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1.
Elife ; 132024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656237

RESUMO

The organization of nucleosomes into chromatin and their accessibility are shaped by local DNA mechanics. Conversely, nucleosome positions shape genetic variations, which may originate from mismatches during replication and chemical modification of DNA. To investigate how DNA mismatches affect the mechanical stability and the exposure of nucleosomal DNA, we used an optical trap combined with single-molecule FRET and a single-molecule FRET cyclization assay. We found that a single base-pair C-C mismatch enhances DNA bendability and nucleosome mechanical stability for the 601-nucleosome positioning sequence. An increase in force required for DNA unwrapping from the histone core is observed for single base-pair C-C mismatches placed at three tested positions: at the inner turn, at the outer turn, or at the junction of the inner and outer turn of the nucleosome. The results support a model where nucleosomal DNA accessibility is reduced by mismatches, potentially explaining the preferred accumulation of single-nucleotide substitutions in the nucleosome core and serving as the source of genetic variation during evolution and cancer progression. Mechanical stability of an intact nucleosome, that is mismatch-free, is also dependent on the species as we find that yeast nucleosomes are mechanically less stable and more symmetrical in the outer turn unwrapping compared to Xenopus nucleosomes.


Assuntos
Pareamento Incorreto de Bases , DNA , Nucleossomos , Nucleossomos/metabolismo , Nucleossomos/química , Nucleossomos/genética , DNA/química , DNA/metabolismo , DNA/genética , Pareamento Incorreto de Bases/genética , Animais , Transferência Ressonante de Energia de Fluorescência , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Xenopus laevis
2.
West J Emerg Med ; 25(2): 186-190, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38596916

RESUMO

Introduction: Virtual interviews (VI) are now a permanent part of pediatric emergency medicine (PEM) recruitment, especially given the cost and equity advantages. Yet inability to visit programs in person can impact decision-making, leading applicants to apply to more programs. Moreover, the cost advantages of VI may encourage applicants to apply to programs farther away than they might otherwise have been willing or able to travel. This could create unnecessary strain on programs. We conducted this study to determine whether PEM fellowship applicants would apply to a larger number of programs and in different geographic patterns with VI (2020 and 2021) as compared to in-person interviews (2018 and 2019). Methods: We conducted an anonymous national survey of all PEM fellows comparing two cohorts: current fellows who interviewed inperson (applied in 2018/2019) and fellows who underwent VIs in 2020/2021 (current fellows and those recently matched in 2021). The study took place in March-April 2022. Questions focused on geographic considerations during interviews and the match. We used descriptive statistics, chi-square and t-tests for analysis. Results: Overall response rate was 42% (231/550); 32% (n = 74) interviewed in person and 68% (n = 157) virtually. Fellows applied to a median of 4/6 geographic regions (interquartile range 2, 5). Most applied for fellowship both in the same region as residency (216, 93%) and outside (192, 83%). Only the Pacific region saw a statistically significant increase in applicants during VI (59.9% vs 43.2%, P = 0.02). There was no statistical difference in the number of programs applied to during in-person vs VI (mean difference (95% confidence interval 0.72, -2.8 - 4.2). A majority matched in their preferred state both during VI (60.4%) and in-person interviews (65.7%). The difference was not statistically significant (P = 0.45). Conclusion: While more PEM fellowship applicants applied outside the geographic area where their residency was and to the Pacific region, there was no overall increase in the number of programs or geographic areas PEM applicants applied to during VI as compared to in-person interview seasons. As this was the first two years of VI, ongoing data collection will further identify trends and the impactof VI.


Assuntos
Internato e Residência , Medicina de Emergência Pediátrica , Criança , Humanos , Coleta de Dados , Bolsas de Estudo
3.
Res Pract Thromb Haemost ; 8(1): 102276, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38226339

RESUMO

Background: Hyperlipidemia is associated with chronic inflammation and thromboinflammation. This is an underlying cause of several cardiovascular diseases, including atherosclerosis. In diseased blood vessels, rampant thrombin generation results in the initiation of the coagulation cascade, activation of platelets, and endothelial cell dysfunction. Coagulation factor (F) XI represents a promising therapeutic target to reduce thromboinflammation, as it is uniquely positioned at an intersection between inflammation and thrombin generation. Objectives: This study aimed to investigate the role of FXI in promoting platelet and endothelial cell activation in a model of hyperlipidemia. Methods: Nonhuman primates (NHPs) were fed a standard chow diet (lean, n = 6) or a high-fat diet (obese, n = 8) to establish a model of hyperlipidemia. Obese NHPs were intravenously administered a FXI blocking antibody (2 mg/kg) and studied at baseline and at 1, 7, 14, 21, and 28 days after drug administration. Platelet activation and inflammatory markers were measured using fluorescence-activated cell sorting or enzyme-linked immunosorbent assay. Molecular imaging was used to quantify vascular cell adhesion molecule 1 (VCAM-1) expression at the carotid bifurcation. Results: Obese NHPs demonstrated increased sensitivity for platelet P-selectin expression and phosphatidylserine exposure in response to platelet GPVI or PAR agonists compared with lean NHPs. Obese NHPs exhibited elevated levels of C-reactive protein, cathepsin D, and myeloperoxidase compared with lean NHPs. Following pharmacological inhibition of FIX activation by FXIa, platelet priming for activation by GPVI or PAR agonists, C-reactive protein levels, and endothelial VCAM-1 levels were reduced in obese NHPs. Conclusion: FXI activation promotes the proinflammatory phenotype of hyperlipidemia by priming platelet activation and inciting endothelial cell dysfunction.

4.
Acad Pediatr ; 24(1): 147-154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37245666

RESUMO

OBJECTIVE: The COVID-19 pandemic resulted in training programs restructuring their curricula. Fellowship programs are required to monitor each fellow's training progress through a combination of formal evaluations, competency tracking, and measures of knowledge acquisition. The American Board of Pediatrics administers subspecialty in-training examinations (SITE) to pediatric fellowship trainees annually and board certification exams at the completion of the fellowship. The objective of this study was to compare SITE scores and certification exam passing rates before and during the pandemic. METHODS: In this retrospective observational study, we collected summative data on SITE scores and certification exam passing rates for all pediatric subspecialties from 2018 to 2022. Trends over time were assessed using analysis of variance (ANOVA) analysis to test for trends across years within one group and t-test analysis to compare groups before and during the pandemic. RESULTS: Data were obtained from 14 pediatric subspecialties. Comparing prepandemic to pandemic scores, Infectious Diseases, Cardiology, and Critical Care Medicine saw statistically significant decreases in SITE scores. Conversely, Child Abuse and Emergency Medicine saw increases in SITE scores. Emergency Medicine saw a statistically significant increase in certification exam passing rates, while Gastroenterology and Pulmonology saw decreases in exam passing rates. CONCLUSIONS: The COVID-19 pandemic resulted in restructuring didactics and clinical care based on the needs of the hospital. There were also societal changes affecting patients and trainees. Subspecialty programs with declining scores and certification exam passing rates may need to assess their educational and clinical programs and adapt to the needs of trainees' learning edges.


Assuntos
COVID-19 , Pandemias , Humanos , Estados Unidos , Criança , Avaliação Educacional , Certificação , Educação de Pós-Graduação em Medicina/métodos
5.
Commun Biol ; 6(1): 885, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644220

RESUMO

Extracellular vesicles (EVs) have been shown as key mediators of extracellular small RNA transport. However, carriers of cell-free messenger RNA (cf-mRNA) in human biofluids and their association with cancer remain poorly understood. Here, we performed a transcriptomic analysis of size-fractionated plasma from lung cancer, liver cancer, multiple myeloma, and healthy donors. Morphology and size distribution analysis showed the successful separation of large and medium particles from other soluble plasma protein fractions. We developed a strategy to purify and sequence ultra-low amounts of cf-mRNA from particle and protein enriched subpopulations with the implementation of RNA spike-ins to control for technical variability and to normalize for intrinsic drastic differences in cf-mRNA amount carried in each plasma fraction. We found that the majority of cf-mRNA was enriched and protected in EVs with remarkable stability in RNase-rich environments. We observed specific enrichment patterns of cancer-associated cf-mRNA in each particle and protein enriched subpopulation. The EV-enriched differentiating genes were associated with specific biological pathways, such as immune systems, liver function, and toxic substance regulation in lung cancer, liver cancer, and multiple myeloma, respectively. Our results suggest that dissecting the complexity of EV subpopulations illuminates their biological significance and offers a promising liquid biopsy approach.


Assuntos
Ácidos Nucleicos Livres , Vesículas Extracelulares , Neoplasias Hepáticas , Neoplasias Pulmonares , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Ácidos Nucleicos Livres/genética , Neoplasias Pulmonares/genética , Vesículas Extracelulares/genética , RNA Mensageiro/genética
6.
Pediatr Emerg Care ; 39(6): 457-461, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37195644

RESUMO

OBJECTIVE: We sought to describe how the Emergency Department Work Index (EDWIN) saturation tool (1) correlates with PED overcrowding during a capacity management activation policy, known internally as Purple Alert and (2) compare overall hospital-wide capacity metrics on days in which the alert was instituted versus days it was not. METHODS: This study was conducted between January 1, 2017 and December 31, 2019 in a 30-bed academic quaternary care, urban PED within a university hospital. The EDWIN tool was implemented in January 2019 and objectively measured the busyness of the PED. To determine correlation with overcrowding, EDWIN scores were calculated at alert initiation. Mean alert hours per month were plotted on a control chart before and after EDWIN implementation. We also compared daily numbers of PED visits, inpatient admissions, and patients left without being seen (LWBS) for days with and without alert initiation to assess whether or not Purple Alert correlated with high PED usage. RESULTS: During the study period, the alert was activated a total of 146 times; 43 times after EDWIN implementation. Mean EDWIN score was 2.5 (SD 0.5, min 1.5, max 3.8) at alert initiation. There were no alert occurrences for EDWIN scores less than 1.5 (not overcrowded). There was no statistically significant difference for mean alert hours per month before and after EDWIN was instituted (21.4 vs 20.2, P = 0.08). Mean numbers of PED visits, inpatient admissions, and patients left without being seen were higher on days with alert activation ( P < 0.001 for all). CONCLUSIONS: The EDWIN score correlated with PED busyness and overcrowding during alert activation and correlated with high PED usage. Future studies could include implementing a real-time Web-based EDWIN score as a prediction tool to prevent overcrowding and verifying EDWIN generalizability at other PED sites.


Assuntos
Hospitalização , Hospitais Pediátricos , Criança , Humanos , Serviço Hospitalar de Emergência , Hospitais Universitários , Pacientes Internados , Estudos Retrospectivos
8.
Psychiatr Serv ; 74(3): 312-315, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36164772

RESUMO

OBJECTIVE: Suicide rates and frequency of pediatric emergency department (ED) visits for suicidal thoughts and behaviors have increased among Black preadolescents in the United States in recent years. This study examined whether characteristics of ED visits and treatment management of preadolescents with suicidal thoughts and behaviors differed by race. METHODS: An electronic medical record query identified patients ages 8-12 (N=504) who visited a pediatric ED with a psychiatric-related chief complaint in 2019. The authors examined suicidal thoughts and behaviors that were reported with the Ask Suicide-Screening Questions tool, ED clinical impression, and ED disposition overall and by race. RESULTS: Compared with other racial groups, Black preadolescents were less likely to report suicidal thoughts, despite equivalent lifetime histories of suicide attempts, and were more likely to be brought to the ED by police and discharged (instead of being admitted to inpatient psychiatric care). CONCLUSIONS: Research to better understand racial disparities in suicide risk among preadolescents can inform prevention efforts.


Assuntos
Ideação Suicida , Tentativa de Suicídio , Criança , Humanos , Estados Unidos , Fatores Raciais , Tentativa de Suicídio/prevenção & controle , Tentativa de Suicídio/psicologia , Hospitalização , Serviço Hospitalar de Emergência
9.
Bull Environ Contam Toxicol ; 110(1): 29, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36576584

RESUMO

This study evaluated the salt tolerance and sodium (Na) bioaccumulation of Typha orientalis, Lepironia articulata, Eleocharis dulcis, Scirpus littoralis, Brachiaria mutica, Paspalum atratum and Setaria sphacelata at five salinity levels of 0, 5, 10, 15 and 20‰ (corresponding to 0, 2.4, 6.9, 12.6 and 18 g NaCl L-1). S. littoralis showed zero-reduction in total dry biomass and was classified as a salt tolerant plant based on the membership function value. The highest Na+ accumulation was observed in S. sphacelata (307.9 mg plant-1) in spite of its salt sensitivity, followed by S. littoralis and T. orientalis at concentration of 155 mg plant-1. Consequently, the Na+ phytoextraction potential of these species can be estimated as 46.2, 23.3 and 23.3 kg ha-1 over 49 days, respectively. Taken together, they show high potential as Na+ hyperaccumulators, and can be selected in the national reclamation program for salt-affected soils in the context adaptation to climate change.


Assuntos
Solo , Áreas Alagadas , Biodegradação Ambiental , Salinidade , Plantas Tolerantes a Sal , Sódio
10.
J Ration Emot Cogn Behav Ther ; : 1-19, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36340869

RESUMO

The simultaneous occurrence of the COVID-19 pandemic and the transition to adulthood have posed particular obstacles to university students' mental health. However, it remains unclear whether hope promotes mental health in the relationship between self-compassion, psychological well-being, and life satisfaction. Therefore, this study investigated the role of hope as a mediator in the relationship between self-compassion, psychological well-being, and life satisfaction among Vietnamese undergraduate students in the context of the COVID-19 pandemic. Participants consisted of 484 students (aged 18-24) from several universities in Vietnam. To measure the four variables in the research model, we opted for the Self-Compassion Scale, the State Hope Scale, the World Health Organization 5-item Well-Being Index, and the Satisfaction With Life Scale. The results showed that (1) self-compassion was significantly positively correlated with psychological well-being, (2) self-compassion was not correlated with life satisfaction, (3) hope was a mediator of the relationship between self-compassion and psychological well-being, and (4) hope was a mediator of the relationship between self-compassion and life satisfaction. These findings suggest interventions on self-compassion to enhance hope and subsequently increase students' mental health, which offers colleges, psychologists, and psychiatrists a guideline to cope with harmful psychological implications during the COVID-19 pandemic.

11.
NPJ Precis Oncol ; 6(1): 28, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468987

RESUMO

Cell-free RNA (cfRNA) in plasma reflects phenotypic alterations of both localized sites of cancer and the systemic host response. Here we report that cfRNA sequencing enables the discovery of messenger RNA (mRNA) biomarkers in plasma with the tissue of origin-specific to cancer types and precancerous conditions in both solid and hematologic malignancies. To explore the diagnostic potential of total cfRNA from blood, we sequenced plasma samples of eight hepatocellular carcinoma (HCC) and ten multiple myeloma (MM) patients, 12 patients of their respective precancerous conditions, and 20 non-cancer (NC) donors. We identified distinct gene sets and built classification models using Random Forest and linear discriminant analysis algorithms that could distinguish cancer patients from premalignant conditions and NC individuals with high accuracy. Plasma cfRNA biomarkers of HCC are liver-specific genes and biomarkers of MM are highly expressed in the bone marrow compared to other tissues and are related to cell cycle processes. The cfRNA level of these biomarkers displayed a gradual transition from noncancerous states through precancerous conditions and cancer. Sequencing data were cross-validated by quantitative reverse transcription PCR and cfRNA biomarkers were validated in an independent sample set (20 HCC, 9 MM, and 10 NC) with AUC greater than 0.86. cfRNA results observed in precancerous conditions require further validation. This work demonstrates a proof of principle for using mRNA transcripts in plasma with a small panel of genes to distinguish between cancers, noncancerous states, and precancerous conditions.

12.
Sci Rep ; 12(1): 2099, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136102

RESUMO

The discovery and utility of clinically relevant circulating biomarkers depend on standardized methods that minimize preanalytical errors. Despite growing interest in studying extracellular vesicles (EVs) and cell-free messenger RNA (cf-mRNA) as potential biomarkers, how blood processing and freeze/thaw impacts the profiles of these analytes in plasma was not thoroughly understood. We utilized flow cytometric analysis to examine the effect of differential centrifugation and a freeze/thaw cycle on EV profiles. Utilizing flow cytometry postacquisition analysis software (FCMpass) to calibrate light scattering and fluorescence, we revealed how differential centrifugation and post-freeze/thaw processing removes and retains EV subpopulations. Additionally, cf-mRNA levels measured by RT-qPCR profiles from a panel of housekeeping, platelet, and tissue-specific genes were preferentially affected by differential centrifugation and post-freeze/thaw processing. Critically, freezing plasma containing residual platelets yielded irreversible ex vivo generation of EV subpopulations and cf-mRNA transcripts, which were not removable by additional processing after freeze/thaw. Our findings suggest the importance of minimizing confounding variation attributed to plasma processing and platelet contamination.


Assuntos
Sangue , Ácidos Nucleicos Livres , Criopreservação , Vesículas Extracelulares , RNA Mensageiro , Citometria de Fluxo , Humanos
14.
Early Interv Psychiatry ; 16(5): 509-517, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34268877

RESUMO

AIM: Paediatric emergency departments (ED) nationwide experience a shared burden of boarding mental health patients. Whilst boarding, some patients have a change in disposition from hospitalization to discharge home. This phenomenon raises concern because EDs often have scarce resources for mental health patients. We sought to understand which patient and clinical factors are associated with a change in disposition outcome. METHODS: A nested age-sex-race frequency-matched case-control study was conducted including paediatric patients who presented to an urban PED for mental healthcare over a 36-month period. Control patients included patients admitted to an inpatient psychiatric facility, whilst case patients were those discharged home. Descriptive statistics and multivariable logistic regression analyses were performed to compare groups. RESULTS: Case patients were more likely to receive intramuscular Haloperidol (OR 2.2 [CI 1.1-4.4]) for agitation and a psychiatric consult (OR 2.3 [1.4-3.9]) whilst boarding. Case patients were also more likely to present with behavioural concerns (OR 1.8 [CI 1.1-3.1]) and have additional complexities such as medical comorbidities (OR 1.8 [CI 1.1-2.9]) or suicidal ideation/attempt (OR 2.6 [CI 1.1-6.1]). Amongst the most common themes for disposition change was improved patient status (58.8%). CONCLUSION: These findings suggest that boarding mental health patients have different disposition outcomes and thus may benefit from patient-specific treatment interventions. Given that patients' statuses may change during the boarding period prompting discharge to home, more focus should be directed to developing brief evidence-based practises that may be implemented in the ED and effectively bridge the gap to outpatient mental health services.


Assuntos
Transtornos Mentais , Saúde Mental , Estudos de Casos e Controles , Criança , Serviço Hospitalar de Emergência , Hospitalização , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Estudos Retrospectivos
15.
Transbound Emerg Dis ; 69(2): 913-918, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33617130

RESUMO

Getah virus (GETV) is a mosquito-borne RNA virus belonging to the family Togaviridae, genus Alphavirus. GETV infection causes diarrhoea and death in piglets, and reproductive failure and abortion in sows. This study conducted a serological survey of GETV infection among domestic pig populations in Thailand. ELISA was used to analyse 1,188 pig serum samples collected from 11 provinces of Thailand during 2017-2018, with 23.1% of the samples being positive for anti-GETV antibodies. The positive ratio of anti-GETV antibodies was significantly higher in nursery (67.9%) and older stages (84.5%) of pigs than in finishing stage (14.2%). Furthermore, we successfully isolated GETV from one pig serum, designated as GETV strain GETV/SW/Thailand/2017, and determined the complete genome sequence (11,689 nt). Phylogenetic analysis demonstrated that our isolate was different from the recent GETV group spreading among pig populations in East Asia and formed a cluster with two GETV strains, namely YN12031 (China, 2015) and LEIV16275Mar (Far-East Russia, 2007). We concluded that two different GETV groups are currently spreading among pig populations in Asian countries.


Assuntos
Alphavirus , Culicidae , Alphavirus/genética , Animais , Feminino , Filogenia , Gravidez , Sus scrofa , Suínos , Tailândia/epidemiologia
16.
Pediatr Emerg Care ; 38(4): e1207-e1212, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34608060

RESUMO

OBJECTIVE: This study aimed to evaluate both applicant and interviewer satisfaction with the virtual interviewing process for pediatric emergency medicine (PEM) fellowship in hopes to improve the fellowship interviewing process. It was proposed that fellowship programs and applicants would prefer virtual interviews over traditional interviews. METHODS: A survey developed in collaboration with UT Southwestern PEM fellowship leaders and national PEM leaders was sent to all PEM fellowship applicants and programs at the conclusion of the 2020 interview season and rank list submission. The applicant survey obtained information on ease of virtual interviews and whether applicants felt that they obtained adequate information from virtual interviews to make informed program selections. Program director surveys collected data on thoughts and feelings about virtual interviews and obstacles encountered during the recruitment season. Both surveys asked about costs for interviews and interview type preference. RESULTS: A response rate of 49% from applicants and 47% from programs was obtained. Virtual interview days were similar in the amount of time and staff hours used compared with traditional days. Applicants spent less on virtual interviews compared with those who underwent traditional interviews (average $725 vs $4312). Programs received more applications than the prior year and spent less money during the virtual cycle. The majority of the applicants (90%) were comfortable with the virtual interview platform, and most (66%) agreed that virtual interviews provided adequate information to determine program rank. Geography was the number 1 rank determining factor. Programs and applicants preferred a form of in-person interviews. CONCLUSIONS: Virtual interviews provide cost savings for both applicants and programs. Despite this, both parties prefer a form of in-person interviews.


Assuntos
COVID-19 , Internato e Residência , Medicina de Emergência Pediátrica , Criança , Bolsas de Estudo , Humanos , SARS-CoV-2
17.
Front Psychol ; 12: 744443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744918

RESUMO

Protecting the mental health of healthcare workers is an urgent global public health priority. Healthcare workers, especially those immersed in palliative care, are prone to burnout due to the intense emotions associated with end-of-life caregiving. This study examines the efficacy of a novel, multimodal, and group-based Mindful-Compassion Art-based Therapy (MCAT) that integrates reflective self-awareness with creative emotional expression for protecting healthcare workers' mental health. A dual-arm open-label waitlist randomized controlled trial was conducted. A total of 56 healthcare workers were recruited from the largest homecare hospice in Singapore and randomized to the immediate-treatment condition of a standardized 6-week, 18-hours MCAT intervention (n=29), or the waitlist-control condition (n=27). Self-administered outcome measures on burnout, resilience, emotional regulation, self-compassion, death attitudes, and quality of life were collected at baseline, post-intervention/second-baseline at 6weeks, and follow-up/post-intervention at 12weeks. Results from mixed model ANOVAs reveal that treatment group participants experienced significant reduction in mental exhaustion, as well as significant improvements in overall emotional regulation, nonreactivity to intrusive thoughts, approach acceptance of death, and afterlife belief as compared to waitlist-control immediately after MCAT completion. Effect sizes of these impacts ranged from medium to large (η 2=0.65 to 0.170). Results from one-way ANOVAs further reveal that the treatment gains of reduced mental exhaustion and increased emotional regulation were maintained among treatment group participants at 12-weeks follow-up compared to baseline, with new benefits identified. These include increased ability to observe and describe one's experiences, elevated overall self-compassion, greater mindful awareness, enhanced common humanity, and better quality of life. Effect sizes of these impacts were large (η 2=0.128 to 0.298). These findings reflect the robust effectiveness and positive residual effects of MCAT for reducing burnout, building resilience, nurturing compassion, fostering collegial support, and promoting mental wellness among healthcare workers. The clinical model and applicability of MCAT in larger and more diverse caregiving contexts, such as family dementia care, are discussed. Clinical Trial Registration: ClinicalTrials.gov # NCT03440606, #NCT04548089.

19.
Mol Cancer Res ; 19(11): 1854-1867, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34330844

RESUMO

Previous transcriptome studies of human pancreatic ductal adenocarcinoma (PDAC) compare non-cancerous pancreatic intraepithelial neoplasias (PanIN) with late-stage PDAC obtained from different patients, thus have limited ability to discern network dynamics that contribute to the disease progression. We demonstrated previously that the 10-22 cell line, an induced pluripotent stem cell-like line reprogrammed from late-stage human PDAC cells, recapitulated the progression from PanINs to PDAC upon transplantation into NOD/LtSz-scid/IL2R-gammanull mice. Herein, we investigated the transition from precursor to PDAC using the isogenic model. We analyzed transcriptomes of genetically tagged 10-22 cells progressing from PanINs to PDAC in mice and validated the results using The Cancer Genome Atlas PDAC dataset, human clinical PanIN and PDAC tissues, and a well-established murine PDAC model. We functionally studied candidate proteins using human normal (H6C7) and cancerous (Miapaca2, Aspc1) pancreatic ductal epithelial cell lines. 10-22 cell-derived PDAC displayed the molecular signature of clinical human PDAC. Expression changes of many genes were transient during PDAC progression. Pathways for extracellular vesicle transport and neuronal cell differentiation were derepressed in the progression of PanINs to PDAC. HMG-box transcription factor 1 (HBP1) and BTB domain and CNC homolog 1 (BACH1) were implicated in regulating dynamically expressed genes during PDAC progression, and their expressions inversely correlated with PDAC patients' prognosis. Ectopic expression of HBP1 increased proliferation and migration of normal and cancerous pancreatic cells, indicating that HBP1 may confer the cell dissemination capacity in early PDAC progression. This unique longitudinal analysis provides insights into networks underlying human PDAC progression and pathogenesis. IMPLICATIONS: Manipulation of HBP1, BACH1, and RUN3 networks during PDAC progression can be harnessed to develop new targets for treating PDAC.


Assuntos
Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Transcriptoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Progressão da Doença , Humanos , Estudos Longitudinais , Camundongos , Análise de Sobrevida
20.
J Investig Med ; 69(2): 408-410, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33443054

RESUMO

The Pediatric Emergency Care Applied Research Network (PECARN) Head Injury/Trauma Algorithm is a well-validated decision rule used to identify patients at low risk of clinically important traumatic brain injuries who may not need head CT. In adult patients with mild head trauma, elevated serum glucose and white cell count (WCC) have been associated with abnormal head CT findings. Currently, glucose or WCC is not considered in pediatric patients. The objective of this study was to determine if elevations in glucose or WCC could be used as additional tools to risk-stratify pediatric trauma patients for intracranial injury (ICI). Data were abstracted from the Maryland Trauma Registry and from electronic medical records for patients at the Johns Hopkins Children's Center from 2017 to 2020. We evaluated 145 encounters that met the inclusion criteria. There were 33 cases of ICI on CT. In addition to higher median glucose and WCC, we found that patients with ICI had a younger median age and were less likely to have other clinically significant injuries than patients without ICI. Following multiple logistic regression analysis, WCC (OR 1.113, 95% CI 1.02 to 1.21), younger age (OR 0.89, 95% CI 0.8 to 0.98), and absence of other injuries (OR 0.41, 95% CI 0.23 to 0.73) were found to be associated with risk of ICI. The area under the curve for our model was 0.79. When used with the PECARN algorithm, our model could help determine which patients may avoid head CT or undergo a shorter observation period.


Assuntos
Traumatismos Craniocerebrais , Contagem de Leucócitos , Glicemia , Criança , Traumatismos Craniocerebrais/diagnóstico , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência , Humanos
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