Use of Mechanical Chest Compression for Resuscitation in Out-Of-Hospital Cardiac Arrest-Device Matters: A Propensity-Score-Based Match Analysis.

Background: Devices for mechanical cardiopulmonary resuscitation (CPR) are recommended when high quality CPR cannot be provided. Different devices are available, but the literature is poor in direct comparison studies. Our aim was to assess whether the type of mechanical chest compressor could affect the probability of return of spontaneous circulation (ROSC) and 30-day survival in Out-of-Hospital Cardiac Arrest (OHCA) patients as compared to manual standard CPR.

Relationship between out-of-hospital cardiac arrests and COVID-19 during the first and second pandemic wave. The importance of monitoring COVID-19 incidence.

Background: The relationship between COVID-19 and out-of-hospital cardiac arrests (OHCAs) has been shown during different phases of the first pandemic wave, but little is known about how to predict where cardiac arrests will increase in case of a third peak.

Aim: To seek for a correlation between the OHCAs and COVID-19 daily incidence both during the two pandemic waves at a provincial level.

Methods: We considered all the OHCAs occurred in the provinces of Pavia, Lodi, Cremona, Mantua and Varese, in Lombardy Region (Italy), from 21/02/2020 to 31/12/2020.

Treatment of out-of-hospital cardiac arrest in the COVID-19 era: A 100 days experience from the Lombardy region.

Introduction: An increase in the incidence of OHCA during the COVID-19 pandemic has been recently demonstrated. However, there are no data about how the COVID-19 epidemic influenced the treatment of OHCA victims.

Methods: We performed an analysis of the Lombardia Cardiac Arrest Registry comparing all the OHCAs occurred in the Provinces of Lodi, Cremona, Pavia and Mantua (northern Italy) in the first 100 days of the epidemic with those occurred in the same period in 2019.

COVID-19 kills at home: the close relationship between the epidemic and the increase of out-of-hospital cardiac arrests.

Aims: An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve.

Methods And Results: We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019.

modeling of the cryptic E2∼ubiquitin-binding site of E6-associated protein (E6AP)/UBE3A reveals the mechanism of polyubiquitin chain assembly.

To understand the mechanism for assembly of Lys-linked polyubiquitin degradation signals, we previously demonstrated that the E6AP/UBE3A ligase harbors two functionally distinct E2∼ubiquitin-binding sites: a high-affinity Site 1 required for E6AP Cys∼ubiquitin thioester formation and a canonical Site 2 responsible for subsequent chain elongation. Ordered binding to Sites 1 and 2 is here revealed by observation of UbcH7∼ubiquitin-dependent substrate inhibition of chain formation at micromolar concentrations. To understand substrate inhibition, we exploited the PatchDock algorithm to model UbcH7∼ubiquitin bound to Site 1, validated by chain assembly kinetics of selected point mutants.

Convergent evolution in the assembly of polyubiquitin degradation signals by the Shigella flexneri IpaH9.8 ligase.

The human pathogen Shigella flexneri subverts host function and defenses by deploying a cohort of effector proteins via a type III secretion system. The IpaH family of 10 such effectors mimics ubiquitin ligases but bears no sequence or structural homology to their eukaryotic counterpoints. Using rates of (125)I-polyubiquitin chain formation as a functional read out, IpaH9.

The active form of E6-associated protein (E6AP)/UBE3A ubiquitin ligase is an oligomer.

Employing 125I-polyubiquitin chain formation as a functional readout of ligase activity, biochemical and biophysical evidence demonstrates that catalytically active E6-associated protein (E6AP)/UBE3A is an oligomer. Based on an extant structure previously discounted as an artifact of crystal packing forces, we propose that the fully active form of E6AP is a trimer, analysis of which reveals a buried surface of 7508Å2 and radially symmetric interacting residues that are conserved within the Hect (homologous to E6AP C terminus) ligase superfamily. An absolutely conserved interaction between Phe(727) and a hydrophobic pocket present on the adjacent subunit is critical for trimer stabilization because mutation disrupts the oligomer and decreases kcat 62-fold but fails to affect E2 ubiquitin binding or subsequent formation of the Hect domain Cys(820) ubiquitin thioester catalytic intermediate.

E6AP/UBE3A ubiquitin ligase harbors two E2~ubiquitin binding sites.

By exploiting (125)I-polyubiquitin chain formation as a functional readout of enzyme activity, we have quantitatively examined the mechanism of human E6AP/UBE3A for the first time. Initial rate studies identify UbcH7 as the cognate E2 carrier protein for E6AP, although related Ubc5 isoforms and the ISG15-specific UbcH8 paralog also support E6AP with reduced efficacy due to impaired binding and catalytic competence. Initial rates of polyubiquitin chain formation displayed hyperbolic kinetics with respect to UbcH7 concentration (K(m) = 57.

Tripartite motif ligases catalyze polyubiquitin chain formation through a cooperative allosteric mechanism.

Ligation of polyubiquitin chains to proteins is a fundamental post-translational modification, often resulting in targeted degradation of conjugated proteins. Attachment of polyubiquitin chains requires the activities of an E1 activating enzyme, an E2 carrier protein, and an E3 ligase. The mechanism by which polyubiquitin chains are formed remains largely speculative, especially for RING-based ligases.

Measuring rates of ubiquitin chain formation as a functional readout of ligase activity.

Specificity within the pathways of ubiquitin conjugation are defined by protein-binding affinities among the components. Enzyme kinetics provides a facile high-resolution experimental approach for quantitating such protein-binding affinities and yields additional mechanistic insights into the transition state of the enzyme-catalyzed reaction. Most ubiquitin ligases form free polyubiquitin chains at a slow rate in the absence of their cognate target protein as a normal step in their overall catalytic cycle.

PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model.

Background: We recently showed that poly(ADP-ribose)polymerase-1 (PARP-1) may play a role in allergen (ovalbumin)-induced airway eosinophilia, potentially through a specific effect on IL-5 production. We also reported that while IL-5 replenishment promotes reversal of eosinophilia in lungs of PARP-1(-/-) mice, IL-4 or Immunoglobulin E replenishment do not, suggesting a potentially significant regulatory relationship between PARP-1 and IL-5.

Objective: To explore the mechanism by which PARP-1 regulates IL-5 production and to determine how PARP-1 inhibition blocks allergen-induced eosinophilia.

Oxidative stress in mouse liver caused by dietary amino acid deprivation: protective effect of methionine.

The aim of this work was to evaluate the effects of a diet depleted of amino acids (protein-free diet, or PFD), as well as the supplementation with methionine (PFD+Met), on the antioxidant status of the female mouse liver. With this purpose, cytosolic protein spots from two-dimensional non-equilibrium pH gel electrophoresis were identified by several procedures, such as mass spectrometry, Western blot, gel matching and enzymatic activity. PFD decreased the contents of catalase (CAT), peroxiredoxin I (Prx-I), and glutathione peroxidase (GPx) by 67%, 37% and 45%, respectively.

The mouse liver content of carbonic anhydrase III and glutathione S-tranferases A3 and P1 depend on dietary supply of methionine and cysteine.

The contents of glutathione S-transferase (GST) subunits, carbonic anhydrase III (CAIII), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a 230 kDa protein are affected by protein deprivation in mouse liver. In order to know if particular amino acids control these contents, the effects of feeding for 5 days with diets containing different amino acids were examined. After an exploration using SDS-PAGE analysis, the action of selected diets was further examined by distinct techniques.

A germin-like protein of wheat leaf apoplast inhibits serine proteases.

A protein resistant to heat and proteolysis that inhibits serine proteases was isolated from wheat leaf apoplasts. Based on trypsin inhibition, its more active form was a 66-69 kDa oligomer. It was dissociated in an 18-21 kDa monomer having an amino terminal sequence identical to the Box A of germins and germin-like proteins.

Two dimensional non equilibrium pH gel electrophoresis mapping of cytosolic protein changes caused by dietary protein depletion in mouse liver.

Two-dimensional non-equilibrium pH gel electrophoresis (2D-NEPHGE) analysis was used to evaluate the effects of dietary protein depletion on the protein composition of mouse liver cytosol. Analysing the cytosol from both normal and protein depleted liver, the position in gels of more than three hundred protein spots was determined. After 5 days of protein depletion, about 20% of the spots either increased or decreased more than 2 fold.

[Inflammatory pseudotumor of the lung. Diagnostic-therapeutic effectiveness of its radical resection].

Clinical, therapeutical observations and experience in 3 cases of pulmonary inflammatory pseudotumors (PIP) are presented. A retrospective analysis is made of cases with pulmonary "mass" suspected as malignant tumor, resected in a general surgery department between 1988 and 1995, and finally diagnosed as inflammatory pseudotumor. Three of the 10 cases originally diagnosed as malignant lung tumor were inflammatory pseudotumor (30%).

[A new case of hepatic adenomatosis. A critical review of the literature].

Liver adenomatosis is a rare disease--only 22 cases are previously described--characterized by multiple adenomas (more than ten) in a normal parenchyma. After a literature review the authors cannot exclude a link between the estroprogestatives use and the development of adenomatosis. Most important risks are bleeding and development of new adenomas, after the operation.

Genome plasticity during the acquisition of embryogenic competence.

Hypocotyl explants from carrot and other species experience concomitant segregation events and differentiation of homeotic structures during the first 20 days of culture on 2,4-dichlorophenoxyacetic acid (2,4-D). In addition to these cyto-morphological changes, significant amounts of nuclear DNA are lost, the molecular details of which we investigate in this paper. We have developed a slot-blot analysis assay to study the DNA content of a series of carrot samples; besides the leaves, this survey ranged over different culture timepoints: hypocotyls, cell lines, and somatic embryo stages.

[Hepatic cystadenocarcinoma].

The biliary cystadenocarcinoma is a rare liver neoplasm with a preoperative difficult diagnosis to make, but increased by ultrasonography. Is reported the case of a caucasian male 78 years old, operated 11 years previously for partial resection of a benign liver cyst. Recurrent cholangitis and obstructive jaundice required a reoperation for right hepatectomy.

Nested allele-specific PCR primers distinguish genetic groups of Uncinula necator.

Isolates of the obligately biotrophic fungus Uncinula necator cluster in three distinct genetic groups (groups I, II, and III). We designed PCR primers specific for these groups in order to monitor field populations of U. necator.

[The spontaneous rupture of a pyogenic liver abscess. A clinical case].

The authors report a case of a large monolocular liver abscess in a patient with gallbladder and choledocic stones and biliary stent, complicated by rupture into the peritoneal cavity, that required surgical treatment. Surgical exploration versus other approach results the choice treatment, as shown by resolution of the pathology.

Stimulation of carrot somatic embryogenesis by proline and serine.

Serine and proline, when added in a wide range of concentrations to Daucus carota cultures during pre-growth in the presence of 2,4-D(2,4-dichlorophenoxyacetic acid), extended in time and quantity the mitotic divisions and stimulated significantly the number of embryos regenerated when the hormone subsequently was omitted from the medium. A specific effect of these amino acids on regeneration is suggested, since proline (as hydroxyproline) and serine are the two major constituents of the cell wall glycoprotein, extensin, which thus may have a morphoregulatory function. The significant role of the conditions during pregrowth of the cultures in the presence of hormone is underlined by the effect of hydroxyproline and D-proline which also stimulate embryogenesis, but alter markedly the development of the embryos.