings of self-criticism were significantly reduced and brain activations were greater in the anterior insula and prefrontal cortical regions such as dlPFC. Pre-post increases in dlPFC activation correlated with increased self-compassion (SCS), suggesting that early self-compassion skills might primarily target self-criticism via dlPFC upregulation. Future controlled studies on self-compassion training in chronic pain populations should extend these results.
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Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Autoimagem , Adulto , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Emoções/fisiologia , Empatia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pacientes , Projetos Piloto , Córtex Pré-Frontal/fisiopatologiaRESUMO
Depression is characterized by altered sensitivity to rewards, with recent evidence suggesting that the ability to sustain responses to rewards across long experimental tasks is diminished. Most work on sustained reward responsiveness has taken a categorical approach and focused on major depressive disorder. However, impairments in reward sensitivity are also found at lower levels of symptom severity and may be relevant for understanding basic mechanisms linking reward processing abnormalities to depression. The current study took a dimensional approach to examine the relation between depression symptoms and sustained reward responsiveness by examining how early neural responses to rewards and losses change over a short time course (i.e., during the experiment). In a sample of 45 unselected undergraduates, changes in the amplitude of the reward positivity (RewP) and feedback negativity (FN) were examined over the course of a simple gambling task using multilevel modeling. Amplitude of the RewP was sustained and amplitude of the FN increased during the task. Unlike prior work focused on clinical populations, depression symptoms in this unselected sample were associated with enhanced RewP and FN responding over the course of the task. Results echo prior work that underscores the importance of examining changes in response to reward across trials and further suggests that sustained responses to both rewards and losses vary in relation to symptom level.
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Encéfalo/fisiopatologia , Depressão/fisiopatologia , Potenciais Evocados/fisiologia , Adolescente , Eletroencefalografia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Determinação da Personalidade , Escalas de Graduação Psiquiátrica , Recompensa , Adulto JovemRESUMO
Sustained treatment of estrogen receptor (ER)-positive breast cancer with ER-targeting drugs results in ER mutations and refractory unresponsive cancers. Androgen receptor (AR), which is expressed in 80%-95% of ER-positive breast cancers, could serve as an alternate therapeutic target. Although AR agonists were used in the past to treat breast cancer, their use is currently infrequent due to virilizing side effects. Discovery of tissue-selective AR modulators (SARMs) has renewed interest in using AR agonists to treat breast cancer. Using translational models, we show that AR agonist and SARM, but not antagonist, inhibit the proliferation and growth of ER-positive breast cancer cells, patient-derived tissues, and patient-derived xenografts (PDX). Ligand-activated AR inhibits wild-type and mutant ER activity by reprogramming the ER and FOXA1 cistrome and rendering tumor growth inhibition. These findings suggest that ligand-activated AR may function as a non-canonical inhibitor of ER and that AR agonists may offer a safe and effective treatment for ER-positive breast cancer.
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OBJECTIVE: Pain catastrophizing is a common feature of chronic pain, including fibromyalgia (FM), and is strongly associated with amplified pain severity and disability. While previous neuroimaging studies have focused on evoked pain response modulation by catastrophizing, the brain mechanisms supporting pain catastrophizing itself are unknown. We designed a functional magnetic resonance imaging (fMRI)-based pain catastrophizing task whereby patients with chronic pain engaged in catastrophizing-related cognitions. We undertook this study to test our hypothesis that catastrophizing about clinical pain would be associated with amplified activation in nodes of the default mode network (DMN), which encode self-referential cognition and show altered functioning in chronic pain. METHODS: During fMRI, 31 FM patients reflected on how catastrophizing (CAT) statements (drawn from the Pain Catastrophizing Scale) impact their typical FM pain experience. Response to CAT statements was compared to response to matched neutral (NEU) statements. RESULTS: During statement reflection, higher fMRI signal during CAT statements than during NEU statements was found in several DMN brain areas, including the ventral (posterior) and dorsal (anterior) posterior cingulate cortex (vPCC and dPCC, respectively). Patients' ratings of CAT statement applicability were correlated solely with activity in the vPCC, a main DMN hub supporting self-referential cognition (r = 0.38, P < 0.05). Clinical pain severity was correlated solely with activity in the dPCC, a PCC subregion associated with cognitive control and sensorimotor processing (r = 0.38, P < 0.05). CONCLUSION: These findings provide evidence that the PCC encodes pain catastrophizing in FM and suggest distinct roles for different PCC subregions. Understanding the brain circuitry encoding pain catastrophizing in FM will prove to be important in identifying and evaluating the success of interventions targeting negative affect in chronic pain management.
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Catastrofização/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Fibromialgia/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Catastrofização/psicologia , Dor Crônica/psicologia , Cognição , Feminino , Fibromialgia/psicologia , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
Ultrasound-guided breast biopsy has emerged as a common method for lesion diagnosis. This study sought to instruct and measure surgical residents' performance in ultrasound-guided breast biopsy and evaluate their thoughts regarding it. Thirteen (n = 13) senior residents completed a written pretest or questionnaire and 2.5 hours of simulated breast core and vacuum needle biopsies. Residents then completed the same written exam, and their biopsy performance was rated. There was 13% overall improvement of written test scores, and 73% resident improved comfort levels with performing biopsies. Successfully performed core biopsies and vacuum biopsies were 86% and 83%, respectively. All residents reported that instruction in ultrasound-guided breast biopsy is very important and should be mandatory in residency training programs. With concentrated instruction, residents are able to learn ultrasound-guided breast biopsy with improvement in objective measures and self-confidence levels. Resident feedback was positive and emphasized the importance of this training in surgical residency curriculums.