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1.
J Clin Pathol ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404474

RESUMO

AIMS: The visualisation of HBV DNA in liver sections of patients with chronic hepatitis B (CHB) in our previous report uncovered a mosaic distribution of viral antigens and nucleic acids. Here we aim to further explore the clinical utility of the in situ hybridisation (ISH) assay for HBV DNA. METHOD: ISH of HBV DNA along with immunohistochemistry (IHC) of HBsAg, HBcAg and routine histopathology analysis was performed in 313 treatment-naive patients with CHB. Serum HBcrAg and HBcAb titre were also measured in addition to basic biochemical and virological parameters. RESULTS: The ISH of HBV DNA, HBsAg and HBcAg showed 95.2%, 97.1% and 42.8% positive rate, respectively. The staining pattern of HBV DNA differs significantly with that of HBsAg. Intrahepatic HBV DNA exhibited high-level of correlations with viral load, HBcrAg and HBsAg titre. In HBeAg-negative patients, higher intrahepatic HBV DNA is associated with histological evidence of liver inflammation and fibrosis, whereas no such trend was observed in HBeAg-positive patients. Finally, a triple staining protocol that combined the detection of HBV DNA, HBsAg and collagen fibre was developed to enable better evaluation of viral replication and antigen expression in the context of disease progression. CONCLUSIONS: The ISH assay for HBV DNA reflects the vigour of intrahepatic viral replication. It is complementary to the routine IHC assay for viral antigens and also related to the histopathological progression of liver diseases. The application of the HBV DNA ISH assay may help a better evaluation of virological and pathological condition of patients with CHB.

2.
Nucleic Acids Res ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32383764

RESUMO

The accurate and reliable prediction of the 3D structures of proteins and their assemblies remains difficult even though the number of solved structures soars and prediction techniques improve. In this study, a free and open access web server, AWSEM-Suite, whose goal is to predict monomeric protein tertiary structures from sequence is described. The model underlying the server's predictions is a coarse-grained protein force field which has its roots in neural network ideas that has been optimized using energy landscape theory. Employing physically motivated potentials and knowledge-based local structure biasing terms, the addition of homologous template and co-evolutionary restraints to AWSEM-Suite greatly improves the predictive power of pure AWSEM structure prediction. From the independent evaluation metrics released in the CASP13 experiment, AWSEM-Suite proves to be a reasonably accurate algorithm for free modeling, standing at the eighth position in the free modeling category of CASP13. The AWSEM-Suite server also features a front end with a user-friendly interface. The AWSEM-Suite server is a powerful tool for predicting monomeric protein tertiary structures that is most useful when a suitable structure template is not available. The AWSEM-Suite server is freely available at: https://awsem.rice.edu.

3.
BMC Cancer ; 20(1): 361, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349713

RESUMO

BACKGROUND: The prognostic nutritional index (PNI), an immunity and nutrition based prognostic score, was correlated with clinical outcomes in different tumors. However, the prognostic significance of PNI has not been investigated in hormone sensitive prostate cancer (PCa). The objective of this study was to determine the prognostic significance of PNI in hormone sensitive PCa. METHODS: Two hundred eighty PCa patients undergoing androgen deprivation therapy (ADT) as first line therapy at three centers were enrolled. The serum albumin levels and peripheral lymphocyte count were measured at the time of diagnosis. PNI was calculated as 10 * serum albumin (g/dL) + 0.005 * total lymphocyte count (per mm3). Patients were categorized in two groups using a cut-off point of 50.2 as calculated by the receiver-operating curve analysis. Univariate and multivariate cox regression analyses were performed to evaluate PNI as a favorable prognostic factor for progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index. RESULTS: Multivariate analyses identified PNI as an independent prognostic indicator with respect to PFS (hazard ratio (HR) = 0.521, p = 0.001), CSS (HR = 0.421, p = 0.002) and OS (HR = 0.429, p = 0.001). Patients with elevated PNI had better clinical outcomes. The addition of PNI to the final models improved predictive accuracy (c-index: 0.758, 0.830 and 0.782) for PFS, CSS and OS compared with the clinicopathological base models (c-index: 0.736, 0.801 and 0.752), which included Gleason score and incidence of metastasis. CONCLUSIONS: Elevated pretreatment PNI was a favorable prognostic indicator for PCa patients treated with ADT.

4.
J Phys Chem Lett ; : 4618-4624, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32459502

RESUMO

An understanding of growth and degradation pathways is significant to solve the problem of the structural instability of all-inorganic perovskite nanocrystals (NCs). However, it is still a great challenge to directly record such dynamic processes with high spatial resolution owing to the existence of complex internal factors even using in situ transmission electron microscopy observation. Here, we employ a glassy matrix to produce CsPbBr3 NCs to ensure that the growth and degradation processes of CsPbBr3 NCs are recorded in the vacuum chamber, which could avoid the influence of the external factors, under electron beam (E-beam) irradiation. In addition, two stages of degradation pathways induced by the E-beam are observed sequentially: (1) a layer-by-layer decomposition and (2) instantaneous vanishing once the radius reaches the critical radius (∼2.3 nm). Indeed, we demonstrated that defects serve as a key flash point that could trigger the structural collapse of CsPbBr3 NCs. Our findings provide critical insights into the general instability issue of all-inorganic perovskite NCs in practical applications.

5.
J Chem Theory Comput ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32396727

RESUMO

Recently several techniques have emerged that significantly enhance the quality of predictions of protein tertiary structures. In this study, we describe the performance of AWSEM-Suite, an algorithm that incorporates template-based modeling and coevolutionary restraints with a realistic coarse-grained force field, AWSEM. With its roots in neural networks, AWSEM contains both physical and bioinformatical energies that have been optimized using energy landscape theory. AWSEM-Suite participated in CASP13 as a server predictor and generated reliable predictions for most targets. AWSEM-Suite ranked eighth in both the free-modeling category and the hard-to-model category and in one case provided the best submitted prediction. Here we critically discuss the prediction performance of AWSEM-Suite using several examples from different categories in CASP13. Structure prediction tests on these selected targets, two of them being hard-to-model targets, show that AWSEM-Suite can achieve high-resolution structure prediction after incorporating both template guidances and coevolutionary restraints even when homology is weak. For targets with reliable templates (template-easy category), introducing coevolutionary restraints sometimes damages the overall quality of the predictions. Free energy profile analyses demonstrate, however, that the incorporations of both of these evolutionarily informed terms effectively increase the funneling of the landscape toward native-like structures while still allowing sufficient flexibility to correct for discrepancies between the correct target structure and the provided guidance. In contrast to other predictors that are exclusively oriented toward structure prediction, the connection of AWSEM-Suite to a statistical mechanical basis and affiliated molecular dynamics and importance sampling simulations makes it suitable for functional explorations.

6.
J Med Chem ; 63(10): 5421-5441, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32352777

RESUMO

Herein, a series of HSP90 inhibitor-SN38 conjugates through ester and carbamate linkage in the 20-OH and 10-OH positions of SN38 were developed for improving the tumor-specific penetration and accumulation of SN38 via extracellular HSP90 (eHSP90)-mediated endocytosis. Mechanistic analyses confirmed that these novel conjugates could bind to eHSP90 and be selectively internalized into the tumor cells, which led to prolonged tumor regression in multiple models of cancer. Among all studied conjugates, compound 18b showed excellent in vitro activities, including acceptable HSP90α affinity and potent antitumor activity. Moreover, compound 18b exhibited superior antitumor activity and low toxicity in HCT116 and Capan-1 xenograft models. Pharmacokinetic analyses in HCT116 and Capan-1 xenografts further confirmed that compound 18b treatment could lead to effective cleavage and extended SN38 exposure at tumor sites. All these encouraging data indicate that this compound is a promising new candidate for cancer therapy and merits further chemical and biological evaluation.

7.
Nat Commun ; 11(1): 2501, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427844

RESUMO

Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.

8.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(5): 602-607, 2020 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-32410428

RESUMO

Objective: To clarify the value of the cortical endo-button as an internal fixator in Latarjet procedure through biomechanical analysis. Methods: Ten pairs of shoulder joints from 6-7 months old male pigs were selected. Each pair was randomly divided into screw group and endo-button group. A 25% glenoid defect model was created, and the porcine infraspinatus tendon and its associated bone were used to simulate conjoint tendon and coracoid process in human body. The bone grafts were fixed with two 3.5 mm screws and double cortical endo-buttons with high-strength sutures in screw group and endo-button group, respectively. The prepared glenoid defect model was fixed on a biomechanical test bench and optical markers were fixed on the glenoid and the bone block, respectively. Then fatigue test was performed to observe whether the graft or internal fixator would failed. During the test, the standard deviations of the relative displacement between the graft and the glenoid of two groups were measured by optical motion measure system for comparison. Finally the maximum failure load comparison was conducted and the maximum failure loads of the two groups were measured and compared. Results: There was no tendon tear, bone fracture, and other graft or internal fixation failure in the two groups during the fatigue test. The standard deviation of the relative displacement of the screw group was (0.007 87±0.001 44) mm, and that of the endo-button group was (0.034 88±0.011 10) mm, showing significant difference between the two groups ( t=7.682, P=0.000). The maximum failure load was (265±39) N in screw group and (275±52) N in endo-button group, showing no significant difference between the two groups ( t=1.386, P=0.199). There were 3 ways of failure: rupture at bone graft's tunnel (6/10 from screw group, 3/10 from endo-button group), tendon tear at the cramp (2/10 from screw group, 2/10 from endo-button group), and tendon tear at the internal fixator interface (2/10 from screw group, 5/10 from endo-button group), showing no significant difference between the two groups ( P=0.395). Conclusion: Although the endo-button fixation fails to achieve the same strong fixation stability as the screw fixation, its fixation stability can achieve the clinical requirements. The two fixation methods can provide similar fixation strength when being used in Latarjet procedure.

9.
Brain Behav Immun ; 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32434046

RESUMO

Microglia express muscarinic G protein-coupled receptors (GPCRs) that sense cholinergic activity and are activated by acetylcholine to potentially regulate microglial functions. Knowledge about how distinct types of muscarinic GPCR signaling regulate microglia function in vivo is still poor, partly due to the fact that some of these receptors are also present in astrocytes and neurons. We generated mice expressing the hM3Dq Designer Receptor Exclusively Activated by Designer Drugs (DREADD) selectively in microglia to investigate the role of muscarinic M3Gq-linked signaling. We show that activation of hM3Dq using clozapine N-oxide (CNO) elevated intracellular calcium levels and increased phagocytosis of FluoSpheres by microglia in vitro. Interestingly, whereas acute treatment with CNO increased synthesis of cytokine mRNA, chronic treatment attenuated LPS-induced cytokine mRNA changes in the brain. No effect of CNO on cytokine expression was observed in DREADD-negative mice. Interestingly, CNO activation of M3Dq in microglia was able to attenuate LPS-mediated decrease in social interactions. These results suggest that chronic activation of M3 muscarinic receptors (the hM3Dq progenitor) in microglia, and potentially other Gq-coupled GPCRs, can trigger an inflammatory-like response that preconditions microglia to decrease their response to further immunological challenges. Our results indicate that hM3Dq can be a useful tool to modulate neuroinflammation and study microglial immunological memory in vivo, which may be applicable for manipulations of neuroinflammation in neurodegenerative and psychiatric diseases.

10.
Nanoscale ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32452500

RESUMO

In situ transmission electron microscopy characterization is a powerful method in investigating the growth mechanism of catalyst-induced semiconductor nanowires. By providing direct evidence on the crystal growth at the atomic level, a real-time in situ heating investigation was carried out on Au-catalyzed <001[combining macron]> InAs nanowires. It was found that the Au catalyst maintained itself in the solid form during the nanowire growth, and maintained a fixed epitaxial relationship with its underlying InAs nanowire, indicating the vapor-solid-solid mechanism. Importantly, the growth of <001[combining macron]> InAs nanowires through a layer-by-layer manner at the catalyst/nanowire interface is evident. This study provides direct insights into the vapor-solid-solid growth and clarified the growth mechanism of <001[combining macron]> III-V nanowires, which provides pathways in controlling the growth of <001[combining macron]> semiconductor nanowires.

11.
J Infect Dis ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32437567

RESUMO

BACKGROUND AND AIMS: Long-term nucleos(t)ide analogues (NAs) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an anti-fibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs. METHODS: CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5mg per day) plus BR (2g three times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥1 point by the Ishak Fibrosis Stage (IFS). RESULTS: Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 week treatment was significantly higher in ETV+BR group (40% versus 31.8%, P=0.0069). Among 388 patients with cirrhosis (i.e., IFS ≥5) at baseline, the rate of cirrhosis reversal (i.e., IFS ≤4) was significantly higher in ETV+BR group (41.5% versus 30.7%, P=0.0103). CONCLUSIONS: Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32434918

RESUMO

Extensive studies in prostate cancer and other malignancies have revealed that l-methionine (l-Met) and its metabolites play a critical role in tumorigenesis. Preclinical and clinical studies have demonstrated that systemic restriction of serum l-Met, either via partial dietary restriction or with bacterial l-Met-degrading enzymes exerts potent antitumor effects. However, administration of bacterial l-Met-degrading enzymes has not proven practical for human therapy because of problems with immunogenicity. As the human genome does not encode l-Met-degrading enzymes, we engineered the human cystathionine-γ-lyase (hMGL-4.0) to catalyze the selective degradation of l-Met. At therapeutically relevant dosing, hMGL-4.0 reduces serum l-Met levels to >75% for >72 h and significantly inhibits the growth of multiple prostate cancer allografts/xenografts without weight loss or toxicity. We demonstrate that in vitro, hMGL-4.0 causes tumor cell death, associated with increased reactive oxygen species, S-adenosyl-methionine depletion, global hypomethylation, induction of autophagy, and robust poly(ADP-ribose) polymerase (PARP) cleavage indicative of DNA damage and apoptosis.

13.
Mov Disord ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392383

RESUMO

BACKGROUND: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32392842

RESUMO

Although adolescents with attention-deficit hyperactivity disorder (ADHD) have a higher risk of suicidality and more problems related to school bullying, and quality of life (QoL) is reportedly associated with school bullying, suicide, and ADHD, no study has examined their correlation. This study examined the complex relationships between QoL, school bullying, suicide, and ADHD symptoms. A total of 203 adolescents with ADHD aged between 12 and 18 years were recruited. School bullying and QoL were examined using the Chinese version of the School Bullying Experience Questionnaire and the Taiwanese Quality of Life Questionnaire for Adolescents. Network model analysis was conducted to graphically present their relationships. We identified triangular correlations between school bullying, QoL, and suicidality, indicating possible pathways from school bullying to suicidality, and the originating or mediating roles of personal competence and psychological well-being. Furthermore, the ADHD symptoms of inattention and hyperactivity/impulsivity may differentially regulate these pathways. Longitudinal studies are warranted to confirm these findings.

16.
Nat Commun ; 11(1): 2439, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415218

RESUMO

The ability to efficiently analyze the activities of biological neural networks can significantly promote our understanding of neural communications and functionalities. However, conventional neural signal analysis approaches need to transmit and store large amounts of raw recording data, followed by extensive processing offline, posing significant challenges to the hardware and preventing real-time analysis and feedback. Here, we demonstrate a memristor-based reservoir computing (RC) system that can potentially analyze neural signals in real-time. We show that the perovskite halide-based memristor can be directly driven by emulated neural spikes, where the memristor state reflects temporal features in the neural spike train. The RC system is successfully used to recognize neural firing patterns, monitor the transition of the firing patterns, and identify neural synchronization states among different neurons. Advanced neuroelectronic systems with such memristor networks can enable efficient neural signal analysis with high spatiotemporal precision, and possibly closed-loop feedback control.

17.
Cancer Cell ; 37(5): 720-734.e13, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32359397

RESUMO

Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to treat other renal cell carcinomas. Comprehensive genomic and transcriptomic profiling of untreated primary RMC tissues was performed to elucidate the molecular landscape of these tumors. We found that RMC was characterized by high replication stress and an abundance of focal copy-number alterations associated with activation of the stimulator of the cyclic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway. Replication stress conferred a therapeutic vulnerability to drugs targeting DNA-damage repair pathways. Elucidation of these previously unknown RMC hallmarks paves the way to new clinical trials for this rare but highly lethal malignancy.

18.
J Mol Neurosci ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32399861

RESUMO

Severe or prolonged stress increases the risk for developing psychopathological disorders. An individual's perception of stress exposure varies greatly, as do its consequences. Numerous individuals demonstrate resilience to psychological stress. The mRNA and microRNA profiles of stress susceptibility and resilience to induced psychological stress in the amygdala remain to be elucidated. In this work, psychological stress was induced in an observer mouse by witnessing a similar individual under attack by an aggressor. After 5 days of psychological stress, the degree of fear memory and anxiety in mice was measured by a social interaction test and elevated plus-maze (EPM) test. mRNA and microRNA profiles were quantified by high-throughput sequencing in amygdala tissue harvested from Control, Susceptible and Resilient mice. In the amygdala of Susceptible versus Resilient mice, the upregulation of peptide, thyrotropin-releasing hormone, ECM receptors, glutamatergic synapse, cytokine-cytokine receptor interaction, long-term depression, PI3K-Akt, oxytocin, GnRH, HIF-1, estrogen, and calcium signaling pathways may be related to psychological stress-induced susceptibility, and their downregulation may be related to resilience. The downregulation of adrenergic synapse, adherens junction, Wnt, sphingolipid, B cell receptor, cAMP, Rap1, and Toll-like receptor signaling pathways may be related to psychological stress-induced susceptibility, and the upregulation may be related to resilience. Results by sequencing of mRNA and microRNA profiles are consistent, in which some are validated by qRT-PCR and dual-luciferase reporter assay. Susceptibility and resilience induced by psychological stresses are caused by the imbalanced regulation of different synapses and signaling pathways in the amygdala.

19.
Macromol Rapid Commun ; : e2000123, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400926

RESUMO

Substituted naphthalimide (NI) moieties are highly versatile and newly recognized aggregation-induced emission (AIE) building blocks for many potentially useful smart molecules, polymers, and nanoparticles. However, the introduction of NI fluorophore into cross-linked polymeric networks to prepare AIE-active hydrogels still remains underdeveloped. Herein, a novel naphthalimide-based aggregation-induced emissive polymeric hydrogel is reported, followed by its proof-of-concept applications as fluorescence pattern switch and biomimetic actuator. The hydrogel, bearing semi-interpenetrating polymer networks, is synthesized starting from N-isopropylacrylamide, hydroxyethyl methacrylate, and a newly designed NI monomer (4-phenoxy-N-allyl-1,8-naphthalimide, PhAN). Rational molecular design for AIE-active PhAN monomer lies in modification of the NI core with rigid and bulky phenoxy group to break its planarity to produce desirable propeller-shaped molecular conformation. The as-prepared hydrogel is proved to be a aggregation-induced blue-light-emitting hydrogel. It also shows volume phase transition behavior and is endowed with thermally responsive synergistic emission and transmittance change, thus enabling simultaneous regulation of two optical properties merely by one single stimulus. These useful advantages further encourage fabrication of several proto-type fluorescence pattern switching and biomimetic actuating devices. This study may not only enlarge the list of fluorescent hydrogels but also serve as a novel smart optical platform for potential anticounterfeiting, sensing, displaying, or actuating applications.

20.
Med Teach ; : 1-6, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32401093

RESUMO

This cross-sectional study involved matriculating, mid-level and graduating medical students (n = 723) who participated in specific transition courses in our medical school curriculum between August 2016 and March 2019. We used a mixed-methods approach (survey and analysis of narrative comments) to study the evolution in perception of the learning environment by medical students with increasing clinical exposure using four different video vignettes. Differences in student perceptions of mistreatment exists at various levels of training. Compared to graduating students, matriculating students were more likely to perceive reprimanding a student on being late as appropriate behavior (80.5% vs 53.3%, p = 0.001), whereas a significantly higher proportion of the graduating students (15.3%, p = 0.001) perceived it as mistreatment. A majority of the matriculating students (84%, p = 0.001) considered the case of an eager student as mistreatment, while a significantly higher proportion of the graduating students (59.5%, p = 0.001) did not think it was mistreatment. Qualitative analysis of comments from students at different stages of training displayed an increased appreciation of their professional responsibilities and nuanced appreciation of body language and tone as contributing factors in determining whether a situation represented inappropriate behavior. Our results demonstrate that students' perceptions of inappropriate behaviors evolve with increased clinical exposure.

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