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OBJECTIVE: To investigate associations of plasma glycated albumin (GA) concentrations in early and midpregnancy with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: We measured GA concentrations using blood samples collected at 10-14 and 15-26 weeks' gestation (GW) in 107 GDM case subjects and 214 control subjects from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. We performed generalized linear mixed-effect regression to test the mean GA difference between GDM case subjects and control subjects and conditional logistic regression to assess prospective associations between GA concentrations and GDM risk. RESULTS: At 15-26 GW, mean GA was lower in GDM case subjects than control subjects (mean 11.90% [95% CI 6.42-32.76] vs. 12.46% [8.45-38.35], adjusted P value for difference = 0.004). Consistently, women with higher GA concentrations tended to have a lower GDM risk, although the associations were not statistically significant. CONCLUSIONS: This study suggests that GA concentrations in midpregnancy might be lower in women who later develop GDM. Further studies are needed to identify the mechanism.
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Anomalous bronchial artery origins may have clinical implications beyond their anatomical curiosity. In this case, identification of such an anomaly led to the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). A 49-year-old male with a history of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) on anticoagulation presented with chest pain and shortness of breath. Laboratory analysis was remarkable for a troponin peak of 14.74 ng/ml, a brain natriuretic peptide level of 602 pg/ml and a D-dimer level of 0.62 µg/ml. Electrocardiogram showed non-specific ST elevation in the anterolateral and inferior leads. Computed tomography angiography (CTA) of the chest was positive for PE involving the right lower lobe pulmonary arterial tree. Echocardiogram showed reduced left ventricular function (ejection fraction 38%) and akinesis of the antero-apical and infero-apical segments. Cardiac catheterization revealed non-obstructive coronary arteries, and an anomalous origin of a right bronchial artery from the right coronary artery. The right bronchial hypertrophied as it supplied collateral flow to the occluded right pulmonary artery. This anomaly and the patient's history of multiple DVT/PEs while on therapeutic levels of warfarin with near normal D-dimer levels raised suspicion for a false positive PE. Pulmonary angiogram revealed chronic occlusion in branches of the right pulmonary artery, mean pulmonary artery pressure of 36 mmHg and no acute thrombus. Ventilation-perfusion scan confirmed the diagnosis of CTEPH. The patient underwent successful pulmonary thromboendarterectomy and subsequently had normalization of mean pulmonary artery pressure. This case underscores the importance of a comprehensive diagnostic approach, and consideration of alternative explanations for imaging findings, that unveiled the diagnosis of a complex and life-threatening condition such as CTEPH. LEARNING POINTS: This case underscores the diagnostic significance of identifying anomalous bronchial artery origin which played a crucial role in the diagnosis of the underlying chronic thromboembolic pulmonary hypertension (CTEPH).It is important to understand the limitations of computed tomography angiography (CTA) chest for diagnosis of CTEPH.
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In an area endemic with Indian visceral leishmaniasis (VL), we performed direct xenodiagnosis to evaluate the transmission of Leishmania donovani from patients with VL-human immunodeficiency virus (HIV) coinfection to the vector sandflies, Phlebotomus argentipes. Fourteen patients with confirmed VL-HIV coinfection, with a median parasitemia of 42 205 parasite genome/mL of blood, were exposed to 732 laboratory-reared pathogen-free female P argentipes sandflies on their lower arms and legs. Microscopy revealed that 16.66% (122/732) of blood-fed flies were xenodiagnosis positive. Notably, 93% (13/14) of the VL-HIV group infected the flies, as confirmed by quantitative polymerase chain reaction and/or microscopy, and were 3 times more infectious than those who had VL without HIV.
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Co-infection , Infections à VIH , Leishmania donovani , Leishmaniose viscérale , Leishmaniose viscérale/épidémiologie , Leishmaniose viscérale/complications , Animaux , Humains , Inde/épidémiologie , Infections à VIH/complications , Infections à VIH/épidémiologie , Femelle , Adulte , Co-infection/virologie , Co-infection/épidémiologie , Co-infection/parasitologie , Leishmania donovani/isolement et purification , Mâle , Phlebotomus/parasitologie , Phlebotomus/virologie , Maladies endémiques , Adulte d'âge moyen , Jeune adulte , Xénodiagnostic , Vecteurs insectes/parasitologie , Vecteurs insectes/virologie , AdolescentRÉSUMÉ
OBJECTIVE: Fetal fibronectin (fFN) testing and transvaginal ultrasound (TVUS) are diagnostic tools used to predict impending spontaneous preterm birth (sPTB) among women presenting with preterm labor (PTL). We evaluated the association between fFN testing or TVUS cervical length (CL) measurement in predicting sPTB, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, and sPTB-related costs. STUDY DESIGN: We conducted a retrospective cohort study using data from the Kaiser Permanente Southern California electronic health system (January 1, 2009-December 31, 2020) using diagnostic and procedure codes, along with a natural language processing algorithm to identify pregnancies with PTL evaluations. PTL evaluation was defined as having fFN and/or TVUS assessment. Outcomes were ascertained using diagnostic, procedural, and diagnosis-related group codes. Multivariable logistic regression assessed the association between fFN and/or TVUS results and perinatal outcomes. RESULTS: Compared with those without PTL evaluations, those with positive fFN tests had higher adjusted odds ratio (adj.OR) for sPTB (2.95, 95% confidence interval [CI]: 2.64, 3.29), RDS (2.34, 95% CI: 2.03, 2.69), and NICU admission (2.24, 95% CI: 2.01, 2.50). In contrast, those who tested negative had lower odds for sPTB (adj.OR: 0.75, 95% CI: 0.70, 0.79), RDS (adj.OR: 0.67, 95% CI: 0.61, 0.73), and NICU admission (adj.OR: 0.74, 95% CI: 0.70, 0.79). Among those with positive fFN results, the odds of sPTB was inversely associated with CL. Health care costs for mothers and neonates were lowest for those with fFN testing only. CONCLUSION: This study demonstrates that positive fFN results were associated with an increased odds of sPTB, RDS, and NICU admission and the association with sPTB was inversely proportional to CL. Additionally, negative fFN results were associated with decreased odds of sPTB, RDS, and NICU admissions. fFN testing may predict these and other sPTB-related adverse outcomes hence its utility should be explored further. Moreover, fFN testing has some cost savings over TVUS. KEY POINTS: · Patients with positive fFN tests had higher odds of sPTB, RDS, and NICU admission.. · Inverse relationship between sPTB and CL among those with positive fFN tests was observed.. · Health care costs for mothers and neonates were lowest for those with fFN testing only..
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Having fast, accurate, and broad spectrum methods for the identification of microorganisms is of paramount importance to public health, research, and safety. Bottom-up mass spectrometer-based proteomics has emerged as an effective tool for the accurate identification of microorganisms from microbial isolates. However, one major hurdle that limits the deployment of this tool for routine clinical diagnosis, and other areas of research such as culturomics, is the instrument time required for the mass spectrometer to analyze a single sample, which can take â¼1 h per sample, when using mass spectrometers that are presently used in most institutes. To address this issue, in this study, we employed, for the first time, tandem mass tags (TMTs) in multiplex identifications of microorganisms from multiple TMT-labeled samples in one MS/MS experiment. A difficulty encountered when using TMT labeling is the presence of interference in the measured intensities of TMT reporter ions. To correct for interference, we employed in the proposed method a modified version of the expectation maximization (EM) algorithm that redistributes the signal from ion interference back to the correct TMT-labeled samples. We have evaluated the sensitivity and specificity of the proposed method using 94 MS/MS experiments (covering a broad range of protein concentration ratios across TMT-labeled channels and experimental parameters), containing a total of 1931 true positive TMT-labeled channels and 317 true negative TMT-labeled channels. The results of the evaluation show that the proposed method has an identification sensitivity of 93-97% and a specificity of 100% at the species level. Furthermore, as a proof of concept, using an in-house-generated data set composed of some of the most common urinary tract pathogens, we demonstrated that by using the proposed method the mass spectrometer time required per sample, using a 1 h LC-MS/MS run, can be reduced to 10 and 6 min when samples are labeled with TMT-6 and TMT-10, respectively. The proposed method can also be used along with Orbitrap mass spectrometers that have faster MS/MS acquisition rates, like the recently released Orbitrap Astral mass spectrometer, to further reduce the mass spectrometer time required per sample.
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Algorithmes , Protéomique , Spectrométrie de masse en tandem , Spectrométrie de masse en tandem/méthodes , Protéomique/méthodes , Humains , Bactéries/isolement et purification , Bactéries/composition chimique , Protéines bactériennes/analyse , Protéines bactériennes/composition chimique , Protéines bactériennes/isolement et purificationRÉSUMÉ
KSR1, a key scaffold protein for the MAPK pathway, facilitates ERK activation upon growth factor stimulation. We recently demonstrated that KSR1 binds the Ca2+-binding protein calmodulin (CaM), thereby providing an intersection between KSR1-mediated and Ca2+ signaling. In this study, we set out to generate a KSR1 point mutant with reduced Ca2+/CaM binding in order to unravel the functional implications of their interaction. To do so, we solved the structural determinants of complex formation. Using purified fragments of KSR1, we showed that Ca2+/CaM binds to the CA3 domain of KSR1. We then used in silico molecular modeling to predict contact residues for binding. This approach identified two possible modes of interaction: (1) binding of extended Ca2+/CaM to a globular conformation of KSR1-CA3 via electrostatic interactions or (2) binding of collapsed Ca2+/CaM to α-helical KSR1-CA3 via hydrophobic interactions. Experimentally, site-directed mutagenesis of the predicted contact residues for the two binding models favored that where collapsed Ca2+/CaM binds to the α-helical conformation of KSR1-CA3. Importantly, replacing KSR1-Phe355 with Asp reduces Ca2+/CaM binding by 76%. The KSR1-F355D mutation also significantly impairs the ability of EGF to activate ERK, which reveals that Ca2+/CaM binding promotes KSR1-mediated MAPK signaling. This work, by uncovering structural insight into the binding of KSR1 to Ca2+/CaM, identifies a KSR1 single-point mutant as a bioreagent to selectively study the crosstalk between Ca2+ and KSR1-mediated signaling.
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Signalisation calcique , Calmoduline , Calmoduline/composition chimique , Liaison aux protéines , Mutation , Mutagenèse dirigée , Calcium/métabolismeRÉSUMÉ
BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.
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Pollution de l'air , Hypertension artérielle gravidique , Matière particulaire , Humains , Femelle , Grossesse , Études rétrospectives , Matière particulaire/effets indésirables , Matière particulaire/analyse , Hypertension artérielle gravidique/épidémiologie , Hypertension artérielle gravidique/étiologie , Adulte , Pollution de l'air/effets indésirables , Californie/épidémiologie , Polluants atmosphériques/effets indésirables , Polluants atmosphériques/analyse , Jeune adulte , Exposition maternelle/effets indésirables , Facteurs de risque , Exposition environnementale/effets indésirablesRÉSUMÉ
OBJECTIVE: Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. STUDY DESIGN: A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. RESULTS: During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. CONCLUSION: The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. KEY POINTS: · Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2.. · The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders.. · White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection..
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Hemoglobin A1c (A1C) is widely used for the diagnosis and management of diabetes. Accurate measurement of A1C is necessary for optimal clinical value. Assay standardization has markedly improved the accuracy and consistency of A1C testing. Devices to measure A1C at point of care (POC) are commercially available, allowing rapid results when the patient is seen. In this review, we describe how standardization of A1C testing was achieved, leading to high-quality results in clinical laboratories. We address the use of POC A1C testing in clinical situations and summarize the advantages and disadvantages of POC A1C testing. We emphasize the importance of considering the limitations of these devices and following correct testing procedures to ensure that accurate A1C results are obtained for optimal care of patients.
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Hémoglobine glyquée , Systèmes automatisés lit malade , Humains , Hémoglobine glyquée/analyse , Hémoglobine glyquée/métabolisme , Systèmes automatisés lit malade/normes , Diabète/sang , Diabète/diagnostic , Diabète/thérapieSujet(s)
Acide acétylsalicylique , , Antiagrégants plaquettaires , Pré-éclampsie , Racisme systémique , Femelle , Humains , Grossesse , Acide acétylsalicylique/usage thérapeutique , Antiagrégants plaquettaires/usage thérapeutique , Pré-éclampsie/ethnologie , Pré-éclampsie/prévention et contrôle , Racisme/ethnologie , Facteurs de risque , États-Unis , Racisme systémique/ethnologieRÉSUMÉ
This article examines the importance of advanced glycation endproducts (AGEs) and summarizes the structure of AGEs, pathological changes associated with AGEs, the contribution of AGEs to metabolic memory, and the value of AGEs as a predictor of diabetic complications and cardiovascular disease in people with and without diabetes. As a practical focus, skin autofluorescence (SAF) is examined as an attractive approach for estimating AGE burden. The measurement of AGEs may be of significant value to specific individuals and groups, including Black and Hispanic/Latino Americans, as they appear to have higher concentrations of hemoglobin A1c (HbA1c) than would be predicted by other metrics of mean glycemia. We hypothesize that if the amount of glycation of HbA1c is greater than expected from measured glucose levels, and if AGEs are accumulating, then this accumulation of AGEs might account for the increased rate of complications of diabetes in populations with high rates of vascular disease and other complications. Thus, identifying and modifying the burden of AGEs based on measurement of AGEs by SAF may turn out to be a worthwhile metric to determine individuals who are at high risk for the complications of diabetes as well as others without diabetes at risk of vascular disease. We conclude that available evidence supports SAF as both a clinical measurement and as a means of evaluating interventions aimed at reducing the risks of vascular disease and diabetic complications.
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The Biomarkers for the Diagnosis of Heart Failure in Diabetes webinar was hosted by Diabetes Technology Society on September 20, 2023, with the objective to review current evidence and management practices of biomarker screening for heart failure in people with diabetes. The webinar discussed (1) the four stages of heart failure, (2) diabetes and heart failure, (3) natriuretic peptide and troponin for diagnosing heart failure in diabetes, (4) emerging composite and investigational biomarkers for diagnosing heart failure, and (5) prevention of heart failure progression. Experts in heart failure from the fields of clinical chemistry, cardiology, and diabetology presented data about the importance of screening for heart failure as an often-unnoticed complication of people with type 1 and type 2 diabetes.
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Marqueurs biologiques , Défaillance cardiaque , Humains , Défaillance cardiaque/diagnostic , Défaillance cardiaque/sang , Marqueurs biologiques/sang , Diabète de type 2/diagnostic , Diabète de type 2/sang , Diabète de type 2/complications , Peptides natriurétiques/sang , Troponine/sangRÉSUMÉ
INTRODUCTION: Perturbations in aromatic (AAAs) and branched-chain amino acids (BCAAs) are seen in decompensated liver disease. The aim of this study was to evaluate the dynamic, postprandial relationship between hepatitis C virus-induced liver disease and amino acid concentrations in patients with compensated liver disease. METHODS: Patients infected with hepatitis C virus underwent a baseline liver biopsy to determine Ishak Fibrosis Score and evaluate the liver transcriptome. Patients ate a standard meal and underwent peripheral vein sampling at defined intervals. Quantitative analysis of amino acids was performed using liquid chromatography-tandem mass spectrometry. RESULTS: At baseline, there was no difference in AAA and BCAA concentrations between patients with cirrhosis and non-cirrhotic patients. After a standard meal, AAAs, but not BCAAs, were elevated in patients with cirrhosis compared with non-cirrhotic patients at every time point. The HepQuant SHUNT fraction was significantly higher in patients with cirrhosis and positively correlated with AAA concentration at all time points, but not BCAA. Analysis of the hepatic transcriptome demonstrated greater downregulation of the AAA degradation pathways than the BCAA degradation pathways. DISCUSSION: At baseline, cirrhotic patients with compensated liver disease have adequate reserve liver function to metabolize AAAs and BCAAs. When faced with a metabolic stressor, such as a standard meal, patients with cirrhosis are less able to metabolize the increased load of AAAs. This impairment correlates with portosystemic shunting. Further evaluation of AAA levels in compensated liver disease might further the understanding of the liver-muscle axis and the role it may play in the development of sarcopenia in liver disease.
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Hépatite C , Maladies du foie , Humains , Acides aminés aromatiques , Hepacivirus/génétique , Cirrhose du foie/étiologie , Cirrhose du foie/métabolisme , Acides aminés , Acides aminés à chaine ramifiée , Hépatite C/complicationsRÉSUMÉ
Whole genome analysis of Leishmania hybrids generated experimentally in sand flies supports a meiotic mechanism of genetic exchange, with Mendelian segregation of the nuclear genome. Here, we perform functional analyses through the generation of double drug-resistant hybrids in vitro and in vivo (during sand fly infections) to assess the importance of conserved meiosis-related genes in recombination and plasmogamy. We report that HOP1 and a HAP2-paralog (HAP2-2) are essential components of the Leishmania meiosis machinery and cell-to-cell fusion mechanism, respectively, since deletion of either gene in one or both parents significantly reduces or completely abrogates mating competence. These findings significantly advance our understanding of sexual reproduction in Leishmania, with likely relevance to other trypanosomatids, by formally demonstrating the involvement of a meiotic protein homolog and a distinct fusogen that mediates non-canonical, bilateral fusion in the hybridizing cells.
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Leishmania , Psychodidae , Animaux , Leishmania/génétique , Reproduction/génétique , Méiose/génétiqueRÉSUMÉ
BACKGROUND: Glycated albumin (GA) has recently been proposed as a screening marker for diabetes among non-pregnant individuals. However, data on GA during pregnancy are sparse and lacking among women of diverse race/ethnicity. We investigated longitudinal concentrations of GA among multiracial pregnant women in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. METHODS: We quantified GA and cardiometabolic biomarkers using longitudinal plasma samples collected at 10 to 14, 15 to 26 (fasting), 23 to 31, and 33 to 39 gestational weeks from 214 pregnant women without gestational diabetes. We examined the distribution of GA across pregnancy and its association with participants' characteristics including race/ethnicity, pre-pregnancy body mass index (ppBMI), and selected cardiometabolic biomarkers. GA trajectories were estimated using a latent class approach. RESULTS: Medians (interquartile range) of GA concentrations were 12.1% (10.6%-13.4%), 12.5% (10.7%-13.8%), 12.4% (10.9%-13.5%), and 11.5% (10.4%-12.5%) at 10 to 14, 15 to 26, 23 to 31, and 33 to 39 weeks, respectively. There were no significant differences in the pattern among different race/ethnic groups (P > 0.53). A minority of women exhibited a GA trajectory characterized by a high concentration of GA at 15 to 26 weeks. GA concentrations were inversely related to ppBMI and plasma low-density lipoprotein and triglyceride concentrations, but were not significantly related to hemoglobin A1c, fasting insulin, or glucose over pregnancy. CONCLUSIONS: In this study of individuals who were normoglycemic before pregnancy, plasma GA concentrations stayed relatively constant over pregnancy, decreasing only in late pregnancy. GA concentrations were inversely related to ppBMI and suboptimal lipid profiles, but did not appear to be a sensitive marker for glucose metabolism in pregnancy.
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Maladies cardiovasculaires , Diabète gestationnel , Enfant , Grossesse , Femelle , Humains , Études longitudinales , Diabète gestationnel/diagnostic , Sérumalbumine/métabolisme , Marqueurs biologiques , Glycémie/métabolismeRÉSUMÉ
Tissue-resident macrophages are critical for tissue homeostasis and repair. We previously showed that dermis-resident macrophages produce CCL24 which mediates their interaction with IL-4+ eosinophils, required to maintain their M2-like properties in the TH1 environment of the Leishmania major infected skin. Here, we show that thymic stromal lymphopoietin (TSLP) and IL-5+ type 2 innate lymphoid cells are also required to maintain dermis-resident macrophages and promote infection. Single cell RNA sequencing reveals the dermis-resident macrophages as the sole source of TSLP and CCL24. Generation of Ccl24-cre mice permits specific labeling of dermis-resident macrophages and interstitial macrophages from other organs. Selective ablation of TSLP in dermis-resident macrophages reduces the numbers of IL-5+ type 2 innate lymphoid cells, eosinophils and dermis-resident macrophages, and ameliorates infection. Our findings demonstrate that dermis-resident macrophages are self-maintained as a replicative niche for L. major by orchestrating localized type 2 circuitries with type 2 innate lymphoid cells and eosinophils.
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Immunité innée , Leishmaniose cutanée , Animaux , Souris , Granulocytes éosinophiles/métabolisme , Interleukine-5/métabolisme , Lymphocytes/métabolisme , Cytokines/métabolisme , Lymphopoïétine stromale thymique , Macrophages/métabolisme , Derme/métabolismeRÉSUMÉ
Importance: Women are especially vulnerable to mental health matters post partum because of biological, emotional, and social changes during this period. However, epidemiologic evidence of an association between air pollution exposure and postpartum depression (PPD) is limited. Objective: To examine the associations between antepartum and postpartum maternal air pollution exposure and PPD. Design, Setting, and Participants: This retrospective cohort study used data from Kaiser Permanente Southern California (KPSC) electronic health records and included women who had singleton live births at KPSC facilities between January 1, 2008, and December 31, 2016. Data were analyzed between January 1 and May 10, 2023. Exposures: Ambient air pollution exposures were assessed based on maternal residential addresses using monthly averages of particulate matter less than or equal to 2.5 µm (PM2.5), particulate matter less than or equal to 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) from spatial interpolation of monitoring station measurements. Constituents of PM2.5 (sulfate, nitrate, ammonium, organic matter, and black carbon) were obtained from fine-resolution geoscience-derived models based on satellite, ground-based monitor, and chemical transport modeling data. Main Outcomes and Measures: Participants with an Edinburgh Postnatal Depression Scale score of 10 or higher during the 6 months after giving birth were referred to a clinical interview for further assessment and diagnosis. Ascertainment of PPD was defined using a combination of diagnostic codes and prescription medications. Results: The study included 340â¯679 participants (mean [SD] age, 30.05 [5.81] years), with 25â¯674 having PPD (7.54%). Increased risks for PPD were observed to be associated with per-IQR increases in antepartum and postpartum exposures to O3 (adjusted odds ratio [AOR], 1.09; 95% CI, 1.06-1.12), PM10 (AOR, 1.02; 95% CI, 1.00-1.04), and PM2.5 (AOR, 1.02; 95% CI, 1. 00-1.03) but not with NO2; PPD risks were mainly associated with PM2.5 organic matter and black carbon. Overall, a higher risk of PPD was associated with O3 during the entire pregnancy and postpartum periods and with PM exposure during the late pregnancy and postpartum periods. Conclusions and Relevance: The study findings suggest that long-term exposure to antepartum and postpartum air pollution was associated with higher PPD risks. Identifying the modifiable environmental risk factors and developing interventions are important public health issues to improve maternal mental health and alleviate the disease burden of PPD.
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Polluants atmosphériques , Pollution de l'air , Dépression du postpartum , Ozone , Grossesse , Humains , Femelle , Adulte , Polluants atmosphériques/effets indésirables , Polluants atmosphériques/analyse , Exposition environnementale/effets indésirables , Études rétrospectives , Dioxyde d'azote , Dépression du postpartum/épidémiologie , Dépression du postpartum/étiologie , Pollution de l'air/effets indésirables , Pollution de l'air/analyse , Matière particulaire/effets indésirables , Matière particulaire/analyse , Période du postpartum , CarboneRÉSUMÉ
BACKGROUND: Patients with diabetic ketoacidosis (DKA), a potentially fatal complication of type 1 diabetes, have hyperglycemia, ketonemia and metabolic acidosis. Blood glucose and blood ketone results are often used to triage patients with suspected DKA. This study aimed to establish how effective blood glucose and blood ketone (beta-hydroxybutyrate, BOHB) measurements are in identifying patients with significant acidosis and sought to validate existing diagnostic BOHB thresholds. METHODS: Initial Emergency Department results on 161 presumptive DKA episodes in 95 patients (42 F, 53 M, age range 14-89 years) containing a complete dataset of D (glucose), K (BOHB) and A (Bicarbonate [HCO3] and pH) results. RESULTS: Blood glucose correlated poorly with BOHB (r = 0.28 p = 0.0003), pH (r= -0.25, p = 0.002) and HCO3 (r= -0.17, p = 0.04). BOHB, though better, was still limited in predicting pH (r = -0.44, p < 0.0001) and HCO3 (r = -0.49, p < 0.0001). A HCO3 of 18mmol/L equated to a BOHB concentration of 4.3mmol/L, whilst a HCO3 of 15mmol/L equated to a BOHB of 4.7mmol/L. Of the 133 of 161 events with HCO3 < 18mmol/L, 22 were not hyperglycemic (> 13.9mmol/L, n = 8), ketonemic (≤ 3mmol/L, n = 9) or either (n = 5). CONCLUSIONS: The commonly employed BOHB diagnostic cutoff of 3mmol/L could not be verified. Since acid-base status was poorly predicted by both glucose and BOHB, this highlights that, regardless of their results, pH and/or HCO3 should also be tested in any patient suspected of DKA.