Genomic Characterization of hlyF-positive Shiga Toxin–Producing Escherichia coli,Italy and the Netherlands, 2000–2019

Shiga toxin–producing Escherichia coli (STEC) O80:H2 has emerged in Europe as a cause of hemolytic uremic syndrome associated with bacteremia. STEC O80:H2 harbors the mosaic plasmid pR444_A, which combines several virulence genes, including hlyF and antimicrobial resistance genes. pR444_A is found in some extraintestinal pathogenic E. coli (ExPEC) strains. We identified and characterized 53 STEC strains with ExPEC-associated virulence genes isolated in Italy and the Netherlands during 2000–2019. The isolates belong to 2 major populations: 1 belongs to sequence type 301 and harbors diverse stx₂ subtypes, the intimin variant eae-ξ, and pO157-like and pR444_A plasmids; 1 consists of strains belonging to various sequence types, some of which lack the pO157 plasmid, the locus of enterocyte effacement, and the antimicrobial resistance–encoding region. Our results showed that STEC strains harboring ExPEC-associated virulence genes can include multiple serotypes and that the pR444_A plasmid can be acquired and mobilized by STEC strains.     

The impact of decentralisation on the performance of health care systems: a non-linear relationship

The European Journal of Health Economics - This paper examines the role of institutions—notably the degree of administrative decentralisation across levels of government—in health care...     

Human liver stem cell-derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia

Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell-derived extracellular vesicles (HLSC-EVs) are able to reduce liver injury and promote regeneration. We investigated the efficacy of a reconditioning strategy with HLSC-EVs in an experimental model of NMP. Following total hepatectomy, rat livers were divided into 4 groups: (i) healthy livers, (ii) warm ischemic livers (60 min of warm ischemia), (iii) warm ischemic livers treated with 5 × 10⁸ HLSC-EVs/g-liver, and (iv) warm ischemic livers treated with a 25 × 10⁸ HLSC-EVs/g-liver. NMP lasted 6 h and HLSC-EVs (Unicyte AG, Germany) were administered within the first 15 min. Compared to controls, HLSC-EV treatment significantly reduced transaminases release. Moreover, HLSC-EVs enhanced liver metabolism by promoting phosphate utilization and pH self-regulation. As compared to controls, the higher dose of HLSC-EV was associated with significantly higher bile production and lower intrahepatic resistance. Histologically, this group showed reduced necrosis and enhanced proliferation. In conclusion, HLSC-EV treatment during NMP was feasible and effective in reducing injury in a DCD model with prolonged warm ischemia.     

Clonal composition and persistence of antigen-specific circulating T follicular helper cells

T follicular helper (T_FH) cells play an essential role in promoting B cell responses and antibody affinity maturation in germinal centers (GC). A subset of memory CD4⁺ T cells expressing the chemokine receptor CXCR5 has been described in human blood as phenotypically and clonally related to GC T_FH cells. However, the antigen specificity and relationship of these circulating T_FH (cT_FH) cells with other memory CD4⁺ T cells remain poorly defined. Combining antigenic stimulation and T cell receptor (TCR) Vβ sequencing, we found T cells specific to tetanus toxoid (TT), influenza vaccine (Flu), or Candida albicans (C.alb) in both cT_FH and non-cT_FH subsets, although with different frequencies and effector functions. Interestingly, cT_FH and non-cT_FH cells specific for C.alb or TT had a largely overlapping TCR Vβ repertoire while the repertoire of Flu-specific cT_FH and non-cT_FH cells was distinct. Furthermore, Flu-specific but not C.alb-specific PD-1⁺ cT_FH cells had a “GC T_FH-like” phenotype, with overexpression of IL21, CXCL13, and BCL6. Longitudinal analysis of serial blood donations showed that Flu-specific cT_FH and non-cT_FH cells persisted as stable repertoires for years. Collectively, our study provides insights on the relationship of cT_FH with non-cT_FH cells and on the heterogeneity and persistence of antigen-specific human cT_FH cells.     

Solubility Enhancement of Nucleosides and Structurally Related Compounds by Complex Formation

Water-soluble vitamins, amino acids, and nontoxic pharmaceutical excipients were studied as solubilizing agents for poorly water-soluble adenine (nucleic acid base), guanosine (nucleoside), and structurally related drugs (acyclovir and triamterene). The apparent solubility of the substrates (adenine, guanosine, acyclovir, or triamterene) was appreciably increased by forming complexes with the ligands (vitamins, amino acids, or other ligand). Apparent association constants (K _a ) values were measured at 25°C in pH 7 phosphate buffer using phase solubility analysis. The effect of combination ligands on substrate solubility was also studied. Additive solubility enhancement was obtained for several ligand pairs.     

Effects of intraperitoneal Ringer's lactate instillation and infusion on postsurgical adhesion formation

We compared the effects of continuous Ringer's lactate infusion and Ringer's lactate instillation on postsurgical adhesion formation in the rat model. The results show that intraperitoneal Ringer's lactate instillation reduces postsurgical adhesions. However, its efficacy is not improved by additional infusion of Ringer's lactate.     

Cyfra 21-1 - a new tumor-marker for lung-cancer

Among 20 known cytokeratins, cytokeratin fragment 19 is a 40 kD acidic molecule whose distibution is restricted to simple or pseudo-stratified epitelia, such as the epithelial layer of the bronchial tree. An immunoradiometric assay, CYFRA 21-1, was used to detect a fragment of cytokeratin 19 in the serum of 90 subjects and compared with serum levels of CEA, NSE and TPA. Sixty-seven consecutive patients with lung cancer and 23 healthy subjects were tested. Cut-off values for tumor markers were considered as the 95% of specificity versus controls. There were 32 adenocarcinomas, 29 squamous carcinomas and 6 other tumors. Increased serum levels of CYFRA 21-1 were found in lung cancer patients compared to controls [1.6 (0.2-3.2) versus 0.5 (0.2-1.8): p<0.001]. In our study TPA was more sensitive than CYFRA 21-1: 49% versus 40%; when we combined both markers the sensitivity increased to 63%. Significant difference in values were found before and after surgery in serum levels of 34 operated patients: p<0.01. We found higher levels of soluble cytokeratin 19 in lung cancer patients and in the adenocarcinoma subgroup. This study does not support the exclusive use of soluble cytokeratin 19 as a specific marker of lung cancer and not only in squamous carcinoma subgroup. This suggested that diagnostic and prognostic sensitivity increase when CYFRA 21-1 and TPA or other markers are combined.     

Surfactant replacement therapy: a multicentric trial comparing two dosage approaches

This is an interim analysis of a multicentric trial that took place in 7 Neonatal Units to compare two initial doses of exigenous pulmonary surfactant (100 mg/kg and 200 mg/kg of phospholipids)by using a porcine surfactant for the treatment of very severe Hyaline Membrane Disease. The initial higher dose produced better oxigenation of arterial blood, reducing the time in high oxygen concentrations,while retreatments were necessary in less than half of the infants receiving 200 mg/kg as initial dose. The protocol of this study allowed the administration of additional doses only when FiO(2) was equal or greater than 0.40 instead of > 0.21, as in a large study recently published, where the same initial doses were given. This resulted in more than 40% reduction in the amount of surfactant administered,with apparently similar clinical outcome.     

Evaluation of compensation filters in pedal radiographs

Compensation filters allow increased visibility of detail in chest, shoulder, spine, hip, knee, and foot radiographs. This study examines use of an anatomic compensation filter to improve imaging in pedal radiographs. Anteroposterior radiographs were obtained of 25 cadaveric feet at two settings with and without the compensation filter. Densitometer readings were taken at ten forefoot anatomic sites. The compensation filter produced statistically significant reductions in densitometer readings at all anatomic sites and at both radiographic settings. Filtration improved imagery of bony structures, provided excellent soft-tissue visualization, and lowered patient exposure.