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1.
Perfusion ; : 2676591241264119, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900997

ABSTRACT

This technical report describes the successful transition from dual lumen, single site veno-venous extracorporeal membrane oxygenation ((dl)V-V ECMO) to single lumen, dual site veno-pulmonary (V-P) ECMO, and subsequently to dual lumen, single site (dl)V-P ECMO involving temporary placement of two cannulas in the main pulmonary artery. No complications were observed during these transitions. This technique could address concerns related to cannula exchanges in VP ECMO. However, caution is warranted and constant monitoring of cannula position using real-time imaging is required when using this technique due to the risk profile.

2.
Am J Bot ; : e16362, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943238

ABSTRACT

PREMISE: Theory predicts and empirical studies have shown that ecologically manipulated communities with high species diversity are resistant to invasion, but do these predictions and results hold true when applied to highly competitive invaders in natural communities? Few studies of diversity-mediated invasion resistance have measured both invasion resistance and invader impact in the same study. METHODS: We used a two-year field experiment to test: (1) diversity-mediated competitive resistance to patch expansion by the grass, Microstegium vimineum; and (2) the competitive effect of M. vimineum on resident plant diversity. We examined responses of M. vimineum to two native plant density-reduction treatments that had opposite effects on species diversity: (1) reducing species richness via the removal of rare species; and (2) reducing dominance by reducing the density of the dominant resident species. We examined the effects of M. vimineum reduction by pre-emergent herbicide on resident diversity in the second year of the study. RESULTS: Neither rare species removal nor dominant species reduction significantly increased M. vimineum density (relative growth rate). The pre-emergent herbicide dramatically reduced M. vimineum in year 2 of the study, but not most resident plants, which were perennials and indirectly benefited from the herbicide at a more productive site, presumably due to reduced competition from M. vimineum. CONCLUSIONS: Diversity-mediated resistance did not effectively deter invasion by a highly competitive invader. In the case of M. vimineum and at more productive sites, it would appear that nearly complete removal of this invader is necessary to preserve plant species diversity.

3.
ASAIO J ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38913958

ABSTRACT

Venopulmonary (VP) extracorporeal membrane oxygenation (ECMO) is a mode capable of supporting both pulmonary and right ventricular (RV) functions. Weaning patients from VP ECMO requires careful assessment of both RV and respiratory system recovery, which may occur at different rates. The weaning strategy described herein begins with weaning of respiratory ECMO support, followed by discontinuation of RV support. We also discuss situations in which the standard weaning strategy may require modification.

4.
ASAIO J ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38768563

ABSTRACT

This review highlights advancements in extracorporeal life support (ECLS), emphasizing the critical role of standardized terminology, particularly for extracorporeal membrane oxygenation (ECMO) in treating right ventricular and respiratory failure. Advocating for the adoption of the Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for ECLS Nomenclature guidelines, it aims to resolve communication barriers in the ECMO field. Focusing on venopulmonary (VP) ECMO utilizing central pulmonary artery (PA) access, this review details surgical approaches and introduces a terminology guide to support effective knowledge exchange and advancements in patient care.

5.
bioRxiv ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38798553

ABSTRACT

Lymphocyte activation involves a transition from quiescence and associated catabolic metabolism to a metabolic state with noted similarities to cancer cells such as heavy reliance on aerobic glycolysis for energy demands and increased nutrient requirements for biomass accumulation and cell division 1-3 . Following antigen receptor ligation, lymphocytes require spatiotemporally distinct "second signals". These include costimulatory receptor or cytokine signaling, which engage discrete programs that often involve remodeling of organelles and increased nutrient uptake or synthesis to meet changing biochemical demands 4-6 . One such signaling molecule, IL-4, is a highly pleiotropic cytokine that was first identified as a B cell co-mitogen over 30 years ago 7 . However, how IL-4 signaling mechanistically supports B cell proliferation is incompletely understood. Here, using single cell RNA sequencing we find that the cholesterol biosynthetic program is transcriptionally upregulated following IL-4 signaling during the early B cell response to influenza virus infection, and is required for B cell activation in vivo . By limiting lipid availability in vitro , we determine cholesterol to be essential for B cells to expand their endoplasmic reticulum, progress through cell cycle, and proliferate. In sum, we demonstrate that the well-known ability of IL-4 to act as a B cell growth factor is through a previously unknown rewiring of specific lipid anabolic programs, relieving sensitivity of cells to environmental nutrient availability.

7.
Nature ; 627(8004): 628-635, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38383790

ABSTRACT

Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types1. Loss of IL-10 signalling results in life-threatening inflammatory bowel disease in humans and mice-however, the exact mechanism by which IL-10 signalling subdues inflammation remains unclear2-5. Here we find that increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10 deficiency. Accordingly, genetic deletion of ceramide synthase 2 (encoded by Cers2), the enzyme responsible for VLC ceramide production, limited the exacerbated inflammatory gene expression programme associated with IL-10 deficiency both in vitro and in vivo. The accumulation of saturated VLC ceramides was regulated by a decrease in metabolic flux through the de novo mono-unsaturated fatty acid synthesis pathway. Restoring mono-unsaturated fatty acid availability to cells deficient in IL-10 signalling limited saturated VLC ceramide production and the associated inflammation. Mechanistically, we find that persistent inflammation mediated by VLC ceramides is largely dependent on sustained activity of REL, an immuno-modulatory transcription factor. Together, these data indicate that an IL-10-driven fatty acid desaturation programme rewires VLC ceramide accumulation and aberrant activation of REL. These studies support the idea that fatty acid homeostasis in innate immune cells serves as a key regulatory node to control pathologic inflammation and suggests that 'metabolic correction' of VLC homeostasis could be an important strategy to normalize dysregulated inflammation caused by the absence of IL-10.


Subject(s)
Inflammation , Interleukin-10 , Sphingolipids , Animals , Humans , Mice , Ceramides/chemistry , Ceramides/metabolism , Fatty Acids, Unsaturated/biosynthesis , Fatty Acids, Unsaturated/metabolism , Homeostasis , Immunity, Innate , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Interleukin-10/deficiency , Interleukin-10/genetics , Interleukin-10/metabolism , Proto-Oncogene Proteins c-rel , Sphingolipids/metabolism
9.
Int J Artif Organs ; 47(1): 35-40, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38053302

ABSTRACT

INTRODUCTION: Diabetic ketoacidosis (DKA) is a common clinical problem. When patients develop severe shock and/or respiratory failure, extracorporeal membrane oxygenation (ECMO) may be considered. This case series describes the clinical presentation and outcomes of patients with DKA supported with ECMO. METHODS: We conducted a retrospective and anonymized review of 15 patients with DKA who required ECMO at our institution. Demographic and ECMO-specific data were collected. Additional variables include ICU length of stay (LOS), acute kidney injury and use of continuous renal replacement therapy, disposition, and mortality. RESULTS: All ECMO cannulations were performed by an intensivist using peripheral vascular access. The majority of patients were female (73%) with a median age of 27 (IQR = 21.5-45) years. A diagnosis of diabetes mellitus (DM) prior to ECMO was present in 11 (73%) patients. Venoarterial ECMO was the initial mode used in 11 (73%) patients. The median duration of ECMO support was 7 (IQR = 6-14) days. The median ICU LOS was 12 (IQR = 8.5-20.5) days, and the median hospital LOS was 21 (IQR = 11-36.5) days. Eight patients had cardiac arrest and underwent extracorporeal cardiopulmonary resuscitation (ECPR) of which 4 (50%) patients survived to discharge. Overall, 10 (66.7%) patients were successfully weaned from ECMO and survived to discharge. CONCLUSION: This is the largest case series regarding the use of ECMO for patients with refractory shock, cardiac arrest, or respiratory failure related to DKA. The findings suggest that ECMO is a viable support option for managing these patients and has excellent outcomes, including patients with cardiac arrest.


Subject(s)
Cardiopulmonary Resuscitation , Diabetes Mellitus , Diabetic Ketoacidosis , Extracorporeal Membrane Oxygenation , Heart Arrest , Respiratory Insufficiency , Humans , Male , Female , Young Adult , Adult , Middle Aged , Extracorporeal Membrane Oxygenation/adverse effects , Diabetic Ketoacidosis/complications , Diabetic Ketoacidosis/therapy , Retrospective Studies , Heart Arrest/etiology , Heart Arrest/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Treatment Outcome , Diabetes Mellitus/etiology
10.
Perfusion ; : 2676591231210457, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37930875

ABSTRACT

The rising application of extracorporeal membrane oxygenation (ECMO) has emphasized the need for consistent and standardized terminology, especially concerning peripheral percutaneous cannulation of the pulmonary artery (PPC-PA). The Extracorporeal Life Support Organization (ELSO) Nomenclature Task Force produced the ELSO Maastricht Treaty for extracorporeal life support (ECLS) Nomenclature to address this challenge. However, adherence to nomenclature recommendations has been poor in publications describing PPC-PA. We aim to describe common nomenclature errors and provide a user-guide for abbreviations that can be used by authors, reviewers, and journal staff to ensure properadherence to standardized nomenclature in publications describing PPC-PA.

11.
bioRxiv ; 2023 May 08.
Article in English | MEDLINE | ID: mdl-37214856

ABSTRACT

Unchecked chronic inflammation is the underlying cause of many diseases, ranging from inflammatory bowel disease to obesity and neurodegeneration. Given the deleterious nature of unregulated inflammation, it is not surprising that cells have acquired a diverse arsenal of tactics to limit inflammation. IL-10 is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types; however, the exact mechanism by which IL-10 signaling subdues inflammation remains unclear. Here, we find that IL-10 signaling constrains sphingolipid metabolism. Specifically, we find increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10-deficient macrophages. Genetic deletion of CerS2, the enzyme responsible for VLC ceramide production, limited exacerbated inflammatory gene expression associated with IL-10 deficiency both in vitro and in vivo , indicating that "metabolic correction" is able to reduce inflammation in the absence of IL-10. Surprisingly, accumulation of saturated VLC ceramides was regulated by flux through the de novo mono-unsaturated fatty acid (MUFA) synthesis pathway, where addition of exogenous MUFAs could limit both saturated VLC ceramide production and inflammatory gene expression in the absence of IL-10 signaling. Together, these studies mechanistically define how IL-10 signaling manipulates fatty acid metabolism as part of its molecular anti-inflammatory strategy and could lead to novel and inexpensive approaches to regulate aberrant inflammation.

12.
Am J Bot ; 109(12): 2006-2017, 2022 12.
Article in English | MEDLINE | ID: mdl-36468545

ABSTRACT

PREMISE: Carnivorous plants are often associated with nutrient-poor soils and fires. Fire can decrease available soil nitrogen (N) and increase light availability, thus potentially favoring carnivory if prey provide N. Prey can also be a source of phosphorus (P), however, and soil P-availability often increases and competition for prey can decrease following fire. Carnivory thus might be more advantageous before fire when prey and/or soil P are more limiting. METHODS: We examined nutrient limitation of growth in a carnivorous plant, Sarracenia alata, in a wet pine savanna in southeastern Mississippi, USA. We measured growth and N:P tissue concentration responses of adult plants to a factorial arrangement of prey capture, neighbor reduction, and addition of N, P, and ash to the soil. We tested two hypotheses: (1) Prey provide N, and neighbor reduction and ash addition increase light and soil P and thus the benefit of carnivory; and (2) Prey provide P, neighbor reduction increases prey and/or P, and prey exclusion reduces growth the most when neighbors are not reduced. RESULTS: The exclusion of prey reduced growth more when neighbors were not reduced, an effect that was ameliorated slightly by the addition of P to the soil (the P-limitation hypothesis). Prey exclusion caused a decrease in tissue P when N was added to the soil. CONCLUSIONS: The results of this study with adult plants differed from those of a previous study using small juvenile plants, suggesting a shift from light limitation to P and prey limitation with increasing size.


Subject(s)
Sarraceniaceae , Phosphorus , Nitrogen/analysis , Carnivory , Nutrients , Soil , Plants
13.
Nature ; 606(7914): 585-593, 2022 06.
Article in English | MEDLINE | ID: mdl-35483404

ABSTRACT

Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA and a sustained interferon (IFN) response, all of which are recapitulated and required for pathology in the SARS-CoV-2-infected MISTRG6-hACE2 humanized mouse model of COVID-19, which has a human immune system1-20. Blocking either viral replication with remdesivir21-23 or the downstream IFN-stimulated cascade with anti-IFNAR2 antibodies in vivo in the chronic stages of disease attenuates the overactive immune inflammatory response, especially inflammatory macrophages. Here we show that SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release interleukin 1 (IL-1) and IL-18, and undergo pyroptosis, thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and the accompanying inflammatory response are necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Notably, this blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 through the production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle.


Subject(s)
COVID-19 , Inflammasomes , Macrophages , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Animals , COVID-19/pathology , COVID-19/physiopathology , COVID-19/virology , Humans , Inflammasomes/metabolism , Interleukin-1 , Interleukin-18 , Lung/pathology , Lung/virology , Macrophages/metabolism , Macrophages/pathology , Macrophages/virology , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pneumonia/metabolism , Pneumonia/virology , Pyroptosis , Receptors, IgG , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
14.
bioRxiv ; 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-34611663

ABSTRACT

Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response all of which are recapitulated and required for pathology in the SARS-CoV-2 infected MISTRG6-hACE2 humanized mouse model of COVID-19 with a human immune system 1-20 . Blocking either viral replication with Remdesivir 21-23 or the downstream IFN stimulated cascade with anti-IFNAR2 in vivo in the chronic stages of disease attenuated the overactive immune-inflammatory response, especially inflammatory macrophages. Here, we show SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release IL-1 and IL-18 and undergo pyroptosis thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and its accompanying inflammatory response is necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Remarkably, this same blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 by production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle.

15.
Int J Biochem Cell Biol ; 142: 106121, 2022 01.
Article in English | MEDLINE | ID: mdl-34808373

ABSTRACT

SSX proteins are normally restricted to spermatogenic cells, but ectopic expression can be observed in many types of human cancer. We recently demonstrated that SSX family members may contribute to tumorigenesis by modifying chromatin structure and, in specific settings, compromise chromatin stability. Here, we used normal and tumorigenic breast epithelial cell line models to further study the effect of ectopic expression of SSX2 on nuclear organization. We show that SSX2 induces the formation of a novel type of nucleoplasmic lamin bodies. Ectopic expression of SSX2 in various breast epithelial cell lines led to the formation of a previously undescribed type of intranuclear bodies containing both A and B type lamins but no other components of the nuclear lamina. SSX2-expressing cells contained a highly variable number of lamin bodies distributed throughout the nuclear space. SSX2-mediated establishment of intranuclear lamin bodies could not be linked to previous molecular interactions of SSX proteins, including polycomb proteins and the Mediator complex, but was, however, dependent on S-phase progression. These results reveal a novel interaction between SSX2 and lamins in the nucleoplasmic space. They further suggest that SSX2 promotes the formation of chromatin neighborhoods supporting the organization of lamins into nuclear bodies. We speculate that this may have implications for the organization and functional regulation of chromatin in cancer cells. Our study contributes to the further understanding of the biology of SSX proteins in tumorigenesis.


Subject(s)
Nuclear Bodies
16.
J Prev Alzheimers Dis ; 8(3): 240-248, 2021.
Article in English | MEDLINE | ID: mdl-34101779

ABSTRACT

BACKGROUND: Intranasally administered insulin has shown promise in both rodent and human studies in Alzheimer's disease; however, both effects and mechanisms require elucidation. OBJECTIVE: We assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer's disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909). DESIGN: A randomized (1:1) double-blind clinical trial. SETTING: Twelve sites across the United States. PARTICIPANTS: Adults with mild cognitive impairment or Alzheimer's disease. INTERVENTION: Participants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled. MEASUREMENTS: Changes from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer's Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale, and a memory composite. RESULTS: The insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer's disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group. CONCLUSION: Intranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin's potential as a therapeutic option for Alzheimer's disease.


Subject(s)
Alzheimer Disease/drug therapy , Biomarkers/cerebrospinal fluid , Cognition/drug effects , Cognitive Dysfunction/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , White Matter/pathology , Activities of Daily Living , Administration, Intranasal , Aged , Brain/physiopathology , Female , Humans , Image Processing, Computer-Assisted/statistics & numerical data , Insulin, Regular, Human/therapeutic use , Magnetic Resonance Imaging , Male , Neuropsychological Tests/statistics & numerical data
18.
J Community Health ; 46(6): 1069-1077, 2021 12.
Article in English | MEDLINE | ID: mdl-33907903

ABSTRACT

The goal of this study was to measure food insecurity among families with children in a low-income district of Lima, Peru and to identify the formal and informal food resources available to them that may affect their food security status. In June-July 2019, we collected data from 329 randomly selected households in Villa El Salvador (Lima, Peru). Following a mixed methods approach, we found that the percentage of households using food assistance programs (FAPs) increased with increasing levels of food insecurity, but two FAPs were heavily used by households regardless of food (in)security. The main reasons for using FAPs included financial need, already being signed up in the program, and believing that the food was of nutritional value; the main reasons for non-use were finding the program unnecessary, dislike or poor perceived quality of the food, and not being able to sign up for the program. Similarly, informal food resources, such as buying food on credit or receiving food from someone outside the household, were incrementally used with increased levels of food insecurity. Our study clarifies the relationship between level of household food insecurity and FAP use - FAPs more commonly used by food insecure households were used because of financial need, whereas the FAPs most commonly used by food secure households were those with automatic enrollment. At a programmatic level, our research highlights the need for making nutritious and preferred foods available in FAPs and standardizing the application of enrollment criteria.


Subject(s)
Food Supply , Poverty , Child , Cross-Sectional Studies , Food Insecurity , Humans , Peru
19.
Trauma Case Rep ; 30: 100373, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33299923

ABSTRACT

Cardiac injury secondary to non-penetrating trauma is more common than thought, albeit, the injury is usually minor and goes undiagnosed without significant sequelae in most cases. Blunt cardiac rupture is much rarer accounting for <0.05% of all trauma cases but lethal in most circumstances. We present a case report of a young trauma victim who presented with both right atrial rupture and traumatic atrial septal disruption (ASD) requiring extra-corporeal life support (ECLS) and surgical repair. Blunt cardiac trauma with chamber rupture and septal disruption is a devastating injury. Stopping the hemorrhage and using ECLS gave our patient time to stabilize before definitive management of her traumatic ASD.

20.
Genes Dev ; 34(23-24): 1735-1752, 2020 12 01.
Article in English | MEDLINE | ID: mdl-33184218

ABSTRACT

FGFs are key developmental regulators that engage a signal transduction cascade through receptor tyrosine kinases, prominently engaging ERK1/2 but also other pathways. However, it remains unknown whether all FGF activities depend on this canonical signal transduction cascade. To address this question, we generated allelic series of knock-in Fgfr1 and Fgfr2 mouse strains, carrying point mutations that disrupt binding of signaling effectors, and a kinase dead allele of Fgfr2 that broadly phenocopies the null mutant. When interrogated in cranial neural crest cells, we identified discrete functions for signaling pathways in specific craniofacial contexts, but point mutations, even when combined, failed to recapitulate the single or double null mutant phenotypes. Furthermore, the signaling mutations abrogated established FGF-induced signal transduction pathways, yet FGF functions such as cell-matrix and cell-cell adhesion remained unaffected, though these activities did require FGFR kinase activity. Our studies establish combinatorial roles of Fgfr1 and Fgfr2 in development and uncouple novel FGFR kinase-dependent cell adhesion properties from canonical intracellular signaling.


Subject(s)
Fibroblast Growth Factors/physiology , Gene Expression Regulation, Developmental/genetics , Signal Transduction/genetics , Animals , Cell Adhesion/genetics , Cell Death/genetics , Cells, Cultured , Mice , Mutation , Neural Crest/cytology , Protein Kinases/metabolism , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Receptors, Fibroblast Growth Factor/genetics , Receptors, Fibroblast Growth Factor/metabolism
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