Effects of psychopathic traits on preferential recall and recognition of emotionally evocative photos.

Psychopathic traits are associated with impaired emotional processing. The present study examines the potential association between psychopathic traits and memory for emotional stimuli. Although a significant body of research suggests that memory is heightened for emotional stimuli, it is unclear how psychopathic traits may disrupt this process. Eighty-two male jail inmates completed an emotional memory task as well as portions of a standardised memory assessment. Psychopathic traits were not associated with the ability to freely recall images of positive, negative or neutral valence that participants had seen more than 15 min prior; psychopathic traits were also not associated with the ability to recognise these previously viewed images when shown them again. Exploratory analyses indicated trends toward reduced accuracy in recognising both positive and negative, but not neutral, emotional stimuli in individuals with higher levels of interpersonal and affective traits of psychopathy. As expected, psychopathy was unrelated to non-emotion-related memory functioning in auditory and visual domains as measured by the Wechsler Memory Scales 4th Edition. Overall, these results do not support the hypothesis that psychopathic traits significantly interfere with memory for emotional stimuli.

A qualitative analysis of adolescent motherhood within the broader family context in Peru.

Objective: The purpose of this study was to characterize the impact of adolescent pregnancy on families and describe the needs of adolescent mothers and their infants in order to assess the need for intervention and identify potential intervention targets. Background: Adolescent mothers and their offspring face an increased risk of mental health problems. Adolescent mothers and their families also face significant resource constraints; 95% live in low- and middle-income countries (LMICs). Cost-effective interventions are needed to improve outcomes for this vulnerable group. Method: This qualitative study conducted in Lima, Peru, consisted of four clinician focus groups and 18 in-depth interviews with adolescent mothers and their family members. Data were coded thematically, and direct content analysis was employed. Results: The study identified the following issues facing adolescent parents: the transition to parenthood, the need for family support, difficulty accessing support, the difficulty for family members of providing support, and ideas about responsibility and adolescent autonomy. Conclusion: Overall, these findings demonstrate the need for interventions that engage families and address barriers to accessing support, including relationship conflict and differing beliefs about responsibility and autonomy. Implications: Interventions are needed for adolescent mothers in LMICs that mobilize family support. Clinicians who care for these patients need to be aware of the family context and the resources available where they practice.

An engineered baculoviral protein and DNA co-delivery system for CRISPR-based mammalian genome editing.

CRISPR-based DNA editing technologies enable rapid and accessible genome engineering of eukaryotic cells. However, the delivery of genetically encoded CRISPR components remains challenging and sustained Cas9 expression correlates with higher off-target activities, which can be reduced via Cas9-protein delivery. Here we demonstrate that baculovirus, alongside its DNA cargo, can be used to package and deliver proteins to human cells. Using protein-loaded baculovirus (pBV), we demonstrate delivery of Cas9 or base editors proteins, leading to efficient genome and base editing in human cells. By implementing a reversible, chemically inducible heterodimerization system, we show that protein cargoes can selectively and more efficiently be loaded into pBVs (spBVs). Using spBVs we achieved high levels of multiplexed genome editing in a panel of human cell lines. Importantly, spBVs maintain high editing efficiencies in absence of detectable off-targets events. Finally, by exploiting Cas9 protein and template DNA co-delivery, we demonstrate up to 5% site-specific targeted integration of a 1.8 kb heterologous DNA payload using a single spBV in a panel of human cell lines. In summary, we demonstrate that spBVs represent a versatile, efficient and potentially safer alternative for CRISPR applications requiring co-delivery of DNA and protein cargoes.

In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2.

Background: Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens. Methods: Here, we developed an integrated approach combining synthetic, computational and structural methods with in vitro antibody selection and in vivo immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs). In vitro generated neutralizing nanobodies and electron cryo-microscopy established authenticity and accessibility of epitopes displayed by ADDoCoV. Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Vaccinating mice resulted in antibodies cross-reacting with VOCs including Delta and Omicron. Conclusion: Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat respiratory viral infections.

Intratumor heterogeneity and cell secretome promote chemotherapy resistance and progression of colorectal cancer.

The major underlying cause for the high mortality rate in colorectal cancer (CRC) relies on its drug resistance, to which intratumor heterogeneity (ITH) contributes substantially. CRC tumors have been reported to comprise heterogeneous populations of cancer cells that can be grouped into 4 consensus molecular subtypes (CMS). However, the impact of inter-cellular interaction between these cellular states on the emergence of drug resistance and CRC progression remains elusive. Here, we explored the interaction between cell lines belonging to the CMS1 (HCT116 and LoVo) and the CMS4 (SW620 and MDST8) in a 3D coculture model, mimicking the ITH of CRC. The spatial distribution of each cell population showed that CMS1 cells had a preference to grow in the center of cocultured spheroids, while CMS4 cells localized at the periphery, in line with observations in tumors from CRC patients. Cocultures of CMS1 and CMS4 cells did not alter cell growth, but significantly sustained the survival of both CMS1 and CMS4 cells in response to the front-line chemotherapeutic agent 5-fluorouracil (5-FU). Mechanistically, the secretome of CMS1 cells exhibited a remarkable protective effect for CMS4 cells against 5-FU treatment, while promoting cellular invasion. Secreted metabolites may be responsible for these effects, as demonstrated by the existence of 5-FU induced metabolomic shifts, as well as by the experimental transfer of the metabolome between CMS1 and CMS4 cells. Overall, our results suggest that the interplay between CMS1 and CMS4 cells stimulates CRC progression and reduces the efficacy of chemotherapy.

Manifestations of Intergenerational Trauma During the Perinatal Period Among Adolescent Mothers in Lima, Peru: A Qualitative Analysis.

Adverse childhood experiences have a lasting impact on health across the life course. The perinatal period offers a unique opportunity to rework problematic dynamics in families experiencing intergenerational trauma. This study explores the family dynamics that are activated during the perinatal period and considers the potential for intervention with adolescent parents and their families in Lima, Peru. This narrative analysis was part of a broader study that included focus groups and in-depth interviews. Of the ten adolescent mothers interviewed, four narratives were selected for presentation in this manuscript. These particular narratives were selected to illustrate the diversity of the experiences among this group and for the exceptional level of detail provided about their life experiences and family relationships. Narrative excerpts were analyzed in the context of the entire interview and the aggregate content of other interviews in order to explore both explicit and implicit meanings. This study identified critical relational shifts among adolescent parents and their families during the perinatal period. In one instance, adolescent parenthood created an opportunity for the family to come together. In the other cases, conflict escalated, relations grew distant, or both. These narrative data demonstrate that intergenerational trauma can interfere with family relationships in the context of adolescent pregnancy and prevent adolescent parents from accessing needed support from their families. Intervention with families could address the impact of trauma and improve communication and collaboration.

Newborn behavioral observations system in rural Pakistan: A feasibility and acceptability study.

The Newborn Behavioral Observations (NBO) system is a relationship-based tool that helps parents recognize their infant's competencies and learn their behavioral cues, with the goals of enhancing parental responsiveness and satisfaction in the infant-parent relationship. In our study, a pediatrician integrated the NBO into 44 pediatric health care visits of infants in rural Pakistan villages, under the remote guidance of two U.S.-based child psychiatrists. A clinician then gave the mothers a survey about their experience of the NBO and found that the mothers were highly satisfied, reporting greater appreciation of their infant's strengths, greater understanding of their infant's behavioral cues, stronger attachment to their infant, and greater self-confidence as a mother. In their consideration of these results, the authors explore cultural reasons for the mothers' responses and generate hypotheses to inform an outcome study of a similar intervention. This was a feasibility and acceptability study and was not randomized, had no control group, and did not use objective measures of outcome.

El sistema de Observaciones de Comportamiento del Recién Nacido (NBO)™ es una herramienta basada en la relación que se enfoca en ayudar a los padres a reconocer las competencias de su infante y aprender sus señales de comportamiento, con el propósito de mejorar la sensibilidad y satisfacción del progenitor en la relación infante-progenitor. En este estudio de probabilidad y aceptabilidad, un clínico pediatra integró el NBO dentro de 44 visitas de cuidado de salud pediátricas a infantes en aldeas rurales en Pakistán, bajo la guía remota de dos siquiatras infantiles con base en los Estados Unidos. Entonces, un clínico les dio a las madres una encuesta acerca de su experiencia con el NBO y se encontró que las madres estaban altamente satisfechas, reportando un mayor aprecio por los puntos fuertes de sus infantes, una mayor comprensión de las señalas de comportamiento de sus infantes, una más fuerte afectividad hacia sus infantes, así como una mayor auto confianza como madre. En sus consideraciones de estos resultados, los autores exploran razones culturales para las respuestas de las madres y generan hipótesis como información para un estudio de resultado de una intervención similar.

Le système d'observation comportementale du nouveau-né (Newborn Behavioral Observations, abrégé selon l'anglais NBO system™) est un outil basé sur la relation se concentrant sur l'aide aux parents à reconnaître les compétences de leur nourrisson et à comprendre leurs signaux de comportement, se donnant pour but de mettre en valeur la réaction parentale et la satisfaction dans la relation nourrisson-parent. Dans cette étude de faisabilité et d'acceptabilité un clinicien en pédiatrie a intégré le NBO dans 44 visites de santé pédiatrique de nourrissons dans des villages du Pakistan rural, sous l'orientation professionnelle à distance de deux psychiatres de l'enfance basés aux Etats-Unis d'Amérique. Un clinicien a ensuite donné aux mères un questionnaires sur leur expérience du NBO et a trouvé que les mères étaient très satisfaites, faisant état d'une plus grande appréciation des forces de leurs nourrissons, d'une plus grande compréhension des signaux de comportement de leur nourrisson, d'un attachement plus fort à leur nourrisson et d'une plus grande confiance en soi en tant que mère. Dans leur considération de ces résultats les auteurs explorent les raisons culturelles expliquant les réponses des mères et génèrent des hypothèses pour informer une étude d'une intervention similaire.

The Development of Cognitive Reappraisal From Early Childhood Through Adolescence: A Systematic Review and Methodological Recommendations.

Cognitive reappraisal is an important emotion regulation strategy that shows considerable developmental change in its use and effectiveness. This paper presents a systematic review of the evidence base regarding the development of cognitive reappraisal from early childhood through adolescence and provides methodological recommendations for future research. We searched Scopus, PsycINFO, and ERIC for empirical papers measuring cognitive reappraisal in normative samples of children and youth between the ages of 3 and 18 years published in peer-reviewed journals through August 9th, 2018. We identified 118 studies that met our inclusion criteria. We first present a quantitative review of the methodologies used to investigate cognitive reappraisal in children and adolescents, with attention to variations in methodologies by the sample age range. We then present a qualitative review of findings with attention to: (1) the age at which children begin to effectively use cognitive reappraisal to regulate their emotions, and (2) developmental changes in cognitive reappraisal from early childhood through adolescence. We consider how methodological differences may contribute to inconsistencies in findings, highlight gaps in the literature that remain to be addressed, and make recommendations for future directions.

Luminescent 1H-1,3-benzazaphospholes.

2-R-1H-1,3-Benzazaphospholes (R-BAPs) are an interesting class of σ2P heterocycles containing P[double bond, length as m-dash]C bonds. While closely related 2-R-1,3-benzoxaphospholes (R-BOPs) have been shown to be highly photoluminescent materials depending on specific R substituents, photoluminescence of R-BAPs has been previously limited to an example having a fused carbazole ring system. Here we detail the synthesis and structural characterization of a new R-BAP (3c, R = 2,2'-dithiophene), and compare its photoluminescence against two previously reported R-BAPs (3a, R, R' = Me and 3b, R = 2-thiophene). The significant fluorescence displayed by the thiophene derivatives 3b (φ = 0.53) and 3c (φ = 0.12) stands in contrast to the weakly emissive methyl substituted analogue 3a (φ = 0.08). Comparative computational investigations of 3a-c offer insights into the interplay between structure-function relationships affecting excited state relaxation processes.

Editorial Perspective: The mental health impact of school closures during the COVID-19 pandemic.

School closures were one of the earlier actions taken as the world tried to contain the COVID-19 outbreak, a decision impacting nearly three-fourths of the learners worldwide. One year into the pandemic, over 200 million students still faced disruptions to their education. Nearing the end of another academic year that has occurred entirely during the pandemic, many schools remained fully or partially closed for in-person education, altering routines and representing potential hardships to the next generation and their families. This article will explore the potential impacts of school closures on children and adolescents related to increased screen time, irregular sleep patterns, less balanced diets, learning difficulties, and changes in social interaction. In addition, we note broader familial difficulties likely accompanying the loss of the mitigating effects of schools and their associated support systems, such as parental stress and work responsibilities, loss of employment, intimate partner violence, child abuse and neglect, and parental substance abuse, which appear to have increased during the pandemic. Considering what is known about the impact from previous natural catastrophes, the populations at risk, and the early but not yet definitive data from the current pandemic, we stress the urgent need for robust data as we prepare for a new academic year in the Northern Hemisphere. Although we currently lack consistent and complete data, signs for concern include a rise in pediatric emergency room visits for mental health and substance use issues in many parts of the world. This paper aims to stimulate a discussion about the potential mental health effects of school closures for children and adolescents in the context of a pandemic.

Relationship between psychopathic traits and performance on the Mini Social Cognition and Emotional Assessment in incarcerated males.

Psychopathy is a constellation of personality traits such as callousness, manipulativeness, and impulsivity, and these traits often co-occur with antisocial behavior. Researchers and clinicians have posited that these traits may be associated with impairments in orbitofrontal cortex functioning, but researchers have rarely assessed this using clinical neuropsychological assessments. In a sample of 87 male inmates in a county jail, this study examined the relationship between psychopathic traits and performance on the Mini Social Cognition and Emotional Assessment (Mini-SEA), an assessment of orbitofrontal cortex functioning. Psychopathy scores (total or factor) were not correlated with Mini-SEA performance. Potential reasons for our null findings and study limitations are discussed. PRACTITIONER POINTS: Psychopathic traits were not associated with performance on a neuropsychological measure assessing orbitofrontal cortex functioning. Deficits in OFC functioning observed in psychopathy may be different in nature, or less severe, than those observed in patients with frontotemporal dementia, who perform poorly on this measure.

Culture - Surprise and the Psychoanalyst.

The author describes how an immersion experience in another culture can benefit the psychoanalyst-and the individual who is a psychoanalyst-by confronting trusted theories and challenging the analyst to create new methods for understanding basic aspects of human experience, such as the meaning of the "self."

Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside.

Tumor-on-chip technology has cemented its importance as an in vitro tumor model for cancer research. Its ability to recapitulate different elements of the in vivo tumor microenvironment makes it promising for translational medicine, with potential application in enabling personalized anti-cancer therapies. Here, we provide an overview of the current technological advances for tumor-on-chip generation. To further elevate the functionalities of the technology, these approaches need to be coupled with effective analysis tools. This aspect of tumor-on-chip technology is often neglected in the current literature. We address this shortcoming by reviewing state-of-the-art on-chip analysis tools for microfluidic tumor models. Lastly, we focus on the current progress in tumor-on-chip devices using patient-derived samples and evaluate their potential for clinical research and personalized medicine applications.

Intersubjectivity: Conceptual Considerations in Meaning-Making With a Clinical Illustration.

This manuscript explores intersubjectivity through a conceptual construct for meaning-making that emphasizes three major interrelated elements-meaning making in interaction, making meaning with the body as well as the mind, and meaning making within an open dynamic system. These three elements are present in the literature on intersubjectivity with a wide range of terms used to describe various theoretical formulations. One objective of this manuscript is to illustrate how such a construct can be useful to understand the meaning-making observed in psychoanalysis, such as in the treatment of a young child on the autistic spectrum. The challenges in establishing an intersubjective state with a child on the autistic spectrum serve to highlight important features of intersubjectivity. As an important background to this clinical illustration, we illustrate the construct with the scientific paradigm of the well-known face-to-face still-face.

Three Ways Isolable Carbenes Can Modulate Emission of NH-Containing Fluorophores.

Fluorescent molecules and materials that exhibit emission changes in response to analytes are of great interest across multiple disciplines. Herein, we investigate the response of NH-containing fluorophores carbazole and 2-phenylbenzimidazole (Ph-BIM) with two representative isolable singlet carbenes. Specifically, N-heterocyclic carbene 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) and cyclic (alkyl)(amino)carbene (2,6-diisopropylphenyl)-4,4-diethyl-2,2-dimethyl-pyrrolidin-5-ylidene (EtCAAC) were discovered to afford three different types of reaction products with carbazole and Ph-BIM. Depending on the reaction pair, hydrogen bonding (1), NH-insertion (2,3), or proton transfer (4) products can be isolated, each displaying variable photophysical responses. These products have been structurally authenticated by single crystal X-ray diffraction and NMR spectrometric methods. Studies of the solution state behavior of 1-4 reveals that these adducts are labile and can reversibly dissociate to free carbenes and fluorophores to varying extents. These equilibria produce concentration dependent solution state behavior as identified and quantified via UV-visible absorption, emission, 1H DOSY, and NMR spectroscopic measurements.

Tumor suppressor candidate 2 (TUSC2, FUS-1) and human cancers.

Tumor suppressor candidate 2 (TUSC2, also known as FUS1) was identified in 2000 as a candidate tumor suppressor gene located in a region on chromosome 3p21.3 that is homozygously deleted in some lung and breast cancers. The deletion is rare in lung and breast cancers, but is frequent in malignant pleural mesothelioma. Evidence to date indicates that TUSC2 behaves as a tumor suppressor in lung cancer; however, its role as a tumor suppressor for other tumor types has not been fully established. Loss of TUSC2 expression at the mRNA and protein levels has been reported in various cancers. While the mechanisms underlying the loss are still not well understood, several microRNAs have been reported to downregulate TUSC2 expression. TUSC2 elicits its anti-tumor effects through regulating G1 cell cycle progression, apoptosis, calcium homeostasis, gene expression, and the activity of various protein tyrosine kinases and Ser/Thr kinases, albeit the precise mechanisms that TUSC2 utilizes to regulate these cellular processes and signaling molecules are still elusive. TUSC2 restoration has been exploited as an anti-cancer therapy in various cancers in preclinical models, and clinically in patients with lung cancer. The first-in-human phase I trial demonstrated desirable safety outcomes. Phase I/II trials are being conducted to evaluate the efficacy of combining TUSC2-nanoparticles with erlotinib, an FDA-approved EGFR inhibitor. This review summarizes recent findings that advanced our understanding of TUSC2 as a novel tumor suppressor and a therapeutic opportunity for treating TUSC2-deficient cancers.

Environmental and Social Change Drive the Explosive Emergence of Zika Virus in the Americas.

Since Zika virus (ZIKV) was detected in Brazil in 2015, it has spread explosively across the Americas and has been linked to increased incidence of microcephaly and Guillain-Barré syndrome (GBS). In one year, it has infected over 500,000 people (suspected and confirmed cases) in 40 countries and territories in the Americas. Along with recent epidemics of dengue (DENV) and chikungunya virus (CHIKV), which are also transmitted by Aedes aegypti and Ae. albopictus mosquitoes, the emergence of ZIKV suggests an ongoing intensification of environmental and social factors that have given rise to a new regime of arbovirus transmission. Here, we review hypotheses and preliminary evidence for the environmental and social changes that have fueled the ZIKV epidemic. Potential drivers include climate variation, land use change, poverty, and human movement. Beyond the direct impact of microcephaly and GBS, the ZIKV epidemic will likely have social ramifications for women's health and economic consequences for tourism and beyond.

"EFFECTIVE VOLUNTEERISM:" HELPING CHILD CAREGIVERS IN DEVELOPING COUNTRIES.

This article proposes a method of volunteering mental health consultation to child caregivers in developing countries in the context of episodic visits and a long-term relationship. It is derived from the author's experience doing this work for approximately 12 years. The two foundational features of the method-the role of a consultant and a long-term relationship-are described. The method is then elaborated in two settings: consultation to caregivers in an orphanage in Central America and at a hospital in India. While these examples are distinct in multiple domains, they have in common the core features of the consultative model and a long-term relationship. Finally, the article briefly addresses challenges that the consultant experiences when working with neglected and traumatized children and the usefulness of reflective practice. It is hoped that an articulation of this method may make it possible for many who might wish to volunteer to do so, in a way that neither interferes significantly with their work and family life at home nor creates the problems of "helicopter volunteering."

Evidence-based design in an intensive care unit: end-user perceptions.

BACKGROUND: The objective of this study was to describe end-user impressions and experiences in a new intensive care unit built using evidence-based design. METHODS: This qualitative study was comprised of early (2-3 months after opening) and late (12-15 months after opening) phase individual interviews with end-users (healthcare providers, support staff, and patient family members) of the newly constructed Foothills Medical Centre intensive care unit in Calgary, Canada. The study unit was the recipient of the Society of Critical Care Medicine Design Citation award in 2012. RESULTS: We conducted interviews with thirty-nine ICU end-users, twenty-four in the early phase and fifteen in the late phase. We identified four themes (eleven sub-themes): atmosphere (abundant natural light and low noise levels), physical spaces (single occupancy rooms, rooms clustered into clinical pods, medication rooms, and tradeoffs of larger spaces), family participation in care (family support areas and social networks), and equipment (usability, storage, and providers connectivity). Abundant natural light was the design feature most frequently associated with a pleasant atmosphere. Participants emphasized the tradeoffs of size and space, and reported that the benefits of additional space (e.g., fewer interruptions due to less noise) out-weighed the disadvantages (e.g., greater distances between patients, families and providers). End-users advised that local patient care policies (e.g., number of visitors allowed at a time) and staffing needed to be updated to reflect the characteristics of the new facility design. CONCLUSIONS: End-users identified design elements for creating a pleasant atmosphere, attention to the tradeoffs of space and size, designing family support areas to encourage family participation in care, and updating patient care policies and staffing to reflect the new physical space as important aspects to consider when building intensive care units. Evidence-based design may optimize ICU structure for patients, patient families and providers.