Teeth Abnormalities in the Dog

Teeth abnormalities can be genetically induced by disturbances in the differentiation of the dental lamina and the tooth buds, and are relatively common in dogs, especially in purebred and line-bred dogs in which the genetic fault has been perpetuated. They are most common in small-breed dogs but occur in large breeds, too. The aim of our study was to investigate permanent tooth anomalies in dogs. In 627 dogs referred for dental treatment we observed the presence of hypodontia, impacted teeth, hyperdontia, supernumerary and hyponumerary roots, focal macrodontia, focal microdontia, gemination, concrescence, fusion, dilaceration and enamel pearls. Teeth anomalies were detected in 288 (45.93%) dogs of different skull shape. The most common anomalies in the observed population were dilaceration of the root with 99 (34.4%) third lower and upper incisors, fourth lower and upper premolars and first lower and upper molars involved and hypodontia with 93 (32.3%) first and second lower and upper premolars, and third lower molars involved. The proportion of an uncommon anomaly, such as fusion, was statistically significant (p < 0.01) for second lower and upper premolars 34 (11.8%) and lower and upper molars. 22 (7.6%) dogs had hyperodontia. The most affected teeth were the second lower and upper incisors. In 18 (6.3%) dogs we observed supernumerary roots. Hyponumerary roots, macro- and microdontia

Virulence potential of faecal <i>Escherichia coli</i> strains isolated from healthy cows and calves on farms in Perm Krai

Cattle are a reservoir of pathogenic and potentially pathogenic Escherichia coli (E. coli) strains, which can pose a threat to human and animal health. The aim of the study was to evaluate the occurrence of 22 virulence-associated genes (VAGs), as well as the prevalence of antimicrobial drug resistance and three different bla-genes among 49 E. coli strains isolated from healthy cattle. The presence of VAGs that are common among diarrheagenic E. coli (DEC) strains and/or extraintestinal pathogenic E. coli (ExPEC) strains was determined by amplifying specific gene sequences by PCR. The following VAGs associated with DEC were found: east1 in 24.5 % of the studied E. coli strains, estI in 10.2 %, ehxA in 8.2 %, stx2 in 6.1 %, eltA in 4.1 %, estII and stx1 in 2.0 % of the studied strains. The prevalence of ExPEC VAGs was: fimH – 91.8 %, afa/draBC – 61.2 %, iutA – 44.9 %, flu – 32.7 %, sfaDE and hlyF – 30.6 %, iroN – 22.4 %, ompT and papC – 20.4 %, kpsMTII and hlyA – 18.4 %, iss – 14.3 %, usp – 2.0 %, cnf1 and iha were not detected among the studied strains. Based on the found co-occurrence of VAGs “classical”, hetero-pathogenic and hybrid-pathogenic E. coli strains were found. E. coli strains isolated from cows had a higher diarrheagenic potential, whereas E. coli strains isolated from calves more frequently contained genes associated with the ExPEC pathotype. Among the studied E. coli strains, 77.6 % were resistant to ampicillin, 49.0 % to tetracycline, 20.4 % to chloramphenicol, 16.3 % to cefoperazone, 16.3 % to ceftriaxone, 16.3 % to aztreonam, 14.3 % to cefepime, 10.2 % to norfloxacin, 10.2 % to ciprofloxacin, 6.1 % to levofloxacin and 2.0 % to gentamicin. All strains were sensitive to meropenem and amikacin. 32.7 % of the studied E. coli strains were found to be multidrug resistant, as they were resistant to at least three groups of antibiotics. With PCR, the blaTEM, blaSHV, and blaCTX-M genes were detected in 100, 31.6, and 26.3 %, respectively, of strains resistant to at least one of the beta-lactam antibiotics. Thus, it was shown that the studied faecal E. coli of healthy cows and calves had a high hetero-pathogenic potential, therefore in the future molecular genetic characterization of these bacteria shall be an important part of the epizootic monitoring

Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study

Purpose: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. Methods: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment (“watch and wait”), chlorambucil treatment only, and patients with other treatment(s). Results: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. Conclusions: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment

Peroral Amphotericin B Polymer Nanoparticles Lead to Comparable or Superior In Vivo Antifungal Activity to That of Intravenous Ambisome® or Fungizone™

Background: Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70–90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical. Methodology: Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113±20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery. Conclusions: The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™and responds only modestly to AmBisome®

Aerosolized Delivery of Antifungal Agents

Pulmonary infections caused by Aspergillus species are associated with significant morbidity and mortality in immunocompromised patients. Although the treatment of pulmonary fungal infections requires the use of systemic agents, aerosolized delivery is an attractive option in prevention because the drug can concentrate locally at the site of infection with minimal systemic exposure. Current clinical evidence for the use of aerosolized delivery in preventing fungal infections is limited to amphotericin B products, although itraconazole, voriconazole, and caspofungin are under investigation. Based on conflicting results from clinical trials that evaluated various amphotericin B formulations, the routine use of aerosolized delivery cannot be recommended. Further research with well-designed clinical trials is necessary to elucidate the therapeutic role and risks associated with aerosolized delivery of antifungal agents. This article provides an overview of aerosolized delivery systems, the intrapulmonary pharmacokinetic properties of aerosolized antifungal agents, and key findings from clinical studies

Outcomes of a Comparison Study into a Group-Based Infant Parenting Programme

This paper reports on a quantitative evaluation of a group-based programme designed to promote parent-infant attachment and child development. Whilst group-based parenting programmes are recommended for treating and preventing conduct disorder in older children, there is, as yet, little evidence as to whether they have a positive effect on very young children and their carers’. Recent UK Government initiatives to support families and improve parenting skills in the first 2 years of children’s lives have increased the demand for the delivery and evaluation of community-based programmes. Eighty mother–child dyads were recruited from nine areas to intervention (n = 54) and control condition (n = 26). Baseline measures were collected in the children’s home when the infants were on average 3-months-old, and follow-up measures were collected 6 months post-baseline (N = 63). Mothers’ positive play behaviours were independently coded from video recordings taken in the home. Other measures included self-reported maternal confidence and mental well-being, assessed infant development and home environment. Socio-demographic data was collected once at baseline. After controlling for baseline scores, control mothers were observed to be significantly less sensitive during play with their baby at the 6 months follow-up with a significant increase in confidence. No differences were found between the groups on the other measures. This paper provides limited evidence for the effectiveness of the Incredible Years Parents and Babies group-based programme delivered in the first year of life. Further evaluation, particularly with parents at increased risk of poorer outcomes is needed to confirm and extend these results

Usefulness of molecular biology performed with formaldehyde-fixed paraffin embedded tissue for the diagnosis of combined pulmonary invasive mucormycosis and aspergillosis in an immunocompromised patient

Immunocompromised patients who develop invasive filamentous mycotic infections can be efficiently treated if rapid identification of the causative fungus is obtained. We report a case of fatal necrotic pneumonia caused by combined pulmonary invasive mucormycosis and aspergillosis in a 66 year-old renal transplant recipient. Aspergillus was first identified during the course of the disease by cytological examination and culture (A. fumigatus) of bronchoalveolar fluid. Hyphae of Mucorales (Rhizopus microsporus) were subsequently identified by culture of a tissue specimen taken from the left inferior pulmonary lobe, which was surgically resected two days before the patient died. Histological analysis of the lung parenchyma showed the association of two different filamentous mycoses for which the morphological features were evocative of aspergillosis and mucormycosis. However, the definitive identification of the associative infection was made by polymerase chain reaction (PCR) performed on deparaffinized tissue sections using specific primers for aspergillosis and mucormycosis. This case demonstrates that discrepancies between histological, cytological and mycological analyses can occur in cases of combined mycotic infection. In this regard, it shows that PCR on selected paraffin blocks is a very powerful method for making or confirming the association of different filamentous mycoses and that this method should be made available to pathology laboratories

Study of cosmogenic activation above ground for the DarkSide-20k experiment

The activation of materials due to exposure to cosmic rays may become an important background source for experiments investigating rare event phenomena. DarkSide-20k, currently under construction at the Laboratori Nazionali del Gran Sasso, is a direct detection experiment for galactic dark matter particles, using a two-phase liquid-argon Time Projection Chamber (TPC) filled with 49.7 tonnes (active mass) of Underground Argon (UAr) depleted in 39Ar. Despite the outstanding capability of discriminating / background in argon TPCs, this background must be considered because of induced dead time or accidental coincidences mimicking dark-matter signals and it is relevant for low-threshold electron-counting measurements. Here, the cosmogenic activity of relevant long-lived radioisotopes induced in the experiment has been estimated to set requirements and procedures during preparation of the experiment and to check that it is not dominant over primordial radioactivity; particular attention has been paid to the activation of the 120 t of UAr used in DarkSide-20k. Expected exposures above ground and production rates, either measured or calculated, have been considered in detail. From the simulated counting rates in the detector due to cosmogenic isotopes, it is concluded that activation in copper and stainless steel is not problematic. The activity of 39Ar induced during extraction, purification and transport on surface is evaluated to be 2.8% of the activity measured in UAr by DarkSide-50 experiment, which used the same underground source, and thus considered acceptable. Other isotopes in the UAr such as 37Ar and 3H are shown not to be relevant due to short half-life and assumed purification methods

Directionality of nuclear recoils in a liquid argon time projection chamber

The direct search for dark matter in the form of weakly interacting massive particles (WIMP) is performed by detecting nuclear recoils (NR) produced in a target material from the WIMP elastic scattering. A promising experimental strategy for direct dark matter search employs argon dual-phase time projection chambers (TPC). One of the advantages of the TPC is the capability to detect both the scintillation and charge signals produced by NRs. Furthermore, the existence of a drift electric field in the TPC breaks the rotational symmetry: the angle between the drift field and the momentum of the recoiling nucleus can potentially affect the charge recombination probability in liquid argon and then the relative balance between the two signal channels. This fact could make the detector sensitive to the directionality of the WIMP-induced signal, enabling unmistakable annual and daily modulation signatures for future searches aiming for discovery. The Recoil Directionality (ReD) experiment was designed to probe for such directional sensitivity. The TPC of ReD was irradiated with neutrons at the INFN Laboratori Nazionali del Sud, and data were taken with 72 keV NRs of known recoil directions. The direction-dependent liquid argon charge recombination model by Cataudella et al. was adopted and a likelihood statistical analysis was performed, which gave no indications of significant dependence of the detector response to the recoil direction. The aspect ratio R of the initial ionization cloud is estimated to be 1.037 +/- 0.027 and the upper limit is R < 1.072 with 90% confidence levelComment: 20 pages, 10 figures, submitted to Eur. Phys. J.

In vivo Hypoxia and a Fungal Alcohol Dehydrogenase Influence the Pathogenesis of Invasive Pulmonary Aspergillosis

Currently, our knowledge of how pathogenic fungi grow in mammalian host environments is limited. Using a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA) and 1H-NMR metabolomics, we detected ethanol in the lungs of mice infected with Aspergillus fumigatus. This result suggests that A. fumigatus is exposed to oxygen depleted microenvironments during infection. To test this hypothesis, we utilized a chemical hypoxia detection agent, pimonidazole hydrochloride, in three immunologically distinct murine models of IPA (chemotherapeutic, X-CGD, and corticosteroid). In all three IPA murine models, hypoxia was observed during the course of infection. We next tested the hypothesis that production of ethanol in vivo by the fungus is involved in hypoxia adaptation and fungal pathogenesis. Ethanol deficient A. fumigatus strains showed no growth defects in hypoxia and were able to cause wild type levels of mortality in all 3 murine models. However, lung immunohistopathology and flow cytometry analyses revealed an increase in the inflammatory response in mice infected with an alcohol dehydrogenase null mutant strain that corresponded with a reduction in fungal burden. Consequently, in this study we present the first in vivo observations that hypoxic microenvironments occur during a pulmonary invasive fungal infection and observe that a fungal alcohol dehydrogenase influences fungal pathogenesis in the lung. Thus, environmental conditions encountered by invading pathogenic fungi may result in substantial fungal metabolism changes that influence subsequent host immune responses