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1.
Emerg Med J ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763520

RESUMO

The Royal College of Emergency Medicine Toxicology Special Interest Group in collaboration with the UK National Poisons Information Service and the Clinical Toxicology Department at Guy's and St Thomas' NHS Foundation Trust has produced guidance to support clinicians working in the ED with the assessment and management of adults with acute opioid toxicity.Considerations regarding identification of acute opioid toxicity are discussed and recommendations regarding treatment options and secondary prevention are made. There is a focus on making recommendations on the best available evidence.

2.
bioRxiv ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38712200

RESUMO

The role of extracellular vesicles (EVs) in human health and disease has garnered considerable attention over the past two decades. However, while several types of EVs are known to interact dynamically with the extracellular matrix and there is great potential value in producing high-fidelity EV micropatterns, there are currently no label-free, high-resolution, and tunable platform technologies with this capability. We introduce Light-induced Extracellular Vesicle Adsorption (LEVA) as a powerful solution to rapidly advance the study of matrix- and surface-bound EVs and other particles. The versatility of LEVA is demonstrated using commercial GFP-EV standards, EVs from glioblastoma bioreactors, and E. coli outer membrane vesicles (OMVs), with the resulting patterns used for single EV characterization, single cell migration on migrasome-mimetic trails, and OMV-mediated neutrophil swarming. LEVA will enable rapid advancements in the study of matrix- and surface-bound EVs and other particles, and should encourage researchers from many disciplines to create novel diagnostic, biomimetic, immunoengineering, and therapeutic screening assays.

3.
Clin Res Cardiol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619575

RESUMO

BACKGROUND: Transcatheter aortic valve implantation (TAVI) serves a growing range of patients with severe aortic stenosis (AS). TAVI has evolved to a streamlined procedure minimizing length of hospital stay. AIMS: To evaluate the safety and efficacy of an early discharge (ED) strategy after TAVI. METHODS: We performed an international, multi-center, prospective observational single-arm study in AS patients undergoing TAVI with the ACURATE valve platform. Eligibility for ED was assessed prior to TAVI and based on prespecified selection criteria. Discharge ≤ 48 h was defined as ED. Primary Valve Academic Research Consortium (VARC)-3-defined 30-day safety and efficacy composite endpoints were landmarked at 48 h and compared between ED and non-ED groups. RESULTS: A total of 252 patients were included. The median age was 82 [25th-75th percentile, 78-85] years and the median Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 2.2% [25th-75th percentile, 1.6-3.3]. ED and non-ED were achieved in 173 (69%) and 79 (31%) patients respectively. Monitoring for conduction disturbances was the principal reason for non-ED (33%). Overall, at 30 days, all-cause mortality was 1%, new permanent pacemaker rate was 4%, and valve- or procedure-related rehospitalization was 4%. There was no difference in the primary safety and efficacy endpoint between the ED and non-ED cohorts (OR 0.84 [25th-75th percentile, 0.31-2.26], p = 0.73, and OR 0.97 [25th-75th percentile, 0.46-2.06], p = 0.94). The need for rehospitalization was similarly low for ED and non-ED groups. CONCLUSION: Early discharge after TAVI with the ACURATE valve is safe and feasible in selected patients. Rhythm monitoring and extended clinical observation protracted hospital stay.

4.
N Engl J Med ; 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38587261

RESUMO

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

5.
Plants (Basel) ; 13(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674573

RESUMO

During the past 30 years, there has been a growing belief in and promotion of agroecosystem diversity for pest management and future food production as an agroecological or nature-based approach. Monoculture agriculture, which produces most of our food, is considered to be highly vulnerable to pests in contrast to plant species-diverse agroecosystems which may possess a greater abundance of natural enemies, keeping pest populations under control. In this paper, we question the role of crop diversity for pest management and explore the relationship between crop and associated diversity and pests through the following processes: environmental stresses that favor monodominance; evolutionary adaptations that resist insect herbivores (genetic resistance response); mechanisms of spatial escape from insect herbivores (escape response); and the role of crop-associated biodiversity. We present strong evidence that not only questions the high vulnerability of monocultures to pest damage but also supports why monocultures continue to produce most of the world's food. Reference is made to the importance of targeted plant breeding and the role of trans-continental crop introduction supported by efficient quarantine for pest management. We conclude that-with the exception of irrigated rice-much more research is needed to better understand the role of crop diversity in agroecosystems for pest management and food production.

6.
Glob Public Health ; 19(1): 2326017, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38468393

RESUMO

Research suggests that health literacy (HL) is critical in preventing and managing health problems. However, over half of adults in Mexico report having inadequate health literacy. Research suggests the parent-child relationship can be a key predictor of developmental competencies; however, little research has examined how dyadic family interactions relate to HL. This study examined whether parent-child relationship conflict was associated with adolescent health literacy among families living in Mexico. Data from a parent-child dyads in Mexico were gathered using online surveys (N = 746, 373 parent-child dyads). Our findings suggested that child-reported family conflict-but not parent-reported family conflict - was associated with lower adolescent health literacy. Researchers and practitioners should consider how parent-child conflict may impact adolescent health outcomes, and prioritise child reports in data collection.


Assuntos
Letramento em Saúde , Adulto , Adolescente , Humanos , Saúde do Adolescente , México , Pais , Relações Pais-Filho
7.
Adv Aerodyn ; 6(1): 7, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464493

RESUMO

This paper investigates a specific case of one of the most popular fluid dynamic simulations, the incompressible flow around an airfoil (NACA 0012 here) at a high Reynolds number (6×106). OpenFOAM software was used to study the effect of domain size and four common choices of boundary conditions on airfoil lift, drag, surface friction, and pressure. We also examine the relation between boundary conditions and the velocity, pressure, and vorticity distributions throughout the domain. In addition to the common boundary conditions, we implement the "point vortex" boundary condition that was introduced many years ago but is now rarely used. We also applied the point vortex condition for the outlet pressure instead of using the traditional Neumann condition. With the airfoil generating significant lift at incidence angles of 5∘,10∘, and 14∘, we confirm a previous finding that the boundary conditions combine with domain size to produce an induced (pressure) drag. The change in the pressure drag with domain size is significant for the commonly-used boundary conditions but is much smaller for the point vortex alternative. The point vortex boundary condition increases the execution time, but this is more than offset by the reduction in domain size needed to achieve a specified accuracy in the lift and drag. This study also estimates the error in total drag and lift due to domain size and shows it can be almost eliminated using the point vortex boundary condition. We also used the impulse form of the momentum equations to study the relation between drag and lift and spurious vorticity, which is generated as a result of using non-exact boundary conditions. These equations reveal that the spurious vorticity throughout the domain is associated with cancelling circulation around the domain boundaries.

8.
J Environ Manage ; 356: 120561, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479290

RESUMO

Recorded particulate matter (PM2.5) hourly trends are compared for fifteen urban recording sites distributed across central England for the period 2018 to 2022. They include 10 urban-background and five urban-traffic (roadside) sites with some located within the same urban area. The sites all show consistent background and peak distributions with mean annual values and standard deviations higher for 2018 and 2019 than for 2020 to 2022. The objective of this study is to demonstrate that trend attributes extracted from hourly recorded univariate PM2.5 trends at these sites can be used to provide reliable short-term hourly predictions and provide valuable insight into the regional variations in the recorded trends. Fifteen trend attributes extracted from the prior 12 h (t-1 to t-12) of recorded PM2.5 data were compiled and used as input to four supervised machine learning models (SML) to forecast PM2.5 concentrations up to 13 h ahead (t0 to t+12). All recording sites delivered forecasts with similar ranges of error levels for specific hours ahead which are consistent with their PM2.5 recorded ranges. Forecasting results for four representative sites are presented in detail using models trained and cross-validated with 2020 and 2021 hourly data to forecast 2021 and 2022 hourly data, respectively. A novel optimized feature selection procedure using a suite of five optimizers is used to improve the efficiency of the forecasting models. The LASSO and support vector regression models generate the best and most generalizable hourly PM2.5 forecasts from trained and validated SML models with mean average error (MAE) of between ∼1 and ∼3 µg/m3 for t0 to t+3 h ahead. A novel overfitting indicator, exploiting the cross-validation mean values, demonstrates that these two models are not affected by overfitting. Forecasts for t+6 to t+12 h forward generate higher MAE values between ∼3 and ∼4 µg/m3 due to their tendency to underestimate some of the extreme PM2.5 peaks. These findings indicate that further model refinements are required to generate more reliable short-term predictions for the t+6 to t+24 h ahead.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Cidades , Monitoramento Ambiental/métodos , Material Particulado/análise , Inglaterra , Previsões , Aprendizado de Máquina , Poluição do Ar/análise
9.
EuroIntervention ; 20(6): e376-e388, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38506739

RESUMO

BACKGROUND: There are limited data regarding treatment for failed balloon-expandable transcatheter heart valves (THVs) in redo-transcatheter aortic valve implantation (TAVI). AIMS: We aimed to assess THV performance, neoskirt height and expansion when performing redo-TAVI with the ACURATE platform inside a SAPIEN 3 (S3) compared to redo-TAVI with an S3 in an S3. METHODS: Redo-TAVI was performed on the bench using each available size of the S3, the ACURATE neo2 (ACn2) and the next-generation ACURATE Prime XL (AC XL) implanted at 2 different depths within 20 mm/23 mm/26 mm/29 mm S3s serving as the "failed" index THV. Hydrodynamic testing was performed to assess THV function. Multimodality assessment was performed using photography, X-ray, microcomputed tomography (micro-CT), and high-speed videos. RESULTS: The ACURATE in S3 combinations had favourable hydrodynamic performance compared to the S3 in S3 for all size combinations. In the 20 mm S3, redo-TAVI with the ACn2 had lower gradients compared to the S3 (mean gradient 16.3 mmHg for the ACn2 vs 24.7 mmHg for the 20 mm S3 in 20 mm S3). Pinwheeling was less marked for the ACURATE THVs than for the S3s. On micro-CT, the S3s used for redo-TAVI were underexpanded across all sizes. This was also observed for the ACURATE platform, but to a lesser extent. CONCLUSIONS: Redo-TAVI with an ACn2/AC XL within an S3 has favourable hydrodynamic performance and less pinwheeling compared to an S3 in S3. This comes at the price of a taller neoskirt.


Assuntos
Insuficiência Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Microtomografia por Raio-X , Catéteres , Valvas Cardíacas
10.
Eur Heart J ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554125

RESUMO

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

11.
Hum Brain Mapp ; 45(4): e26625, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38433665

RESUMO

Estimated age from brain MRI data has emerged as a promising biomarker of neurological health. However, the absence of large, diverse, and clinically representative training datasets, along with the complexity of managing heterogeneous MRI data, presents significant barriers to the development of accurate and generalisable models appropriate for clinical use. Here, we present a deep learning framework trained on routine clinical data (N up to 18,890, age range 18-96 years). We trained five separate models for accurate brain age prediction (all with mean absolute error ≤4.0 years, R2 ≥ .86) across five different MRI sequences (T2 -weighted, T2 -FLAIR, T1 -weighted, diffusion-weighted, and gradient-recalled echo T2 *-weighted). Our trained models offer dual functionality. First, they have the potential to be directly employed on clinical data. Second, they can be used as foundation models for further refinement to accommodate a range of other MRI sequences (and therefore a range of clinical scenarios which employ such sequences). This adaptation process, enabled by transfer learning, proved effective in our study across a range of MRI sequences and scan orientations, including those which differed considerably from the original training datasets. Crucially, our findings suggest that this approach remains viable even with limited data availability (as low as N = 25 for fine-tuning), thus broadening the application of brain age estimation to more diverse clinical contexts and patient populations. By making these models publicly available, we aim to provide the scientific community with a versatile toolkit, promoting further research in brain age prediction and related areas.


Assuntos
Encéfalo , Rememoração Mental , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Encéfalo/diagnóstico por imagem , Difusão , Neuroimagem , Aprendizado de Máquina
12.
Lab Chip ; 24(7): 1867-1874, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38487919

RESUMO

Microfluidic lab-on-a-chip technologies enable the analysis and manipulation of small fluid volumes and particles at small scales and the control of fluid flow and transport processes at the microscale, leading to the development of new methods to address a broad range of scientific and medical challenges. Microfluidic and lab-on-a-chip technologies have made a noteworthy impact in basic, preclinical, and clinical research, especially in hematology and vascular biology due to the inherent ability of microfluidics to mimic physiologic flow conditions in blood vessels and capillaries. With the potential to significantly impact translational research and clinical diagnostics, technical issues and incentive mismatches have stymied microfluidics from fulfilling this promise. We describe how accessibility, usability, and manufacturability of microfluidic technologies should be improved and how a shift in mindset and incentives within the field is also needed to address these issues. In this report, we discuss the state of the microfluidic field regarding current limitations and propose future directions and new approaches for the field to advance microfluidic technologies closer to translation and clinical use. While our report focuses on using blood as the prototypical biofluid sample, the proposed ideas and research directions can be extrapolated to other areas of hematology, oncology, biology, and medicine.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Microfluídica/métodos , Técnicas Analíticas Microfluídicas/métodos , Dispositivos Lab-On-A-Chip , Pesquisa Translacional Biomédica
14.
Exp Mol Med ; 56(3): 583-599, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38424192

RESUMO

Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.


Assuntos
Tendinopatia , Tendões , Camundongos , Animais , Humanos , Tendões/patologia , Tendinopatia/etiologia , Tendinopatia/patologia , Inflamação/patologia , RNA , Citocinas
15.
Am J Sports Med ; 52(4): 977-986, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38384192

RESUMO

BACKGROUND: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint. PURPOSE: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score. RESULTS: All patient-reported outcome measures improved (P < .0001) up to 2 years after surgery. Apart from the significant increase (P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life (P = .010) and Sport and Recreation (P < .001), as well as a greater knee extensor strength LSI (P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill (P = .027), there were no other MRI-based differences (P > .05). CONCLUSION: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes.


Assuntos
Cartilagem Articular , Traumatismos do Joelho , Osteoartrite , Humanos , Condrócitos/transplante , Qualidade de Vida , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/cirurgia , Cartilagem Articular/lesões , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Traumatismos do Joelho/cirurgia , Transplante Autólogo/métodos , Dor , Seguimentos
16.
Gut ; 73(5): 751-769, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38331563

RESUMO

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.


Assuntos
Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , Doença Pulmonar Obstrutiva Crônica/etiologia , Pulmão/metabolismo , Pulmão/patologia , Pneumonia/etiologia , Inflamação/metabolismo , Carboidratos/farmacologia
17.
Protein Expr Purif ; 217: 106442, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38336119

RESUMO

A novel tandem affinity tag is presented that enables the use of cation exchange resins for initial affinity purification, followed by an additional column step for enhanced purity and affinity tag self-removal. In this method, the highly charged heparin-binding tag binds strongly and selectively to either a strong or weak cation exchange resin based on electrostatic interactions, effectively acting as an initial affinity tag. Combining the heparin-binding tag (HB-tag) with the self-removing iCapTag™ provides a means for removing both tags in a subsequent self-cleaving step. The result is a convenient platform for the purification of diverse tagless proteins with a range of isoelectric points and molecular weights. In this work, we demonstrate a dual column process in which the tagged protein of interest is first captured from an E. coli cell lysate using a cation exchange column via a fused heparin-binding affinity tag. The partially purified protein is then diluted and loaded onto an iCapTag™ split-intein column, washed, and then incubated overnight to release the tagless target protein from the bound tag. Case studies are provided for enhanced green fluorescent protein (eGFP), beta galactosidase (ßgal), maltose binding protein (MBP) and beta lactamase (ßlac), where overall purity and host cell DNA clearance is provided. Overall, the proposed dual column process is shown to be a scalable platform technology capable of accessing both the high dynamic binding capacity of ion exchange resins and the high selectivity of affinity tags for the purification of recombinant proteins.


Assuntos
Escherichia coli , Heparina , Proteínas Recombinantes de Fusão/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/química , Cromatografia de Afinidade/métodos , Heparina/metabolismo
19.
Sci Rep ; 14(1): 22, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167893

RESUMO

For complex and multi-layered clastic oil reservoir formations, modeling lithofacies and petrophysical parameters is essential for reservoir characterization, history matching, and uncertainty quantification. This study introduces a real oilfield case study that conducted high-resolution geostatistical modeling of 3D lithofacies and petrophysical properties for rapid and reliable history matching of the Luhais oil reservoir in southern Iraq. For capturing the reservoir's tidal depositional setting using data collected from 47 wells, the lithofacies distribution (sand, shaly sand, and shale) of a 3D geomodel was constructed using sequential indicator simulation (SISIM). Based on the lithofacies modeling results, 50 sets of porosity and permeability distributions were generated using sequential Gaussian simulation (SGSIM) to provide insight into the spatial geological uncertainty and stochastic history matching. For each rock type, distinct variograms were created in the 0° azimuth direction, representing the shoreface line. The standard deviation between every pair of spatial realizations justified the number of variograms employed. An upscaled version of the geomodel, incorporating the lithofacies, permeability, and porosity, was used to construct a reservoir-flow model capable of providing rapid, accurate, and reliable production history matching, including well and field production rates.

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