Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013–2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries

First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA

The NOvA experiment has seen a 4.4σ signal of ν̄e appearance in a 2 GeV ν̄μ beam at a distance of 810 km. Using 12.33×1020 protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν̄μ→ν̄e candidates with a background of 10.3 and 102 ν̄μ→ν̄μ candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm322|=2.48-0.06+0.11×10-3 eV2/c4 and sin2θ23 in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δCP=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ23 values in the upper octant by 1.6σ

A Kernel to Exploit Informative Missingness in Multivariate Time Series from EHRs

A large fraction of the electronic health records (EHRs) consists of clinical measurements collected over time, such as lab tests and vital signs, which provide important information about a patient's health status. These sequences of clinical measurements are naturally represented as time series, characterized by multiple variables and large amounts of missing data, which complicate the analysis. In this work, we propose a novel kernel which is capable of exploiting both the information from the observed values as well the information hidden in the missing patterns in multivariate time series (MTS) originating e.g. from EHRs. The kernel, called TCK$_{IM}$, is designed using an ensemble learning strategy in which the base models are novel mixed mode Bayesian mixture models which can effectively exploit informative missingness without having to resort to imputation methods. Moreover, the ensemble approach ensures robustness to hyperparameters and therefore TCK$_{IM}$ is particularly well suited if there is a lack of labels - a known challenge in medical applications. Experiments on three real-world clinical datasets demonstrate the effectiveness of the proposed kernel.Comment: 2020 International Workshop on Health Intelligence, AAAI-20. arXiv admin note: text overlap with arXiv:1907.0525

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Low frequency of asymptomatic carriage of toxigenic Clostridium difficile in an acute care geriatric hospital: prospective cohort study in Switzerland

Abstract Background The role of asymptomatic carriers of toxigenic Clostridium difficile (TCD) in nosocomial cross-transmission remains debatable. Moreover, its relevance in the elderly has been sparsely studied. Objectives To assess asymptomatic TCD carriage in an acute care geriatric population. Methods We performed a prospective cohort study at the 296-bed geriatric hospital of the Geneva University Hospitals. We consecutively recruited all patients admitted to two 15-bed acute-care wards. Patients with C. difficile infection (CDI) or diarrhoea at admission were excluded. First bowel movement after admission and every two weeks thereafter were sampled. C. difficile toxin B gene was identified using real-time polymerase chain-reaction (BD MAXTMCdiff). Asymptomatic TCD carriage was defined by the presence of the C. difficile toxin B gene without diarrhoea. Results A total of 102 patients were admitted between March and June 2015. Two patients were excluded. Among the 100 patients included in the study, 63 were hospitalized and 1 had CDI in the previous year, and 36 were exposed to systemic antibiotics within 90 days prior to admission. Overall, 199 stool samples were collected (median 2 per patient, IQR 1-3). Asymptomatic TCD carriage was identified in two patients (2 %). Conclusions We found a low prevalence of asymptomatic TCD carriage in a geriatric population frequently exposed to antibiotics and healthcare. Our findings suggest that asymptomatic TCD carriage might contribute only marginally to nosocomial TCD cross-transmission in our and similar healthcare settings

Mouse Acetylcholinesterase Enhances Neurite Outgrowth of Rat R28 Cells Through Interaction With Laminin-1

The enzyme acetylcholinesterase (AChE) terminates synaptic transmission at cholinergic synapses by hydrolyzing the neurotransmitter acetylcholine, but can also exert ‘non-classical’, morpho-regulatory effects on developing neurons such as stimulation of neurite outgrowth. Here, we investigated the role of AChE binding to laminin-1 on the regulation of neurite outgrowth by using cell culture, immunocytochemistry, and molecular biological approaches. To explore the role of AChE, we examined fiber growth of cells overexpressing different forms of AChE, and/or during their growth on laminin-1. A significant increase of neuritic growth as compared with controls was observed for neurons over-expressing AChE. Accordingly, addition of globular AChE to the medium increased total length of neurites. Co-transfection with PRIMA, a membrane anchor of AChE, led to an increase in fiber length similar to AChE overexpressing cells. Transfection with an AChE mutant that leads to the retention of AChE within cells had no stimulatory effect on neurite length. Noticeably, the longest neurites were produced by neurons overexpressing AChE and growing on laminin-1, suggesting that the AChE/laminin interaction is involved in regulating neurite outgrowth. Our findings demonstrate that binding of AChE to laminin-1 alters AChE activity and leads to increased neurite growth in culture. A possible mechanism of the AChE effect on neurite outgrowth is proposed due to the interaction of AChE with laminin-1

Conidiation Color Mutants of Aspergillus fumigatus Are Highly Pathogenic to the Heterologous Insect Host Galleria mellonella

The greater wax moth Galleria mellonella has been widely used as a heterologous host for a number of fungal pathogens including Candida albicans and Cryptococcus neoformans. A positive correlation in pathogenicity of these yeasts in this insect model and animal models has been observed. However, very few studies have evaluated the possibility of applying this heterologous insect model to investigate virulence traits of the filamentous fungal pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Here, we have examined the impact of mutations in genes involved in melanin biosynthesis on the pathogenicity of A. fumigatus in the G. mellonella model. Melanization in A. fumigatus confers bluish-grey color to conidia and is a known virulence factor in mammal models. Surprisingly, conidial color mutants in B5233 background that have deletions in the defined six-gene cluster required for DHN-melanin biosynthesis caused enhanced insect mortality compared to the parent strain. To further examine and confirm the relationship between melanization defects and enhanced virulence in the wax moth model, we performed random insertional mutagenesis in the Af293 genetic background to isolate mutants producing altered conidia colors. Strains producing conidia of previously identified colors and of novel colors were isolated. Interestingly, these color mutants displayed a higher level of pathogenicity in the insect model compared to the wild type. Although some of the more virulent color mutants showed increased resistance to hydrogen peroxide, overall phenotypic characterizations including secondary metabolite production, metalloproteinase activity, and germination rate did not reveal a general mechanism accountable for the enhanced virulence of these color mutants observed in the insect model. Our observations indicate instead, that exacerbated immune response of the wax moth induced by increased exposure of PAMPs (pathogen-associated molecular patterns) may cause self-damage that results in increased mortality of larvae infected with the color mutants. The current study underscores the limitations of using this insect model for inferring the pathogenic potential of A. fumigatus strains in mammals, but also points to the importance of understanding the innate immunity of the insect host in providing insights into the pathogenicity level of different fungal strains in this model. Additionally, our observations that melanization defective color mutants demonstrate increased virulence in the insect wax moth, suggest the potential of using melanization defective mutants of native insect fungal pathogens in the biological control of insect populations