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1.
Nucleic Acids Res ; 52(6): 3450-3468, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38412306

RESUMO

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.


Assuntos
Baculoviridae , Sistemas CRISPR-Cas , DNA , Edição de Genes , Proteínas Virais , Animais , Humanos , Baculoviridae/genética , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , DNA/genética , Edição de Genes/métodos , Proteínas Virais/genética , Linhagem Celular
2.
Memory ; : 1-9, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795360

RESUMO

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.

3.
Healthc Q ; 27(1): 42-50, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38881484

RESUMO

The Bridge-to-Home program was launched as a 16-month collaborative from 2018 to 2020 to improve care transitions out of hospital using a patient engagement-focused quality improvement (QI) initiative. Teams that participated in the collaborative were able to implement elements of the patient-oriented care transitions bundle, improve experience of care transitions and increase capacity for patient engagement for both patient partners and providers. In this article, we highlight three case studies of teams in different types of organizations with different levels of patient engagement maturation. Key enablers and barriers are identified with a specific lens on engagement efforts to co-produce changes in the processes and experience of care. These cases illustrate that providing support for patient engagement when leading a QI initiative is mutually reinforcing, where patient engagement and QI support and strengthen each other, resulting in increased success of the quality initiative and increased capacity for patient engagement.


Assuntos
Participação do Paciente , Melhoria de Qualidade , Humanos , Participação do Paciente/métodos , Estudos de Casos Organizacionais , Alta do Paciente , Cuidado Transicional , Serviços de Assistência Domiciliar/organização & administração , Comportamento Cooperativo
4.
Infant Ment Health J ; 44(1): 125-132, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36519510

RESUMO

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.


Assuntos
Técnicas de Observação do Comportamento , Relações Mãe-Filho , Recém-Nascido , Lactente , Feminino , Humanos , Criança , Técnicas de Observação do Comportamento/métodos , Estudos de Viabilidade , Paquistão , Mães
5.
J Child Psychol Psychiatry ; 63(5): 608-612, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34763363

RESUMO

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.


Assuntos
COVID-19 , Pandemias , Adolescente , COVID-19/prevenção & controle , Criança , Humanos , Saúde Mental , Pandemias/prevenção & controle , SARS-CoV-2 , Instituições Acadêmicas
6.
Br J Clin Psychol ; 61(3): 867-874, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34779514

RESUMO

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.


Assuntos
Prisioneiros , Cognição Social , Transtorno da Personalidade Antissocial/psicologia , Cognição , Emoções , Humanos , Masculino
7.
J Am Chem Soc ; 141(30): 12055-12063, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31322901

RESUMO

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.

8.
Infant Ment Health J ; 37(6): 692-700, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27870192

RESUMO

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."


Assuntos
Cuidadores , Países em Desenvolvimento , Pessoal de Saúde , Serviços de Saúde Mental , Voluntários , Altruísmo , Cuidadores/psicologia , Criança , Educação Médica , El Salvador , Pessoal de Saúde/psicologia , Humanos , Índia , Voluntários/psicologia
9.
BMC Anesthesiol ; 15: 57, 2015 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-25907437

RESUMO

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.


Assuntos
Atitude do Pessoal de Saúde , Projeto Arquitetônico Baseado em Evidências/normas , Família/psicologia , Arquitetura Hospitalar/normas , Unidades de Terapia Intensiva/normas , Satisfação Pessoal , Adulto , Alberta , Participação da Comunidade , Feminino , Humanos , Iluminação , Masculino , Pessoa de Meia-Idade , Ruído , Quartos de Pacientes/normas , Apoio Social
10.
Psychoanal Study Child ; 69: 261-74, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27337819

RESUMO

Observations of videotaped sessions of the analytic treatment of a four-year-old autistic boy offer insights into the meanings and the mechanisms of transference. These observations illustrate the well-known fact that the relationship of transference to symbolization is ambiguous. They also demonstrate that multiple simultaneous meanings exist in a transference field, and many of these meanings emerge from partially or nonsymbolized domains of experience, including and perhaps most important, bodily experience. Whereas many clinicians would agree with these proposals, finding supportive data for them is difficult. One way to explore nonsymbolized phenomena is by analyzing the observable data in videotapes of an autistic child with limited symbolic capacity. Then these data can be put together with the emerging symbolic communications of the child as well as the countertransference reactions of the analyst and some of the biological processes contributing to these meanings. In this study, complex interactions between and among transference reactions of varying degrees of symbolization and in different domains of meaning may provide clues to transference in patients of all ages.


Assuntos
Transtorno Autístico/terapia , Terapia Familiar/métodos , Terapia Psicanalítica/métodos , Transferência Psicológica , Pré-Escolar , Seguimentos , Humanos , Masculino , Gravação em Vídeo
11.
J Exp Biol ; 217(Pt 17): 3133-45, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24948643

RESUMO

The eyes of the horseshoe crab, Limulus polyphemus, are a model for studies of visual function and the visual systems of euarthropods. Much is known about the structure and function of L. polyphemus photoreceptors, much less about their photopigments. Three visible-light-sensitive L. polyphemus opsins were characterized previously (LpOps1, 2 and 5). Here we characterize a UV opsin (LpUVOps1) that is expressed in all three types of L. polyphemus eyes. It is expressed in most photoreceptors in median ocelli, the only L. polyphemus eyes in which UV sensitivity was previously detected, and in the dendrite of eccentric cells in lateral compound eyes. Therefore, eccentric cells, previously thought to be non-photosensitive second-order neurons, may actually be UV-sensitive photoreceptors. LpUVOps1 is also expressed in small photoreceptors in L. polyphemus ventral larval eyes, and intracellular recordings from these photoreceptors confirm that LpUVOps1 is an active, UV-sensitive photopigment. These photoreceptors also express LpOps5, which we demonstrate is an active, long-wavelength-sensitive photopigment. Thus small photoreceptors in ventral larval eyes, and probably those of the other larval eyes, have dual sensitivity to UV and visible light. Interestingly, the spectral tuning of small ventral photoreceptors may change day to night, because the level of LpOps5 in their rhabdoms is lower during the day than during the night, whereas LpUVOps1 levels show no diurnal change. These and previous findings show that opsin co-expression and the differential regulation of co-expressed opsins in rhabdoms is a common feature of L. polyphemus photoreceptors.


Assuntos
Caranguejos Ferradura/química , Caranguejos Ferradura/efeitos da radiação , Opsinas/química , Células Fotorreceptoras de Invertebrados/química , Células Fotorreceptoras de Invertebrados/fisiologia , Raios Ultravioleta , Sequência de Aminoácidos , Animais , Olho Composto de Artrópodes/química , Olho Composto de Artrópodes/fisiologia , Olho/metabolismo , Regulação da Expressão Gênica/efeitos da radiação , Luz , Opsinas/metabolismo , Visão Ocular/fisiologia
12.
Psychoanal Study Child ; 68: 191-208, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26173334

RESUMO

My comments focus on a consideration of three issues central to child psychoanalysis stimulated by rereading the classic paper by Berta Bornstein, "The Analysis of a Phobic Child: Some Problems of Theory and Technique in Child Analysis": (1) the importance of "co-creativity" and its use in analysis to repair disruptions in the mother-child relationship; (2) working analytically with the "inner world of the child "; and (3) the fundamental importance of multiple simultaneous meaning-making processes. I begin with a discussion of current thinking about the importance of interactive processes in developmental and therapeutic change and then lead to the concepts of "co-creativity" and interactive repair, elements that are missing in the "Frankie" paper. The co-creative process that I outline includes multiple contributions that Frankie and his caregivers brought to their relationships--his mother, his father, his nurse, and even his analyst. I then address the question of how child analysts can maintain a central focus on the inner world of the child while still taking into account the complex nature of co-creativity in the change process. Finally, I discuss insights into the multiple simultaneous meaning-making processes in the analytic relationship to effect therapeutic change, including what I call the "sandwich model," an attempt to organize this complexity so that is more accessible to the practicing clinician. In terms of the specific case of Frankie, my reading of the case suggests that failure to repair disruptions in the mother-child relationship from infancy through the time of the analytic treatment was central to Frankie's problems. My hypothesis is that, rather than the content of his analyst's interpretations, what was helpful to Frankie in the analysis was the series of attempts at interactive repair in the analytic process. Unfortunately, the case report does not offer data to test this hypothesis. Indeed, one concluding observation from my reading of this classic case is how useful it would be for the contemporary analyst to pay attention to the multifaceted co-creative process in order to explain and foster the therapeutic change that can occur in analysis.


Assuntos
Transtornos Fóbicos/terapia , Terapia Psicanalítica/métodos , Humanos , Masculino
13.
Methods Mol Biol ; 2829: 301-327, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38951346

RESUMO

Efficient genome editing by using CRISPR technologies requires simultaneous and efficient delivery of multiple genetically encoded components to mammalian cells. Amongst all editing approaches, prime editing (PE) has the unique potential to perform seamless genome rewriting, in the absence of DNA double-strand breaks (DSBs). The cargo capacity required for efficient PE delivery to mammalian cells stands at odd with the limited packaging capacity of traditional viral delivery vectors. By contrast, baculovirus (BV) has a large synthetic DNA capacity and can efficiently transduce mammalian cells. Here we describe a protocol for the assembly of baculovirus vectors for multiplexed prime editing in mammalian cells.


Assuntos
Baculoviridae , Sistemas CRISPR-Cas , Edição de Genes , Vetores Genéticos , Baculoviridae/genética , Edição de Genes/métodos , Vetores Genéticos/genética , Humanos , Animais , Células HEK293
14.
Fam Relat ; 73(2): 1046-1066, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38523658

RESUMO

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.

15.
J Child Adolesc Trauma ; 16(1): 21-30, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36776635

RESUMO

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.

16.
Cell Death Dis ; 14(5): 306, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37142595

RESUMO

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.


Assuntos
Neoplasias Colorretais , Secretoma , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico
17.
Antib Ther ; 6(4): 277-297, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38075238

RESUMO

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.

18.
Infant Ment Health J ; 33(4): 339-349, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28520172

RESUMO

This article considers the influence of infant research on psychodynamic theory and practice. Infant research highlights the dramatic effects of the early caregiving relationship on development throughout the life span. It also provides important perspectives on psychotherapeutic processes. This article highlights such elements as empathy, mutual recognition and attachment, along with elaborating the intersubjective and transactional systems perspectives. In addition, it stresses the powerful role of nonverbal, implicit communication and meaning-making, which play a greater role in human relational experience-and therefore in the therapeutic process-than previously understood. In addition to clarifying these general orientations, the article describes specific therapeutic strategies based on the expanded developmental knowledge.

19.
Front Psychol ; 13: 875964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814075

RESUMO

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.

20.
RSC Adv ; 13(1): 594-601, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36605673

RESUMO

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.

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