Comparative genomic analysis and molecular examination of the diversity of enterotoxigenic Escherichia coli isolates from Chile

Enterotoxigenic Escherichia coli (ETEC) is one of the most common diarrheal pathogens in the low- and middle-income regions of the world, however a systematic examination of the genomic content of isolates from Chile has not yet been undertaken. Whole genome sequencing and comparative analysis of a collection of 125 ETEC isolates from three geographic locations in Chile, allowed the interrogation of phylogenomic groups, sequence types and genes specific to isolates from the different geographic locations. A total of 80.8% (101/125) of the ETEC isolates were identified in E. coli phylogroup A, 15.2% (19/125) in phylogroup B, and 4.0% (5/125) in phylogroup E. The over-representation of genomes in phylogroup A was significantly different from other global ETEC genomic studies. The Chilean ETEC isolates could be further subdivided into sub-clades similar to previously defined global ETEC reference lineages that had conserved multi-locus sequence types and toxin profiles. Comparison of the gene content of the Chilean ETEC identified genes that were unique based on geographic location within Chile, phylogenomic classifications or sequence type. Completion of a limited number of genomes provided insight into the ETEC plasmid content, which is conserved in some phylogenomic groups and not conserved in others. These findings suggest that the Chilean ETEC isolates contain unique virulence factor combinations and genomic content compared to global reference ETEC isolates

Resistance to Fracture of Two All-Ceramic Crown Materials Following Endodontic Access

Statement of problem There is currently no protocol for managing endodontic access openings for all-ceramic crowns. A direct restorative material is generally used to repair the access opening, rendering a repaired crown as the definitive restoration. This endodontic procedure, however, may weaken the restoration or initiate microcracks that may propagate, resulting in premature failure of the restoration. Purpose The purpose of this in vitro study was to evaluate how an endodontic access opening prepared through an all-ceramic crown altered the structural integrity of the ceramic, and the effect of a repair of this access on the load to failure of an all-ceramic crown. Material and methods Twenty-four alumina (Procera) and 24 zirconia (Procera) crowns were fabricated and cemented (Rely X Luting Plus Cement) onto duplicate epoxy resin dies. Twelve crowns of each were accessed to simulate root canal treatment therapy. Surface defects of all accessed specimens were evaluated with an environmental scanning electron microscope. The specimens were repaired with a porcelain repair system (standard adhesive resin/composite resin protocol) and were loaded to failure in a universal testing machine. Observations made visually and microscopically noted veneer delamination from the core, core fracture, shear within the veneer porcelain, or a combination thereof. A Kruskal-Wallis test was used to determine if a significant difference (α=.05) in load to failure existed between the 4 groups, and a Mann-Whitney test with a Bonferroni correction (P Results All specimens exhibited edge chipping around the access openings. Some displayed larger chips within the veneering porcelain, and 4 zirconia crowns showed radial crack formation. There was a significant difference in load to failure among all groups with the exception of the alumina intact and repaired specimens (P=.695). The alumina crowns generally showed fracture of the coping with the veneering porcelain still bonded to the core, whereas the zirconia copings tended not to fracture but experienced veneering porcelain delamination. Conclusion Endodontic access through all-ceramic crowns resulted in a significant loss of strength in the zirconia specimens but not in the alumina specimens

Nature of eclipsing pulsars

We present a model for pulsar radio eclipses in some binary systems, and test this model for PSRs B1957+20 and J2051-0827. We suggest that in these binaries the companion stars are degenerate dwarfs with strong surface magnetic fields. The magnetospheres of these stars are permanently infused by the relativistic particles of the pulsar wind. We argue that the radio waves emitted by the pulsar split into the eigenmodes of the electron-positron plasma as they enter the companion's magnetosphere and are then strongly damped due to cyclotron resonance with the ambient plasma particles. Our model explains in a natural way the anomalous duration and behavior of radio eclipses observed in such systems. In particular, it provides stable, continuous, and frequency-dependent eclipses, in agreement with the observations. We predict a significant variation of linear polarization both at eclipse ingress and egress. In this paper we also suggest several possible mechanisms of generation of the optical and $X$-ray emission observed from these binary systems.Comment: 12 pages, 5 figures, submitted to Ap

Reports of COVID-19 vaccine adverse events in predominantly Republican vs Democratic states

IMPORTANCE: Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored. OBJECTIVE: To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican votes in the 2020 US presidential election. EXPOSURE: State-level percentage of Republican votes in the 2020 US presidential election. MAIN OUTCOMES AND MEASURES: Rates of any AE among COVID-19 vaccine recipients, rates of any severe AE among vaccine recipients, and the proportion of AEs reported as severe. RESULTS: A total of 620 456 AE reports (mean [SD] age of vaccine recipients, 51.8 [17.6] years; 435 797 reports from women [70.2%]; a vaccine recipient could potentially file more than 1 report, so reports are not necessarily from unique individuals) for COVID-19 vaccination were identified from the VAERS database. Significant associations between state political inclination and state AE reporting were observed for all 3 outcomes: a 10% increase in Republican voting was associated with increased odds of AE reports (odds ratio [OR], 1.05; 95% CI, 1.05-1.05; P \u3c .001), severe AE reports (OR, 1.25; 95% CI, 1.24-1.26; P \u3c .001), and the proportion of AEs reported as severe (OR, 1.21; 95% CI, 1.20-1.22; P \u3c .001). These associations were seen across all age strata in stratified analyses and were more pronounced among older subpopulations. CONCLUSIONS AND RELEVANCE: This cross-sectional study found that the more states were inclined to vote Republican, the more likely their vaccine recipients or their clinicians reported COVID-19 vaccine AEs. These results suggest that either the perception of vaccine AEs or the motivation to report them was associated with political inclination

Comparative genomics and transcriptomics of Escherichia coli isolates carrying virulence factors of both enteropathogenic and enterotoxigenic E. coli

AbstractEscherichia coli that are capable of causing human disease are often classified into pathogenic variants (pathovars) based on their virulence gene content. However, disease-associated hybrid E. coli, containing unique combinations of multiple canonical virulence factors have also been described. Such was the case of the E. coli O104:H4 outbreak in 2011, which caused significant morbidity and mortality. Among the pathovars of diarrheagenic E. coli that cause significant human disease are the enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). In the current study we use comparative genomics, transcriptomics, and functional studies to characterize isolates that contain virulence factors of both EPEC and ETEC. Based on phylogenomic analysis, these hybrid isolates are more genomically-related to EPEC, but appear to have acquired ETEC virulence genes. Global transcriptional analysis using RNA sequencing, demonstrated that the EPEC and ETEC virulence genes of these hybrid isolates were differentially-expressed under virulence-inducing laboratory conditions, similar to reference isolates. Immunoblot assays further verified that the virulence gene products were produced and that the T3SS effector EspB of EPEC, and heat-labile toxin of ETEC were secreted. These findings document the existence and virulence potential of an E. coli pathovar hybrid that blurs the distinction between E. coli pathovars.</jats:p

The suction effect during freak wave slamming on a fixed platform deck: Smoothed particle hydrodynamics simulation and experimental study

During the process of wave slamming on a structure with sharp corners, the wave receding after wave impingement can induce strong negative pressure (relative to the atmospheric pressure) at the bottom of the structure, which is called the suction effect. From the practical point of view, the suction force induced by the negative pressure, coinciding with the gravity force, pulls the structure down and hence increases the risk of structural damage. In this work, the smoothed particle hydrodynamics (SPH) method, more specifically the δ+SPH model, is adopted to simulate the freak wave slamming on a fixed platform with the consideration of the suction effect, i.e., negative pressure, which is a challenging issue because it can cause the so-called tensile instability in SPH simulations. The key to overcome the numerical issue is to use a numerical technique named tensile instability control (TIC). Comparative studies using SPH models with and without TIC will show the importance of this technique in capturing the negative pressure. It is also found that using a two-phase simulation that takes the air phase into account is essential for an SPH model to accurately predict the impact pressure during the initial slamming stage. The freak wave impacts with different water depths are studied. All the multiphase SPH results are validated by our experimental data. The wave kinematics/dynamics and wave impact features in the wave-structure interacting process are discussed, and the mechanism of the suction effect characterized by the negative pressure is carefully analyzed

Survival analysis of mortality and development of lupus nephritis in patients with systemic lupus erythematosus up to 40-years of follow-up

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have increased mortality compared with age and sex-matched controls. Lupus nephritis (LN) is a severe manifestation of SLE and an important cause of death. We carried out a retrospective survival analysis to investigate factors that could influence risk of mortality and LN in a large multi-ethnic cohort of patients with SLE. METHODS: By careful review of medical records, we identified 496 patients with SLE for whom we had complete information regarding period of observation and occurrence of death and nephritis. Patients were stratified into groups according to sex, ethnicity, age at start of follow-up and time-period of diagnosis. Kaplan-Meier analysis was used to investigate differences between the groups. RESULTS: Of 496 patients in the study, 91(18.3%) died, 165(33.3%) developed LN and 33(6.7%) developed end-stage renal failure. There was no difference between men and women in either mortality or development of LN. Caucasian patients were significantly less likely to develop LN than other ethnic groups (p< 0.0001) but not less likely to die. Patients diagnosed before the median age of 28 years were significantly more likely to develop LN (p< 0.0001) but significantly less likely to die (p= 0.0039) during the period of observation. There has been a significant improvement in survival between patients diagnosed between 1978-1989 and those diagnosed between 2006-11 (p= 0.019). CONCLUSION: In our cohort, non-Caucasian ethnicity and younger age at diagnosis are associated with risk of developing LN. There is evidence of improvement in survival of patients with SLE over time

ATM Regulates Insulin-Like Growth Factor 1-Secretory Clusterin (IGF-1-sCLU) Expression that Protects Cells against Senescence

Downstream factors that regulate the decision between senescence and cell death have not been elucidated. Cells undergo senescence through three pathways, replicative senescence (RS), stress-induced premature senescence (SIPS) and oncogene-induced senescence. Recent studies suggest that the ataxia telangiectasia mutant (ATM) kinase is not only a key protein mediating cellular responses to DNA damage, but also regulates cellular senescence induced by telomere end exposure (in RS) or persistent DNA damage (in SIPS). Here, we show that expression of secretory clusterin (sCLU), a known pro-survival extracellular chaperone, is transcriptionally up-regulated during both RS and SIPS, but not in oncogene-induced senescence, consistent with a DNA damage-inducible mechanism. We demonstrate that ATM plays an important role in insulin-like growth factor 1 (IGF-1) expression, that in turn, regulates downstream sCLU induction during senescence. Loss of ATM activity, either by genomic mutation (ATM-deficient fibroblasts from an ataxia telangiectasia patient) or by administration of a chemical inhibitor (AAI, an inhibitor of ATM and ATR), blocks IGF-1-sCLU expression in senescent cells. Downstream, sCLU induction during senescence is mediated by IGF-1R/MAPK/Egr-1 signaling, identical to its induction after DNA damage. In contrast, administration of an IGF-1 inhibitor caused apoptosis of senescent cells. Thus, IGF-1 signaling is required for survival, whereas sCLU appears to protect cells from premature senescence, as IMR-90 cells with sCLU knockdown undergo senescence faster than control cells. Thus, the ATM-IGF-1-sCLU pathway protects cells from lethality and suspends senescence