Plasma Protein Concentration Research Articles

The Impact of Inflammation on the In Vivo Activity of the Renal Transporters OAT1/3 in Pregnant Women Diagnosed with Acute Pyelonephritis.

Inflammation can regulate hepatic drug metabolism enzymes and transporters. The impact of inflammation on renal drug transporters remains to be elucidated. We aimed to quantify the effect of inflammation (caused by acute pyelonephritis) on the in vivo activity of renal OAT1/3, using the probe drug furosemide. Pregnant women (second or third trimester) received a single oral dose of furosemide 40 mg during acute pyelonephritis (Phase 1; n = 7) and after its resolution (Phase 2; n = 7; by treatment with intravenous cefuroxime 750 mg TID for 3-7 days), separated by 10 to 14 days. The IL-6, IFN-γ, TNF-α, MCP-1, and C-reactive protein plasma concentrations were higher in Phase I vs. Phase II. The pregnant women had a lower geometric mean [CV%] furosemide CLsecretion (3.9 [43.4] vs. 6.7 [43.8] L/h) and formation clearance to the glucuronide (1.1 [85.9] vs. 2.3 [64.1] L/h) in Phase 1 vs. Phase 2. Inflammation reduced the in vivo activity of renal OAT1/3 (mediating furosemide CLsecretion) and UGT1A9/1A1 (mediating the formation of furosemide glucuronide) by approximately 40% and 54%, respectively, presumably by elevating the plasma cytokine concentrations. The dosing regimens of narrow therapeutic window OAT drug substrates may need to be adjusted during inflammatory conditions.

Expressions of Insulin-like Growth Factor System among Different Breeds Impact Piglets' Growth during Weaning.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among three pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TYB), and Xiangcun black (XCB) piglets (20 piglets per breed) were selected at 21 and 24 (3 days of post-weaning) days of age to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF-system-related components in different tissues. The plasma IGFBP-3 concentration in TYB piglets was higher (p > 0.05) than in the XCB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (p < 0.05) in the kidney, but it was higher (p < 0.05) in the spleen of XCB and TYB piglets. At 24 days of age, the IGF-1 expression was higher (p < 0.05) in the kidney of TYB piglets than in the XCB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XCB and TYB piglets were lower (p < 0.05) compared with the DR piglets. Weaning down-regulated (p < 0.05) IGF-1 expression in the jejunum, spleen, and liver of piglets, while it up-regulated (p < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman's correlation analysis showed a negative correlation (p < 0.05) between plasma IGFBP-2 and IGFBP-5 concentration and the organ indices of piglets. Collectively, there were significant differences in the IGF system components among the three pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

Mechanism of hyperproteinemia-induced damage to female reproduction in a genetic silkworm model

Hyperproteinemia is a metabolic disorder characterized by abnormally elevated plasma protein concentrations (PPC) in humans and animals. Here, a genetic silkworm model with high PPC was employed to investigate the effect of elevated PPC on female reproduction. Transcriptomic analysis revealed that high PPC induces downregulation of the ovarian development-related genes and disrupts ovarian sugar metabolism. Biochemical and endocrinal analyses revealed that high PPC increases trehalose and glucose levels in hemolymph and glycogen content in the fat body through activation of the gluconeogenic pathway and inhibition of the Insulin/Insulin-like growth factor signaling pathway-the serine/threonine kinase (IIS-AKT) pathway, thus disrupting characteristic metabolic homeostasis of sugar in the ovary. These resulted in ovarian developmental delay as well as reduced number and poor quality of eggs. Insulin supplementation effectively increased egg numbers by lowering blood sugar. These collective results provide new insights into the mechanisms by which high PPC negatively affects female reproduction and support the potential therapeutic effects of insulin.

Improving Women's Health.

This invited Team Profile was created by the McClements and the Wen groups, Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney (Australia); and the Kaitu'u-Lino/Hannan groups, Mercy Hospital for Women, the University of Melbourne (Australia). They recently published an article on the development and validation of the first-in-class point-of-care assay for preeclampsia diagnosis. This assay can detect and quantify the concentration of FKBPL and CD44 proteins in human plasma in 15 minutes with high sensitivity and specificity enabling timely diagnosis of early-onset preeclampsia. "Quantitative Point of Care Tests for Timely Diagnosis of Early-Onset Preeclampsia with High Sensitivity and Specificity", S. M. Ghorbanpour, S. Wen, T.'u. J. Kaitu'u-Lino, N. J. Hannan, D. Jin, L. McClements, Angew. Chem. Int. Ed. 2023, 62, e202301193.

Improving Women's Healt

AbstractThis invited Team Profile was created by the McClements and the Wen groups, Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney (Australia); and the Kaitu'u‐Lino/Hannan groups, Mercy Hospital for Women, the University of Melbourne (Australia). They recently published an article on the development and validation of the first‐in‐class point‐of‐care assay for preeclampsia diagnosis. This assay can detect and quantify the concentration of FKBPL and CD44 proteins in human plasma in 15 minutes with high sensitivity and specificity enabling timely diagnosis of early‐onset preeclampsia. “Quantitative Point of Care Tests for Timely Diagnosis of Early‐Onset Preeclampsia with High Sensitivity and Specificity”, S. M. Ghorbanpour, S. Wen, T.'u. J. Kaitu'u‐Lino, N. J. Hannan, D. Jin, L. McClements,, Angew. Chem. Int. Ed. Engl. 2023, 62, e202301193.

The nutrition and immunity (nutrIMM) study: protocol for a non-randomized, four-arm parallel-group, controlled feeding trial investigating immune function in obesity and type 2 diabetes.

Individuals with obesity and/or type 2 diabetes are at higher risk of infection and have worse prognoses compared to healthy individuals. Several factors may influence immune responses in this population, including high adiposity, hyperglycemia, and unhealthy dietary habits. However, there is insufficient data on the independent or clustered contribution of these factors to obesity-related immune dysfunction, especially accounting for dietary intake. This study aims to establish the independent contribution of obesity and hyperglycemia to immune dysfunction independent of diet in adults with and without obesity with or without type 2 diabetes. The Nutrition and Immunity (nutrIMM) study is a single-centre, non-randomized, four-arm, parallel-group, controlled feeding trial. It will enroll adults without obesity (Lean-NG) and with obesity and three metabolic phenotypes of normoglycemia, glucose intolerance, and type 2 diabetes. Participants will be assigned to one of four groups and will consume a standard North American-type diet for 4 weeks. The primary outcomes are plasma concentration of C-reactive protein and concentration of ex-vivo interleukin-2 secreted upon stimulation of T cells with phytohemagglutinin. This will be the first controlled feeding study examining the contribution of obesity, hyperglycemia, and diet on systemic inflammation, immune cell phenotype, and function in adults of both sexes. Results of this clinical trial can ultimately be used to develop personalized dietary strategies to optimize immune function in individuals with obesity with different immune and metabolic profiles. ClinicalTrials.gov, identifier NCT04291391.

A randomized controlled trial to examine the impact of a multi-strain probiotic on self-reported indicators of depression, anxiety, mood, and associated biomarkers.

To examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels. In a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented with a single capsule of MSP (a total daily dose of 4 × 109 colony forming units [CFU] comprised of a 1 × 109 CFU dose from each of the following strains: Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6 weeks of supplementation and 3 weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined. BDI, STAI, and total LEIDS-R scores were reduced from baseline (p < 0.05) with MSP supplementation after 4 and 6 weeks of supplementation and 3 weeks after supplementation while no changes (p > 0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower (p < 0.05) after supplementation. Plasma serotonin concentrations in MSP were increased from baseline after 6 weeks of supplementation and 3 weeks after ceasing supplementation. No changes (p > 0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups. MSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6 weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortisol. https://classic.clinicaltrials.gov/ct2/show/NCT05343533, NCT05343533.

No impact of a high-fat meal coupled with intermittent hypoxemia on acute kidney injury biomarkers in adults with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high-fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle-aged to older individuals with OSA (54.4 years [6.4]) consumed a high-fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) at any measured time points. In both groups, plasma concentrations of interleukin-18 (IL-18) increased after 6 h during normoxia only (p = 0.033, ηp 2 = 0.122), and plasma concentrations of liver-type fatty acid-binding protein (L-FABP) transiently decreased after 3 h in both conditions (p = 0.008, ηp 2 = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.

126 Complement Factor I protein concentration in human plasma and ocular tissue samples stratified by AMD genotypes and phenotypes

126 Complement Factor I protein concentration in human plasma and ocular tissue samples stratified by AMD genotypes and phenotypes

Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140,000 subjects.

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant associations with PCa risk, including 16 previously reported proteins and eight novel proteins. Of them, 14 proteins showed negative associations and 10 showed positive associations with PCa risk. For 18 of the identified proteins, potential functional somatic changes of encoding genes were detected in PCa patients in The Cancer Genome Atlas (TCGA). Genes encoding these proteins were significantly involved in cancer-related pathways. We further identified drugs targeting the identified proteins, which may serve as candidates for drug repurposing for treating PCa. In conclusion, this study identifies novel protein biomarker candidates for PCa risk, which may provide new perspectives on the etiology of PCa and improve its therapeutic strategies.

Perioperative brain injury marker concentrations in neonatal open-heart surgery: a prospective observational study.

Neonates with critical congenital heart defects undergoing open-heart surgery on cardiopulmonary bypass circulation are at risk for white matter brain injury. This article reports on pre- and postoperative plasma concentrations of brain injury markers glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and Tau, and their respective associations with white matter lesions detected on postoperatively performed brain MRI. Forty term newborns with isolated critical congenital heart defects were included in a prospective observational study. Brain injury marker plasma concentrations were determined prior to surgery and at postoperative days 1, 2 and 3. Brain magnetic resonance imaging was performed pre- and postoperatively. Concentrations of brain injury markers were analysed using ultrasensitive single molecule array technology. Absolute pre- and postoperative plasma biomarker concentrations, and postoperative concentrations adjusted for preoperative concentrations were used for subsequent analysis. Plasma concentrations of GFAP, NfL and Tau displayed a well-defined temporal trajectory after neonatal cardiopulmonary bypass circulation. GFAP and Tau reached peak concentrations at postoperative day 2 (median concentrations 170.5 and 67.2 pg/ml, respectively), whereas NfL continued to increase throughout the study period (median concentration at postoperative day 3 191.5 pg/ml). Adjusted Tau at postoperative day 2 was significantly higher in infants presenting with white matter lesions on postoperative MRI compared to infants without white matter injury.

Aging Increases Enterocyte Damage during a 3-Hour Exposure to Very Hot and Dry Heat: A Preliminary Study.

Profound heat stress can damage the gastrointestinal barrier, leading to microbial translocation from the gut and subsequent systemic inflammation. Despite the greater vulnerability of older people to heat wave-related morbidity and mortality, it is unknown if age modulates gastrointestinal barrier damage and inflammation during heat stress. Therefore, the aim of this study was to determine if aging impacted enterocyte damage and systemic inflammatory responses to a 3-h exposure to very hot and dry (47 °C, 15% humidity) heat with accompanying activities of daily living (intermittent activity at 3 METS). Data from 16 young (age 21 to 39 years) and 16 older (age 65 to 76 years) humans were used to address this aim. In each group, log-transformed plasma concentrations of intestinal fatty acid binding protein (I-FABPlog), interleukin-8 (IL-8log), and tissue factor (TFlog) were assessed as indices of enterocyte damage, systemic inflammation, and blood coagulation, respectively, before and after the 3-h heat exposure. In the younger cohort, I-FABPlog concentration did not increase from pre to post heat exposure (p = 0.264, d = 0.20), although it was elevated in the older group (p = 0.014, d = 0.67). The magnitude of the increase in I-FABPlog was greater in the older participants (p = 0.084, d = 0.55). Across all participants, there was no correlation between the change in core temperature and the change in IFABPlog. There was no change in IL-8log in the younger group (p = 0.193, d = 0.23) following heat exposure, but we observed a decrease in IL-8log in the older group (p = 0.047, d = 0.48). TFlog decreased in the younger group (p = 0.071, d = 0.41), but did not change in the older group (p = 0.193, d = 0.15). Our data indicate that I-FABPlog concentration (an index of enterocyte damage) is increased in older humans during a 3-h extreme heat exposure. Future studies should determine whether this marker reflects increased gastrointestinal barrier permeability in older individuals during heat exposure.

Baseline fibroblast growth factor 23 is associated with long-term mortality in ST-elevation myocardial infarction-results from the augsburg myocardial infarction registry.

The aim of this study was to investigate the association between inflammatory plasma protein concentrations and long-term mortality in patients with ST-elevation myocardial infarction (STEMI). For 343 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 inflammatory plasma proteins were measured at the index event using the OLINK inflammation panel. In multivariable-adjusted Cox regression models, the association between each plasma protein and all-cause long-term mortality was investigated. Median follow-up time was 7.6 (IQR: 2.4) years. For plasma protein that showed a strong association with long-term mortality, a 5-year survival ROC analysis was performed. One plasma protein, namely Fibroblast Growth Factor 23 (FGF-23), was particularly well associated with long-term mortality in the multivariable-adjusted Cox model with an FDR-adjusted p-value of <0.001 and a Hazard Ratio (HR) of 1.57 [95% CI: 1.29-1.91]. In the 5-years ROC analysis, an AUC of 0.6903 [95% CI: 0.594-0.781] was estimated for FGF-23. All other plasma protein didńt show strong associations, each marker with FDR-adjusted p-values >0.05 in the multivariable-adjusted Cox models. FGF-23 is independently associated with long-term mortality after STEMI and might play an important role in the response to myocardial injury. The results suggest FGF-23 to be a useful marker in the long-term treatment of STEMI patients and a potential target for drug development.

Microencapsulation of Lactobacillus plantarum in the alginate/chitosan improves immunity, disease resistance, and growth of Nile tilapia (Oreochromis niloticus).

This study evaluated the effects of microencapsulation of L. plantarum (as a probiotic) with chitosan/alginate biopolymers (MLCA) on innate immune response, disease resistance, and growth performance of Nile tilapia (Oreochromis niloticus). Four hundred and eighty fish were randomly distributed in glass tanks (150 L) and fed with diets including diet 1: control; diet 2: 10 g kg-1 microcapsules; diet 3: 108 CFU g-1 L. plantarum; and diet 4: 10 g kg-1 MLCA for 60 days. The hematology and biochemical indices, lysozyme activity, alternative complement activities, respiratory burst, serum bactericidal activity, as well as growth performance parameters (specific growth rate, feed conversion ratio) were analyzed. White blood cells, plasma protein and globulin concentration, serum lysozyme, and respiratory burst activities of fish were significantly increased (P < 0.05) in the MLCA diet. A challenge test against Streptococcus agalactiae, at the end of the experiment, showed the highest survival rate of the fish fed with MLCA. Moreover, the fish fed with MLCA showed a significant improvement in SGR (3.12 ± 0.18%) and FCR (1.23 ± 0.20) and had the highest growth performance. These results suggest longer stability of probiotics in the microcapsules, and their immunomodulatory effect can be considered a promising immunostimulant and growth enhancer in the Nile tilapia diet.

PCSK9 Involvement in Autism Etiology: Sequence Variations, Protein Concentration, and Promoter Methylation

Besides its main role in the control of blood cholesterol, PCSK9 has a role in the regulation of neuronal development and apoptosis. We suggest, for the first time, the possible involvement of PCSK9 in autism. In this case-control study, Sanger sequencing was used to analyze sequence variations in the PCSK9 gene exons and their flanking intronic sequences. ELISA assay was used to determine the plasma concentration of PCSK9. The methylation percentage of the PCSK9 gene promoter was assessed by methylation-specific PCR (MSP). Forty-three variants were found; out of them, seven showed differential frequency between patients and controls. rs.45448095, rs.45613943, rs.630431, rs.529500286, and rs.45439391 are risk factors for autism, while rs.11800231 and rs.483462 are protective variants. The concentration of plasma PCSK9 protein was significantly elevated and the methylation percentage of PCSK9 gene promoter was significantly lower in cases than in controls (P <0.001 and = 0.002, respectively). ROC curve analysis identified an area under the curve (AUC) of 0.915 for plasma protein concentration and 0.693 for percent gene promoter methylation. In addition, two new variants were identified (g.23809C>T in intron 11 and g.24071T>G in 3' UTR). This is the first study to investigate the correlation between PCSK9 protein and autism and suggests the potential involvement of PCSK9 as one of the susceptibility genes for autism. Further studies with a larger number of subjects are recommended.

Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis.

Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syndrome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients. We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5μm (PM2.5), and PM < 10μm (PM10) using weighted averages of daily levels from monitors within 50km of subjects' residences. Subjects were followed for 6days for ARDS by the Berlin Criteria. The association between each pollutant and ARDS was determined using multivariable logistic regression adjusting for preselected confounders. In 764 subjects, we measured plasma concentrations of inflammatory proteins at presentation and tested for an association between pollutant exposure and protein concentration via linear regression. ARDS developed in 754 (41%) subjects. Short- and long-term exposures to SO2, NO2, and PM2.5 were associated with ARDS risk (SO2: odds ratio (OR) for the comparison of the 75-25th long-term exposure percentile 1.43 (95% confidence interval (CI) 1.16, 1.77); p < 0.01; NO2: 1.36 (1.06, 1.74); p = 0.04, PM2.5: 1.21 (1.04, 1.41); p = 0.03). Long-term exposures to these three pollutants were also associated with plasma interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor-1 concentrations. Short and long-term exposures to ambient SO2, PM2.5, and NO2 are associated with increased ARDS risk in sepsis, representing potentially modifiable environmental risk factors for sepsis-associated ARDS.

Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort.

Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates. We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva. The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score. This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.

Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis

Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients. To identify the genes and pathways associated with idiopathic MFC. This was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022. Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients. This study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10-9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10-8). In proteomic analysis of 87 patients, the risk allele G of rs7535263 in the CFH gene was strongly associated with increased plasma concentrations of factor H-related (FHR) proteins (eg, FHR-2, likelihood ratio test, adjusted P = 1.1 × 10-3) and proteins involved in platelet activation and the complement cascade. Results suggest that CFH gene variants increase systemic concentrations of key factors of the complement and coagulation cascades, thereby conferring susceptibility to idiopathic MFC. These findings suggest that the complement and coagulation pathways may be key targets for the treatment of idiopathic MFC.

Association between fatty liver index and blood coagulation markers: a population-based study

BackgroundPopulation-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.MethodsAfter the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.ResultsIn the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.ConclusionIn this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.

Studying the effectiveness of varieties of anticoagulant therapy programs in patients with a severe course of COVID-19 (analysis of own clinical observations)

Background. Currently, there is no internationally approved protocol for anticoagulant therapy (ACT) in patients with COVID-19 that describes the different types of ACT programs depending on the severity of COVID-19. The objective: to determine optimal ACT programs. Materials and methods. A retrospective ana­lysis of ACT programs was conducted in 268 patients with extremely severe COVID-19 who were treated in the intensive care units. Results. The article presents the results of retrospective analysis of ACT programs in 268 patients with a very severe course of COVID-19 treated in the general intensive care unit in 2021. ACT programs in 162 patients who died because of COVID-19 and in 106 survived patients were studied separately. The total duration of hospital stay was from 9 to 55 days. ACT programs were mostly in line with Euro­pean guidelines/instructions. ACT included a stepwise combination of unfractionated heparin, low-molecular-weight heparins, and oral anticoagulants depending on the clinical course, concomitant pathology, and laboratory parameters. The systemic inflammatory response was characterized by the concentration of C-reactive protein in the blood plasma within the range of 54.7–331.4 mg/l (on average 95.4 ± 73.4 mg/ml), ferritin of 208–2094 μg/l (on average 947.16 ± 872.00 μg/l), interleukin-6 of 33.9–507.4 pg/ml (on average 152.60 ± 201.15 pg/ml). The level of D-dimer in blood plasma ranged from 3.74 to 82.0 μg/ml (on average 8.200 ± 3.525 μg/ml). Platelet content in peripheral blood ranged from 372 × 109/l to 72 × 109/l. Conclusions. The optimal ACT program in patients with severe and extremely severe COVID-19 is a program of sequential change of anticoagulant drugs to enhance their anticoagulant effect, which can be controlled by laboratory tests.