Aberrant neural event segmentation during a continuous social narrative in trauma-exposed older adolescents and young adults

Post-traumatic stress and major depressive disorders are associated with "overgeneral" autobiographical memory, or impaired recall of specific life events. Interpersonal trauma exposure, a risk factor for both conditions, may influence how symptomatic trauma-exposed (TE) individuals segment everyday events. The ability to parse experience into units (event segmentation) supports memory. Neural state transitions occur within a cortical hierarchy and play a key role in event segmentation, with regions like the occipital cortex, angular gyrus, and striatum involved in parsing event structure. We examined whether interpersonal trauma exposure was associated with alterations in the cortical hierarchy and striatal activity at neural state transitions in symptomatic TE versus healthy control (HC) individuals. Fifty older adolescents and young adults (29 TE, 21 HC) viewed the film "Partly Cloudy" during functional magnetic resonance imaging. A greedy-state boundary search algorithm assessed the optimal number of events, quality, and segmentation agreement of neural state transitions in the occipital cortex and angular gyrus. Striatal (nucleus accumbens, caudate, and putamen) activity was assessed at occipital and angular gyrus-evoked state transitions. Compared to HCs, TE participants displayed less occipital and greater angular gyrus-evoked optimal number of neural state transitions. TE participants also displayed lower quality of neural state segmentation solutions in occipital and angular cortices compared to HCs. Additionally, TE participants had less putamen activity at angular gyrus-evoked state transitions than HCs. This investigation provides neurobiological insights into aberrant event segmentation in symptomatic TE individuals, shedding light on mechanisms influencing overgeneral memory in trauma-related disorders

Anhedonia and Delay Discounting: Differing Patterns of Brain-Behavior Relationships in Healthy Control Participants Versus Individuals With Posttraumatic Stress Disorder

BackgroundAnhedonia may contribute to individual differences in delay discounting (DD). In prior work, we found that higher anhedonia was associated with shallower DD in healthy control (HC) participants but steeper DD in individuals with posttraumatic stress disorder (PTSD). In this study, we aimed to directly compare the relationship between anhedonia and DD across groups and to identify functional brain correlates of this interaction.MethodsParticipants (HC group: n = 23, DSM-5 PTSD group: n = 23) completed a questionnaire assessing anhedonia (Snaith-Hamilton Pleasure Scale [SHAPS]), task-based functional magnetic resonance imaging of decision making including DD, and resting-state functional magnetic resonance imaging. Task-based activity and resting-state functional connectivity were evaluated in reward-related regions that have also been implicated in PTSD (nucleus accumbens [NAcc], right anterior insula).ResultsHigher SHAPS scores were associated with steeper DD in PTSD, but there was no relationship between DD and SHAPS in the HC group. There was a significant group-by-SHAPS interaction for NAcc activity, t31 = 2.92, p = .007: Greater NAcc activity when immediate rewards were chosen was associated with higher SHAPS in the PTSD group but lower SHAPS in the HC group. In resting-state functional connectivity, there was a group-by-SHAPS interaction between the NAcc seed and right parietal and frontal pole clusters.ConclusionsThese results extend prior findings that anhedonia is associated with steeper DD in PTSD and demonstrate that this behavioral finding occurs in the context of NAcc hyperactivity to immediate rewards and hyperconnectivity in anhedonic individuals with PTSD

Implications of the nuclear pore barrier for non-small cell lung cancer malignancy and therapy

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Unconditioned Response to a Naturally Aversive Stimulus is Associated with Sensitized Defensive Responding and Self-Reported Fearful Traits in a PTSD Sample

Unconditioned responding (UCR) to a naturally aversive stimulus is associated with defensive responding to a conditioned threat cue (CS+) and a conditioned safety cue (CS-) in trauma-exposed individuals during fear acquisition. However, the relationships of UCR with defensive responding during extinction training, posttraumatic stress disorder (PTSD) symptom severity, and fearful traits in trauma-exposed individuals are not known. In a sample of 100 trauma-exposed adults with a continuum of PTSD severity, we recorded startle responses and skin conductance responses (SCR) during fear acquisition and extinction training using a 140 psi, 250-ms air blast to the larynx as the unconditioned stimulus. We explored dimensional associations of two different measures of UCR (unconditioned startle and unconditioned SCR) with conditioned defensive responding to CS+ and CS-, conditioned fear (CS+ minus CS-), PTSD symptom severity, and a measure of fearful traits (composite of fear survey schedule, anxiety sensitivity index, and Connor-Davidson resilience scale). Unconditioned startle was positively associated with startle potentiation to the threat cue and the safety cue across both learning phases (CS+ Acquisition, CS- Acquisition, CS+ Extinction Training, CS- Extinction Training) and with fearful traits. Unconditioned SCR was positively associated with SCR to the CS+ and CS- and SCR difference score during Acquisition. Neither type of UCR was associated with PTSD symptom severity. Our findings suggest that UCR, particularly unconditioned startle to a naturally aversive stimulus, may inform research on biomarkers and treatment targets for symptoms of pervasive and persistent fear in trauma-exposed individuals

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

Introduction: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been investigated in PTSD. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analyses), and EC (secondary) using Neurite Orientation Dispersion and Density Imaging.Methods: Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure.Results: Higher PACAP levels were associated with greater EC NDI (β = 0.0099, q = 0.032) and lower EC ODI (β = -0.0073, q = 0.047), and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures.Conclusions: Circulating PACAP levels were associated with altered neuronal density of the EC but not the hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits in PTSD

Image acquisition and quality assurance in the Boston Adolescent Neuroimaging of Depression and Anxiety study

The Connectomes Related to Human Diseases (CRHD) initiative was developed with the Human Connectome Project (HCP) to provide high-resolution, open-access, multi-modal MRI data to better understand the neural correlates of human disease. Here, we present an introduction to a CRHD project, the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, which is collecting multimodal neuroimaging, clinical, and neuropsychological data from 225 adolescents (ages 14–17), 150 of whom are expected to have a diagnosis of depression and/or anxiety. Our transdiagnostic recruitment approach samples the full spectrum of depressed/anxious symptoms and their comorbidity, consistent with NIMH Research Domain Criteria (RDoC). We focused on an age range that is critical for brain development and for the onset of mental illness. This project sought to harmonize imaging sequences, hardware, and functional tasks with other HCP studies, although some changes were made to canonical HCP methods to accommodate our study population and questions. We present a thorough overview of our imaging sequences, hardware, and scanning protocol. We detail similarities and dif-ferences between this study and other HCP studies. We evaluate structural-, diffusion-, and functional-image-quality measures that may be influenced by clinical factors (e.g., disorder, symptomatology). Signal-to-noise and motion estimates from the first 140 adolescents suggest minimal influence of clinical factors on image quality. We anticipate enrollment of an additional 85 participants, most of whom are expected to have a diagnosis of anxiety and/or depression. Clinical and neuropsychological data from the first 140 participants are currently freely available through the National Institute of Mental Health Data Archive (NDA)

Produção científica da enfermagem sobre transplante de células-tronco hematopoéticas de sangue do cordão umbilical

Introdução: O Transplante de Células-Tronco Hematopoéticas (TCTH) é um procedimento que substitui células doentes por células sadias, por meio da infusão de células-tronco hematopoéticas. Objetivo: Identificar na literatura as publicações da enfermagem que abordem o TCTH de Sangue de Cordão Umbilical (SCU). Método: Trata-se de uma revisão integrativa, para qual se realizou buscas por meio das bases de dados eletrônicas: Biblioteca Virtual em Saúde, National Library of Medicine (PUBMED/MEDLINE), Science Direct e SCOPUS. Foram estabelecidos os seguintes critérios de inclusão: estudos disponíveis em qualquer idioma, estudos que abordassem o TCTH de sangue de cordão umbilical e estudo publicado na íntegra. Resultados: O processo de busca eletrônica dos estudos resultou em um total de 978 estudos, dos quais cinco compuseram a amostra da revisão. Os estudos selecionados abordaram o conhecimento dos enfermeiros sobre o transplante de SCU, a coleta e armazenamento do SCU e o banco de SCU. Conclusão: O presente estudo proporcionou a percepção da importância do papel do enfermeiro no TCTH de SCU, visto que seu empenho junto à equipe dos bancos públicos de SCU é importante para alcançar melhores resultados, com a ampliação do número de doadores e maior satisfação dos clientes e seus familiares.Introducción: El trasplante de células madre hematopoyéticas (TCMH) es un procedimiento que reemplaza las células enfermas a las células sanas, a través de la infusión de células madre hematopoyéticas. Objetivo: Identificar en la literatura las publicaciones de enfermería que se ocupan de la sangre de cordón umbilical La sangre (UCB) TCMH. Método: Se trata de una revisión integradora, para lo cual allanó a través de bases de datos electrónicas: Biblioteca Virtual en Salud, Biblioteca Nacional de Medicina (PubMed/MEDLINE), Science Direct y Scopus. Se establecieron los siguientes criterios de inclusión: los estudios disponibles en cualquier idioma, los estudios que abordaron la sangre del cordón umbilical TPH y el estudio en su totalidad. Resultados: El proceso de búsqueda electrónica de los estudios dieron como resultado un total de 978 estudios, de los cuales cinco fueron incluidas en la muestra de revisión. Los estudios seleccionados abordan el conocimiento del personal de enfermería en el trasplante de SCU, la recogida y almacenamiento de sangre del cordón umbilical y el Banco de SCU. Conclusión: Este estudio proporciona la percepción de la importancia del papel de la enfermera en TPH de SCU, como su compromiso con el equipo de los bancos públicos UCB es importante para lograr mejores resultados al aumentar el número de donantes y el aumento de la satisfacción del cliente y sus familias.Introduction: Hematopoietic stem cell transplantation (HSCT) is a procedure that replaces diseased cells with healthy cells by infusing hematopoietic stem cells. Objective: To identify in the literature the nursing publications that addresses HSCT of Umbilical Cord Blood (UCB). Method: This is an integrative review, which has been searched through electronic databases: Virtual Health Library, National Library of Medicine (PUBMED/MEDLINE), Science Direct and SCOPUS. The following inclusion criteria were established: studies available in any language, studies addressing HSCT of umbilical cord blood and a study published in its entirety. Results: The electronic search process of the studies resulted in a total of 978 studies, of which five comprised the review sample. The selected studies addressed the nurses' knowledge about SCU transplantation, the collection and storage of SCU and the SCU database. Conclusion: The present study provided an insight into the importance of the role of nurses in HSCTWC, since their commitment to the team of SCU public banks is important to achieve better results, with a larger number of donors and greater customer satisfaction And their families

Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study

Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR-=-0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR-=-0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR-=-0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported. What's new? How much does behavior really affect cancer risk? These authors set out to measure just that. First, they created a Healthy Lifestyle Index, which quantified five modifiable behaviors, such as smoking and physical activity. Then, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), they assigned each participant a score between 0 and 4 on each of the behaviors. It turned out that with each point added to a person's Healthy Lifestyle Index score, breast cancer risk fell by 3%, suggesting that public programs to help women maintain these behaviors could be worthwhile for cancer prevention

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Assessment of Brain Age in Posttraumatic Stress Disorder: Findings from the ENIGMA PTSD and Brain Age Working Groups

Background Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. Method Adult subjects (N = 2229; 56.2% male) aged 18–69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA-PGC PTSD sites underwent T1-weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel-wise (brainageR) and region-of-interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age − chronological age) controlling for chronological age, sex, and scan site. Results BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three-way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. Discussion Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age-related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan