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1.
PLoS One ; 19(5): e0294839, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768148

RESUMO

Rare species are often considered inferior competitors due to occupancy of small ranges, specific habitats, and small local populations. However, the phylogenetic relatedness and rarity level (level 1-7 and common) of interacting species in plant-plant interactions are not often considered when predicting the response of rare plants in a biotic context. We used a common garden of 25 species of Tasmanian Eucalyptus, to differentiate non-additive patterns in the biomass of rare versus common species when grown in mixtures varying in phylogenetic relatedness and rarity. We demonstrate that rare species maintain progressively positive non-additive responses in biomass when interacting with phylogenetically intermediate, less rare and common species. This trend is not reflected in common species that out-performed in monocultures compared to mixtures. These results offer predictability as to how rare species' productivity will respond within various plant-plant interactions. However, species-specific interactions, such as those involving E. globulus, yielded a 97% increase in biomass compared to other species-specific interaction outcomes. These results are important because they suggest that plant rarity may also be shaped by biotic interactions, in addition to the known environmental and population factors normally used to describe rarity. Rare species may utilize potentially facilitative interactions with phylogenetically intermediate and common species to escape the effects of limiting similarity. Biotically mediated increases in rare plant biomass may have subsequent effects on the competitive ability and geographic occurrence of rare species, allowing rare species to persist at low abundance across plant communities. Through the consideration of species rarity and evolutionary history, we can more accurately predict plant-plant interaction dynamics to preserve unique ecosystem functions and fundamentally challenge what it means to be "rare".


Assuntos
Biomassa , Eucalyptus , Filogenia , Eucalyptus/crescimento & desenvolvimento , Eucalyptus/genética , Ecossistema , Evolução Biológica , Especificidade da Espécie , Plantas/classificação
2.
JCI Insight ; 9(8)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502186

RESUMO

BACKGROUNDSurvivors of pneumonia, including SARS-CoV-2 pneumonia, are at increased risk for cognitive dysfunction and dementia. In rodent models, cognitive dysfunction following pneumonia has been linked to the systemic release of lung-derived pro-inflammatory cytokines. Microglia are poised to respond to inflammatory signals from the circulation, and their dysfunction has been linked to cognitive impairment in murine models of dementia and in humans.METHODSWe measured levels of 55 cytokines and chemokines in bronchoalveolar lavage fluid and plasma from 341 patients with respiratory failure and 13 healthy controls, including 93 unvaccinated patients with COVID-19 and 203 patients with other causes of pneumonia. We used flow cytometry to sort neuroimmune cells from postmortem brain tissue from 5 patients who died from COVID-19 and 3 patients who died from other causes for single-cell RNA-sequencing.RESULTSMicroglia from patients with COVID-19 exhibited a transcriptomic signature suggestive of their activation by circulating pro-inflammatory cytokines. Peak levels of pro-inflammatory cytokines were similar in patients with pneumonia irrespective of etiology, but cumulative cytokine exposure was higher in patients with COVID-19. Treatment with corticosteroids reduced expression of COVID-19-specific cytokines.CONCLUSIONProlonged lung inflammation results in sustained elevations in circulating cytokines in patients with SARS-CoV-2 pneumonia compared with those with pneumonia secondary to other pathogens. Microglia from patients with COVID-19 exhibit transcriptional responses to inflammatory cytokines. These findings support data from rodent models causally linking systemic inflammation with cognitive dysfunction in pneumonia and support further investigation into the role of microglia in pneumonia-related cognitive dysfunction.FUNDINGSCRIPT U19AI135964, UL1TR001422, P01AG049665, P01HL154998, R01HL149883, R01LM013337, R01HL153122, R01HL147290, R01HL147575, R01HL158139, R01ES034350, R01ES027574, I01CX001777, U01TR003528, R21AG075423, T32AG020506, F31AG071225, T32HL076139.


Assuntos
COVID-19 , Citocinas , Microglia , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/complicações , Microglia/metabolismo , Microglia/imunologia , Citocinas/metabolismo , Citocinas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Pulmão/metabolismo , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/metabolismo , Adulto , Encéfalo/metabolismo , Encéfalo/imunologia , Encéfalo/patologia
3.
Sensors (Basel) ; 24(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38339514

RESUMO

A large portion of the pipe infrastructure used in the chemical processing industry is susceptible to corrosion under insulation (CUI). Eddy current-based magnetic sensing is one of the methods that can be used as an early detector of this corrosion. However, the large sensor-to-pipe distances used in this method, due to the presence of insulation, limits the sensitivity to corrosion. This paper will describe the development of instrumentation and methods based on eddy current sensing with thin-film magnetic sensors. In particular, it focuses on the influence of the sensor angle relative to the radial magnetic field. The influence of this parameter on the amplitude of the measured signal was investigated by both finite element simulations and experimental observations. The measured magnetic field was found to be highly sensitive to small changes in sensor angle, with the estimated depth of a defect changing at a rate of 11.2 mm/degree of sensor rotation for small angles. It is also shown that a sensor aligned with the radial direction should be avoided, with an optimal sensor angle between 0.5 and 4 degrees. With the sensor in this angle range, the simulations have shown it should be possible to resolve the depth of corrosion to a resolution of 0.1 mm.

4.
Philos Trans A Math Phys Eng Sci ; 382(2269): 20230052, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342208

RESUMO

Rapid environmental change, natural resource overconsumption and increasing concerns about ecological sustainability have led to the development of 'Essential Variables' (EVs). EVs are harmonized data products to inform policy and to enable effective management of natural resources by monitoring global changes. Recent years have seen the instigation of new EVs beyond those established for climate, oceans and biodiversity (ECVs, EOVs and EBVs), including Essential Geodiversity Variables (EGVs). EGVs aim to consistently quantify and monitor heterogeneity of Earth-surface and subsurface abiotic features, including geology, geomorphology, hydrology and pedology. Here we assess the status and future development of EGVs to better incorporate geodiversity into policy and sustainable management of natural resources. Getting EGVs operational requires better consensus on defining geodiversity, investments into a governance structure and open platform for curating the development of EGVs, advances in harmonizing in situ measurements and linking heterogeneous databases, and development of open and accessible computational workflows for global digital mapping using machine-learning techniques. Cross-disciplinary collaboration and partnerships with governmental and private organizations are needed to ensure the successful development and uptake of EGVs across science and policy. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Clima
5.
6.
Nat Microbiol ; 8(12): 2406-2419, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37973868

RESUMO

Understanding drivers of terrestrial fungal communities over large scales is an important challenge for predicting the fate of ecosystems under climate change and providing critical ecological context for bioengineering plant-microbe interactions in model systems. We conducted an extensive molecular and microscopy field study across the contiguous United States measuring natural variation in the Populus fungal microbiome among tree species, plant niche compartments and key symbionts. Our results show clear biodiversity hotspots and regional endemism of Populus-associated fungal communities explained by a combination of climate, soil and geographic factors. Modelling climate change impacts showed a deterioration of Populus mycorrhizal associations and an increase in potentially pathogenic foliar endophyte diversity and prevalence. Geographic differences among these symbiont groups in their sensitivity to environmental change are likely to influence broader forest health and ecosystem function. This dataset provides an above- and belowground atlas of Populus fungal biodiversity at a continental scale.


Assuntos
Micorrizas , Populus , Árvores/microbiologia , Ecossistema , Populus/microbiologia , Biodiversidade
7.
J Anim Ecol ; 92(12): 2309-2322, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37859560

RESUMO

Biodiversity-stability relationships have frequently been studied in ecology, with the recent integration of traits to explain community stability over time. Classical theory underlying the biodiversity-stability relationship posits that different species' responses to the environment should stabilise community-level properties (e.g. biomass or abundance) through compensatory dynamics. However, functional response traits, which aim to predict how species respond to environmental change, are still rarely integrated into studies of ecological stability. Such traits should mechanistically drive community stability, both in terms of community abundance (functional variability) and composition (compositional variability). In turn, whether and how functional or compositional stability scales to affect temporal variation in functional effect traits (a proxy for ecosystem functioning) remains largely unknown, but is key to consistent ecosystem functioning under environmental change. Here, we explore the diversity-stability relationship in bird communities using annual survey data across 98 sites in central Romania, in combination with global trait databases and structural equation models. We show that higher response trait diversity promotes compositional variability directly, and functional variability indirectly via species asynchrony. In turn, functional variability impacts the temporal stability of effect trait diversity. Multiple facets of diversity and community stability differ between natural forests and agricultural or human-dominated survey sites, and the relationship between response diversity and functional variability is mediated by land cover. Further integration of response-and-effect trait frameworks into studies of community stability will enhance understanding of the drivers of biodiversity change, allowing targeted conservation decision-making with a focus on stable ecosystem functioning in the face of global environmental change.


Assuntos
Biodiversidade , Ecossistema , Animais , Humanos , Romênia , Florestas , Aves
8.
bioRxiv ; 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37546860

RESUMO

Neurological impairment is the most common finding in patients with post-acute sequelae of COVID-19. Furthermore, survivors of pneumonia from any cause have an elevated risk of dementia1-4. Dysfunction in microglia, the primary immune cell in the brain, has been linked to cognitive impairment in murine models of dementia and in humans5. Here, we report a transcriptional response in human microglia collected from patients who died following COVID-19 suggestive of their activation by TNF-α and other circulating pro-inflammatory cytokines. Consistent with these findings, the levels of 55 alveolar and plasma cytokines were elevated in a cohort of 341 patients with respiratory failure, including 93 unvaccinated patients with COVID-19 and 203 patients with other causes of pneumonia. While peak levels of pro-inflammatory cytokines were similar in patients with pneumonia irrespective of etiology, cumulative cytokine exposure was higher in patients with COVID-19. Corticosteroid treatment, which has been shown to be beneficial in patients with COVID-196, was associated with lower levels of CXCL10, CCL8, and CCL2-molecules that sustain inflammatory circuits between alveolar macrophages harboring SARS-CoV-2 and activated T cells7. These findings suggest that corticosteroids may break this cycle and decrease systemic exposure to lung-derived cytokines and inflammatory activation of microglia in patients with COVID-19.

10.
Am J Med ; 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37220832

RESUMO

BACKGROUND: Persistent multi-organ symptoms after coronavirus disease 2019 (COVID-19) have been termed "long COVID" or "post-acute sequelae of SARS-CoV-2 infection." The complexity of these clinical manifestations posed challenges early in the pandemic as different ambulatory models formed out of necessity to manage the influx of patients. Little is known about the characteristics and outcomes of patients seeking care at multidisciplinary post-COVID centers. METHODS: We performed a retrospective cohort study of patients evaluated at our multidisciplinary comprehensive COVID-19 center in Chicago, Ill, between May 2020 and February 2022. We analyzed specialty clinic utilization and clinical test results according to severity of acute COVID-19. RESULTS: We evaluated 1802 patients a median of 8 months from acute COVID-19 onset, including 350 post-hospitalization and 1452 non-hospitalized patients. Patients were seen in 2361 initial visits in 12 specialty clinics, with 1151 (48.8%) in neurology, 591 (25%) in pulmonology, and 284 (12%) in cardiology. Among the patients tested, 742/878 (85%) reported decreased quality of life, 284/553 (51%) had cognitive impairment, 195/434 (44.9%) had alteration of lung function, 249/299 (83.3%) had abnormal computed tomography chest scans, and 14/116 (12.1%) had elevated heart rate on rhythm monitoring. Frequency of cognitive impairment and pulmonary dysfunction was associated with severity of acute COVID-19. Non-hospitalized patients with positive SARS-CoV-2 testing had findings similar to those with negative or no test results. CONCLUSIONS: The experience at our multidisciplinary comprehensive COVID-19 center shows common utilization of multiple specialists by long COVID patients, who harbor frequent neurologic, pulmonary, and cardiologic abnormalities. Differences in post-hospitalization and non-hospitalized groups suggest distinct pathogenic mechanisms of long COVID in these populations.

11.
J Med Internet Res ; 25: e43127, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37023418

RESUMO

BACKGROUND: High levels of seamless, bidirectional health information exchange continue to be broadly limited among provider groups despite the vast array of benefits that interoperability entails for patient care and the many persistent efforts across the health care ecosystem directed at advancing interoperability. As provider groups seek to act in their strategic best interests, they are often interoperable and exchange information in certain directions but not others, leading to the formation of asymmetries. OBJECTIVE: We aimed to examine the correlation at the provider group level between the distinct directions of interoperability with regard to sending health information and receiving health information, to describe how this correlation varies across provider group types and provider group sizes, and to analyze the symmetries and asymmetries that arise in the exchange of patient health information across the health care ecosystem as a result. METHODS: We used data from the Centers for Medicare & Medicaid Services (CMS), which included interoperability performance information for 2033 provider groups within the Quality Payment Program Merit-based Incentive Payment System and maintained distinct performance measures for sending health information and receiving health information. In addition to compiling descriptive statistics, we also conducted a cluster analysis to identify differences among provider groups-particularly with respect to symmetric versus asymmetric interoperability. RESULTS: We found that the examined directions of interoperability-sending health information and receiving health information-have relatively low bivariate correlation (0.4147) with a significant number of observations exhibiting asymmetric interoperability (42.5%). Primary care providers are generally more likely to exchange information asymmetrically than specialty providers, being more inclined to receive health information than to send health information. Finally, we found that larger provider groups are significantly less likely to be bidirectionally interoperable than smaller groups, although both are asymmetrically interoperable at similar rates. CONCLUSIONS: The adoption of interoperability by provider groups is more nuanced than traditionally considered and should not be seen as a binary determination (ie, to be interoperable or not). Asymmetric interoperability-and its pervasive presence among provider groups-reiterates how the manner in which provider groups exchange patient health information is a strategic choice and may pose similar implications and potential harms as the practice of information blocking has in the past. Differences in the operational paradigms among provider groups of varying types and sizes may explain their varying extents of health information exchange for sending and receiving health information. There continues to remain substantial room for improvement on the path to achieving a fully interoperable health care ecosystem, and future policy efforts directed at advancing interoperability should consider the practice of being asymmetrically interoperable among provider groups.


Assuntos
Troca de Informação em Saúde , Idoso , Humanos , Estados Unidos , Medicare , Ecossistema , Atenção à Saúde
12.
Trends Ecol Evol ; 38(8): 736-748, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37003934

RESUMO

Geodiversity - the abiotic heterogeneity of Earth's (sub)surface - is gaining recognition for its ecological links to biodiversity. However, theoretical and conceptual knowledge of geodiversity-trait diversity relationships is currently lacking and can improve understanding of abiotic drivers of community assembly. Here we synthesise the state of knowledge of these relationships. We find that some components of geodiversity (e.g., topographic heterogeneity) elicit strong trait responses, whereas other components (e.g., substrate heterogeneity) have marginal effects in driving trait distributions. However, current knowledge is lacking in key aspects, including geodiversity's effect on trait-specific diversity and intraspecific variation. We call for the explicit inclusion of geodiversity when relating environmental drivers to trait diversity, taking advantage of the increasing availability of trait and geodiversity data.


Assuntos
Biodiversidade , Fenótipo
13.
Prev Sci ; 24(1): 173-185, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36223044

RESUMO

Childhood adversity and toxic stress have been associated with poor mental and physical health. This study examined if Parent Connext, a program that integrates adversity screening and parent coaching by co-located specialists within pediatric primary care, had an impact on health care utilization. This stepped wedge cluster randomized controlled trial evaluated Parent Connext across six pediatric primary care practices. All practices (clusters) were in the control period during year 1. Three practices were randomized to begin the Parent Connext intervention in year 2, and three practices were randomized to begin in year 3. Medical records of all patients under age 8 treated at these practices during these 3 years were queried retrospectively for participant-level primary outcomes (sick visits, emergency department visits, hospitalizations) and secondary outcomes (well-child and immunization adherence, referrals). The study sample included 27,419 patients followed for an average 1.39 (SD = 0.66) years in the control period and 1.07 (SD = 0.60) years in the intervention period. During the intervention period, patients had significantly fewer sick visits (IRR = 0.91, p < 0.001) which aligned with our hypothesis, decreased odds of well-child visit adherence (OR = 0.88, p < 0.001) which was unexpected, and increased odds of receiving a referral (OR = 1.45, p < 0.001). The odds of an emergency department visit, hospitalization, and 2-year immunization adherence did not differ between periods. Parent Connext resulted in a significant reduction in child sick visits, highlighting the potential benefit of two-generation approaches to pediatric care for child health.


Assuntos
Saúde da Criança , Tutoria , Humanos , Criança , Estudos Retrospectivos , Pais , Atenção Primária à Saúde
15.
Commun Biol ; 5(1): 1213, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357488

RESUMO

Climate change is having profound effects on species distributions and is likely altering the distribution of genetic variation across landscapes. Maintaining population genetic diversity is essential for the survival of species facing rapid environmental change, and variation loss will further ecological and evolutionary change. We used trait values of spring foliar leaf-out phenology of 400 genotypes from three geographically isolated populations of Populus angustifolia grown under common conditions, in concert with stacked species distribution modeling, to ask: (a) How will climate change alter phenological variation across the P. angustifolia species-range, and within populations; and (b) will the distribution of phenological variation among and within populations converge (become more similar) in future climatic conditions? Models predicted a net loss of phenological variation in future climate scenarios on 20-25% of the landscape across the species' range, with the trailing edge population losing variation on as much as 47% of the landscape. Our models also predicted that population's phenological trait distributions will become more similar over time. This stacked distribution model approach allows for the identification of areas expected to experience the greatest loss of genetically based functional trait variation and areas that may be priorities to conserve as future genetic climate refugia.


Assuntos
Mudança Climática , Populus , Folhas de Planta/genética , Estações do Ano , Populus/genética , Fenótipo
16.
Ann Clin Biochem ; 59(6): 410-419, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36154484

RESUMO

BACKGROUND: Cardiac toxicity resulting in long-term complications are recognised side effect of anthracycline-based chemotherapy used in the treatment of breast cancer. Current management modality involves measurement of left ventricular ejection fraction which has inherent limitations due to its dependence on haemodynamic conditions, and inability to detect subclinical changes in left ventricular systolic function. This study aimed to evaluate changes in the concentration of cardiac biomarkers present in serum as indicators of cardiac toxicity in breast cancer patients undergoing Epirubicin-based chemotherapy. METHODS: Eighty-one breast cancer patients elected to undergo Epirubicin chemotherapy were recruited. Blood samples taken at baseline, mid-cycle and final cycle of chemotherapy were analysed for hs-cTnT, NT-proBNP and sST2. Longitudinal changes in biomarkers were compared to pre-treatment baseline values and between treatment groups. RESULTS: At mid-cycle, mean cumulative dose of 265 mg/m2 of FEC elicited a 270% change in hs-cTnT but with no significant change in NT-proBNP and sST2. At the final cycle, mean cumulative dose of 340 mg/m2 of FEC elicited a 565% change in hs-cTnT with no significant change in NT-proBNP and sST2. There was progressive increase in hs-cTnT from baseline with increasing cumulative dose of Epirubicin. At mid-cycle, median hs-cTnT was 7.4 ng/L (IQR: 5.6-9.3) vs. baseline of 2.0 ng/L (IQR: 2.0-4.7) p < 0.001. Final cycle median hs-cTnT versus baseline was 13.3 ng/L (IQR: 8.2-22.1) vs. 2.0 ng/L (IQR: 2.0-4.7) p < 0.001. CONCLUSION: Serial measurement of hs-cTnT but not NT-proBNP or sST2 during Epirubicin chemotherapy has important value in the early determination cardiomyocytes damage.


Assuntos
Neoplasias da Mama , Peptídeo Natriurético Encefálico , Humanos , Feminino , Troponina T , Cardiotoxicidade , Epirubicina/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Volume Sistólico , Função Ventricular Esquerda , Fragmentos de Peptídeos , Biomarcadores
17.
PLoS One ; 17(9): e0274892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36121872

RESUMO

Identifying and predicting how species ranges will shift in response to climate change is paramount for conservation and restoration. Ecological niche models are the most common method used to estimate potential distributions of species; however, they traditionally omit knowledge of intraspecific variation that can allow populations to respond uniquely to change. Here, we aim to test how population X environment relationships influence predicted suitable geographic distributions by comparing aggregated population-level models with species-level model predictions of suitable habitat within population ranges and across the species' range. We also test the effect of two variable selection methods on these predictions-both addressing the possibility of local adaptation: Models were built with (a) a common set, and number, of predictors and, (b) a unique combination and number of predictors specific to each group's training extent. Our study addresses the overarching hypothesis that populations have unique environmental niches, and specifically that (1) species-level models predict more suitable habitat within the ranges of genetic populations than individual models built from those groups, particularly when compared models are built with the same set of environmental predictors; and (2) aggregated genetic population models predict more suitable habitat across the species' range than the species-level model, an = d this difference will increase when models are trained with individualized predictors. We found the species models predicted more habitat within population ranges for two of three genetic groups regardless of variable selection, and that aggregated population models predicted more habitat than species' models, but that individualized predictors increased this difference. Our study emphasizes the extent to which changes to model predictions depend on the inclusion of genetic information and on the type and selection of predictors. Results from these modeling decisions can have broad implications for predicting population-level ecological and evolutionary responses to climate change.


Assuntos
Ecossistema , Árvores , Aclimatação , Adaptação Fisiológica , Mudança Climática
18.
Diabetologia ; 65(9): 1541-1554, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35687178

RESUMO

AIMS/HYPOTHESIS: We have previously shown that diabetes causes pericyte dysfunction, leading to loss of vascular integrity and vascular cognitive impairment and dementia (VCID). Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), used in managing type 2 diabetes mellitus, improve the cognitive function of diabetic individuals beyond glycaemic control, yet the mechanism is not fully understood. In the present study, we hypothesise that GLP-1 RAs improve VCID by preventing diabetes-induced pericyte dysfunction. METHODS: Mice with streptozotocin-induced diabetes and non-diabetic control mice received either saline (NaCl 154 mmol/l) or exendin-4, a GLP-1 RA, through an osmotic pump over 28 days. Vascular integrity was assessed by measuring cerebrovascular neovascularisation indices (vascular density, tortuosity and branching density). Cognitive function was evaluated with Barnes maze and Morris water maze. Human brain microvascular pericytes (HBMPCs), were grown in high glucose (25 mmol/l) and sodium palmitate (200 µmol/l) to mimic diabetic conditions. HBMPCs were treated with/without exendin-4 and assessed for nitrative and oxidative stress, and angiogenic and blood-brain barrier functions. RESULTS: Diabetic mice treated with exendin-4 showed a significant reduction in all cerebral pathological neovascularisation indices and an improved blood-brain barrier (p<0.05). The vascular protective effects were accompanied by significant improvement in the learning and memory functions of diabetic mice compared with control mice (p<0.05). Our results showed that HBMPCs expressed the GLP-1 receptor. Diabetes increased GLP-1 receptor expression and receptor nitration in HBMPCs. Stimulation of HBMPCs with exendin-4 under diabetic conditions decreased diabetes-induced vascular inflammation and oxidative stress, and restored pericyte function (p<0.05). CONCLUSIONS/INTERPRETATION: This study provides novel evidence that brain pericytes express the GLP-1 receptor, which is nitrated under diabetic conditions. GLP-1 receptor activation improves brain pericyte function resulting in restoration of vascular integrity and BBB functions in diabetes. Furthermore, the GLP-1 RA exendin-4 alleviates diabetes-induced cognitive impairment in mice. Restoration of pericyte function in diabetes represents a novel therapeutic target for diabetes-induced cerebrovascular microangiopathy and VCID.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Pericitos , Animais , Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Exenatida/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Camundongos , Pericitos/metabolismo
20.
Frontline Gastroenterol ; 13(1): 73-76, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34966534

RESUMO

Recent interim guidance from the British Society of Gastroenterology, aligned to historical paediatric practice, advises a no-biopsy protocol (NBP) for adults with high anti-tissue transglutaminase (tTG-IgA) titres and other clinical factors. A 7-year retrospective review identified 433 patients with positive tTG-IgA. Of these 433, 98 (23%) fulfilled the high titre criteria for an NBP which may have reduced endoscopic burden on the service. A high titre versus low titre translated in a 95% versus 75% histological confirmation of coeliac disease (p<0.01). The addition of anti-endomysial antibody analyses impacted minimally on these predictive rates. Our data support an NBP approach for selected patients. Of concern, however, was the finding that a third of patients with positive titres were not referred for a biopsy despite national guidance at the time advocating it. A clear message needs to be transmitted that the NBP is only for those with high titre, as opposed to any tTG-IgA positivity.

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