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1.
PLoS One ; 19(8): e0308838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39163400

RESUMO

Several known biomarkers have been used to understand the physiological responses of humans to various short and long-term interventions such as exercise or dietary interventions. However, little exploratory work has been conducted to identify novel biomarkers in human saliva that could enable non-invasive physiological research to understand acute responses to interventions such as reducing sedentary time. The purpose of this study was to identify novel biomarkers in the saliva (cytokines, growth factors and vascular factors) that respond to prolonged (4 hours) and interrupted sitting (4 hours of sitting interrupted by 3 minutes of walking at 60% of maximal heart rate every 27 minutes) in young, healthy males and females. We also sought to determine whether responsive biomarkers would differ by sex. Participants (n = 24, 21.2 ± 2.2 years, 50% female) completed a prolonged sitting (PS) session and an interrupted sitting (IS) session in random order. Individual saliva samples were pooled into a male sample and a female sample to identify responsive biomarkers using a human cytokine antibody membrane array (42 targets). Several novel biomarkers were responsive in both sexes (e.g., IL-8, Angiogenin, VEGF, and EGF), in females only (e.g., TNF-α and IL-13), and in males only (e.g., IL-3, RANTES, and IL-12p40/p70). Importantly, several biomarkers appear to be responsive to the 4-hour prolonged and interrupted sitting sessions (e.g., TNF-α, IL-8, IL-3, RANTES, EGF, Angiogenin, and VEGF). This work highlights new directions for researchers aiming to investigate the effect of short-term or acute interventions on different physiological pathways using non-invasive methods. Our work clearly indicates that human saliva samples can provide a wealth of insight into physiological responses, and that a number of biomarkers can be used to understand changes induced by acute interventions such as interrupting prolonged sitting.


Assuntos
Biomarcadores , Estudos Cross-Over , Saliva , Comportamento Sedentário , Humanos , Saliva/metabolismo , Saliva/química , Masculino , Feminino , Biomarcadores/análise , Biomarcadores/metabolismo , Adulto Jovem , Citocinas/metabolismo , Citocinas/análise , Adulto
2.
J Vasc Interv Radiol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945294

RESUMO

Retransplantation has been the primary treatment for hepatic artery thrombosis (HAT) in patients with orthotopic liver transplant (OLT); however, because of scarcity of grafts, endovascular revascularization via mechanical thrombectomy offers an alternative to retransplantation should it provide similar long-term benefits. Data regarding a series of 8 patients with hepatic artery thrombectomies across 10 procedures (1 early HAT and 9 late HAT) utilizing stent retriever and/or suction catheter were collected. All had technically successful restoration of flow with stent placement of the anastomotic stenosis in 8 cases. Two patients required reintervention for HAT at 18 and 701 days after primary intervention, with the first dying from liver failure but with a patent hepatic artery on explant. One case had a procedure-related adverse event, hepatic artery dissection, Society of Interventional Radiology (SIR) adverse event classification of 2. Technical success was achieved in all procedures, demonstrating promise in effectively treating HAT in patients with OLT.

3.
Clin Cancer Res ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829906

RESUMO

PURPOSE: To propose a novel recursive partitioning analysis (RPA) classification model in patients with IDH-wildtype glioblastomas that incorporates the recently expanded conception of the extent of resection (EOR) in terms of both supramaximal and total resections. EXPERIMENTAL DESIGN: This multicenter cohort study included a developmental cohort of 622 patients with IDH-wildtype glioblastomas from a single institution (Severance Hospital) and validation cohorts of 536 patients from three institutions (Seoul National University Hospital, Asan Medical Center, and Heidelberg University Hospital). All patients completed standard treatment including concurrent chemoradiotherapy and underwent testing to determine their IDH mutation and MGMTp methylation status. EORs were categorized into either supramaximal, total, or non-total resections. A novel RPA model was then developed and compared to a previous RTOG RPA model. RESULTS: In the developmental cohort, the RPA model included age, MGMTp methylation status, KPS, and EOR. Younger patients with MGMTp methylation and supramaximal resections showed a more favorable prognosis (class I: median overall survival [OS] 57.3 months), while low-performing patients with non-total resections and without MGMTp methylation showed the worst prognosis (class IV: median OS 14.3 months). The prognostic significance of the RPA was subsequently confirmed in the validation cohorts, which revealed a greater separation between prognostic classes for all cohorts compared to the previous RTOG RPA model. CONCLUSIONS: The proposed RPA model highlights the impact of supramaximal versus total resections and incorporates clinical and molecular factors into survival stratification. The RPA model may improve the accuracy of assessing prognostic groups.

4.
Sci Rep ; 14(1): 8379, 2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600116

RESUMO

Macrophage responses to activation are fluid and dynamic in their ability to respond appropriately to challenges, a role integral to host defence. While bacteria can influence macrophage differentiation and polarization into pro-inflammatory and alternatively activated phenotypes through direct interactions, many questions surround indirect communication mechanisms mediated through secretomes derived from gut bacteria, such as lactobacilli. We examined effects of secretome-mediated conditioning on THP-1 human monocytes, focusing on the ability of the Lacticaseibacillus rhamnosus R0011 secretome (LrS) to drive macrophage differentiation and polarization and prime immune responses to subsequent challenge with lipopolysaccharide (LPS). Genome-wide transcriptional profiling revealed increased M2-associated gene transcription in response to LrS conditioning in THP-1 cells. Cytokine and chemokine profiling confirmed these results, indicating increased M2-associated chemokine and cytokine production (IL-1Ra, IL-10). These cells had increased cell-surface marker expression of CD11b, CD86, and CX3CR1, coupled with reduced expression of the M1 macrophage-associated marker CD64. Mitochondrial substrate utilization assays indicated diminished reliance on glycolytic substrates, coupled with increased utilization of citric acid cycle intermediates, characteristics of functional M2 activity. LPS challenge of LrS-conditioned THP-1s revealed heightened responsiveness, indicative of innate immune priming. Resting stage THP-1 macrophages co-conditioned with LrS and retinoic acid also displayed an immunoregulatory phenotype with expression of CD83, CD11c and CD103 and production of regulatory cytokines. Secretome-mediated conditioning of macrophages into an immunoregulatory phenotype is an uncharacterized and potentially important route through which lactic acid bacteria and the gut microbiota may train and shape innate immunity at the gut-mucosal interface.


Assuntos
Lacticaseibacillus rhamnosus , Monócitos , Humanos , Monócitos/metabolismo , Secretoma , Lipopolissacarídeos , Citocinas/metabolismo , Quimiocinas/metabolismo , Imunidade
5.
Mol Nutr Food Res ; 68(7): e2300770, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38522032

RESUMO

SCOPE: Gastro-AD (GAD) is a soy flour derived product that undergoes an industrial fermentation with Lactobacillus delbrueckii R0187 and has demonstrated clinical effects in gastroesophageal reflux and peptic ulcer symptom resolution. The aim of this study is to describe and link GAD's metabolomic profile to plausible mechanisms that manifest and explain the documented clinical outcomes. METHODS AND RESULTS: 1H NMR spectroscopy with multivariate statistical analysis is used to characterize the prefermented soy flour and GAD products. The acquired spectra are screened using various resources and the molecular assignments are confirmed using total correlation spectroscopy (TOCSY). Peaks corresponding to different metabolites are integrated and compared between the two products for relative changes. HPLC and GC are used to quantify some specific molecules. NMR analyses demonstrate significant changes in the composition of various assigned bioactive moieties. HPLC and GC analysis demonstrate deglycation of isoflavones after fermentation, resulting in estrogenically active secondary metabolites that have been previously shown to help to reduce inflammation. CONCLUSION: The identification of bioactive molecules, such as genistein and SCFAs, capable of modulating anti-inflammatory signaling cascades in the stomach's gastric and neuroendocrine tissues can explain the reported biological effects in GAD and is supported by in vivo data.


Assuntos
Genisteína , Isoflavonas , Genisteína/metabolismo , Isoflavonas/metabolismo , Suplementos Nutricionais , Fermentação
7.
CJEM ; 26(1): 40-46, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38206515

RESUMO

PURPOSE: The release of the ChatGPT prototype to the public in November 2022 drastically reduced the barrier to using artificial intelligence by allowing easy access to a large language model with only a simple web interface. One situation where ChatGPT could be useful is in triaging patients arriving to the emergency department. This study aimed to address the research problem: "can emergency physicians use ChatGPT to accurately triage patients using the Canadian Triage and Acuity Scale (CTAS)?". METHODS: Six unique prompts were developed independently by five emergency physicians. An automated script was used to query ChatGPT with each of the 6 prompts combined with 61 validated and previously published patient vignettes. Thirty repetitions of each combination were performed for a total of 10,980 simulated triages. RESULTS: In 99.6% of 10,980 queries, a CTAS score was returned. However, there was considerable variations in results. Repeatability (use of the same prompt repeatedly) was responsible for 21.0% of overall variation. Reproducibility (use of different prompts) was responsible for 4.0% of overall variation. Overall accuracy of ChatGPT to triage simulated patients was 47.5% with a 13.7% under-triage rate and a 38.7% over-triage rate. More extensively detailed text given as a prompt was associated with greater reproducibility, but minimal increase in accuracy. CONCLUSIONS: This study suggests that the current ChatGPT large language model is not sufficient for emergency physicians to triage simulated patients using the Canadian Triage and Acuity Scale due to poor repeatability and accuracy. Medical practitioners should be aware that while ChatGPT can be a valuable tool, it may lack consistency and may frequently provide false information.


ABSTRAIT: OBJECTIF: La sortie du prototype ChatGPT au public en novembre 2022 a considérablement réduit l'obstacle à l'utilisation de l'intelligence artificielle en permettant un accès facile à un grand modèle de langage avec une interface web simple. Une situation où ChatGPT pourrait être utile est de trier les patients qui arrivent au service d'urgence. Cette étude visait à résoudre le problème de la recherche : «Les médecins d'urgence peuvent-ils utiliser ChatGPT pour trier avec précision les patients à l'aide de l'Échelle canadienne de triage et d'acuité (ECTC) ?¼. MéTHODES: Six invites uniques ont été élaborées indépendamment par cinq urgentologues. Un script automatisé a été utilisé pour interroger ChatGPT avec chacune des six invites combinées à 61 vignettes de patients validées et précédemment publiées. Trente répétitions de chaque combinaison ont été réalisées pour un total de 10980 triages simulés. RéSULTATS: Dans 99.6 % des 10980 requêtes, un score CTAS a été obtenu. Cependant, il y a eu des variations considérables dans les résultats. La répétabilité (utilisation répétée de la même invite) était responsable de 21.0 % de la variation globale. La reproductibilité (utilisation de différentes invites) était responsable de 4.0 % de la variation globale. La précision globale de ChatGPT pour le triage des patients simulés était de 47.5 %, avec un taux de sous-triage de 13.7 % et un taux de triage supérieur de 38.7 %. Un texte plus détaillé donné à titre d'invite était associé à une plus grande reproductibilité, mais à une augmentation minimale de la précision. CONCLUSIONS: Cette étude suggère que le modèle actuel de ChatGPT en langage large n'est pas suffisant pour permettre aux médecins d'urgence de trier des patients simulés à l'aide de l'échelle canadienne de triage et d'acuité en raison de la faible répétabilité et de la faible précision. Les médecins doivent être conscients que, bien que ChatGPT puisse être un outil précieux, il peut manquer de cohérence et fournir fréquemment de fausses informations.


Assuntos
Inteligência Artificial , Triagem , Humanos , Triagem/métodos , Reprodutibilidade dos Testes , Canadá , Serviço Hospitalar de Emergência
8.
Prehosp Disaster Med ; 38(6): 697-698, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37970889

RESUMO

The recently published Model Core Content of Disaster Medicine introduces proposed curriculum elements for specialized education and training in Disaster Medicine. This editorial comments on the publishing decision for the manuscript.


Assuntos
Medicina de Desastres , Educação de Graduação em Medicina , Humanos , Medicina de Desastres/educação , Currículo
9.
Prehosp Disaster Med ; 38(5): 570-580, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37675480

RESUMO

The application and provision of prehospital care in disasters and mass-casualty incident response in Europe is currently being explored for opportunities to improve practice. The objective of this translational science study was to align common principles of approach and action and to identify how technology can assist and enhance response. To achieve this objective, the application of a modified Delphi methodology study based on statements derived from key findings of a scoping review was undertaken. This resulted in 18 triage, eight life support and damage control interventions, and 23 process consensus statements. These findings will be utilized in the development of evidence-based prehospital mass-casualty incident response tools and guidelines.


Assuntos
Planejamento em Desastres , Serviços Médicos de Emergência , Incidentes com Feridos em Massa , Humanos , Triagem/métodos , Técnica Delphi
10.
Eur J Appl Physiol ; 123(6): 1271-1281, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36781426

RESUMO

PURPOSE: Experimental studies have shown that prolonged sitting for 2-8 h can cause changes to vascular and metabolic markers; the response of pro-inflammatory cytokines is relatively unexplored. The purpose of this study is to determine the response of interleukin-8 (IL-8) to prolonged and interrupted sitting. METHODS: Healthy participants (n = 24, 21.1 years ± 2.2, 50% female) completed a prolonged sitting session (4 h) and an interrupted sitting session (4 h of sitting with 3 min of walking at 60%HRmax, every 30 min) in random order. Saliva and capillary plasma were collected at the beginning (T1) and at the end of each session (T2). RESULTS: Salivary concentrations of IL-8 increased during the prolonged (T1 median: 22.09 pg/mL, T2 median: 86.18 pg/mL; p = < 0.01, ES - 0.55) and interrupted (T1 median: 22.09 pg/mL, T2 median: 51.99 pg/mL; p = 0.021, ES - 0.34) sessions; however, the increase during interrupted sitting was lower (PS median: 134.4%, range: - 43.96 to 1115.69 and IS median: 50.8%, range: - 75.5 to 356.35; p = 0.011, ES - 0.53). In the sub-sample of males, salivary IL-8 did not increase in the interrupted session (T1 median: 22.09, range: 3.496-699.12, and T2 median: 24.96, range: 5.11-533.5, p = > 0.05, ES - 0.16). No significant findings were observed for IL-8 in the plasma. CONCLUSION: Prolonged sitting appears to increase concentrations of the pro-inflammatory cytokine IL-8 while interrupting this sitting with short bouts of walking blunts this response. Sex appears to moderate this relationship; however, there appears to be a large amount of individual variability.


Assuntos
Interleucina-8 , Feminino , Humanos , Masculino , Citocinas , Comportamento Sedentário , Caminhada/fisiologia , Adulto Jovem
12.
Front Microbiol ; 13: 980989, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246229

RESUMO

Certain lactic acid bacteria (LAB) are associated with immune modulatory activities including down-regulation of pro-inflammatory gene transcription and expression. While host antigen-presenting cells (APCs) and intestinal epithelial cells (IEC) can interact directly with both pathogenic and commensal bacteria through innate immune pattern recognition receptors, recent evidence indicates indirect communication through secreted molecules is an important inter-domain communication mechanism. This communication route may be especially important in the context of IEC and APC interactions which shape host immune responses within the gut environment. We have previously shown that the Lacticaseibacillus rhamnosus R0011 secretome (LrS) dampens pro-inflammatory gene transcription and mediator production from Tumor Necrosis Factor-α and Salmonella enterica serovar Typhimurium secretome (STS)-challenged HT-29 IECs through the induction of negative regulators of innate immunity. However, many questions remain about interactions mediated through these bacterial-derived soluble components and the resulting host immune outcomes in the context of IEC and APC interactions. In the present study, we examined the ability of the LrS to down-regulate pro-inflammatory gene transcription and cytokine production from STS-challenged T84 human IEC and THP-1 human monocyte co-cultures. Cytokine and chemokine profiling revealed that apically delivered LrS induces apical secretion of macrophage inhibitory factor (MIF) and down-regulates STS-induced pro-inflammatory mediator secretion into the apical and basolateral chambers of the T84/THP-1 co-culture. Transcriptional profiling confirmed these results, as the LrS attenuated STS challenge-induced CXCL8 and NFκB1 expression in T84 IECs and THP-1 APCs. Interestingly, the LrS also reversed STS-induced damage to monolayer transepithelial resistance (TER) and permeability, results which were confirmed by ZO-1 gene expression and immunofluorescence visualization of ZO-1 expression in T84 IEC monolayers. The addition of a MIF-neutralizing antibody abrogated the ability of the LrS to reverse STS-induced damage to T84 IEC monolayer integrity, suggesting a novel role for MIF in maintaining IEC barrier function and integrity in response to soluble components derived from LAB. The results presented here provide mechanistic evidence for indirect communication mechanisms used by LAB to modulate immune responses to pathogen challenge, using in vitro approaches which allow for IEC and APC cell communication in a context which more closely mimics that which occurs in vivo.

13.
Front Public Health ; 10: 676704, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35284379

RESUMO

Background: Mass casualty incidents (MCIs) can occur as a consequence of a wide variety of events and often require overwhelming prehospital and emergency support and coordinated emergency response. A variety of disaster triage systems have been developed to assist health care providers in making difficult choices with regards to prioritization of victim treatment. The simple triage and rapid treatment (START) triage system is one of the most widely used triage algorithms; however, the research literature addressing real-world or simulation studies documenting the classification accuracy of personnel using START is lacking. Aims and Objectives: To explore the existing literature related to the current state of knowledge about studies assessing the classification accuracy of the START triage system. Design: Scoping review based on Arksey and O'Malley's methodological framework and narrative synthesis based on methods described by Popay and colleagues were performed. Results: The literature search identified 1,820 citations, of which 32 studies met the inclusion criteria. Thirty were peer-reviewed articles and 28 published in the last 10 years (i.e., 2010 and onward). Primary research studies originated in 13 countries and included 3,706 participants conducting triaging assessments involving 2,950 victims. Included studies consisted of five randomized controlled trials, 17 non-randomized controlled studies, eight descriptive studies, and two mixed-method studies. Simulation techniques, mode of delivery, contextual features, and participants' required skills varied among studies. Overall, there was no consistent reporting of outcomes across studies and results were heterogeneous. Data were extracted from the included studies and categorized into two themes: (1) typology of simulations and (2) START system in MCIs simulations. Each theme contains sub-themes regarding the development of simulation employing START as a system for improving individuals' preparedness. These include types of simulation training, settings, and technologies. Other sub-themes include outcome measures and reference standards. Conclusion: This review demonstrates a variety of factors impacting the development and implementation of simulation to assess characteristics of the START system. To further improve simulation-based assessment of triage systems, we recommend the use of reporting guidelines specifically designed for health care simulation research. In particular, reporting of reference standards and test characteristics need to improve in future studies.


Assuntos
Incidentes com Feridos em Massa , Algoritmos , Simulação por Computador , Humanos , Triagem
14.
Am J Cardiol ; 168: 135-141, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35058054

RESUMO

Multisystem inflammatory syndrome (MIS) is a severe complication described in a minority of patients with COVID-19. Myocarditis has been reported in patients with COVID-19, including MIS. In this study, we compared the clinical characteristics and cardiac magnetic resonance (CMR) findings of COVID-19 myocarditis in patients with and without MIS. In the 330 patients with COVID-19 who were referred for CMR at our institution between July 24, 2020, to March 31, 2021, 40 patients were identified as having myocarditis, MIS myocarditis (n = 21) and non-MIS myocarditis (n = 19). MIS myocarditis was characterized by global myocardial inflammation/edema with significantly elevated native T1, whereas only regional inflammation, and edema were noted in the non-MIS group. Distinct late gadolinium enhancement (LGE) patterns-inferior myocardial involvement in non-MIS myocarditis and septal involvement in MIS myocarditis-were identified. The LGE burden was comparable between the 2 groups (5.9% vs 6.6%, MIS vs non-MIS group, p = 0.83). Myocarditis was diagnosed more frequently by CMR in the MIS group (70% vs 6.3%, MIS vs non-MIS, p <0.001). In the 20 patients with a sequential CMR study at a median 102-day follow-up, 25% had persistent myocardial edema. The LGE burden improved over time, from a median of 5.0% (interquartile range 3.4% to 7.3%) to 3.2% (interquartile range 2.0% to 3.8%; p <0.001). In conclusion, MIS and non-MIS myocarditis exhibit distinct characteristics by CMR. Persistent LGE and edema were common at follow-up CMR examination in both groups.


Assuntos
COVID-19 , Miocardite , COVID-19/complicações , Meios de Contraste , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Miocardite/diagnóstico por imagem , Miocardite/patologia , Miocárdio/patologia , Valor Preditivo dos Testes
15.
J Mech Behav Biomed Mater ; 120: 104583, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34062373

RESUMO

This paper focuses on utilizing the Fused Deposition Modeling (FDM) to manufacture Polycaprolactone/Nano-Hydroxyapatite/Chitin-Nano-Whisker nanocomposite scaffolds and their subsequent characterization for biomedical applications. FDM nanocomposite filaments were manufactured in multiple nanocomposite formulations of Polycaprolactone/Nano-Hydroxyapatite (nHA), Polycaprolactone/Chitin-Nano-Whisker (CNW), and Polycaprolactone/nHA/CNW using a green method. The FDM processing conditions were optimized using Taguchi orthogonal array method. The mechanical, biodegradation, and biocompatibility properties of the bone tissue scaffolds were assessed. A preosteoblast mouse bone cell line was used for cell proliferation and attachment assays. The results indicated that CNW content in the filaments slightly increases the mechanical properties of the 3D printed parts, and the nanocomposite with 3% CNW content exhibited significant improvement in the cell proliferation and attachment properties of the scaffolds. The nHA content considerably improved the mechanical properties of the scaffolds. The nHA and CNW nanofillers increased the biodegradation rate of PCL. In general, considering all types of responses, a green manufactured nanocomposite of PCL/nHA/CNW can significantly increase the biological and mechanical properties of the 3D printed products for bone tissue scaffolds.


Assuntos
Nanocompostos , Alicerces Teciduais , Animais , Quitina , Durapatita , Camundongos , Poliésteres , Engenharia Tecidual
16.
Proc Natl Acad Sci U S A ; 117(47): 29720-29729, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33139533

RESUMO

Forest vulnerability to drought is expected to increase under anthropogenic climate change, and drought-induced mortality and community dynamics following drought have major ecological and societal impacts. Here, we show that tree mortality concomitant with drought has led to short-term (mean 5 y, range 1 to 23 y after mortality) vegetation-type conversion in multiple biomes across the world (131 sites). Self-replacement of the dominant tree species was only prevalent in 21% of the examined cases and forests and woodlands shifted to nonwoody vegetation in 10% of them. The ultimate temporal persistence of such changes remains unknown but, given the key role of biological legacies in long-term ecological succession, this emerging picture of postdrought ecological trajectories highlights the potential for major ecosystem reorganization in the coming decades. Community changes were less pronounced under wetter postmortality conditions. Replacement was also influenced by management intensity, and postdrought shrub dominance was higher when pathogens acted as codrivers of tree mortality. Early change in community composition indicates that forests dominated by mesic species generally shifted toward more xeric communities, with replacing tree and shrub species exhibiting drier bioclimatic optima and distribution ranges. However, shifts toward more mesic communities also occurred and multiple pathways of forest replacement were observed for some species. Drought characteristics, species-specific environmental preferences, plant traits, and ecosystem legacies govern postdrought species turnover and subsequent ecological trajectories, with potential far-reaching implications for forest biodiversity and ecosystem services.


Assuntos
Secas/mortalidade , Florestas , Biodiversidade , Mudança Climática/mortalidade , Ecossistema , Especificidade da Espécie , Árvores/fisiologia
17.
Curr Res Food Sci ; 3: 51-58, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32914120

RESUMO

Fermented dairy products have become attractive functional foods for the delivery of probiotics and their biologically active metabolites. The aim of this study was to examine the immunomodulatory activity of milk fermented with the probiotic lactic acid bacterium Lactobacillus rhamnosus R0011 (LrF) on macrophages challenged with lipopolysaccharide (LPS), a potent pro-inflammatory stimulus. To this end, human THP-1 or U937 monocytes were differentiated into resting macrophages then stimulated with LPS and co-incubated with the LrF or with milk controls. Levels of pro-inflammatory and immunoregulatory cytokines were determined by enzyme-linked immunosorbent assays. Culturing of LPS-stimulated U937 macrophages with either the whole or filtered LrF resulted in an increase in Interleukin (IL)-1Ra production relative to the negative control. THP-1 macrophages cultured with the LrF demonstrated an increase in LPS-induced IL-10 and IL-1ß production, while production of LPS-induced IL-6, sCD54, IL-8, IL-1ß, TNF-α, IL-12p70 and Transforming Growth Factor-ß (TGF-ß) was unaffected. Further, the LrF induced the expression of DC-SIGN and CD206, markers of immunoregulatory M2 macrophage polarization, in LPS-challenged THP-1 macrophages. Taken together, milk fermented with L. rhamnosus R0011 increased regulatory cytokine production from LPS-challenged U937 and THP-1 macrophages, while simultaneously up-regulating the production of IL-1ß and expression of DC-SIGN and CD206, a profile characteristic of polarization into the immunoregulatory M2 macrophage phenotype.

18.
Scand J Trauma Resusc Emerg Med ; 28(1): 86, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843062

RESUMO

BACKGROUND: Well-prepared humanitarian workers are now more necessary than ever. Essential to the preparation process are: clearly defined learning objectives, curricula tailored to the nuances of humanitarian settings, simulation-based training, and evaluation. This manuscript describes a training program designed to prepare medical residents for their first field deployment with Médecins Sans Frontières and presents the results of a pilot assessment of its effectiveness. METHODS: The training was jointly developed by the Research Center in Emergency and Disaster Medicine- CRIMEDIM of the Università del Piemonte Orientale, Novara, Italy, and the humanitarian aid organization Médecins Sans Frontières- Italy (MSF-Italy); the following topics were covered: disaster medicine, public health, safety and security, infectious diseases, psychological support, communication, humanitarian law, leadership, and job-specific skills. It used a blended-learning approach consisting of a 3-month distance learning module; 1-week instructor-led coaching; and a field placement with MSF. We assessed its effectiveness using the first three levels of Kirkpatrick's training evaluation model. RESULTS: Eight residents took part in the evaluation. Four were residents in emergency medicine, 3 in anesthesia, and 1 in pediatrics; 3 of them were female and the median age was 31 years. Two residents were deployed in Pakistan, 1 in Afghanistan, 1 in the Democratic Republic of Congo, 1 in Iraq, 2 in Haiti and 1 on board of the MSF Mediterranean search & rescue ship. Mean deployment time was 3 months. The average median score for the overall course was 5 (excellent). There was a significant improvement in post-test multiple choice scores (p = 0.001) and in residents' overall performance scores (P = 0.000001). CONCLUSION: Residents were highly satisfied with the training program and their knowledge and skills improved as a result of participation. TRIAL REGISTRATION: This study was approved by the Institutional Ethics Committee (date 24-02-2016, study code UPO.2015.4.10).


Assuntos
Internato e Residência , Missões Médicas , Adulto , Altruísmo , Competência Clínica , Currículo , Feminino , Recursos em Saúde/provisão & distribuição , Humanos , Itália , Aprendizagem , Masculino , Projetos Piloto , Avaliação de Programas e Projetos de Saúde
19.
J Immunol ; 204(9): 2523-2534, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238458

RESUMO

Recent evidence suggests that lactic acid bacteria communicate with host cells via secretome components to influence immune responses but less is known about gut-pathogen secretomes, impact of lactic acid bacteria secretomes on host-pathogen interactions, and the mechanisms underlying these interactions. Genome-wide microarrays and cytokine profiling were used to interrogate the impact of the Lactobacillus rhamnosus R0011 secretome (LrS) on TNF-α and Salmonella enterica subsp. enterica serovar Typhimurium secretome (STS)-induced outcomes in human intestinal epithelial cells. The LrS attenuated both TNF-α- and STS-induced gene expression involved in NF-κB and MAPK activation, as well as expression of genes involved in other immune-related signaling pathways. Specifically, the LrS induced the expression of dual specificity phosphatase 1 (DUSP1), activating transcription factor 3 (ATF3), and tribbles pseudokinase 3 (TRIB3), negative regulators of innate immune signaling, in HT-29 intestinal epithelial cells challenged with TNF-α or STS. TNF-α- and STS-induced acetylation of H3 and H4 histones was attenuated by the LrS, as was the production of TNF-α- and STS-induced proinflammatory cytokines and chemokines. Interestingly, the LrS induced production of macrophage migration inhibitory factor (MIF), a cytokine involved in host-microbe interactions at the gut interface. We propose that the LrS attenuates proinflammatory mediator expression through increased transcription of negative regulators of innate immune activity and changes in global H3 and H4 histone acetylation. To our knowledge, these findings provide novel insights into the complex multifaceted mechanisms of action behind secretome-mediated interdomain communication at the gut-mucosal interface.


Assuntos
Células Epiteliais/imunologia , Inflamação/imunologia , Intestinos/imunologia , Lacticaseibacillus rhamnosus/imunologia , Salmonelose Animal/imunologia , Salmonella typhimurium/imunologia , Fator de Necrose Tumoral alfa/imunologia , Acetilação , Animais , Linhagem Celular Tumoral , Citocinas/imunologia , Células Epiteliais/microbiologia , Expressão Gênica/imunologia , Células HT29 , Histonas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/imunologia , Inflamação/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Intestinos/microbiologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Salmonelose Animal/microbiologia , Sorogrupo , Transdução de Sinais/fisiologia , Transcrição Gênica/imunologia
20.
Disaster Med Public Health Prep ; 14(4): 514-520, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32223776

RESUMO

OBJECTIVE: This study compared live instructor-led training with video-based instruction in personal protective equipment (PPE) donning and doffing. It assessed the difference in performance between (1) attending 1 instructor-led training session in donning and doffing PPE at 1 month prior to assessment, and (2) watching training videos for 1 month. METHODS: This randomized controlled trial pilot study divided 21 medical students and junior doctors into 2 groups. Control group participants attended 1 instructor-led training session. Video group participants watched training videos demonstrating the same procedures, which they could freely watch again at home. After 1 month, a doctor performed a blind evaluation of performance using checklists. RESULTS: Nineteen participants were assessed after 1 month. The mean donning score was 84.8/100 for the instructor-led group and 88/100 for the video group; mean effect size was 3.2 (95% CI: -7.5 to 9.5). The mean doffing score was 79.1/100 for the instructor-led group and 73.9/100 for the video group; mean effect size was 5.2 (95% CI: -7.6 to 18). CONCLUSION: Our study found no significant difference in donning and doffing scores between instructor-led and video lessons. Video training could be a fast and resource-efficient method of training in PPE donning and doffing in responding to the COVID-19 pandemic.


Assuntos
Pessoal de Saúde/educação , Pessoal de Saúde/psicologia , Equipamento de Proteção Individual , Ensino/normas , Pessoal de Saúde/estatística & dados numéricos , Humanos , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Projetos Piloto , Ensino/classificação , Ensino/estatística & dados numéricos
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