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1.
Proc Natl Acad Sci U S A ; 120(31): e2308798120, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37487074

RESUMO

Mammalian infants depend on parental care for survival, with numerous consequences for their behavioral development. We investigated the epigenetic and neurodevelopmental mechanisms mediating the impact of early biparental care on development of alloparenting behavior, or caring for offspring that are not one's own. We find that receiving high parental care early in life leads to slower epigenetic aging of both sexes and widespread male-specific differential expression of genes related to synaptic transmission and autism in the nucleus accumbens. Examination of parental care composition indicates that high-care fathers promote a male-specific increase in excitatory synapses and increases in pup retrieval behavior as juveniles. Interestingly, females raised by high-care fathers have the opposite behavioral response and display fewer pup retrievals. These results support the concept that neurodevelopmental trajectories are programmed by different features of early-life parental care and reveal that male neurodevelopmental processes are uniquely sensitive to care by fathers.


Assuntos
Comportamento Animal , Pai , Humanos , Feminino , Animais , Masculino , Comportamento Animal/fisiologia , Comportamento Materno/fisiologia , Núcleo Accumbens , Pais , Comportamento Paterno , Arvicolinae/fisiologia
2.
Ann Surg ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38375660

RESUMO

OBJECTIVE: To identify well-being threats for surgeons and anesthesiologists and develop interventions using the Quality of Life Improvement (QOLI) approach. BACKGROUND: Developing feasible perioperative well-being interventions requires identifying shared and specialty-specific well-being needs. The QOLI framework integrates human-centered design, implementation science, and quality improvement to address well-being needs. METHODS: Anesthesia and surgery faculty in eight perioperative departments at an academic medical center completed cross-sectional surveys containing validated measures of well-being and workplace satisfaction, and open-ended questions about professional motivations, pain points, strategies for improvement, and well-being priorities. Using template analysis, we analyzed open-ended survey data and presented resulting themes at a joint-specialty town hall for live-voting to identify well-being priorities. RESULTS: 104 perioperative faculty completed the survey. Across specialties, higher MHC-SF scores (representative of individual global well-being) were associated with higher satisfaction with workplace control, values, decision latitude, and social support. Anesthesiologists reported lower satisfaction and control than surgeons across multiple domains. Template analysis yielded five areas for intervention: (1) Work culture, (2) Work environment/resources, (3) Sources of fulfillment, (4) Work/life harmony, (5) Financial compensation. Surgeons and anesthesiologists both prioritized high-quality patient care but differed in their other top priorities. The most frequently cited well-being threats for surgeons were OR inefficiencies/delays and excessive workload, while anesthesiologists cited understaffing and unpredictable work hours. CONCLUSIONS: Surgeons and anesthesiologists share many needs and priorities, with pain points that are often negatively synergistic. Applying the QOLI approach across specialties allows for well-being interventions that honor complexity and promote the development of feasible solutions.

3.
Ann Surg ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38258586

RESUMO

OBJECTIVE: To review the evidence on mindfulness-based interventions (MBIs) for surgeons. BACKGROUND: Healthcare professionals have alarmingly high rates of burnout, yet little is known about psychological factors that support resilience. MBIs, which involve codified training in specific skills such as self-awareness, emotional regulation, and perspective-taking, have shown benefit to professionals in high stress environments, but have had limited implementation in the healthcare workplace and in surgery. To our knowledge, there has not been a scoping review of MBIs in surgery to date. METHODS: We conducted a scoping review of the evidence for the feasibility and effectiveness of MBIs for surgeons, including evidence on interventions that explicitly train mindfulness, which spans multiple cohorts and settings, utilizing different methodologies and outcome measures. RESULTS: This scoping review yielded 24 studies, including two mixed method/qualitative studies, nine randomized control trials, three non-randomized interventional studies, and eight single-arm interventional studies. CONCLUSIONS: We find that MBIs in surgery 1) are feasible in surgical contexts, with implementation science providing insights on sustainability; 2) increase mindfulness, 3) improve well-being in terms of burnout and both psychological and neurophysiological measures of stress, and 4) enhance performance as measured in executive function, surgical skills, and communication skills. These conclusions are supported by psychometric measures, observations of technical skills, and neurophysiological evidence. Future directions include studying MBIs in larger and more diverse populations, and iteratively tailoring mindfulness-based interventions to other healthcare contexts.

4.
Dev Psychobiol ; 66(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38533486

RESUMO

Exogenous oxytocin (OT) is widely used to induce or augment labor with little understanding of the impact on offspring development. In rodent models, including the prairie vole (Microtus ochrogaster), it has been shown that oxytocin administered to mothers can affect the nervous system of the offspring with long lasting behavioral effects especially on sociality. Here, we examined the hypothesis that perinatal oxytocin exposure could have epigenetic and transcriptomic consequences. Prairie voles were exposed to exogenous oxytocin, through injections given to the mother just prior to birth, and were studied at the time of weaning. The outcome of this study revealed increased epigenetic age in oxytocin-exposed animals compared to the saline-exposed group. Oxytocin exposure led to 900 differentially methylated CpG sites (annotated to 589 genes), and 2 CpG sites (2 genes) remained significantly different after correction for multiple comparisons. Differentially methylated CpG sites were enriched in genes known to be involved in regulation of gene expression and neurodevelopment. Using RNA-sequencing we also found 217 nominally differentially expressed genes (p<0.05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior; after corrections for multiple comparisons 6 genes remained significantly differentially expressed. Finally, we found that maternal oxytocin administration led to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth may have long lasting epigenetic consequences. A need for further investigation of how oxytocin administration impacts development and behavior throughout the lifespan is supported by these outcomes.


Assuntos
Ocitocina , Receptores de Ocitocina , Animais , Feminino , Gravidez , Masculino , Humanos , Ocitocina/metabolismo , Mães , Núcleo Accumbens/metabolismo , Comportamento Social , Epigênese Genética , Arvicolinae
5.
Ann Surg ; 277(3): 397-404, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36124776

RESUMO

OBJECTIVE: To conduct a scoping review of literature on financial implications of surgical resident well-being. BACKGROUND: Surgeon well-being affects clinical outcomes, patient experience, and health care economics. However, our understanding of the relationship between surgical resident well-being and organizational finances is limited. METHODS: Authors searched PubMed, Web of Science, and Embase with no date or language restrictions. Searches of the gray literature included hand references of articles selected for data extraction and reviewing conference abstracts from Embase. Two reviewers screened articles for eligibility based on title and abstract then reviewed eligible articles in their entirety. Data were extracted and analyzed using conventional content analysis. RESULTS: Twenty-five articles were included, 5 (20%) published between 2003 and 2010, 12 (48%) between 2011 and 2018, and 8 (32%) between 2019 and 2021. One (4%) had an aim directly related to the research question, but financial implications were not considered from the institutional perspective. All others explored factors impacting well-being or workplace sequelae of well-being, but the economics of these elements were not the primary focus. Analysis of content surrounding financial considerations of resident well-being revealed 5 categories; however, no articles provided a comprehensive business case for investing in resident well-being from the institutional perspective. CONCLUSIONS: Although the number of publications identified through the present scoping review is relatively small, the emergence of publications referencing economic issues associated with surgical resident well-being may suggest a growing recognition of this area's importance. This scoping review highlights a gap in the literature, which should be addressed to drive the system-level change needed to improve surgical resident well-being.


Assuntos
Internato e Residência , Cirurgiões , Humanos , Progressão da Doença
6.
Horm Behav ; 150: 105314, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36731301

RESUMO

Cesarean delivery is associated with diminished plasma levels of several 'birth-signaling' hormones, such as oxytocin and vasopressin. These same hormones have been previously shown to exert organizational effects when acting in early life. For example, our previous work found a broadly gregarious phenotype in prairie voles exposed to oxytocin at birth. Meanwhile, cesarean delivery has been previously associated with changes in social behavior and metabolic processes related to oxytocin and vasopressin. In the present study, we investigated the long-term neurodevelopmental consequences of cesarean delivery in prairie voles. After cross-fostering, vole pups delivered either via cesarean or vaginal delivery were studied throughout development. Cesarean-delivered pups responded to isolation differently in terms of their vocalizations (albeit in opposite directions in the two experiments), huddled in less cohesive groups under warmed conditions, and shed less heat. As young adults, we observed no differences in anxiety-like or alloparental behavior. However, in adulthood, cesarean-delivered voles of both sexes failed to form partner preferences with opposite sex conspecifics. In a follow-up study, we replicated this deficit in partner-preference formation among cesarean-delivered voles and were able to normalize pair-bonding behavior by treating cesarean-delivered vole pups with oxytocin (0.25 mg/kg) at delivery. Finally, we detected minor differences in regional oxytocin receptor expression within the brains of cesarean-delivered voles, as well as microbial composition of the gut. Gene expression changes in the gut epithelium indicated that cesarean-delivered male voles have altered gut development. These results speak to the possibility of unintended developmental consequences of cesarean delivery, which currently accounts for 32.9 % of deliveries in the U.S. and suggest that further research should be directed at whether hormone replacement at delivery influences behavioral outcomes in later life.


Assuntos
Pradaria , Ocitocina , Animais , Feminino , Masculino , Ocitocina/metabolismo , Seguimentos , Ligação do Par , Vasopressinas/metabolismo , Comportamento Social , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Arvicolinae/fisiologia
7.
J Surg Res ; 291: 488-495, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37536190

RESUMO

INTRODUCTION: To explore and begin to operationalize workplace elements that influence general surgery (GS) resident wellbeing. Tailoring workplace wellbeing interventions is critical to their success. Occupational science has revealed that a person-centered approach to identifying positive and negative workplace influences can inform tailoring while accounting for individual differences. To our knowledge, this approach has not been applied to the surgical training environment. METHODS: A national sample of GS residents from 16 Accreditation Council for Graduate Medical Education training programs ranked the importance of workplace elements via an anonymous survey. Latent profile analysis was performed to identify shared patterns of workplace element prioritization and their relation to levels of flourishing, a measure of global wellbeing. RESULTS: GS trainee respondents (n = 300, 34% response rate - average for studies with this sample population) expressed a hierarchy of workplace element importance which differed by gender and race. "Skills to manage stress" and "a team you feel a part of" were prioritized higher by non-males than males. Residents of color and residents underrepresented in medicine, respectively, prioritized "recognition of work/effort" and "skills to manage stress" more than White and overrepresented in medicine residents. Flourishing prevalence varied by 40% with small differences in the specific profile of workplace element prioritization. CONCLUSIONS: Differences in prioritization of workplace elements reveal subtle but important differences that may guide the design of wellbeing interventions for different populations within surgery.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Local de Trabalho , Educação de Pós-Graduação em Medicina , Inquéritos e Questionários , Emoções , Cirurgia Geral/educação
8.
Adv Neonatal Care ; 23(6): 583-595, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37948632

RESUMO

BACKGROUND: Stress from preterm infant admission to the neonatal intensive care unit (NICU) is associated with infant and maternal physiologic changes, including endocrine and epigenetic alterations. Little is known about the mechanisms connecting NICU stress to biologic changes, and whether preterm infant and maternal stress are reciprocal. As a preliminary step, feasibility and acceptability of measuring indicators of stress are required. PURPOSE: This study evaluated the feasibility and acceptability of research examining perceptions and biologic markers of stress in premature infant-maternal dyads during and after NICU hospitalization. METHODS: We evaluated study feasibility using a longitudinal descriptive design. Acceptability was measured via a maternal questionnaire. Exploratory data regarding hospitalization, perceptions of stress, social support and social determinants of health, and biologic markers of stress were collected during the first week of life and again 3 months after NICU. RESULTS: Forty-eight mothers were eligible for the study, 36 mothers were approached, 20 mothers consented to participate, and 14 mothers completed data collection. Mothers reported high levels of study acceptability despite also voicing concern about the sharing of genetic data. Exploration of DNA methylation of SLC6A4 in preterm infants was significant for a strong correlation with perception of total chronic stress. IMPLICATIONS FOR PRACTICE AND RESEARCH: Clinical practice at the bedside in the NICU should include standardized screening for and early interventions to minimize stress. Complex research of stress is feasible and acceptable. Future research should focus on linking early life stress with epigenetic alterations and evaluation of the dyad for reciprocity.


Assuntos
Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Lactente , Feminino , Recém-Nascido , Humanos , Estudos de Viabilidade , Mães , Hospitalização , Biomarcadores , Proteínas da Membrana Plasmática de Transporte de Serotonina
9.
Pharmacol Rev ; 72(4): 829-861, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912963

RESUMO

Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein-coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. SIGNIFICANCE STATEMENT: Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.


Assuntos
Ocitocina/farmacologia , Ocitocina/fisiologia , Animais , Humanos , Ocitocina/química , Ocitocina/metabolismo
10.
Psychosom Med ; 84(8): 874-884, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36044606

RESUMO

OBJECTIVE: Early life trauma (ELT) and HIV are associated with social processing deficits. In people with HIV (PWH), we examined whether facial emotion identification accuracy differs by ELT and whether neuroendocrine factors including cortisol, oxytocin (OT), and arginine vasopressin, and/or immune system measures play a role in the ELT-performance association. METHODS: We used secondary data from the placebo condition of a pharmacologic challenge study in PWH. Presence of ELT was measured with the Childhood Trauma Questionnaire (at least moderate experiences of sexual, physical, and/or emotional abuse). Social processing was measured with the Facial Emotion Perception Test (FEPT). Salivary immune system measures and cortisol were sampled across a 5-hour study session. Blood was collected at study session start (12 pm ) to measure OT and arginine vasopressin. We examined the association of ELT with FEPT and five biological moderators (from principal components analysis of 12 biomarkers) of ELT-FEPT associations. RESULTS: Of 58 PWH (42 men; mean [standard deviation] age = 33.7 [8.9] years), 50% endorsed ELT. ELT-exposed PWH demonstrated lower identification accuracy across all emotional expressions (unstandardized ß [ B ] = 0.13; standard error [SE] = 0.05; p = .021, d = 0.63) and had higher OT levels compared with ELT-unexposed PWH ( t(1,56) = 2.12, p = .039; d = 0.57). For total accuracy, an OT/C-reactive protein factor moderated the ELT-FEPT association ( B = 0.14; SE = 0.05; p = .014); accuracy was lower in ELT-exposed PWH versus ELT-unexposed PWH when the factor was low but not when high. Similar results were obtained for fearful, neutral, and happy faces ( p values < .05). Regardless of ELT, a myeloid migration (MCP-1/MMP-9) factor was associated with reduced accuracy ( p values < .05). CONCLUSIONS: Our pilot findings suggest that ELT may alter social processing in PWH, and OT and C-reactive protein may be a target for improving social processing in ELT-exposed PWH, and myeloid migration markers may be a target in PWH more generally.


Assuntos
Infecções por HIV , Ocitocina , Adulto , Arginina Vasopressina , Proteína C-Reativa , Feminino , Infecções por HIV/complicações , Humanos , Hidrocortisona , Inflamação , Masculino , Metaloproteinase 9 da Matriz , Percepção Social
11.
J Surg Res ; 277: A25-A35, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35307162

RESUMO

Emotional regulation is increasingly gaining acceptance as a means to improve well-being, performance, and leadership across high-stakes professions, representing innovation in thinking within the field of surgical education. As one part of a broader cognitive skill set that can be trained and honed, emotional regulation has a strong evidence base in high-stress, high-performance fields. Nevertheless, even as Program Directors and surgical educators have become increasingly aware of this data, with emerging evidence in the surgical education literature supporting efficacy, hurdles to sustainable implementation exist. In this white paper, we present evidence supporting the value of emotional regulation training in surgery and share case studies in order to illustrate practical steps for the development, adaptation, and implementation of emotional regulation curricula in three key developmental contexts: basic cognitive skills training, technical skills acquisition and performance, and preparation for independence. We focus on the practical aspects of each case to elucidate the challenges and opportunities of introducing and adopting a curricular innovation into surgical education. We propose an integrated curriculum consisting of all three applied contexts for emotional regulation skills and advocate for the dissemination of such a longitudinal curriculum on a national level.


Assuntos
Regulação Emocional , Liderança , Competência Clínica , Currículo
12.
Ann Surg ; 273(3): 424-432, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773637

RESUMO

OBJECTIVE: To determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers. SUMMARY OF BACKGROUND AND DATA: Tailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown. METHODS: In 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity"). RESULTS: Neither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls. CONCLUSIONS: This pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.


Assuntos
Adaptação Fisiológica , Esgotamento Profissional/prevenção & controle , Esgotamento Profissional/psicologia , Estresse Ocupacional/patologia , Estresse Ocupacional/prevenção & controle , Resiliência Psicológica , Cirurgiões/psicologia , Adulto , Educação de Pós-Graduação em Medicina , Feminino , Cirurgia Geral/educação , Humanos , Internato e Residência , Masculino , Projetos Piloto
13.
Psychol Med ; 51(6): 1001-1010, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31910929

RESUMO

BACKGROUND: Multiple lines of evidence suggest the presence of altered neuroimmune processes in patients with schizophrenia (Sz) and severe mood disorders. Recent studies using a novel free water diffusion tensor imaging (FW DTI) approach, proposed as a putative biomarker of neuroinflammation, atrophy, or edema, have shown significantly increased FW in patients with Sz. However no studies to date have investigated the longitudinal stability of FW alterations during the early course of psychosis, nor have studies focused separately on FE psychosis patients with Sz or bipolar disorder (BD) with psychotic features. METHODS: The current study included 188 participants who underwent diffusion magnetic resonance imaging scanning at baseline. Sixty-four participants underwent follow-up rescanning after 12 months. DTI-based alterations in patients were calculated using voxelwise tract-based spatial statistics and region of interest analyses. RESULTS: Patients with FE psychosis, both Sz and BD, exhibited increased FW at illness onset which remained unchanged over the 12-month follow-up period. Preliminary analyses suggested that antipsychotic medication exposure was associated with higher FW in gray matter that reached significance in the BD group. Higher FW in white matter correlated with negative symptom severity. CONCLUSIONS: Our results support the presence of elevated FW at the onset of psychosis in both Sz and BD, which remains stable during the early course of the illness, with no evidence of either progression or remission.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Biomarcadores , California , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Água , Adulto Jovem
14.
J Surg Res ; 263: A1-A12, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678414

RESUMO

Mental skills and emotional regulation training are gaining acceptance in surgical education as vital elements of surgeon development. These skills can effectively enhance technical skill development, improve well-being, and promote career longevity. There is evidence emerging in the surgical education literature to support the incorporation of mental skills and emotional regulation training curricula in residency training. In this study, we present the existing evidence supporting the use of this training with high performers to reduce stress and optimize well-being and performance. We also consider the recent research emerging in surgical education that offers validity evidence for use of mental skills training with surgeons. Finally, we provide a framework to guide the incorporation of these skills throughout the career of a surgeon and suggest methods to promote the development of mental skills training efforts nationally.


Assuntos
Currículo/tendências , Internato e Residência/organização & administração , Estresse Ocupacional/prevenção & controle , Especialidades Cirúrgicas/educação , Cirurgiões/psicologia , Competência Clínica , Regulação Emocional , Humanos , Internato e Residência/tendências , Estresse Ocupacional/psicologia , Cirurgiões/educação
15.
Microsc Microanal ; 27(4): 659-665, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33973507

RESUMO

Investigating the earliest stages of crystallization requires the transmission electron microscope (TEM) and is particularly challenging for materials which can be affected by the electron beam. Typically, when imaging at magnifications high enough to observe local crystallinity, the electron beam's current density must be high to produce adequate image contrast. Yet, minimizing the electron dose is necessary to reduce the changes caused by the beam. With the advent of a sensitive, high-speed, direct-detection camera for a TEM that is corrected for spherical aberration, it is possible to probe the early stages of crystallization at the atomic scale. High-quality images with low contrast can now be analyzed using new computing methods. In the present paper, this approach is illustrated for crystallization in a Ge2Sb2Te5 (GST-225) phase-change material which can undergo particularly rapid phase transformations and is sensitive to the electron beam. A thin (20 nm) film of GST-225 has been directly imaged in the TEM and the low-dose images processed using Python scripting to extract details of the nanoscale nuclei. Quantitative analysis of the processed images in a video sequence also allows the growth of such nuclei to be followed.

16.
Microsc Microanal ; 27(2): 257-265, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33860742

RESUMO

This paper characterizes novel "star" defects in GaN films grown with metal­organic vapor phase deposition (MOVPE) on GaN substrates with electron channeling contrast imaging (ECCI) and high-resolution electron backscatter diffraction (HREBSD). These defects are hundreds of microns in size and tend to aggregate threading dislocations at their centers. They are the intersection of six nearly ideal low-angle tilt boundaries composed of $\langle a\rangle$-type pyramidal edge dislocations, each on a unique slip system.

17.
Anal Chem ; 92(1): 766-773, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31769659

RESUMO

One challenge associated with the discovery and development of monoclonal antibody (mAb) therapeutics is the determination of heavy chain and light chain pairing. Advances in MS instrumentation and MS/MS methods have greatly enhanced capabilities for the analysis of large intact proteins yielding much more detailed and accurate proteoform characterization. Consequently, direct interrogation of intact antibodies or F(ab')2 and Fab fragments has the potential to significantly streamline therapeutic mAb discovery processes. Here, we demonstrate for the first time the ability to efficiently cleave disulfide bonds linking heavy and light chains of mAbs using electron capture dissociation (ECD) and 157 nm ultraviolet photodissociation (UVPD). The combination of intact mAb, Fab, or F(ab')2 mass, intact LC and Fd masses, and CDR3 sequence coverage enabled determination of heavy chain and light chain pairing from a single experiment and experimental condition. These results demonstrate the potential of top-down and middle-down proteomics to significantly streamline therapeutic antibody discovery.


Assuntos
Anticorpos Monoclonais/química , Sequência de Aminoácidos , Antineoplásicos Imunológicos/química , Fragmentos Fab das Imunoglobulinas/análise , Cadeias Pesadas de Imunoglobulinas/análise , Cadeias Leves de Imunoglobulina/análise , Espectrometria de Massas , Fotólise , Trastuzumab/química , Raios Ultravioleta
18.
Mol Psychiatry ; 24(5): 633-642, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30242229

RESUMO

Episodic memory deficits are consistently documented as a core aspect of cognitive dysfunction in schizophrenia patients, present from the onset of the illness and strongly associated with functional disability. Over the past decade, research using approaches from experimental cognitive neuroscience revealed disproportionate episodic memory impairments in schizophrenia (Sz) under high cognitive demand relational encoding conditions and relatively unimpaired performance under item-specific encoding conditions. These specific deficits in component processes of episodic memory reflect impaired activation and connectivity within specific elements of frontal-medial temporal lobe circuits, with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively intact function of ventrolateral prefrontal cortex and variable results in the hippocampus. We propose that memory deficits can be understood within the broader context of cognitive deficits in Sz, where impaired DLPFC-related cognitive control has a broad impact across multiple cognitive domains. The therapeutic implications of these findings are discussed.


Assuntos
Cognição/fisiologia , Memória/fisiologia , Esquizofrenia/fisiopatologia , Adulto , Mapeamento Encefálico , Transtornos Cognitivos/fisiopatologia , Disfunção Cognitiva/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/fisiopatologia , Memória Episódica , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Psicologia do Esquizofrênico , Lobo Temporal/fisiopatologia
19.
Birth ; 47(2): 220-226, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32003064

RESUMO

BACKGROUND: The cesarean birth rate in the United States is 32%, and there is discussion about the cause of high surgical birth rates. Our purpose was to determine whether mode of birth is influenced by maternal, nurse, and system factors. METHODS: Secondary analysis of a data set of 163 women having postdates labor induction with oxytocin. Kaplan-Meier survival curves were calculated to compare the time for patients to reach an infusion rate of 6 mU/min, consistent with endogenous oxytocin levels in active labor. We used the log-rank test to evaluate survival curve differences. Multiple logistic regression and Cox proportional hazards models were conducted and included covariates that had statistically significant bivariate relationships with the time variable, or were clinically meaningful. RESULTS: The mean time to reach 6 mU/min was longer for women who birthed by cesarean (172.5 minutes) than for women who had vaginal birth (125.0 minutes, P = .024). The mean time to reach 6 mU/min was also longer for women admitted on night shift (147.0 minutes) than day shift (110.2 minutes, P = .018). No maternal characteristics were significantly related to the time to reach a rate of 6 mU/min. CONCLUSIONS: Even during the initial hours of labor induction, it is important that the oxytocin infusion is titrated appropriately to aid women in achieving timely vaginal birth. Intrapartum nurses should receive education about the pharmacokinetics of intravenous oxytocin to understand proper administration of this high-alert medication.


Assuntos
Cesárea/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Adulto , Índice de Massa Corporal , Feminino , Humanos , Estimativa de Kaplan-Meier , Trabalho de Parto , Modelos Logísticos , Obesidade/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Modelos de Riscos Proporcionais , Estados Unidos
20.
Surg Innov ; 27(6): 669-674, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32894031

RESUMO

Background. Esophagogastroduodenoscopy (EGD) is an important tool in the evolving specialty of acute care surgery (ACS). Understanding the types of nonelective EGDs performed by ACS groups is important for the development of ACS programs and the training of future general surgeons. Methods. We conducted a retrospective review of all EGDs performed by ACS surgeons at a single urban academic center over a 5-year period (January 2013-December 2018). Results. A total of 495 EGDs were performed, of which 129 (26%) were urgent, nonelective procedures. Patients who underwent urgent EGD were younger than those who underwent elective procedures (median 55 vs 60 years, P = .03), had higher American Society of Anesthesiologists (ASA) classes (median ASA 3 vs 2, P = .0002), and longer hospital stays (median 5 days vs 0 days, P < .0001). The most common indications for urgent endoscopies were the management of leak, dysphagia, or stenosis in patients with a history of foregut surgery, followed by the management of esophageal perforation. The success rate of endoscopic therapy was high (median 88%, interquartile range (IQR) 78-89%). However, some patients required multiple interventions (median 1, IQR 1-3), and patients treated for leaks were less likely to be successfully treated with endoscopic therapy alone than patients treated for other indications (success rate 65% vs 88%, P = .003). Conclusions. Our experience suggests that EGD has an important role in current ACS practice and that endoscopic management is safe and effective in a range of urgent surgical scenarios. Future ACS surgeons should be facile with endoscopic techniques.


Assuntos
Cirurgiões , Endoscopia Gastrointestinal , Humanos , Tempo de Internação , Estudos Retrospectivos
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