Characterization of the ear canal bacterial flora present in hearing Aids (HA) wearing subjects

The use of hearing aids (HA) is considered a predisposing factor for ear microbial infections. We undertook this study to compare the presence and nature of the microbial flora inhabiting of ears of HA and non-HA (nHA) users. Swab samples of the ears of HA and nHA users were collected from the Institute of Otolaryngology, “Cattolica del Sacro Cuore” University “Agostino Gemelli”, Rome, Italy. Swab samples were taken from the ear canal of 57 HA and 33 nHA users. The components of the microbial flora present on each swab sample were identified and characterized at the level of species. A total of 41 different bacterial species were identified. A statistically significant prevalence of polymicrobial communities was found in ears presenting signs of inflammation (2.5 ± 1.7 vs 2.1 ± 1.3; P = 0.02) and in HA users (2.3 ± 1.2 vs 1.7 ± 1.0; P = 0.002). Few putative pathogens were detected. Candida albicans spp. was not isolated in our study. A small number of swab samples presented no microbial growth. Bacterial species isolated from HA users with and without inflammation were assayed for the ability to form a biofilm. Among gram-positive and gram-negative bacteria, S. aureus, CoNS, P. aeruginosa, and K. pneumoniae were found to be strong biofilm producers. S. aureus and P. aeruginosa, isolated only from the ears of HA and nHA users presenting signs of inflammation, were further analyzed for their antibiotic-resistance profile and characterized by the Multilocus Sequence Typing (MLST) assay. The highest rates of antibacterial resistance were in S. aureus to a penicillin (75.5%) and in P. aeruginosa, to amoxicillin-clavulanic acid, cefotaxime, ertapenem, tigecycline and trimethoprim-sulfamethoxazole (100%). Moreover, three S. aureus strains (37.5%) were methicillin-resistant (MRSA). Of the eight S. aureus isolates, we identified six sequence types (ST) indicating that 75% are likely independent clones. For what it concerned P. aeruginosa, six different STs were assigned. Interestingly, two out of the six strains presented newly identified ST values. This study sheds new light on the combined effect of the presence of HA devices and signs of external ear inflammation on the composition of the ear bacterial flora. Our results reinforce the need to practice careful hygiene of HA devices to prevent serious ear canal infections

The mechanical stimulation of myotubes counteracts the effects of tumor-derived factors through the modulation of the activin/follistatin ratio

Activin negatively affects muscle fibers and progenitor cells in aging (sarcopenia) and in chronic diseases characterized by severe muscle wasting (cachexia). High circulating activin levels predict poor survival in cancer patients. However, the relative impact of activin in mediating muscle atrophy and hampered homeostasis is still unknown. To directly assess the involvement of activin, and its physiological inhibitor follistatin, in cancer-induced muscle atrophy, we cultured C2C12 myotubes in the absence or in the presence of a mechanical stretching stimulus and in the absence or presence of C26 tumor-derived factors (CM), so as to mimic the mechanical stimulation of exercise and cancer cachexia, respectively. We found that CM induces activin release by myotubes, further exacerbating the negative effects of tumor-derived factors. In addition, mechanical stimulation is sufficient to counteract the adverse tumor-induced effects on muscle cells, in association with an increased follistatin/activin ratio in the cell culture medium, indicating that myotubes actively release follistatin upon stretching. Recombinant follistatin counteracts tumor effects on myotubes exclusively by rescuing fusion index, suggesting that it is only partially responsible for the stretch-mediated rescue. Therefore, besides activin, other tumor-derived factors may play a significant role in mediating muscle atrophy. In addition to increasing follistatin secretion mechanical stimulation induces additional beneficial responses in myotubes. We propose that in animal models of cancer cachexia and in cancer patients purely mechanical stimuli play an important role in mediating the rescue of the muscle homeostasis reported upon exercise

Susceptibility testing of colistin for acinetobacter baumannii: How far are we from the truth?

Acinetobacter baumannii is involved in life-threatening nosocomial infections, mainly in the intensive care units (ICUs), and often colistin may represent the last therapeutic opportunity. The susceptibility to colistin of 51 epidemiologically typed A. baumannii strains isolated in 2017 from clinical samples of patients hospitalized in the ICU of a tertiary care academic hospital was investigated. All isolates were carbapenem-resistant due to the presence of the blaOXA-23 gene in sequence group 1 (international clonal lineage II) and sequence group 4 (related to international clonal lineage II) isolates, and to the blaOXA-24/40 gene in sequence group 2 (international clonal lineage I) isolates. Vitek®2, agar diffusion, and broth microdilution tests showed major discordancy (≥2 dilution factors) in the minimum inhibitory concentration (MIC) values for colistin in 24 out of 51 isolates, resulting in erroneous reporting of qualitative susceptibility data for eight isolates. In growth kinetics experiments in the presence of colistin, five isolates grew with drug concentrations above the susceptibility breakpoint when incubated for >12 h, and three isolates showed the presence of heteroresistant subpopulations. This study highlights that the high frequency of isolation of carbapenem-resistant A. baumannii strains in high-risk infectious wards requires an accurate application of methods for detecting susceptibility to antibiotics, in particular to colistin, so as to ensure a correct therapeutic approach

A surge of late-occurring meiotic double-strand breaks rescues synapsis abnormalities in spermatocytes of mice with hypomorphic expression of SPO11

Meiosis is the biological process that, after a cycle of DNA replication, halves the cellular chromosome complement, leading to the formation of haploid gametes. Haploidization is achieved via two successive rounds of chromosome segregation, meiosis I and II. In mammals, during prophase of meiosis I, homologous chromosomes align and synapse through a recombination-mediated mechanism initiated by the introduction of DNA double-strand breaks (DSBs) by the SPO11 protein. In male mice, if SPO11 expression and DSB number are reduced below heterozygosity levels, chromosome synapsis is delayed, chromosome tangles form at pachynema, and defective cells are eliminated by apoptosis at epithelial stage IV at a spermatogenesis-specific endpoint. Whether DSB levels produced in Spo11 +/− spermatocytes represent, or approximate, the threshold level required to guarantee successful homologous chromosome pairing is unknown. Using a mouse model that expresses Spo11 from a bacterial artificial chromosome, within a Spo11 −/− background, we demonstrate that when SPO11 expression is reduced and DSBs at zygonema are decreased (approximately 40 % below wild-type level), meiotic chromosome pairing is normal. Conversely, DMC1 foci number is increased at pachynema, suggesting that under these experimental conditions, DSBs are likely made with delayed kinetics at zygonema. In addition, we provide evidences that when zygotene-like cells receive enough DSBs before chromosome tangles develop, chromosome synapsis can be completed in most cells, preventing their apoptotic elimination

Achromobacter spp. adaptation in cystic fibrosis infection and candidate biomarkers of antimicrobial resistance

Achromobacter spp. can establish occasional or chronic lung infections in patients with cystic fibrosis (CF). Chronic colonization has been associated with worse prognosis highlighting the need to identify markers of bacterial persistence. To this purpose, we analyzed phenotypic features of 95 Achromobacter spp. isolates from 38 patients presenting chronic or occasional infection. Virulence was tested in Galleria mellonella larvae, cytotoxicity was tested in human bronchial epithelial cells, biofilm production in static conditions was measured by crystal violet staining and susceptibility to selected antibiotics was tested by the disk diffusion method. The presence of genetic loci associated to the analyzed phenotypic features was evaluated by a genome-wide association study. Isolates from occasional infection induced significantly higher mortality of G. mellonella larvae and showed a trend for lower cytotoxicity than chronic infection isolates. No significant difference was observed in biofilm production among the two groups. Additionally, antibiotic susceptibility testing showed that isolates from chronically-infected patients were significantly more resistant to sulfonamides and meropenem than occasional isolates. Candidate genetic biomarkers associated with antibiotic resistance or sensitivity were identified. Achromobacter spp. strains isolated from people with chronic and occasional lung infection exhibit different virulence and antibiotic susceptibility features, which could be linked to persistence in CF lungs. This underlines the possibility of identifying predictive biomarkers of persistence that could be useful for clinical purposes

Kickstarting Choreographic Programming

We present an overview of some recent efforts aimed at the development of Choreographic Programming, a programming paradigm for the production of concurrent software that is guaranteed to be correct by construction from global descriptions of communication behaviour

Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes

Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors--and how this cross talk influences physiological processes--is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors

Measurement of the WZ production cross section in pp collisions at [Formula: see text] and 8[Formula: see text] and search for anomalous triple gauge couplings at [Formula: see text].

The WZ production cross section is measured by the CMS experiment at the CERN LHC in proton-proton collision data samples corresponding to integrated luminosities of 4.9[Formula: see text] collected at [Formula: see text], and 19.6[Formula: see text] at [Formula: see text]. The measurements are performed using the fully-leptonic WZ decay modes with electrons and muons in the final state. The measured cross sections for [Formula: see text] are [Formula: see text] [Formula: see text] and [Formula: see text] [Formula: see text]. Differential cross sections with respect to the [Formula: see text] boson [Formula: see text], the leading jet [Formula: see text], and the number of jets are obtained using the [Formula: see text] data. The results are consistent with standard model predictions and constraints on anomalous triple gauge couplings are obtained

Depletion of Nonlinearity in Magnetohydrodynamic Turbulence: Insights from Analysis and Simulations

We build on recent developments in the study of fluid turbulence [Gibbon \textit{et al.} Nonlinearity 27, 2605 (2014)] to define suitably scaled, order-$m$ moments, $D_m^{\pm}$, of $\omega^\pm= \omega \pm j$, where $\omega$ and $j$ are, respectively, the vorticity and current density in three-dimensional magnetohydrodynamics (MHD). We show by mathematical analysis, for unit magnetic Prandtl number $P_M$, how these moments can be used to identify three possible regimes for solutions of the MHD equations; these regimes are specified by inequalities for $D_m^{\pm}$ and $D_1^{\pm}$. We then compare our mathematical results with those from our direct numerical simulations (DNSs) and thus demonstrate that 3D MHD turbulence is like its fluid-turbulence counterpart insofar as all solutions, which we have investigated, remain in \textit{only one of these regimes}; this regime has depleted nonlinearity. We examine the implications of our results for the exponents $q^{\pm}$ that characterize the power-law dependences of the energy spectra $\mathcal{E}^{\pm}(k)$ on the wave number $k$, in the inertial range of scales. We also comment on (a) the generalization of our results to the case $P_M \neq 1$ and (b) the relation between $D_m^{\pm}$ and the order-$m$ moments of gradients of hydrodynamic fields, which are used in characterizing intermittency in turbulent flows.Comment: 14 pages, 3 figure

Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the di erences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with di erent ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516G>T (rs3745274), 785A>G (rs2279343) and 983T>C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed di erent haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic pro le. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a di erent haplotype structure due to the di erent genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence