RESUMO
Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.
Assuntos
COVID-19/imunologia , Citocinas/imunologia , Imunoglobulina G/imunologia , Receptores de IgG/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , COVID-19/metabolismo , COVID-19/virologia , Criança , Citocinas/metabolismo , Feminino , Glicosilação , Humanos , Imunoglobulina G/metabolismo , Interleucina-6 , Masculino , Pessoa de Meia-Idade , Receptores de IgG/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Antibodies result from the competition of B cell lineages evolving under selection for improved antigen recognition, a process known as affinity maturation. High-affinity antibodies to pathogens such as HIV, influenza, and SARS-CoV-2 are frequently reported to arise from B cells whose receptors, the precursors to antibodies, are encoded by particular immunoglobulin alleles. This raises the possibility that the presence of particular germline alleles in the B cell repertoire is a major determinant of the quality of the antibody response. Alternatively, initial differences in germline alleles' propensities to form high-affinity receptors might be overcome by chance events during affinity maturation. We first investigate these scenarios in simulations: when germline-encoded fitness differences are large relative to the rate and effect size variation of somatic mutations, the same germline alleles persistently dominate the response of different individuals. In contrast, if germline-encoded advantages can be easily overcome by subsequent mutations, allele usage becomes increasingly divergent over time, a pattern we then observe in mice experimentally infected with influenza virus. We investigated whether affinity maturation might nonetheless strongly select for particular amino acid motifs across diverse genetic backgrounds, but we found no evidence of convergence to similar CDR3 sequences or amino acid substitutions. These results suggest that although germline-encoded specificities can lead to similar immune responses between individuals, diverse evolutionary routes to high affinity limit the genetic predictability of responses to infection and vaccination.
Assuntos
COVID-19 , Animais , Camundongos , COVID-19/genética , SARS-CoV-2/genética , Anticorpos , Alelos , Células GerminativasRESUMO
Although all-trans-retinoic acid (atRA) is a key regulator of intestinal immunity, its role in colorectal cancer (CRC) is unknown. We found that mice with colitis-associated CRC had a marked deficiency in colonic atRA due to alterations in atRA metabolism mediated by microbiota-induced intestinal inflammation. Human ulcerative colitis (UC), UC-associated CRC, and sporadic CRC specimens have similar alterations in atRA metabolic enzymes, consistent with reduced colonic atRA. Inhibition of atRA signaling promoted tumorigenesis, whereas atRA supplementation reduced tumor burden. The benefit of atRA treatment was mediated by cytotoxic CD8(+) T cells, which were activated due to MHCI upregulation on tumor cells. Consistent with these findings, increased colonic expression of the atRA-catabolizing enzyme, CYP26A1, correlated with reduced frequencies of tumoral cytotoxic CD8(+) T cells and with worse disease prognosis in human CRC. These results reveal a mechanism by which microbiota drive colon carcinogenesis and highlight atRA metabolism as a therapeutic target for CRC.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/imunologia , Microbiota/imunologia , Tretinoína/metabolismo , Animais , Linfócitos T CD8-Positivos/metabolismo , Carcinogênese/imunologia , Colo/imunologia , Colo/metabolismo , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ácido Retinoico 4 Hidroxilase/metabolismo , Transdução de Sinais/imunologia , Regulação para Cima/imunologiaRESUMO
BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.
Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Pele , População do Sudeste Asiático , Humanos , Estudo de Associação Genômica Ampla , Fenótipo , VietnãRESUMO
BACKGROUND: Acutely highlighted during the COVID-19 pandemic, the tenuousness of the blood supply continues to be a lynchpin of the most important medical procedures. Online advertisements have become a mainstay in donor recruitment. We set out to determine the effectiveness of online search ads and variations thereof on blood donations with an emphasis on first-time donors. STUDY DESIGN AND METHODS: From September 01, 2022 through March 31, 2023, we performed a campaign comparison experiment through a major search-ads platform with two distinct messages: one altruistic ("Altruistic") and one with a prospect of rewards ("Promotion"). We developed a method to track donation outcomes and associated them with impressions, click-throughs, and conversions. We compared the performance of the Altruistic and Promotion arms to a control group that was not associated with any search-ads ("Baseline"). RESULTS: Analyzing 34,157 donations during the study period, the Promotion group, and not Altruistic, had a significant difference of first-time donors over Baseline (24% vs. 12%, p = 7e-6). We analyzed 49,305 appointments and discovered that appointments made from the Altruistic arm resulted in a significantly higher percentage of donations when compared to Baseline (57% vs. 53%, p = .009); however, the Promotion group had a higher percentage of donations from first-time donors when compared to Baseline (12% vs. 8%, p = .006). CONCLUSION: We developed a method for determining the effectiveness of online search ads on donation outcomes. Rewards/promotions messaging was most effective at recruiting first-time donors. Our methodology is generalizable to different blood centers to explore messaging effectiveness among their unique communities.
Assuntos
Publicidade , Altruísmo , Doadores de Sangue , COVID-19 , Humanos , Publicidade/métodos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Masculino , SARS-CoV-2 , Pandemias , Internet , Adulto , Seleção do Doador/métodosRESUMO
Alzheimer's disease is one of the causes associated with the early stages of dementia. Nowadays, the main treatment available is to inhibit the actions of the acetylcholinesterase (AChE) enzyme, which has been identified as responsible for the disease. In this study, computational methods were used to examine the structure and therapeutic ability of chemical compounds extracted from Millettia brandisiana natural products against AChE. This plant is commonly known as a traditional medicine in Vietnam and Thailand for the treatment of several diseases. Furthermore, machine learning helped us narrow down the choice of 85 substances for further studies by molecular docking and molecular dynamics simulations to gain deeper insights into the interactions between inhibitors and disease proteins. Of the five top-choice substances, γ-dimethylallyloxy-5,7,2,5-tetramethoxyisoflavone emerges as a promising substance due to its large free binding energy to AChE and the high thermodynamic stability of the resulting complex.
Assuntos
Acetilcolinesterase , Inibidores da Colinesterase , Millettia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Compostos Fitoquímicos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/isolamento & purificação , Acetilcolinesterase/metabolismo , Acetilcolinesterase/química , Millettia/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Humanos , TermodinâmicaRESUMO
BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion-associated HEV infections. MATERIALS AND METHODS: We screened 10,002 randomly selected donations over an 8-month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT-qPCR). Donor demographic information, including gender, age, self-identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity. RESULTS: A total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT-qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties. CONCLUSION: Although HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk.
Assuntos
Vírus da Hepatite E , Hepatite E , Humanos , Doadores de Sangue , Anticorpos Anti-Hepatite , Hepatite E/epidemiologia , Vírus da Hepatite E/genética , Imunoglobulina G , Imunoglobulina M , RNA Viral , Estudos Soroepidemiológicos , Masculino , FemininoRESUMO
Cellular senescence is emerging as a driver of idiopathic pulmonary fibrosis (IPF), a progressive and fatal disease with limited effective therapies. The senescence-associated secretory phenotype (SASP), involving the release of inflammatory cytokines and profibrotic growth factors by senescent cells, is thought to be a product of multiple cell types in IPF, including lung fibroblasts. NF-κB is a master regulator of the SASP, and its activity depends on the phosphorylation of p65/RelA. The purpose of this study was to assess the role of Pim-1 kinase as a driver of NF-κB-induced production of inflammatory cytokines from low-passage IPF fibroblast cultures displaying markers of senescence. Our results demonstrate that Pim-1 kinase phosphorylates p65/RelA, activating NF-κB activity and enhancing IL-6 production, which in turn amplifies the expression of PIM1, generating a positive feedback loop. In addition, targeting Pim-1 kinase with a small molecule inhibitor dramatically inhibited the expression of a broad array of cytokines and chemokines in IPF-derived fibroblasts. Furthermore, we provide evidence that Pim-1 overexpression in low-passage human lung fibroblasts is sufficient to drive premature senescence, in vitro. These findings highlight the therapeutic potential of targeting Pim-1 kinase to reprogram the secretome of senescent fibroblasts and halt IPF progression.
Assuntos
Fibrose Pulmonar Idiopática , Pneumonia , Humanos , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/farmacologia , NF-kappa B/metabolismo , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Senescência Celular , Pulmão/metabolismo , Pneumonia/metabolismo , Citocinas/metabolismoRESUMO
BACKGROUND: Pathogen reduction technology (PRT) effectively mitigates bacterial contamination in platelets but is more likely to produce low yield units. Although low dose transfusion using conventional platelets has not been associated with increased bleeding, these findings have not been reproduced with PRT-treated platelets. STUDY DESIGN AND METHODS: Platelet transfusions in a tertiary adult hospital were retrospectively reviewed. Comparisons were made between PRT-treated regular (PRT-PR) and low (PRT-PL) yield platelets. Outcomes examined included the number of platelets and RBCs transfused, transfusion-free interval, and corrected count increment (CCI). Subgroup analyses were also performed on hematology-oncology inpatients and outpatients, as well as non-hematology-oncology patients. RESULTS: Platelet utilization per patient remained mostly unchanged (mean 2.9-4.3 units per patient per month) even when the frequency of PRT-PL transfusion increased. Among 1402 patients examined, the number of platelets and RBCs transfused was not significantly different between patients first transfused with PRT-PR versus PRT-PL (mean number of platelet units = 2.8 vs. 3.1, p = 0.38; mean number of RBC units = 4.8 vs. 4.3, p = 0.93). Among 10,257 platelet transfusions examined, the transfusion-free interval (hazard ratio = 1.05, 95% confidence interval 1.00-1.10) and CCI (10.2 vs. 11.0, p = 0.70) were comparable between PRT-PR and PRT-PL units. Similar findings were observed in all subgroups, except for shortened transfusion-free intervals among hematology-oncology inpatients. CONCLUSION: PRT-PR and PRT-PL units may be used in an equivalent manner to maintain an adequate platelet inventory, since there was only a minor difference in time between transfusions.
Assuntos
Neoplasias , Trombocitopenia , Adulto , Plaquetas/microbiologia , Hemorragia , Humanos , Neoplasias/terapia , Transfusão de Plaquetas , Estudos RetrospectivosRESUMO
BACKGROUND: Blood centers have a dual mission to protect donors and patients; donor safety is paramount to maintaining an adequate blood supply. Elucidating donor factors associated with adverse reactions (AR) is critical to this mission. STUDY DESIGN/METHODS: A retrospective cohort analysis of whole blood donors from 2003 to 2020 was conducted at a single blood center in northern California. Adjusted odds ratios (AORs) with 95% CIs for ARs were estimated via multivariable logistic regression on demographics, donation history, and physical examination data. Where appropriate, Wilcoxon-Rank Sum and chi-squared tests were used to determine significance. RESULTS: First-time blood donors (FTD) exhibited a higher AR rate than repeat donors (4.4% vs. 1.9% p < .0001). When compared with FTDs without AR, FTDs with ARs (FT-AR) were less likely to return (30.0% vs. 47.3%, p < .0001), and, of those who returned, had a higher rate of reaction 20.2% versus 2.8% (p < .001). Factors found to be associated with FT-AR (younger age, increased heart rate, and higher diastolic blood pressure) still correlated positively with AR on return donation, but to a lower degree. FTD who potentially witnessed an AR had a lower return rate (44.6% vs. 47.3%, p = <.001) and donated fewer units (2.38 vs. 3.37, p < .001) when compared to FTD who did not witness an AR. CONCLUSION: The AR on FTD increases the AR likelihood of return donation. Longitudinal analysis shows that a time-based deferral policy targeted at FT-AR young donors can reduce the number of ARs while not dramatically impacting the blood supply.
Assuntos
Doadores de Sangue , Demência Frontotemporal , Estudos de Coortes , Humanos , Modelos Logísticos , Estudos RetrospectivosRESUMO
BACKGROUND: Bacterial contamination in platelets remain a major public health concern, which prompted the US Food and Drug Administration guidance for bacterial contamination mitigation. Pathogen reduction technology (PRT) is one mitigation strategy that has shown success in Europe over the last decade. Therefore, our center sought to transition from a dual system of bacterial culturing (BacT) and PRT to full PRT. METHODS: A 1 month pilot study was conducted to simulate 100% PRT conditions. Our center also collected baseline data on key platelet production metrics in the 4 months prior to 100% PRT and compared it to the 4 months post-implementation. RESULTS: The pilot study showed no statistical differences in split rate, proportion of low-yield products, or proportion of single, double, and triple collections. The only observed difference was an 11 min increase in the average duration of double collections. Our baseline versus post-implementation monitoring showed no difference in split rate, discard rate, percentage of low-yield units, and average yield of low yield units. Statistical differences were detected in the proportion of single, double, and triple collections, as well as the average yield of full dose products. Roughly 20% of our inventory consisted of low-yield products. DISCUSSION: With suitable mitigation strategies, transitioning to a full PRT inventory may result in higher net margins while not adversely affecting overall platelet production. A pilot study is a good way to project potential effects of switching from a dual BacT and PRT inventory to full PRT, and can be adopted by other centers aiming to make the transition.
Assuntos
Remoção de Componentes Sanguíneos , Plaquetas , Plaquetas/microbiologia , Europa (Continente) , Humanos , Projetos Piloto , Transfusão de Plaquetas , TecnologiaRESUMO
BACKGROUND: At the start of the coronavirus disease 2019 (COVID-19) pandemic, widespread blood shortages were anticipated. We sought to determine how hospital blood supply and blood utilization were affected by the first wave of COVID-19. STUDY DESIGN AND METHODS: Weekly red blood cell (RBC) and platelet (PLT) inventory, transfusion, and outdate data were collected from 13 institutions in the United States, Brazil, Canada, and Denmark from March 1st to December 31st of 2020 and 2019. Data from the sites were aligned based on each site's local first peak of COVID-19 cases, and data from 2020 (pandemic year) were compared with data from the corresponding period in 2019 (pre-pandemic baseline). RESULTS: RBC inventories were 3% lower in 2020 than in 2019 (680 vs. 704, p < .001) and 5% fewer RBCs were transfused per week compared to 2019 (477 vs. 501, p < .001). However, during the first COVID-19 peak, RBC and PLT inventories were higher than normal, as reflected by deviation from par, days on hand, and percent outdated. At this time, 16% fewer inpatient beds were occupied, and 43% fewer surgeries were performed compared to 2019 (p < .001). In contrast to 2019 when there was no correlation, there was, in 2020, significant negative correlations between RBC and PLT days on hand and both percentage occupancy of inpatient beds and percentage of surgeries performed. CONCLUSION: During the COVID-19 pandemic in 2020, RBC and PLT inventories remained adequate. During the first wave of cases, significant decreases in patient care activities were associated with excess RBC and PLT supplies and increased product outdating.
Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , Transfusão de Eritrócitos , Eritrócitos , Hospitais , Humanos , Estados UnidosRESUMO
Fibroblast activation is transient in successful wound repair but persistent in fibrotic pathologies. Understanding fibroblast deactivation during successful wound healing may provide new approaches to therapeutically reverse fibroblast activation. To characterize the gene programs that accompany fibroblast activation and reversal during lung fibrosis resolution, we used RNA sequencing analysis of flow sorted Col1α1-GFP-positive and CD45-, CD31-, and CD326-negative cells isolated from the lungs of young mice exposed to bleomycin. We compared fibroblasts isolated from control mice with those isolated at Days 14 and 30 after bleomycin exposure, representing the peak of extracellular matrix deposition and an early stage of fibrosis resolution, respectively. Bleomycin exposure dramatically altered fibroblast gene programs at Day 14. Principal component and differential gene expression analyses demonstrated the predominant reversal of these trends at Day 30. Upstream regulator and pathway analyses of reversing "resolution" genes identified novel candidate antifibrotic genes and pathways. Two genes from these analyses that were decreased in expression at Day 14 and reversed at Day 30, Aldh2 and Nr3c1, were selected for further analysis. Enhancement of endogenous expression of either gene by CRISPR activation in cultured human idiopathic pulmonary fibrosis fibroblasts was sufficient to reduce profibrotic gene expression, fibronectin deposition, and collagen gel compaction, consistent with roles for these genes in fibroblast deactivation. This combination of RNA sequencing analysis of freshly sorted fibroblasts and hypothesis testing in cultured idiopathic pulmonary fibrosis fibroblasts offers a path toward identification of novel regulators of lung fibroblast deactivation, with potential relevance to understanding fibrosis resolution and its failure in human disease.
Assuntos
Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Animais , Bleomicina , Sistemas CRISPR-Cas , Células Cultivadas , Modelos Animais de Doenças , Fibroblastos/patologia , Edição de Genes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Camundongos Transgênicos , RNA-Seq , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Remissão Espontânea , Transdução de Sinais , Fatores de Tempo , TranscriptomaRESUMO
We investigated feasibility and accuracy of an interferon-γ release assay (IGRA) for detection of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whole blood IGRA accurately distinguished between convalescent and uninfected healthy blood donors with a predominantly CD4+â T-cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the coronavirus disease 2019 pandemic.
Assuntos
COVID-19 , Testes de Liberação de Interferon-gama , Anticorpos Antivirais , Humanos , SARS-CoV-2 , Linfócitos TRESUMO
BACKGROUND: Several risk mitigation steps have improved the safety of platelets in regard to bacterial contamination, but this continues to be a concern today. A Food and Drug Administration (FDA) Guidance issued in December 2018 aims to further limit this risk. The guidance offers multiple pathways for compliance, and hospital blood banks will have to collaborate with blood donor centers to assess various factors before deciding which method is most appropriate for them. METHODS AND MATERIALS: Our institution considered several factors before moving forward with pathogen reduction technology. This included an assessment of platelet shelf-life, bacterial testing requirements, the efficacy of low-yield platelets, and managing a mixed platelet inventory. The decision to transition to pathogen-reduced platelets was associated with complex collection and processing limitations that resulted in either an increase in platelets that were over-concentrated or products with a low platelet yield. RESULTS: Through trials of various collection settings with unique target volumes and target platelet yields, our blood donor center was able to optimize the production. At the hospital end, this transition required a thorough review of low-yield platelet products and their clinical efficacy. Additionally, this implementation necessitated collaboration with clinical colleagues, comprehensive education, and training. CONCLUSIONS: Pathogen-reduced platelets would be the most efficient way for our institution to be compliant. This summary may serve as a roadmap for other institutions that are considering which FDA prescribed method to use and provide support for those that have decided on pathogen reduction technology but need to optimize their collections to best utilize low-yield products.
Assuntos
Plaquetas , Trombocitopenia , Bancos de Sangue , Plaquetas/microbiologia , Humanos , Transfusão de Plaquetas/métodosRESUMO
Lipid metabolism and inflammation contribute to CVD development. This study investigated whether the consumption of cranberries (CR; Vaccinium macrocarpon) can alter HDL metabolism and prevent inflammation in mice expressing human apo A-I transgene (hApoAITg), which have similar HDL profiles to those of humans. Male hApoAITg mice were fed a modified American Institute of Nutrition-93M high-fat/high-cholesterol diet (16 % fat, 0·25 % cholesterol, w/w; n 15) or the high-fat/high-cholesterol diet containing CR (5 % dried CR powder, w/w, n 16) for 8 weeks. There were no significant differences in body weight between the groups. Serum total cholesterol, non-HDL-cholesterol and TAG concentrations were significantly lower in the control than CR group with no significant differences in serum HDL-cholesterol and apoA-I. Mice fed CR showed significantly lower serum lecithin-cholesterol acyltransferase activity than the control. Liver weight and steatosis were not significantly different between the groups, but hepatic expression of genes involved in cholesterol metabolism was significantly lower in the CR group. In the epididymal white adipose tissue (eWAT), the CR group showed higher weights with decreased expression of genes for lipogenesis and fatty acid oxidation. The mRNA abundance of F4/80, a macrophage marker and the numbers of crown-like structures were less in the CR group. In the soleus muscle, the CR group also demonstrated higher expression of genes for fatty acid ß-oxidation and mitochondrial biogenesis than those of the control. In conclusion, although CR consumption elicited minor effects on HDL metabolism, it prevented obesity-induced inflammation in eWAT with concomitant alterations in soleus muscle energy metabolism.
Assuntos
Frutas , Hipercolesterolemia , Hiperlipidemias , Metabolismo dos Lipídeos , Vaccinium macrocarpon , Animais , Apolipoproteína A-I/genética , Colesterol na Dieta/administração & dosagem , Dieta Hiperlipídica , Ácidos Graxos/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Hiperlipidemias/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Extratos Vegetais/metabolismoRESUMO
BACKGROUND: AABB standards require a policy for assessing transfusing ABO-incompatible plasma. After a fatal hemolytic event with incompatible plasma, our institution instituted platelet donor population titer method for ABO antibodies on the PK7300, with high-titer being defined as having isohemagglutinin titers greater than 256. We recently switched titering platforms to the Neo Iris and we seek to determine the equivalent isohemagglutinin high-titer cutoff on the Neo Iris as compared to the PK7300. METHODS: We measured the titers on 299 apheresis platelet donors and compared its performance characteristics at various cutoffs to the PK7300 reference standard. Discrepant results were manually diluted and retested on the Neo Galileo. Furthermore, since the Neo Iris is able to determine isotype and antigen specific titers, we also characterized these features in our donor population. RESULTS: IgM titer of 128 on the Neo Iris has better accuracy compared to the titer of 64 (94 % vs 93.6 %). Eleven of sixteen discordant results were in agreement with Neo Iris. Blood group O had the highest IgG antibody titers for both anti-A and anti-B (p = 8.4E-17 and 4.3E-09, respectively). Additionally, group O donors exhibited lower anti-A2 than anti-A1 IgG titers. DISCUSSION: The Neo Iris titer cut-off of 128 had the best overall accuracy and correlation with a 256 cut-off on our laboratory developed test on the PK7300 platform. Additionally, we found that group O donors had the highest titer antibodies, with typically higher IgG titers than IgM, and generally multiple dilution levels greater than other blood types.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação Transfusional , Adulto JovemRESUMO
BACKGROUND: With more hospitals using low-titer group O whole blood in trauma resuscitation, having an efficient screening method for low-titer donors is critical. Our blood center uses an automated screen for high-titer isohemagglutinins in our platelet donations while collecting detailed donor demographic information. Using this data, we can identify key demographics often associated with titer status, thereby helping develop a donor-triaging method for titering. STUDY DESIGN AND METHODS: Titer results were read with an automated microplate system as either high or low, based on agglutination, with a cutoff equivalent to 1:256 (both anti-A and anti-B). Donor demographic data analyzed included date of donation, blood group, age, gender, and ethnicity. RESULTS: 57,508 donations were collected from 2073 unique donors between 2014 and 2018. We found the following demographics to be correlated with titer status: gender, ABO blood group, age, and ethnicity. Variability in titer status was identified in 215 individuals. This represented around 10 % of the total unique donors and was split equally amongst gender. We also found that donors between the ages of 41-60 ha d the highest likelihood of having variability in titer status, peaking at 13 %, and this proportion declined past age 60. CONCLUSION: Titer status is associated with the following donor demographics: gender, ABO type, age, and ethnicity. We also discovered that variability in titer status is correlated with age. In blood centers that do not have automated and routine titer screening procedure, these findings could be used as a method to efficiently identify low-titer donors a-priori.
Assuntos
Doadores de Sangue/estatística & dados numéricos , Tipagem e Reações Cruzadas Sanguíneas/métodos , Hemaglutininas/sangue , Programas de Rastreamento/métodos , Adulto , Idoso , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and can lead to increased risk of postoperative adverse events. However, atrial fibrillation and postoperative adverse events are preventable. In this study, a risk index was developed to predict atrial fibrillation after cardiac surgery. METHODS: A prospective cohort study of 405 patients who had undergone adult cardiac surgery from 2015 September to 2016 August at Heart Institute of HCMC and Cho Ray Hospital were obtained. In order to predict POAF, a logistic regression model was developed, and a risk score was derived and validated by bootstrap. RESULTS: In our study, 98 patients developed POAF (24.2%). The risk score included three significant risk factors (age ≥ 60, left atrial diameter > 41 mm, Coronary Artery Bypass Graft with concomitant mitral valve replacement or repair) that were consistent with other reports. Each of these risk factors was assigned one point. The total risk score ranges from 0 to 3 (AUC = 0.69, 95% CI: 0.63-0.75) with the best cutoff point at 1. According to this scoring system, the incidences of POAF in patients associated with each score of 0, 1, 2, and 3 were 8.6%, 30.1%, 40.8%, and 58.3% respectively. Bootstrapping with 5000 samples confirmed the final model provided was consistent with predictions. CONCLUSIONS: We developed and validated a simple risk score based on clinical variables that can be obtained before surgery in order to accurately predict the risk of POAF in patients undergoing cardiac surgery.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Adulto , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Eletrocardiografia , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: O-negative red blood cells (ON-RBC) are a precious resource and the international blood banking community has become increasingly concerned with its inappropriate utilization. AABB recently made several recommendations to address the issue. Solutions must be multifaceted and involve donor centers, blood banks, and clinical departments. From the perspective of a hospital blood bank, it is difficult to rely solely on increased donor recruitment and ubiquitous blood typing of the entire in-patient population. We therefore focused on interventions within the blood bank to optimize inventory and policies to ensure appropriate ON-RBC utilization. STUDY DESIGN AND METHODS: Transfusion data over one year was examined for the rate of out-of-group/inappropriate ON-RBC. Furthermore, we assessed whether that rate was related to product life on the day of transfusion. We also examined our stock inventory levels and how excess inventory can contribute to inappropriate ON-RBC usage. RESULTS: The ON-RBC inventory level was decreased in order to reduce the rate of inappropriate transfusions while maintaining a safe level for optimal patient care. Compared to baseline, our intervention caused ON-RBCs to be transfused earlier in their shelf-life (9.27 vs. 11.15 days from expiration [DFE], p = 0.0012). This reduced the overall rate of inappropriate ON-RBC transfusions (67% vs. 54%, p = 0.0035), approximating 185 units of ON-RBC saved over the course of 6 months. CONCLUSIONS: A data-driven approach to optimize stock inventory levels is widely applicable; it can be adopted by numerous institutions to improve utilization and establish a benchmark for the broader blood banking community.