The taxonomy of the order Piroplasmida, which includes a number of clinically and economically relevant organisms, is a hotly debated topic amongst parasitologists. Three genera (Babesia, Theileria, ...and Cytauxzoon) are recognized based on parasite life cycle characteristics, but molecular phylogenetic analyses of 18S sequences have suggested the presence of five or more distinct Piroplasmida lineages. Despite these important advancements, a few studies have been unable to define the taxonomic relationships of some organisms (e.g. C. felis and T. equi) with respect to other Piroplasmida. Additional evidence from mitochondrial genome sequences and synteny should aid in the inference of Piroplasmida phylogeny and resolution of taxonomic uncertainties. In this study, we have amplified, sequenced, and annotated seven previously uncharacterized mitochondrial genomes (Babesia canis, Babesia vogeli, Babesia rossi, Babesia sp. Coco, Babesia conradae, Babesia microti-like sp., and Cytauxzoon felis) and identified additional ribosomal fragments in ten previously characterized mitochondrial genomes. Phylogenetic analysis of concatenated mitochondrial and 18S sequences as well as cox1 amino acid sequence identified five distinct Piroplasmida groups, each of which possesses a unique mitochondrial genome structure. Specifically, our results confirm the existence of four previously identified clades (B. microti group, Babesia sensu stricto, Theileria equi, and a Babesia sensu latu group that includes B. conradae) while supporting the integration of Theileria and Cytauxzoon species into a single fifth taxon. Although known biological characteristics of Piroplasmida corroborate the proposed phylogeny, more investigation into parasite life cycles is warranted to further understand the evolution of the Piroplasmida. Our results provide an evolutionary framework for comparative biology of these important animal and human pathogens and help focus renewed efforts toward understanding the phylogenetic relationships within the group.
•Post-marketing surveillance is essential to monitor COVID-19 vaccine safety patterns.•Spontaneous reporting shows a comparable reporting pattern for basic and booster vaccines.•Spontaneous reporting ...shows similar reporting patterns for heterologous vaccination sequences.
The rapid roll-out of novel COVID-19 vaccines made near real-time post-marketing safety surveillance essential to identify rare and long-term adverse events following immunization (AEFIs). In light of the ongoing booster vaccination campaigns, it is key to monitor changes in observed safety patterns post-vaccination. The effect of sequential COVID-19 vaccinations, as well as heterologous vaccination sequences, on the observed post-vaccination safety pattern, remains largely unknown.
The primary objective of this study was to describe the profile of spontaneously reported AEFIs following COVID-19 vaccination in the Netherlands, including the primary and booster series. Reports from consumers and healthcare professionals were collected via a COVID-19 vaccine-tailored online reporting form by the National Pharmacovigilance Centre Lareb (Lareb) between 6 January 2021 and 31 August 2022. The data were used to describe the most frequently reported AEFIs per vaccination moment, the consumer experienced burden per AEFI, and differences in AEFIs reported for homologous and heterologous vaccination sequences.
Lareb received 227,884 spontaneous reports over a period of twenty months. Overall, a high degree of similarity in local and systemic AEFIs per vaccination moment was observed, with no apparent change in the number of reports of serious adverse events after multiple COVID-19 vaccinations. No differences in the pattern of reported AEFIs per vaccination sequence was observed.
Spontaneous reported AEFIs demonstrated a similar reporting pattern for homologous and heterologous primary and booster series of COVID-19 vaccination in the Netherlands.
Context. Recent observations from NASA’s Kepler mission detected the first planets in circumbinary orbits. The question we try to answer is where these planets formed in the circumbinary disk and how ...far inside they migrated to reach their present location. Aims. We investigate the first and most delicate phase of planet formation when planetesimals accumulate to form planetary embryos. Methods. We use the hydrodynamical code FARGO to study the evolution of the disk and of a test population of planetesimals embedded in it. With this hybrid hydrodynamical-N-body code we can properly account for the gas drag force on the planetesimals and for the gravitational force of the disk on them. Results. The numerical simulations show that the gravity of the eccentric disk on the planetesimal swarm excites their eccentricities to much higher values than those induced by the binary perturbations only within 10 AU from the stars. Moreover, the disk gravity prevents a full alignment of the planetesimal pericenters. Both these effects lead to high impact velocities, beyond the critical value for erosion. Conclusions. Planetesimal accumulation in circumbinary disks appears to be prevented close to the stellar pair by the gravitational perturbations of the circumbinary disk. The observed planets possibly formed in the outer regions of the disk and then migrated inside by tidal interaction with the disk.
Enterococcus cecorum (EC) is the dominant enteric commensal of adult chickens and contributes to the gut consortia of many avian and mammalian species. While EC infection is an uncommon zoonosis, ...like other enterococcal species it can cause life-threating nosocomial infection in people. In contrast to other enterococci which are considered opportunistic pathogens, emerging pathogenic strains of EC cause outbreaks of musculoskeletal disease in broiler chickens. Typical morbidity and mortality is comparable to other important infectious diseases of poultry. In molecular epidemiologic studies, pathogenic EC strains were found to be genetically clonal. These findings suggested acquisition of specific virulence determinants by pathogenic EC. To identify divergent genomic features and acquired virulence determinants in pathogenic EC; comparative genomic analysis was performed on genomes of 3 pathogenic and 3 commensal strains of EC. Pathogenic isolates had smaller genomes with a higher GC content, and they demonstrated large regions of synteny compared to commensal isolates. A molecular phylogenetic analysis demonstrated sequence divergence in pathogenic EC genomes. At a threshold of 98% identity, 414 predicted proteins were identified that were highly conserved in pathogenic EC but not in commensal EC. Among these, divergent CRISPR-cas defense loci were observed. In commensal EC, the type IIA arrangement typical for enterococci was present; however, pathogenic EC had a type IC locus, which is novel in enterococci but commonly observed in streptococci. Potential mediators of virulence identified in this analysis included a polysaccharide capsular locus similar to that recently described for E. faecium, an epa-like locus, and cell wall associated proteins which may bind host extracellular matrix. This analysis identified specific genomic regions, coding sequences, and predicted proteins which may be related to the divergent evolution and increased virulence of emerging pathogenic strains of EC.
Aim:To evaluate the effects of intravitreal bevacizumab for non-proliferative type 2 idiopathic macular telangiectasia (type 2 IMT) within a mean follow-up period of 18 months.Methods:The authors ...retrospectively studied six eyes of five patients with type 2 IMT who received two doses of intravitreal bevacizumab (1.5 mg) at a 4-week interval, followed by further applications depending on disease activity. Examinations included biomicroscopy, standardised visual acuity (VA) testing, fluorescein angiography, retinal thickness analysis by optical coherence tomography and fundus-controlled microperimetry.Results:Mean follow-up time was 18 months (range 16–21 months). The mean VA at four selected time points (1 month after second treatment, 1 month and 3–4 months after last treatment, and at last visit) increased significantly (by 8.8, 6.3, 7.7 and 8.7 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively; all p⩽0.05). Parafoveal leakage in fluorescein angiography and mean central retinal thickness decreased in all eyes following treatment. A rebound effect was observed after 3–4 months, and at the last visit, retinal thickness was increased in selected retinal sectors including the fellow eye.Conclusion:Inhibition of vascular endothelial growth factor (VEGF) by intravitreally injected bevacizumab may lead to functional improvement as well as a transient decrease in leakage and retinal thickness in patients with type 2 IMT. A VEGF-mediated active disease stage in which treatment might be most effective is discussed.
We numerically explore planet formation around α Centauri A by focusing on the crucial planetesimals-to-embryos phase. Our approach is significantly improved with respect to the earlier work of ...Marzari & Scholl, since our deterministic N-body code computing the relative velocities between test planetesimals handles bodies with different size. Due to this step-up, we can derive the accretion versus fragmentation trend of a planetesimal population having any given size distribution. This is a critical aspect of planet formation in binaries since the pericenter alignment of planetesimal orbits due to the gravitational perturbations of the companion star and to gas friction strongly depends on size. Contrary to Marzari & Scholl, we find that, for the nominal case of a Minimum-Mass Solar Nebula gas disc, the region beyond ∼0.5 au from the primary is strongly hostile to planetesimal accretion. In this area, impact velocities between different-sized bodies are increased, by the differential orbital phasing, to values too high to allow mutual accretion. For any realistic size distribution for the planetesimal population, this accretion-inhibiting effect is the dominant collision outcome and the accretion process is halted. Results are relatively robust with respect to the profile and density of the gas disc. Except for an unrealistic almost gas-free case, the inner ‘accretion-safe’ area never extends beyond 0.75 au. We conclude that planet formation is very difficult in the terrestrial region around α Centauri A, unless it started from fast-formed very large (>30 km) planetesimals. Notwithstanding these unlikely initial conditions, the only possible explanation for the presence of planets around 1 au from the star would be the hypothetical outward migration of planets formed closer to the star or a different orbital configuration in the binary's early history. Our conclusions differ from those of several studies focusing on the later embryos-to-planets stage, confirming that the planetesimals-to-embryos phase is more affected by binary perturbations.
Aim:To characterise the ocular phenotype of a family segregating the splice site mutation c.2189+1G>T in the tyrosine kinase receptor gene MERTK.Methods:Five affected children of a consanguineous ...Moroccan family were investigated by ophthalmic examinations, including fundus photography, autofluorescence (FAF) imaging, optical coherence tomography (OCT), psychophysical and electrophysiological methods.Results:Affected children were between 5 and 19 years of age, allowing an estimation of disease progression. Electroretinography demonstrated loss of scotopic and photopic function in the first decade of life. Younger siblings showed drusen-like deposits with focal relatively increased FAF in the macular area. With increasing age, a yellowish lesion with relatively increased FAF and subsequent macular atrophy developed. Visual acuity deteriorated with age and ranged between 20/50 in the best eye of the youngest affected and 20/400 in the worst eye of the oldest affected sibling. Spectral-domain OCT revealed debris-like material in the subneurosensory space.Conclusion:The splice site mutation c.2189+1G>T in MERTK causes rod–cone dystrophy with a distinct macular phenotype. The debris in the subneurosensory space resembles that in the Royal College of Surgeons (RCS) rat being the mertk animal model. Patients might therefore benefit from advances in gene therapy that were previously achieved in the RCS rat.
Context. Hydrodynamical simulations of two giant planets embedded in a gaseous disk have shown that in case of a smooth convergent migration they end up trapped into a mean motion resonance. These ...findings have led to the conviction that the onset of dynamical instability causing close encounters between the planets can occur only after the dissipation of the gas when the eccentricity damping is over. Aims. We show that a system of three giant planets may undergo planet-planet scattering when the gaseous disk, with density values comparable to that of the minimum mass solar nebula, is still interacting with the planets. Methods. The hydrodynamical code FARGO–2D–1D is used to model the evolution of the disk and planets, modified to properly handle close encounters between the massive bodies. Results. Our simulations predict a variety of different outcomes of the scattering phase, which includes orbital exchange, planet merging and scattering of a planet in a hyperbolic orbit. Conclusions. This implies that the final fate of a multiplanet system under the action of the disk torques is not necessarily a packed resonant configuration.
Aims. We study the evolution of circumstellar massive disks around the primary star of a binary system focusing on the computation of disk eccentricity. In particular, we concentrate on its ...dependence on the binary eccentricity. Self-gravitation is included in our numerical simulations. Our standard model assumes a semimajor axis for the binary of 30 AU, the most probable value according to the present binary statistics. Methods. Two-dimensional hydrodynamical computations are performed with FARGO. Besides the dynamical standard method to determine disk eccentricities, we apply a morphological method which may allow a better comparison with observations. Results. Self-gravitation leads to disks that, on average, have low eccentricity. Moreover, the orientation of the disk computed with the standard dynamical method always librates instead of circulating as in simulations without self-gravitation. The disk eccentricity decreases with the binary eccentricity, a result found also in models without self-gravitation. Conclusions. Disk self-gravitation appears to be an important factor in determining the evolution of a massive disk in a binary system. High eccentricity binaries are not necessarily a hostile environment for planetary accretion.
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