Search Results (84)

A 75-year-old male was admitted with worsening anemia and spontaneous bruising in the left abdominal wall and paraspinal region. Laboratory workup revealed low factor XIII (FXIII) activity levels. Cryoprecipitate transfusions raised his FXIII level, but still fluctuated drastically, ranging from 4 to 43% was discharged 3 days later once his bleeding was managed. Three days later, he was readmitted for severe pain and new bruising in his latissimus dorsi and lateral right thigh. CT-scan revealed hemothorax and arterial bleeding requiring an urgent angiogram with embolization. Chromogenic and functional FXIII assays were unable to elucidate an inhibitor at this time. Management included FXIII concentrate, rituximab, and prednisone; the patient was discharged 12 days later with FXIII levels of 50%. After prednisone tapering, FXIII levels decreased drastically. This case exemplified that higher levels of FXIII are required to prevent bleeding diatheses rather than the previously reported minimum of 5% activity. Despite the diagnostic uncertainty of laboratory testing, the shortened half-life of FXIII activity following replacement therapy and favorable response to immunotherapy indicates that the bleeding diathesis was caused by an acquired inhibitor. Full article

Chronic thromboembolic pulmonary disease (CTEPD) is a severe long-term complication of acute pulmonary thromboembolism (PTE). Its pathogenesis is multifactorial, involving incomplete thrombus resolution, hemodynamic burden, comorbidities, and genetic factors. However, the contribution of inherited thrombophilic mutations to CTEPD development remains controversial. This retrospective cohort study included 204 patients diagnosed with acute PTE at a tertiary referral center between December 2023 and December 2024. Baseline demographic, clinical, laboratory, and echocardiographic data were collected. Genetic analysis assessed Factor II, Factor V Leiden, MTHFR C677T, MTHFR A1298C, Factor XIII V34L, and PAI-1 4G/5G polymorphisms. Patients were followed for at least 12 months for the development of CTEPD, defined according to guideline-based hemodynamic and imaging criteria. During follow-up, 17 patients (8.3%) developed CTEPD. Patients with CTEPD were significantly older and had higher baseline and follow-up systolic pulmonary artery pressure (sPAP) (p < 0.001), elevated NT-proBNP and troponin levels (both p < 0.001), and more frequent comorbidities, including cardiac and renal disease. Multivariate logistic regression identified comorbid diseases (HR: 0.17, 95% CI: 0.039–0.80, p = 0.025) and genetic thrombophilic factors (HR: 0.30, 95% CI: 0.10–0.91, p = 0.034) as independent predictors. Among genetic variants, only the PAI-1 4G/5G polymorphism was significantly associated with CTEPD (p = 0.001). Our study demonstrates that advanced age, comorbid diseases, elevated cardiac biomarkers, and genetic predisposition are associated with the development of CTEPD after acute PTE, while the PAI-1 4G/5G polymorphism may contribute to CTEPD susceptibility within a multifactorial context. Full article

Dengue and COVID-19 are viral diseases characterized by coagulopathies, with Dengue associated with fibrinolysis and COVID-19 with prothrombotic events. Furthermore, cross-reactivity between anti-SARS-CoV-2 and anti-DENV antibodies may confer protective immunity or exacerbate disease severity. Our investigation explored the impact of prior COVID-19 exposure on the immunopathogenesis of Dengue, focusing on hemostatic parameters. We quantified nitrites, procoagulant, anticoagulant, and fibrinolytic mediators in the plasma of Dengue patients before and after the COVID-19 pandemic. We also evaluated the influence of plasma from dengue patients on platelet activation in vitro using platelets from healthy donors exposed to DENV-2. Hemorrhagic manifestations were more frequent in pre-COVID-19 Dengue, while nitrite levels were elevated in post-COVID-19 Dengue patients, particularly among those without hemorrhagic signs. Among procoagulant factors, tissue factor (TF) levels were increased in post-COVID-19 Dengue, whereas Factor XIII was higher in pre-COVID-19 Dengue. In contrast, antithrombin (an anticoagulant) and plasminogen (a profibrinolytic factor) were more elevated in pre-COVID-19 Dengue than in post-COVID-19 cases. In vitro, DENV-2-infected platelets exposed to plasma of Dengue patients before and after COVID-19 showed decreased nitrite production in relation to DENV-2 alone. These findings suggest that prior COVID-19 exposure may influence hemostatic responses in Dengue, potentially modulating disease pathophysiology and opening new avenues for research and therapeutic strategies. Full article

Carotid artery intima–media thickness (cIMT), a pre-clinical vascular change that accompanies atherosclerosis is considered as a cardiovascular risk factor. Coagulation factor XIII (FXIII) stabilizes the fibrin clot and increases its resistance to fibrinolysis. Regarding FXIII Val34Leu polymorphism, the protective effect of the Leu34 allele in the presence of elevated fibrinogen levels against myocardial infarction was demonstrated. Our aim was to investigate the effect of FXIII polymorphisms on cIMT. Patients with obesity (n = 69), type 2 diabetes mellitus (T2DM) (n = 104), and age- and sex-matched healthy controls (n = 82) were enrolled. FXIII polymorphisms (Val34Leu, His95Arg, Intron-K C>G) were determined by RT-PCR with FRET detection and melting curve analysis. cIMT was determined by B-mode ultrasound. Differences in cIMT between control (median: 0.5965, IQR: 0.5115–0.6580 mm) and T2DM (median: 0.7105, IQR: 0.5948–0.7568 mm), as well as between obese (median: 0.6105, IQR: 0.5455–0.6780 mm) and diabetic groups, were found (p < 0.0001 and p = 0.003, respectively). Genotype and allele frequencies of the studied polymorphisms did not differ between subgroups. In the study group (n = 255) after adjustment for age and sex, the presence of Intron-K G allele showed a significant and independent protective effect against cIMT progression in a separate model (p = 0.005) and after adjusting for other parameters associated with cIMT (p = 0.015). FXIII Intron-K G allele provides a protective effect against subclinical vascular disease in the studied population, and this effect is independent of the presence of obesity, as well as T2DM, Leu34 allele, and fibrinogen levels. Full article

Dermatofibroma is a common mesenchymal skin lesion that typically presents as a firm, slow-growing nodule. Generally, such lesions are asymptomatic; however, they can also cause discomfort in some cases. Ulceration is an uncommon feature of dermatofibroma, and diagnosis in such cases is often difficult. We report a case of a 67-year-old female with multiple comorbidities, including pancreatic cancer undergoing neoadjuvant chemotherapy, who was admitted for acute pulmonary embolism. The patient presented with an incidental medial thigh lesion. The lesion was asymptomatic, ulcerated, and oozing pus one month before presentation. Clinical examination revealed a 3 × 2 cm deep ulcer with a punched-out edge, a dry yellow-white base, and a firm violaceous border. Histopathology confirmed dermatofibroma with epidermal hyperplasia, dermal spindle cell proliferation, histiocytes, and collagen trapping. Immunohistochemistry was positive for CD68, CD10, and Factor XIII. Due to the deteriorating condition of the patient, no intervention was provided to her, and she succumbed to her primary illness. This case is unique due to its atypical ulcerative presentation in a patient with complex systemic illness and emphasizes distinguishing between benign lesions and malignant mimics, especially in cases which have ambiguous clinical presentation. Full article

The syndrome “bassess richesses” is a vector-borne disease of sugar beet in Germany. The gammaproteobacterium ‘Candidatus Arsenophonus phytopathogenicus’ causes reduced sugar content and biomass, growth abnormalities, and yellowing. Co-infection with the 16SrXII-P stolbur phytoplasmas often leads to more severe symptoms and a risk of complete economic loss. This yellowing agent of the Mollicutes class had not been described before, so its differences from other stolbur phytoplasmas remained unanswered. The genome of strain GOE was sequenced, providing a resource to analyze its characteristics. Phylogenetic position was revised, genome organization was compared, and functional reconstructions of metabolic and virulence factors were performed. Average nucleotide identity analysis indicates that GOE represents a new ‘Ca. Phytoplasma’ species. Our results show that GOE is also distinct from other stolbur phytoplasmas in terms of smaller genome size and G+C content. Its reductive evolution is reflected in conserved membrane protein repertoire and minimal metabolism. The encoding of a riboflavin kinase indicates a lost pathway of phytoplasmas outside the groups 16SrXII and 16SrXIII. GOE shows a complete tra5 transposon harboring orthologs of SAP11, SAP54, and SAP05 effectors indicating an original phytoplasma pathogenicity island. Our results deepen the understanding of phytoplasma evolution and reaffirm the heterogeneity of stolbur phytoplasmas. Full article

Individual differences in environmental sensitivity are linked to stress-related psychiatric symptoms. In previous research, we found that high environmental sensitivity can be a risk factor for increased inflammation and gut permeability, particularly when gut microbiome diversity is low. However, the specific gut bacterial taxa involved in this interaction remain unclear. As a preliminary study, this research aimed to identify the key gut microbiome taxa associated with this relationship. Environmental sensitivity, gut microbiome composition, gut permeability (lipopolysaccharide-binding protein, LBP), and inflammation (C-reactive protein, CRP) biomarkers were evaluated in 88 participants. The interaction between environmental sensitivity and the relative abundance of the family Marinifilaceae (genus Butyricimonas) was a predictor of CRP levels. Similarly, the interaction between environmental sensitivity and relative abundance of the family Barnesiellaceae (genus Coprobacter), the family Akkermansiaceae (genus Akkermansia), the genus Family XIII AD3011 group, the genus GCA-900066225, or the genus Ruminiclostridium 1 predicted LBP levels. Individuals with high environmental sensitivity exhibited elevated CRP or LBP levels when the relative abundance of these taxa was low. Conversely, highly sensitive individuals had lower CRP or LBP levels when the relative abundance of these taxa was high. This study suggests that specific taxa serve as one of the protective factors against inflammation and gut permeability in individuals with high environmental sensitivity. Further in-depth studies are needed to confirm these associations and understand the underlying mechanisms. Full article

Background/Objectives: This study aims to investigate the role of congenital single nucleotide thrombophilia in young females with early recurrent pregnancy loss (RPL). Methods: We studied 120 pregnant females with RPL and 80 matched females as a control with no RPL. Females were aged ≤ 35 years, had at least two consecutive first-trimester RPLs, and the acquired cause of RPL was excluded. A matched control group of 80 pregnant women with no RPL was studied. Coagulation tests included prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), a Factor XIII functional assay, and detecting IgM and IgG anti-beta2-Glycoprotein I (β2GPI) antibodies by an ELISA. The DNA samples were tested for Factor V Leiden, Factor II G20210A, Methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), FXIII V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, endothelial protein C receptor (EPCR) A4600G, and endothelial protein C receptor (EPCR) G4678C. Results: Of the single nucleotide gene mutations investigated, the most relevant mutations were MTHFR C677T, MTHFR A1298C, heterozygous FXIII Val34Leu, and heterozygous FXIII 1694 C>T. Each of them conferred a statistically significant effect. There was a statistically significant protective role for the endothelial protein C receptor (EPCR) A2/A2, wild FXIII Val34Leu, and heterozygousFXIII1694 C>T. Conclusions: Our findings suggest the important role of congenital single nucleotide thrombophilia mutations in young Middle Eastern women with early RPL, particularly MTHFR mutations and FXIII Val34Leu. We found a protective effect of EPCR A2/A2, wild FXIIIVal34Leu, and heterozygous FXIII1694 C>T. We recommend additional studies to explore detrimental factors and protective factors. Full article

The basic helix–loop–helix (bHLH) superfamily is the second-largest transcription factor family that participates in a wide range of biological processes in plants, including iron homeostasis. Although the family has been studied in several plant species, a comprehensive investigation is still needed for peanut (Arachis hypogaea). Here, a genome-wide analysis identified 373 AhbHLH genes in peanut, which were divided into 14 groups or subfamilies according to phylogenetic analysis. Clustered members generally share similar gene/protein structures, supporting the evolutionary relationships among AhbHLH proteins. Most AhbHLHs experienced whole-genome or segmental duplication. The majority of AhbHLH proteins had a typical bHLH domain, while several phylogenetic groups, including Group VI, X, XIII, and XIV, had the HLH domain. The expression of several AhbHLH genes, including AhbHLH001.3, AhbHLH029.1/.2, AhbHLH047.1/.2, AhbHLH115.1/.2, AhbHLH097.1/.2, AhbHLH109.4, and AhbHLH135.1, was induced by Fe deficiency for both cultivars, or at least in Silihong, suggesting an important role in the Fe deficiency response in peanut. Nine genes (AhbHLH001.3, AhbHLH029.1/.2, AhbHLH047.1/.2, AhbHLH097.1/.2, and AhbHLH115.1/.2) were specifically induced by Fe deficiency in Silihong, and their expression was higher in Silihong than that in Fenghua 1. These genes might be responsible for higher tolerance to Fe deficiency in Silihong. Our findings provide comprehensive information for further elucidating the regulatory mechanism of Fe homeostasis in peanut. Full article

The structure of aspirated coronary thrombus in ST-segment elevation myocardial infarction (STEMI) is still being studied. Our aims were to characterize coronary thrombi of different ages, focusing on the appearance of activated protein C (APC/PC) and its relation to the elements of neutrophil extracellular traps (NETs), and the factors closely related to fibrin as factor XIII (FXIII) and α2 plasmin inhibitor (α2-PI). The thrombi of n = 24 male patients with atherosclerotic coronary plaque rupture related to native coronary artery occlusion were selected for histopathology analysis. Thrombus age was distinguished as fresh, lytic, and organized, and then analyzed by immunofluorescent staining and confocal microscopy. FXIII was present at a high level and showed a high degree of co-localization with fibrin in all stages of thrombus evolution. The amount of α2-PI was low in the fresh thrombi, which increased significantly to the lytic phase. It was evenly distributed and consistently associated with fibrin. APC/PC appeared in the fresh thrombus and remained constant during its evolution. The presence of NET marker and CD66b was most dominant in the lytic phase. APC/PC co-localization with the elements of NET formation shows its role in NET degradation. These observations suggest the importance of searching for further targeted therapeutic strategies in STEMI patients. Full article

Glomerular kidney diseases typically begin insidiously and can progress to end stage kidney failure. Early onset of therapy can slow down disease progression. Early diagnosis is required to ensure such timely therapy. The goal of our study was to evaluate protein biomarkers (BMs) for common nephropathies that have been described for children with Alport syndrome. Nineteen candidate BMs were determined by commercial ELISA in children with congenital anomalies of the kidneys and urogenital tract, inflammatory kidney injury, or diabetes mellitus. It is particularly essential to search for kidney disease BMs in children because they are a crucial target group that likely exhibits early disease stages and in which misleading diseases unrelated to the kidney are rare. Only minor differences in blood between affected individuals and controls were found. However, in urine, several biomarker candidates alone or in combination seemed to be promising indicators of renal injury in early disease stages. The BMs of highest sensitivity and specificity were collagen type XIII, hyaluronan-binding protein 2, and complement C4-binding protein. These proteins are unrelated to inflammation markers or to risk factors for and signs of renal failure. In conclusion, our study evaluated several strong candidates for screening for early stages of kidney diseases and can help to establish early nephroprotective regimens. Full article

The addition of glycerin, vitamin C, and niacinamide to pig diets increased the redness of longissimus dorsi; however, it remains unclear how these supplements affect gut microbiota and metabolites. A total of 84 piglets (20.35 ± 2.14 kg) were randomly allotted to groups A (control), B (glycerin-supplemented), C (vitamin C and niacinamide-supplemented), and D (glycerin, vitamin C and niacinamide-supplemented) during a feeding experiment. Metagenomic and metabolomic technologies were used to analyze the fecal compositions of bile acids, metabolites, and microbiota. The results showed that compared to pigs in group A, pigs in group D had lower virulence factor expressions of lipopolysaccharide (p < 0.05), fatty acid resistance system (p < 0.05), and capsule (p < 0.01); higher fecal levels of ferric ion (p < 0.05), allolithocholic acid (p < 0.01), deoxycholic acid (p < 0.05), tauroursodeoxycholic acid dihydrate (p < 0.01), glycodeoxycholic acid (p < 0.05), L-proline (p < 0.01) and calcitriol (p < 0.01); and higher (p < 0.05) abundances of iron-acquiring microbiota (Methanobrevibacter, Clostridium, Clostridiaceae, Clostridium_sp_CAG_1000, Faecalibacterium_sp_CAG_74_58_120, Eubacteriales_Family_XIII_Incertae_Sedis, Alistipes_sp_CAG_435, Alistipes_sp_CAG_514 and Methanobrevibacter_sp_YE315). Supplementation with glycerin, vitamin C, and niacinamide to pigs significantly promoted the growth of iron-acquiring microbiota in feces, reduced the expression of some virulence factor genes of fecal pathogens, and increased the fecal levels of ferric ion, L-proline, and some secondary bile acids. The administration of glycerol, vitamin C, and niacinamide to pigs may serve as an effective measure for muscle redness improvement by altering the compositions of fecal microbiota and metabolites. Full article

The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). Here, we tested whether WEE1 exhibits crosstalk with the AKT/GSK3 kinase pathway for coordinated regulation of FGF14/Nav1.2 channel complex assembly and function. Using the in-cell split luciferase complementation assay (LCA), we found that the WEE1 inhibitor II and GSK3 inhibitor XIII reduce the FGF14/Nav1.2 complex formation, while the AKT inhibitor triciribine increases it. However, combining WEE1 inhibitor II with either one of the other two inhibitors abolished its effect on the FGF14/Nav1.2 complex formation. Whole-cell voltage-clamp recordings of sodium currents (I_Na) in HEK293 cells co-expressing Nav1.2 channels and FGF14-GFP showed that WEE1 inhibitor II significantly suppresses peak I_Na density, both alone and in the presence of triciribine or GSK3 inhibitor XIII, despite the latter inhibitor’s opposite effects on I_Na. Additionally, WEE1 inhibitor II slowed the tau of fast inactivation and caused depolarizing shifts in the voltage dependence of activation and inactivation. These phenotypes either prevailed or were additive when combined with triciribine but were outcompeted when both WEE1 inhibitor II and GSK3 inhibitor XIII were present. Concerted regulation by WEE1 inhibitor II, triciribine, and GSK3 inhibitor XIII was also observed in long-term inactivation and use dependency of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase—in concert with the AKT/GSK3 pathway—in regulating the Nav1.2 channelosome. Full article

Background and Aims: In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study’s main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA). Methods: The study was conducted in two groups of 84 patients with AIS: group I—with thrombolytic therapy and group II—without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients’ activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil–lymphocyte ratio (NLR index), and the concentration of factor XIII-A. Results: In group I, the concentration of XIII-A decreased significantly between day 1 and 7 (p < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I. Conclusions: In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis. Full article

Pope Leo XIII’s publication of Aeterni Patris (1879) was a major factor in the great revival of Thomistic thought in the late 19th and the first half of the 20th centuries. Among the authors that took up the challenge implicit in the Pope’s document of bringing Aquinas and his thought into the intellectual debates of the times we find two interesting proposals. The first is that of Juan González Arintero, a Spanish Dominican, and the second one is that of Josef Donat, a Jesuit born and raised in the Austrian Empire. Arintero is mostly known in Catholic circles for his influential works on mysticism, but in fact he devoted much of his early work to the subject of evolution, and how it could interact with the Catholic faith in general, and with Thomism in particular. Donat is the author of a Summa Philosophiae Christianae, a collection that was widely read in Catholic seminaries well into the 20th century. In this paper we will focus on the differing ways in which these authors tackled the problems and questions presented by Darwinian evolutionism to the post-Aeterni Patris Thomism. Full article