Decreased Levels of Soluble Developmental Endothelial Locus-1 Are Associated with Thrombotic Microangiopathy in Pregnancy.

HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome is a life-threatening complication of pregnancy, which is often secondary to preeclampsia. To date, there is no biomarker in clinical use for the early stratification of women with preeclampsia who are under increased risk of HELLP syndrome. Herein, we show that the levels of circulating developmental endothelial locus-1 (DEL-1), which is an extracellular immunomodulatory protein, are decreased in patients with HELLP syndrome compared to preeclampsia. DEL-1 levels are also negatively correlated with the circulating levels of kidney injury molecule-1 (KIM-1), which is a biomarker for disorders associated with kidney damage. Receiver-operating characteristic curve analysis for DEL-1 levels and the DEL-1 to KIM-1 ratio demonstrates that these values could be used as a potential biomarker that distinguishes patients with HELLP syndrome and preeclampsia. Finally, we show that placental endothelial cells are a source for DEL-1, and that the expression of this protein in placenta from patients with HELLP syndrome is minimal. Taken together, this study shows that DEL-1 is downregulated in HELLP syndrome both in the circulation and at the affected placental tissue, suggesting a potential role for this protein as a biomarker, which must be further evaluated.

Legionella pneumophila: The Journey from the Environment to the Blood.

An outbreak of a potentially fatal form of pneumonia in 1976 and in the annual convention of the American Legion was the first time that Legionella spp. was identified. Thereafter, the term Legionnaires' disease (LD) was established. The infection in humans is transmitted by the inhalation of aerosols that contain the microorganisms that belong to the Legionellaceae family and the genus Legionella. The genus Legionella contains genetically heterogeneous species and serogroups. The Legionella pneumophila serogroup 1 (Lp1) is the most often detected strain in outbreaks of LD. The pathogenesis of LD infection initiates with the attachment of the bacterial cells to the host cells, and subsequent intracellular replication. Following invasion, Legionella spp. activates its virulence mechanisms: generation of specific compartments of Legionella-containing vacuole (LCV), and expression of genes that encode a type IV secretion system (T4SS) for the translocation of proteins. The ability of L. pneumophila to transmigrate across the lung's epithelium barrier leads to bacteremia, spread, and invasion of many organs with subsequent manifestations, complications, and septic shock. The clinical manifestations of LD depend on the bacterial load in the aerosol, the virulence factors, and the immune status of the patient. The infection has two distinct forms: the non- pneumatic form or Pontiac fever, which is a milder febrile flu-like illness, and LD, a more severe form, which includes pneumonia. In addition, the extrapulmonary involvement of LD can include heart, brain, abdomen, and joints.

The Emerging Role of the Gut Microbiome in Cardiovascular Disease: Current Knowledge and Perspectives.

The collection of normally non-pathogenic microorganisms that mainly inhabit our gut lumen shapes our health in many ways. Structural and functional perturbations in the gut microbial pool, known as "dysbiosis", have been proven to play a vital role in the pathophysiology of several diseases, including cardiovascular disease (CVD). Although therapeutic regimes are available to treat this group of diseases, they have long been the main cause of mortality and morbidity worldwide. While age, sex, genetics, diet, tobacco use, and alcohol consumption are major contributors (World Health Organization, 2018), they cannot explain all of the consequences of CVD. In addition to the abovementioned traditional risk factors, the constant search for novel preventative and curative tools has shed light on the involvement of gut bacteria and their metabolites in the pathogenesis of CVD. In this narrative review, we will discuss the established interconnections between the gut microbiota and CVD, as well as the plausible therapeutic perspectives.

Levels of Produced Antibodies after Vaccination with mRNA Vaccine; Effect of Previous Infection with SARS-CoV-2.

The aim of this study was to estimate the immunogenic effect of mRNA vaccine against SARS-CoV-2. This study included 510 participants who received mRNA vaccine. The measurement of anti-COVID-19 antibodies was performed using the Abbott SARS-CoV-2 IgG quantitative assay (Abbott). Overall, mean titer of anti-Spike antibodies was 19,319.2 ± 1787.5 AU/mL. Vaccination induced a robust immunogenic response in those previously infected with SARS-CoV-2 compared with non-infected subjects. Additionally, individuals that were asymptomatic after vaccination produced lower levels of antibodies compared to feverish individuals. In conclusion, remarkably high levels of anti-Spike COVID-19 antibodies were observed after vaccination.

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19.

Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.

The Usefulness of Rare Blood Group Systems in the Risk Determination for Severe COVID-19.

The newly identified human coronavirus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on a detailed analysis of clinical manifestation. It was reported that blood type O individuals were less likely to become infected by SARS-CoV, while blood type A individuals have an increased risk of severe illness. The Forssman antigen, or Forssman glycolipid synthase (FS), was first described in 1911 by John Frederick Forssman. Blood type A/B glycosyltransferases (AT/BTs) and Forssman glycolipid synthase (FS) are encoded by the evolutionarily related ABO (A/B alleles) and GBGT1 genes. In this article, based on published studies about the pathogenesis of the COVID-19, we hypothesize the possible relationship between the COVID-19 infection and rare blood type systems, such as the Forssman antigen system.

Inverse association between Helicobacter pylori infection and childhood asthma in Greece: a case-control study.

INTRODUCTION: Helicobacter pylori infection is a well-established etiological factor for a variety of diseases such as peptic ulcer and gastric cancer. On the other hand, there is ongoing research suggesting that H. pylori might have a beneficial effect through a pivotal influence in the immunological response especially in asthma. The aim of the current case-control study was to evaluate the prevalence of H. pylori infection in asthmatic children. METHODS: Twenty-seven children with exacerbation of persistent asthma, aged 8.6±4.5 years (18 males, 9 females) and 54 age-sex-matched non-asthmatic controls were enrolled. Clinical examination and laboratory investigations were performed. Detection of H. pylori antigen (HpSA) in stool samples was performed by a commercial kit (bioNexia® kit, BioMérieux). Serum specific IgG antibodies were detected by a rapid chromatographic immunoassay (DIAsourceImmunoAssays). Serum IgE concentration was determined by electrochemiluminescence (ECL) (Roche Elecsys) and IgE levels ≥ 90 IU/mL were considered significantly elevated. RESULTS: In 3 (11.1%) of the 27 asthmatic children H. pylori infection (based on both detection of HpSA and specific IgG-Abs) was established, whereas as many as 16 of the 54 (29.6%) non-asthmatic ones were found infected (odds ratio 0.1; 95%CI, 0.039-0.305, p=0.026). CONCLUSIONS: Our findings reveal an inverse relationship between H. pylori infection and children's persistent asthma in Greece.

Study of Antiphospholipid Antibodies in Patients with Arterial Hypertension.

Antiphospholipid syndrome (APS) is a multifactorial, autoantibody-mediated disease. Antiphospholipid antibodies (aPL) directed against negatively charged phospholipids or various combinations of phospholipid-binding proteins seem to be an independent pathogenic factor that plays a critical role in APS. Unfortunately, their role in hypertension is not fully elucidated. The aim of our study was to determine aPL titers in hypertension patients and investigate the association of aPL with renal impairment parameters. Forty-seven patients with arterial hypertension (22 males, 46.8% and 25 females, 53.2%), aged 41⁻85 years old (mean 65.9 ± 10.1 years), and 21 age-sex-matched subjects without severe hypertension as control group (8 males, 13 females, 38.1% vs. 61.9%), mean age 61 ± 11.3 years, were enrolled in this study. Patients with other risk factors like Rheumatoid Arthritis and Systematic Lupus Erythematosus (SLE), both viral and bacterial acute infections, and cancer were excluded from the study. The aPL (anticardiolipin (ACA) and anti-b2GPI antibodies, IgG and IgM) were measured by ELISA (Aesculisa, Aesku Diagnostics, Wendelsheim, Germany) with a cutoff of 15 GPL/MPL for ACA and 15 U/mL for b2GPI. Serum Neutrophil gelatinase-associated lipocalin (sNGAL) was measured by ELISA kits (BioVendor, Brno, Czech Republic). Biochemical analysis such as serum creatinine (Cr), were measured by automated analyzer and finally estimated glomerular filtration rate (e-GFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Fifteen patients were positive for ACA IgG (31.9%), two for anti-b2GPI IgM (4.2%), and three for anti-b2GPI IgG (6.3%). Furthermore, three persons from control group were positive in anti-b2GPI IgG (14.27%). The serum level of anti-b2GPI IgG was significantly higher in patients compared to healthy controls (p = 0.013). The level of sNGAL (59.63 ± 41.5 ng/mL vs. 45.5 ± 21.5 ng/mL, p = 0.14) was not higher in hypertensive patients than in the age-sex-matched control group. Additionally, the sNGAL level was found to be directly and positively correlated in patients with positive ACA IgG (r² = 0,945, p < 0.0001). These results demonstrate that autoimmunity may be one of the pathogenetic factors of hypertension and aPL antibodies might be a potential marker of renal involvement.

Environmental surveillance and molecular epidemiology of waterborne pathogen Legionella pneumophila in health-care facilities of Northeastern Greece: a 4-year survey.

A 4-year proactive environmental surveillance of Legionella spp. in the water distribution and cooling systems of five health-care facilities was carried out as part of the strategy for the prevention of hospital-acquired Legionnaires' disease in Northeastern Greece. Legionella spp. were detected in 71 out of 458 collected samples. The majority of strains belonged to Legionella pneumophila serogroups 2-15 (75.0%), while all L. pneumophila serogroup 1 strains (23.6%) were isolated from a single hospital. The highest percentage of positive samples was found in distal sites (19.4%), while no Legionella strains were detected in cooling systems. Each hospital was colonized at least once with L. pneumophila, while remedial actions resulted in significant reduction of Legionella concentration. The molecular epidemiology of environmental L. pneumophila strains was also investigated using random amplified polymorphic DNA (RAPD) and multi-gene sequence-based analysis. Based on RAPD patterns, L. pneumophila serogroups 2-15 and serogroup 1 strains were classified into 24 and 9 operational taxonomic units (OTUs), respectively. Sequencing of housekeeping and diversifying pressure-related genes recommended by European Working Group for Legionella Infections (EWGLI) revealed not only a high intraspecies variability but also the circulation and persistence of one specific genotyping profile in the majority of hospitals. This study highlights the necessity for diachronic surveillance of Legionella in health-care facilities by adopting both cultural and molecular methods.

First report of Legionella pneumophila in car cabin air filters. Are these a potential exposure pathway for professional drivers?

Recent findings have identified professional drivers as being at an increased risk of Legionnaires' disease. Our hypothesis was that used car cabin air filters represent a reservoir of Legionella bacteria, and thus a potential pathway for contamination. We analysed used cabin air filters from various types of car. The filters were analysed by culture and by molecular methods. Our findings indicated that almost a third of air filters were colonized with Legionella pneumophila. Here, we present the first finding of Legionella spp. in used car cabin air filters. Further investigations are needed in order to confirm this exposure pathway. The presence of Legionella bacteria in used cabin air filters may have been an unknown source of infection until now.