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1.
Nature ; 595(7866): 289-294, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34194041

RESUMO

The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))-which kill liver-stage and blood-stage parasites, respectively-and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) three months after immunization ( https://clinicaltrials.gov/ , NCT02511054 and NCT03083847). We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, two out of nine (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with seven out of eight (87.5%) individuals protected against homologous and seven out of nine (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected six out of six (100%) participants against heterologous CHMI three months after immunization. All homologous (four out of four) and heterologous (eight out of eight) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.


Assuntos
Anticorpos Neutralizantes/imunologia , Fígado/imunologia , Fígado/parasitologia , Vacinas Antimaláricas/imunologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Vacinas Atenuadas/imunologia , Adulto , Animais , Formação de Anticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Estágios do Ciclo de Vida/imunologia , Malária/sangue , Malária/imunologia , Malária/parasitologia , Malária/prevenção & controle , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/química , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/crescimento & desenvolvimento , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo , Vacinação/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/química
2.
PLoS Pathog ; 19(8): e1011525, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37535497

RESUMO

Through the association of protein complexes to DNA, the eukaryotic nuclear genome is broadly organized into open euchromatin that is accessible for enzymes acting on DNA and condensed heterochromatin that is inaccessible. Chemical and physical alterations to chromatin may impact its organization and functionality and are therefore important regulators of nuclear processes. Studies in various fungal plant pathogens have uncovered an association between chromatin organization and expression of in planta-induced genes that are important for pathogenicity. This review discusses chromatin-based regulation mechanisms as determined in the fungal plant pathogen Verticillium dahliae and relates the importance of epigenetic transcriptional regulation and other nuclear processes more broadly in fungal plant pathogens.


Assuntos
Ascomicetos , Verticillium , Epigênese Genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Ascomicetos/genética , Verticillium/genética , Eucromatina/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Proteínas Fúngicas/metabolismo
3.
Brain ; 147(6): 2214-2229, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38802114

RESUMO

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.


Assuntos
Aquaporina 4 , Traumatismos por Explosões , Sistema Glinfático , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Aquaporina 4/metabolismo , Traumatismos por Explosões/complicações , Traumatismos por Explosões/patologia , Traumatismos por Explosões/metabolismo , Concussão Encefálica/metabolismo , Concussão Encefálica/complicações , Concussão Encefálica/patologia , Concussão Encefálica/fisiopatologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Lobo Frontal/diagnóstico por imagem , Sistema Glinfático/metabolismo , Sistema Glinfático/patologia , Imageamento por Ressonância Magnética , Camundongos Endogâmicos C57BL , Veteranos
4.
Artigo em Inglês | MEDLINE | ID: mdl-38564376

RESUMO

RATIONALE: The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD. Results of clinical trials with MSCs for many disorders do not yet match the promising preclinical studies. A lack of specific criteria to define functionally distinct MSCs persists. OBJECTIVES: To determine and correlate single-cell UC-MSC transcriptomic profile with therapeutic potential. METHODS: UC-MSCs from five term donors and human neonatal dermal fibroblasts (HNDFs, control cells of mesenchymal origin) transcriptomes were investigated by single-cell RNA sequencing analysis (scRNA-seq). The lung-protective effect of UC-MSCs with a distinct transcriptome and control HNDFs was tested in vivo in hyperoxia-induced neonatal lung injury in rats. MEASUREMENTS AND MAIN RESULTS: UC-MSCs showed limited transcriptomic heterogeneity, but were different from HNDFs. Gene ontology enrichment analysis revealed distinct - progenitor-like and fibroblast-like - UC-MSC subpopulations. Only the treatment with progenitor-like UC-MSCs improved lung function and structure and attenuated pulmonary hypertension in hyperoxia-exposed rat pups. Moreover, scRNA-seq identified major histocompatibility complex class I as a molecular marker of non-therapeutic cells and associated with decreased lung retention. CONCLUSIONS: UC-MSCs with a progenitor-like transcriptome, but not with a fibroblast-like transcriptome, provide lung protection in experimental BPD. High expression of major histocompatibility complex class I is associated with reduced therapeutic benefit. scRNA-seq may be useful to identify subsets of MSCs with superior repair capacity for clinical application.

5.
New Phytol ; 241(3): 1266-1276, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37984076

RESUMO

The fungal pathogen, Magnaporthe oryzae Triticum pathotype, causing wheat blast disease was first identified in South America and recently spread across continents to South Asia and Africa. Here, we studied the genetic relationship among isolates found on the three continents. Magnaporthe oryzae strains closely related to a South American field isolate B71 were found to have caused the wheat blast outbreaks in South Asia and Africa. Genomic variation among isolates from the three continents was examined using an improved B71 reference genome and whole-genome sequences. We found strong evidence to support that the outbreaks in Bangladesh and Zambia were caused by the introductions of genetically separated isolates, although they were all close to B71 and, therefore, collectively referred to as the B71 branch. In addition, B71 branch strains carried at least one supernumerary mini-chromosome. Genome assembly of a Zambian strain revealed that its mini-chromosome was similar to the B71 mini-chromosome but with a high level of structural variation. Our findings show that while core genomes of the multiple introductions are highly similar, the mini-chromosomes have undergone marked diversification. The maintenance of the mini-chromosome and rapid genomic changes suggest the mini-chromosomes may serve important virulence or niche adaptation roles under diverse environmental conditions.


Assuntos
Ascomicetos , Magnaporthe , Triticum , Triticum/genética , Bangladesh/epidemiologia , Zâmbia/epidemiologia , Magnaporthe/genética , Cromossomos , Doenças das Plantas/microbiologia
6.
Med Educ ; 58(5): 566-574, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37655515

RESUMO

PURPOSE: Mayer's theory of multimedia learning proposes that personalisation and embodiment (P/E) can improve outcomes in e-Learning. The authors hypothesised that an e-Learning module enhanced by P/E principles would lead to higher knowledge, perceived P/E and motivation among health care professionals, compared with an unenhanced module. METHODS: The authors conducted a randomised trial comparing two versions of a 30-minute multimedia e-Learning module addressing the antibiotic management of pneumonia. The unenhanced format used slides with voiceover (human voice but no visible speaker), formal language and no specific P/E strategies. The enhanced format additionally implemented P/E strategies including conversational style, polite language, visible author, social congruence, human-like presence and professional presence by subtly changing the script and substituting several short videos of subject matter experts. Participants included pharmacists, physicians and advanced practice providers from three academic and several community hospitals. Outcomes included knowledge, perceived P/E (assessed by the Congruence Personalisation Questionnaire, CPQ), motivation (assessed via the Instructional Materials Motivation Survey [IMMS] and Motivated Strategies for Learning Questionnaire [MSLQ]) and course satisfaction. RESULTS: There were 406 participants including 225 pharmacists, 109 physicians and 72 advanced practice providers. Post-module knowledge was slightly higher for the enhanced versus the unenhanced format, but the difference did not reach statistical significance (adjusted mean difference, 0.04 of 10 possible, [95% CI -0.26, 0.34], p = 0.78; Cohen d 0.02). Participant perceptions of P/E (measured via CPQ) were significantly greater for the enhanced format (difference 0.46 of 5 possible [0.35, 0.56], p < 0.001; Cohen d 0.85), as were motivational features of the e-Learning course (measured via IMMS) (difference 0.14 of 5 possible [0.02, 0.26], p = 0.02; Cohen d 0.24). Participants' overall motivational orientation (measured via MSLQ) and course satisfaction were not significantly different between the two formats (p > 0.05). CONCLUSION: Application of P/E principles to an e-Learning module led to greater perceived P/E and motivational features but did not influence knowledge.


Assuntos
Instrução por Computador , Médicos , Humanos , Aprendizagem , Pessoal de Saúde/educação , Motivação
7.
PLoS Genet ; 17(2): e1009376, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33534835

RESUMO

Transcriptional dynamic in response to environmental and developmental cues are fundamental to biology, yet many mechanistic aspects are poorly understood. One such example is fungal plant pathogens, which use secreted proteins and small molecules, termed effectors, to suppress host immunity and promote colonization. Effectors are highly expressed in planta but remain transcriptionally repressed ex planta, but our mechanistic understanding of these transcriptional dynamics remains limited. We tested the hypothesis that repressive histone modification at H3-Lys27 underlies transcriptional silencing ex planta, and that exchange for an active chemical modification contributes to transcription of in planta induced genes. Using genetics, chromatin immunoprecipitation and sequencing and RNA-sequencing, we determined that H3K27me3 provides significant local transcriptional repression. We detail how regions that lose H3K27me3 gain H3K27ac, and these changes are associated with increased transcription. Importantly, we observed that many in planta induced genes were marked by H3K27me3 during axenic growth, and detail how altered H3K27 modification influences transcription. ChIP-qPCR during in planta growth suggests that H3K27 modifications are generally stable, but can undergo dynamics at specific genomic locations. Our results support the hypothesis that dynamic histone modifications at H3K27 contributes to fungal genome regulation and specifically contributes to regulation of genes important during host infection.


Assuntos
Ascomicetos/genética , Regulação da Expressão Gênica de Plantas , Código das Histonas/genética , Histonas/genética , Plantas/genética , Transcrição Gênica , Acetilação , Ascomicetos/fisiologia , Genômica/métodos , Histonas/metabolismo , Interações Hospedeiro-Patógeno/genética , Lisina/metabolismo , Metilação , Plantas/metabolismo , Plantas/microbiologia , RNA-Seq/métodos
8.
Med Teach ; : 1-11, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38803296

RESUMO

PURPOSE: To validate the Motivated Strategies for Learning Questionnaire (MSLQ), which measures learner motivations; and the Instructional Materials Motivation Survey (IMMS), which measures the motivational properties of educational activities. METHODS: Participants (333 pharmacists, physicians, and advanced practice providers) completed the MSLQ, IMMS, Congruence-Personalization Questionnaire (CPQ), and a knowledge test immediately following an online learning module (April 2021). We randomly divided data for split-sample analysis using confirmatory factor analysis (CFA), exploratory factor analysis (EFA), and the multitrait-multimethod matrix. RESULTS: Cronbach alpha was ≥0.70 for most domains. CFA using sample 1 demonstrated suboptimal fit for both instruments, including 3 negatively-worded IMMS items with particularly low loadings. Revised IMMS (RIMMS) scores (which omit negatively-worded items) demonstrated better fit. Guided by EFA, we identified a novel 3-domain, 11-item 'MSLQ-Short Form-Revised' (MSLQ-SFR, with domains: Interest, Self-efficacy, and Attribution) and the 4-domain, 12-item RIMMS as the best models. CFA using sample 2 confirmed good fit. Correlations among MSLQ-SFR, RIMMS, and CPQ scores aligned with predictions; correlations with knowledge scores were small. CONCLUSIONS: Original MSLQ and IMMS scores show poor model fit, with negatively-worded items notably divergent. Revised, shorter models-the MSLQ-SFR and RIMMS-show satisfactory model fit (internal structure) and relations with other variables.

9.
Med Teach ; : 1-15, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627020

RESUMO

PURPOSE: Management reasoning is a distinct subset of clinical reasoning. We sought to explore features to be considered when designing assessments of management reasoning. METHODS: This is a hybrid empirical research study, narrative review, and expert perspective. In 2021, we reviewed and discussed 10 videos of simulated (staged) physician-patient encounters, actively seeking actions that offered insights into assessment of management reasoning. We analyzed our own observations in conjunction with literature on clinical reasoning assessment, using a constant comparative qualitative approach. RESULTS: Distinguishing features of management reasoning that will influence its assessment include management scripts, shared decision-making, process knowledge, illness-specific knowledge, and tailoring of the encounter and management plan. Performance domains that merit special consideration include communication, integration of patient preferences, adherence to the management script, and prognostication. Additional facets of encounter variation include the clinical problem, clinical and nonclinical patient characteristics (including preferences, values, and resources), team/system characteristics, and encounter features. We cataloged several relevant assessment approaches including written/computer-based, simulation-based, and workplace-based modalities, and a variety of novel response formats. CONCLUSIONS: Assessment of management reasoning could be improved with attention to the performance domains, facets of variation, and variety of approaches herein identified.

10.
Sensors (Basel) ; 24(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732910

RESUMO

IoT has seen remarkable growth, particularly in healthcare, leading to the rise of IoMT. IoMT integrates medical devices for real-time data analysis and transmission but faces challenges in data security and interoperability. This research identifies a significant gap in the existing literature regarding a comprehensive ontology for vulnerabilities in medical IoT devices. This paper proposes a fundamental domain ontology named MIoT (Medical Internet of Things) ontology, focusing on cybersecurity in IoMT (Internet of Medical Things), particularly in remote patient monitoring settings. This research will refer to similar-looking acronyms, IoMT and MIoT ontology. It is important to distinguish between the two. IoMT is a collection of various medical devices and their applications within the research domain. On the other hand, MIoT ontology refers to the proposed ontology that defines various concepts, roles, and individuals. MIoT ontology utilizes the knowledge engineering methodology outlined in Ontology Development 101, along with the structured life cycle, and establishes semantic interoperability among medical devices to secure IoMT assets from vulnerabilities and cyberattacks. By defining key concepts and relationships, it becomes easier to understand and analyze the complex network of information within the IoMT. The MIoT ontology captures essential key terms and security-related entities for future extensions. A conceptual model is derived from the MIoT ontology and validated through a case study. Furthermore, this paper outlines a roadmap for future research, highlighting potential impacts on security automation in healthcare applications.


Assuntos
Segurança Computacional , Internet das Coisas , Humanos , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Telemedicina/métodos
11.
Int J Mol Sci ; 25(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38256223

RESUMO

Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood-brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.


Assuntos
Traumatismos por Explosões , Concussão Encefálica , Lesões do Sistema Vascular , Animais , Humanos , Células Endoteliais , Astrócitos , Inflamação
12.
Radiology ; 306(2): e220266, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36194112

RESUMO

Background Substantial interreader variability exists for common tasks in CT imaging, such as detection of hepatic metastases. This variability can undermine patient care by leading to misdiagnosis. Purpose To determine the impact of interreader variability associated with (a) reader experience, (b) image navigation patterns (eg, eye movements, workstation interactions), and (c) eye gaze time at missed liver metastases on contrast-enhanced abdominal CT images. Materials and Methods In a single-center prospective observational trial at an academic institution between December 2020 and February 2021, readers were recruited to examine 40 contrast-enhanced abdominal CT studies (eight normal, 32 containing 91 liver metastases). Readers circumscribed hepatic metastases and reported confidence. The workstation tracked image navigation and eye movements. Performance was quantified by using the area under the jackknife alternative free-response receiver operator characteristic (JAFROC-1) curve and per-metastasis sensitivity and was associated with reader experience and image navigation variables. Differences in area under JAFROC curve were assessed with the Kruskal-Wallis test followed by the Dunn test, and effects of image navigation were assessed by using the Wilcoxon signed-rank test. Results Twenty-five readers (median age, 38 years; IQR, 31-45 years; 19 men) were recruited and included nine subspecialized abdominal radiologists, five nonabdominal staff radiologists, and 11 senior residents or fellows. Reader experience explained differences in area under the JAFROC curve, with abdominal radiologists demonstrating greater area under the JAFROC curve (mean, 0.77; 95% CI: 0.75, 0.79) than trainees (mean, 0.71; 95% CI: 0.69, 0.73) (P = .02) or nonabdominal subspecialists (mean, 0.69; 95% CI: 0.60, 0.78) (P = .03). Sensitivity was similar within the reader experience groups (P = .96). Image navigation variables that were associated with higher sensitivity included longer interpretation time (P = .003) and greater use of coronal images (P < .001). The eye gaze time was at least 0.5 and 2.0 seconds for 71% (266 of 377) and 40% (149 of 377) of missed metastases, respectively. Conclusion Abdominal radiologists demonstrated better discrimination for the detection of liver metastases on abdominal contrast-enhanced CT images. Missed metastases frequently received at least a brief eye gaze. Higher sensitivity was associated with longer interpretation time and greater use of liver display windows and coronal images. © RSNA, 2022 Online supplemental material is available for this article.


Assuntos
Neoplasias Hepáticas , Masculino , Humanos , Adulto , Neoplasias Hepáticas/patologia , Erros de Diagnóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
13.
Stem Cells ; 40(5): 479-492, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35445270

RESUMO

Late lung development is a period of alveolar and microvascular formation, which is pivotal in ensuring sufficient and effective gas exchange. Defects in late lung development manifest in premature infants as a chronic lung disease named bronchopulmonary dysplasia (BPD). Numerous studies demonstrated the therapeutic properties of exogenous bone marrow and umbilical cord-derived mesenchymal stromal cells (MSCs) in experimental BPD. However, very little is known regarding the regenerative capacity of resident lung MSCs (L-MSCs) during normal development and in BPD. In this study we aimed to characterize the L-MSC population in homeostasis and upon injury. We used single-cell RNA sequencing (scRNA-seq) to profile in situ Ly6a+ L-MSCs in the lungs of normal and O2-exposed neonatal mice (a well-established model to mimic BPD) at 3 developmental timepoints (postnatal days 3, 7, and 14). Hyperoxia exposure increased the number and altered the expression profile of L-MSCs, particularly by increasing the expression of multiple pro-inflammatory, pro-fibrotic, and anti-angiogenic genes. In order to identify potential changes induced in the L-MSCs transcriptome by storage and culture, we profiled 15 000 Ly6a+ L-MSCs after in vitro culture. We observed great differences in expression profiles of in situ and cultured L-MSCs, particularly those derived from healthy lungs. Additionally, we have identified the location of Ly6a+/Col14a1+ L-MSCs in the developing lung and propose Serpinf1 as a novel, culture-stable marker of L-MSCs. Finally, cell communication analysis suggests inflammatory signals from immune and endothelial cells as main drivers of hyperoxia-induced changes in L-MSCs transcriptome.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Células-Tronco Mesenquimais , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/terapia , Células Endoteliais , Humanos , Hiperóxia/genética , Hiperóxia/metabolismo , Recém-Nascido , Pulmão/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Análise de Sequência de RNA
14.
Brain Behav Immun ; 110: 222-236, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36907289

RESUMO

BACKGROUND: Repetitive blast-related mild traumatic brain injury (mTBI) caused by exposure to high explosives is increasingly common among warfighters as well as civilians. While women have been serving in military positions with increased risk of blast exposure since 2016, there are few published reports examining sex as a biological variable in models of blast mTBI, greatly limiting diagnosis and treatment capabilities. As such, here we examined outcomes of repetitive blast trauma in female and male mice in relation to potential behavioral, inflammatory, microbiome, and vascular dysfunction at multiple timepoints. METHODS: In this study we utilized a well-established blast overpressure model to induce repetitive (3x) blast-mTBI in both female and male mice. Acutely following repetitive exposure, we measured serum and brain cytokine levels, blood-brain barrier (BBB) disruption, fecal microbial abundance, and locomotion and anxiety-like behavior in the open field assay. At the one-month timepoint, in female and male mice we assessed behavioral correlates of mTBI and PTSD-related symptoms commonly reported by Veterans with a history of blast-mTBI using the elevated zero maze, acoustic startle, and conditioned odorant aversion paradigms. RESULTS: Repetitive blast exposure resulted in both similar (e.g., increased IL-6), and disparate (e.g., IL-10 increase only in females) patterns of acute serum and brain cytokine as well as gut microbiome changes in female and male mice. Acute BBB disruption following repetitive blast exposure was apparent in both sexes. While female and male blast mice both exhibited acute locomotor and anxiety-like deficits in the open field assay, only male mice exhibited adverse behavioral outcomes that lasted at least one-month. DISCUSSION: Representing a novel survey of potential sex differences following repetitive blast trauma, our results demonstrate unique similar yet divergent patterns of blast-induced dysfunction in female vs. male mice and highlight novel targets for future diagnosis and therapeutic development.


Assuntos
Traumatismos por Explosões , Concussão Encefálica , Transtornos de Estresse Pós-Traumáticos , Veteranos , Feminino , Masculino , Camundongos , Animais , Humanos , Concussão Encefálica/complicações , Caracteres Sexuais , Transtornos de Estresse Pós-Traumáticos/etiologia , Ansiedade , Traumatismos por Explosões/complicações
15.
Med Educ ; 57(4): 349-358, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36454138

RESUMO

INTRODUCTION: Engaging learners in continuing medical education (CME) is challenging. Recently, CME courses have transitioned to livestreamed CME, with learners viewing live, in-person courses online. The authors aimed to (1) compare learner engagement and teaching effectiveness in livestreamed with in-person CME and (2) determine how livestream engagement and teaching effectiveness is associated with (A) interactivity metrics, (B) presentation characteristics and (C) medical knowledge. METHODS: A 3-year, non-randomised study of in-person and livestream CME was performed. The course was in-person for 2018 but transitioned to livestream for 2020 and 2021. Learners completed the Learner Engagement Inventory and Teaching Effectiveness Instrument after each presentation. Both instruments were supported by content, internal structure and relations to other variables' validity evidence. Interactivity metrics included learner use of audience response, questions asked by learners and presentation views. Presentation characteristics included presentations using audience response, using pre/post-test format, time of day and words per slide. Medical knowledge was assessed by audience response. A repeated measures analysis of variance (anova) was used for comparisons and a mixed model approach for correlations. RESULTS: A total of 159 learners (response rate 27%) completed questionnaires. Engagement did not significantly differ between in-person or livestream CME. (4.56 versus 4.53, p = 0.64, maximum 5 = highly engaged). However, teacher effectiveness scores were higher for in-person compared with livestream (4.77 versus 4.71 p = 0.01, maximum 5 = highly effective). For livestreamed courses, learner engagement was associated with presentation characteristics, including presentation using of audience response (yes = 4.57, no = 4.45, p < .0001), use of a pre/post-test (yes = 4.62, no = 4.54, p < .0001) and time of presentation (morning = 4.58, afternoon = 4.53, p = .0002). Significant associations were not seen for interactivity metrics or medical knowledge. DISCUSSION: Livestreaming may be as engaging as in-person CME. Although teaching effectiveness in livestreaming was lower, this difference was small. CME course planners should consider offering livestream CME while exploring strategies to enhance teaching effectiveness in livestreamed settings.


Assuntos
Educação Médica Continuada , Ensino , Humanos , Inquéritos e Questionários
16.
Clin Exp Dermatol ; 48(6): 648-659, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-36753386

RESUMO

Dermatological diseases are widespread and have a significant impact on the quality of life of patients; however, access to appropriate care is often limited. Improved early training during medical school represents a potential upstream solution. This scoping review explores dermatology education during medical school, with a focus on identifying the factors associated with optimizing the preparation of future physicians to provide care for patients with skin disease. A literature search was conducted using online databases (Embase, MEDLINE, CINAHL and Scopus) to identify relevant studies. The Joanna Briggs Institute methodological framework for scoping reviews was used, including quantitative and qualitative data analysis following a grounded theory approach. From 1490 articles identified, 376 articles were included. Most studies were from the USA (46.3%), UK (16.2%), Germany (6.4%) and Canada (5.6%). Only 46.8% were published as original articles, with a relatively large proportion either as letters (29.2%) or abstracts (12.2%). Literature was grouped into three themes: teaching content, delivery and assessment. Core learning objectives were country dependent; however, a common thread was the importance of skin cancer teaching and recognition that diversity and cultural competence need greater fostering. Various methods of delivery and assessment were identified, including computer-aided and online, audiovisual, clinical immersion, didactic, simulation and peer-led approaches. The advantages and disadvantages of each need to be weighed when deciding which is most appropriate for a given learning outcome. The broader teaching-learning ecosystem is influenced by (i) community health needs and medical school resources, and (ii) the student and their ability to learn and perform. Efforts to optimize dermatology education may use this review to further investigate and adapt teaching according to local needs and context.


Assuntos
Dermatologia , Humanos , Ecossistema , Qualidade de Vida , Faculdades de Medicina , Aprendizagem
17.
Med Teach ; 45(9): 1025-1037, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36763491

RESUMO

PURPOSE: To expand understanding of patient-clinician interactions in management reasoning. METHODS: We reviewed 10 videos of simulated patient-clinician encounters to identify instances of problematic and successful communication, then reviewed the videos again through the lens of two models of shared decision-making (SDM): an 'involvement-focused' model and a 'problem-focused' model. Using constant comparative qualitative analysis we explored the connections between these patient-clinician interactions and management reasoning. RESULTS: Problems in patient-clinician interactions included failures to: encourage patient autonomy; invite the patient's involvement in decision-making; convey the health impact of the problem; explore and address concerns and questions; explore the context of decision-making (including patient preferences); meet the patient where they are; integrate situational preferences and priorities; offer >1 viable option; work with the patient to solve a problem of mutual concern; explicitly agree to a final care plan; and build the patient-clinician relationship. Clinicians' 'management scripts' varied along a continuum of prioritizing clinician vs patient needs. Patients also have their own cognitive scripts that guide their interactions with clinicians. The involvement-focused and problem-focused SDM models illuminated distinct, complementary issues. CONCLUSIONS: Management reasoning is a deliberative interaction occurring in the space between individuals. Juxtaposing management reasoning alongside SDM generated numerous insights.


Assuntos
Tomada de Decisões , Pacientes Ambulatoriais , Humanos , Comunicação , Gravação de Videoteipe , Relações Médico-Paciente , Participação do Paciente/psicologia
18.
Med Teach ; 45(2): 167-178, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36170876

RESUMO

PURPOSE: The Lean Startup approach allows innovators (including innovative educators) to rapidly identify and refine promising ideas into models that actually work. Our aim is to outline key principles of Lean Startup, apply these to health professions education, and illustrate these using personal experience. METHODS AND RESULTS: All innovations are grounded in numerous assumptions; these assumptions should be explicitly identified, prioritized, and empirically tested ('validated learning'). To identify and test assumptions, innovators need to get out of the office and interact with customers (learners, teachers, administrators, etc). Assumptions are tested using multiple quick cycles of Build (a 'minimal viable product' [MVP]), Measure (using metrics that relate meaningfully to the assumption), and Learn (interpret data and decide to persevere with further refinements, or pivot to a new direction). The MVP is a product version that allows testing of one or more key assumptions with the least effort. We describe a novel 'Lean Education Canvas' that synopsizes an innovation and its business model on one page, to help identify assumptions and monitor progress. We illustrate these principles using three cases from health professions education. CONCLUSIONS: Lean Startup has tremendous potential for rapid, robust innovation and evaluation in education.[Box: see text].


Assuntos
Docentes de Medicina , Aprendizagem , Humanos , Escolaridade , Ocupações em Saúde
19.
J Environ Manage ; 342: 118085, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37229934

RESUMO

Economic impacts of protected areas (PAs) are receiving more attention in recent years and methodology in this area is advancing. Multiple studies have illustrated that PAs are a potent land use strategy to generate multiple and direct economic benefits. These benefits are driven by tourism as the central economic activity in PAs worldwide. This study takes the case of Snæfellsjökull, Vatnajökull and þingvellir National Parks (NPs) in Iceland, characterized by limited regional economic data and multi-destination and -purpose visitor travel patterns. Its main objective is to advance understanding of the economic impacts related to PAs in the context of limited data availability. Our analysis is based on the widely used Money Generation Model (MGM2) -methodology, localized to the Icelandic context by using Icelandic labour data and national input-output (I-O) tables regionalized using the Flegg Location Quotient (FLQ). We provide a consistent approach for handling multi-destination and -purpose trips, and separating spending data between local and overall impacts. Based on 2019 visitor and economic data, the visitors (N = 2087) spent, on average, $113 per day in the parks and generated estimated total economic impacts between $30-99 MM with 347-1140 jobs generated across the study sites. For example, in Vatnajökull NP's southern region, the jobs supported locally by the park constituted 36% of all the jobs in the municipalities. Combined tax revenue to the state from the three parks was $88 MM. The localized methodology generated similar economic impacts as earlier studies but showed that employment impacts were previously overestimated by the default models. Our approach and findings can be used as a reference for others applying the MGM2 or similar methods, and they support policy development, decision-making and informed discussion between researchers, practitioners in PA and tourism management, municipalities and communities around PAs. Being able to show economic impacts is increasingly important for PAs to ensure sustained funding amid budget cuts and the transition of government bodies to business units. Limitations of the study include a lack of winter data for Vatnajökull and þingvellir NPs and broad categorization of the Icelandic economic data used in the I-O table regionalization. In further research, a comprehensive sustainability analysis is needed to complement the economic impact analysis and site-specific factors could be analysed in more detail.


Assuntos
Conservação dos Recursos Naturais , Parques Recreativos , Conservação dos Recursos Naturais/métodos , Islândia , Viagem , Formulação de Políticas
20.
Environ Monit Assess ; 195(5): 612, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37099207

RESUMO

Drought has major consequences for agricultural activity, economy, and the environment. For improved drought management, it is necessary to assess drought severity, frequency, and the potential of drought occurrence. The purpose of this study is to use drought indices, standardized precipitation index (SPI), and vegetation condition index (VCI) to characterize the severity of drought and investigate the association between drought severity and subjective well-being among local farmers. The SPI was used to quantify precipitation deficits at various time scales, while the VCI was utilized to monitor crop and vegetation drought conditions. Throughout the period 2000-2017, satellite data were incorporated, as well as a household survey of rice farmers in the dry zone research region in northeastern Thailand. The findings suggest that extreme droughts occur more frequently in the central part of the northeastern region of Thailand than in the rest of the region. The influence of drought on farmers' wellbeing was evaluated at various drought severity levels. Drought and overall wellbeing are strongly linked at the household level. Thai farmers in drought-prone areas are dissatisfied with their livelihoods more than farmers in less-affected area. It is intriguing that farmers who live in drought-prone areas are more content with their lives, their communities, and their occupations than farmers who live in less drought-prone areas. In this context, using proper drought indices could potentially improve the utility of governmental interventions and community-based programs targeted at assisting drought-affected people.


Assuntos
Secas , Fazendeiros , Humanos , Tailândia , Monitoramento Ambiental , Agricultura
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