When good bugs go bad: Epidemiology and antimicrobial resistance profiles of Corynebacterium striatum, an emerging multidrug-resistant, opportunistic pathogen

ABSTRACT Infections with Corynebacterium striatum have been described in the literature over the last 2 decades, with the majority being bacteremia, central line infections, and occasionally, endocarditis. In recent years, the frequency of C. striatum infections appears to be increasing; a factor likely contributing to this is the increased ease and accuracy of the identification of Corynebacterium spp., including C. striatum , from clinical cultures. The objective of this study was to retrospectively characterize C. striatum isolates recovered from specimens submitted as part of routine patient care at a 1,250-bed, tertiary-care academic medical center. Multiple strain types were recovered, as demonstrated by repetitive-sequence-based PCR. Most of the strains of C. striatum characterized were resistant to antimicrobials commonly used to treat Gram-positive organisms, such as penicillin, ceftriaxone, meropenem, clindamycin, and tetracycline. The MIC 50 for ceftaroline was &gt;32 μg/ml. Although there are no interpretive criteria for susceptibility with telavancin, it appeared to have potent in vitro efficacy against this species, with MIC 50 and MIC 90 values of 0.064 and 0.125 μg/ml, respectively. Finally, as previously reported in case studies, we demonstrated rapid in vitro development of daptomycin resistance in 100% of the isolates tested ( n = 50), indicating that caution should be exhibited when using daptomycin for the treatment of C. striatum infections. C. striatum is an emerging, multidrug-resistant pathogen that can be associated with a variety of infection types. </jats:p

Comparison of sample preparation methods, instrumentation platforms, and contemporary commercial databases for identification of clinically relevant mycobacteria by matrix-assisted laser desorption ionization - Time of flight mass spectrometry

When mycobacteria are recovered in clinical specimens, timely species-level identification is required to establish the clinical significance of the isolate and facilitate optimization of antimicrobial therapy. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has recently been reported to be a reliable and expedited method for identification of mycobacteria, although various specimen preparation techniques and databases for analysis are reported across studies. Here we compared two MALDI-TOF MS instrumentation platforms and three databases: Bruker Biotyper Real Time Classification 3.1 (Biotyper), Vitek MS Plus Saramis Premium (Saramis), and Vitek MS v3.0. We evaluated two sample preparation techniques and demonstrate that extraction methods are not interchangeable across different platforms or databases. Once testing parameters were established, a panel of 157 mycobacterial isolates (including 16 Mycobacterium tuberculosis isolates) was evaluated, demonstrating that with the appropriate specimen preparation, all three methods provide reliable identification for most species. Using a score cutoff value of ≥1.8, the Biotyper correctly identified 133 (84.7%) isolates with no misidentifications. Using a confidence value of ≥90%, Saramis correctly identified 134 (85.4%) isolates with one misidentification and Vitek MS v3.0 correctly identified 140 (89.2%) isolates with one misidentification. The levels of accuracy were not significantly different across the three platforms (P = 0.14). In addition, we show that Vitek MS v3.0 requires modestly fewer repeat analyses than the Biotyper and Saramis methods (P = 0.04), which may have implications for laboratory workflow

Brown-pigmented Mycobacterium mageritense as a cause of prosthetic valve endocarditis and bloodstream infection

Mycobacterium spp. are a rare cause of endocarditis. Herein, we describe a case of Mycobacterium mageritense prosthetic valve endocarditis. This organism produced an unusual brown pigment on solid media. Cultures of valve tissue for acid-fast bacilli might be considered in some cases of apparently culture-negative prosthetic valve endocarditis

Evaluation of the Vitek MS matrix-assisted laser desorption ionization–time of flight mass spectrometry system for identification of clinically relevant filamentous fungi

Invasive fungal infections have a high rate of morbidity and mortality, and accurate identification is necessary to guide appropriate antifungal therapy. With the increasing incidence of invasive disease attributed to filamentous fungi, rapid and accurate species-level identification of these pathogens is necessary. Traditional methods for identification of filamentous fungi can be slow and may lack resolution. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has emerged as a rapid and accurate method for identification of bacteria and yeasts, but a paucity of data exists on the performance characteristics of this method for identification of filamentous fungi. The objective of our study was to evaluate the accuracy of the Vitek MS for mold identification. A total of 319 mold isolates representing 43 genera recovered from clinical specimens were evaluated. Of these isolates, 213 (66.8%) were correctly identified using the Vitek MS Knowledge Base, version 3.0 database. When a modified SARAMIS (Spectral Archive and Microbial Identification System) database was used to augment the version 3.0 Knowledge Base, 245 (76.8%) isolates were correctly identified. Unidentified isolates were subcultured for repeat testing; 71/319 (22.3%) remained unidentified. Of the unidentified isolates, 69 were not in the database. Only 3 (0.9%) isolates were misidentified by MALDI-TOF MS (including Aspergillus amoenus [n = 2] and Aspergillus calidoustus [n = 1]) although 10 (3.1%) of the original phenotypic identifications were not correct. In addition, this methodology was able to accurately identify 133/144 (93.6%) Aspergillus sp. isolates to the species level. MALDI-TOF MS has the potential to expedite mold identification, and misidentifications are rare

Self‐pollination in island and mainland populations of the introduced hummingbird‐pollinated plant, Nicotiana glauca (Solanaceae)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142032/1/ajb20672.pd

What Is the Role of Astrocyte Calcium in Neurophysiology?

Astrocytes comprise approximately half of the volume of the adult mammalian brain and are the primary neuronal structural and trophic supportive elements. Astrocytes are organized into distinct nonoverlapping domains and extend elaborate and dense fine processes that interact intimately with synapses and cerebrovasculature. The recognition in the mid 1990s that astrocytes undergo elevations in intracellular calcium concentration following activation of G protein-coupled receptors by synaptically released neurotransmitters demonstrated not only that astrocytes display a form of excitability but also that astrocytes may be active participants in brain information processing. The roles that astrocytic calcium elevations play in neurophysiology and especially in modulation of neuronal activity have been intensely researched in recent years. This review will summarize the current understanding of the function of astrocytic calcium signaling in neurophysiological processes and discuss areas where the role of astrocytes remains controversial and will therefore benefit from further study

Early Left-Hemispheric Dysfunction of Face Processing in Congenital Prosopagnosia: An MEG Study

Electrophysiological research has demonstrated the relevance to face processing of a negative deflection peaking around 170 ms, labelled accordingly as N170 in the electroencephalogram (EEG) and M170 in magnetoencephalography (MEG). The M170 was shown to be sensitive to the inversion of faces and to familiarity-two factors that are assumed to be crucial for congenital prosopagnosia. In order to locate the cognitive dysfunction and its neural correlates, we investigated the time course of neural activity in response to these manipulations.Seven individuals with congenital prosopagnosia and seven matched controls participated in the experiment. To explore brain activity with high accuracy in time, we recorded evoked magnetic fields (275 channel whole head MEG) while participants were looking at faces differing in familiarity (famous vs. unknown) and orientation (upright vs. inverted). The underlying neural sources were estimated by means of the least square minimum-norm-estimation (L2-MNE) approach.The behavioural data corroborate earlier findings on impaired configural processing in congenital prosopagnosia. For the M170, the overall results replicated earlier findings, with larger occipito-temporal brain responses to inverted than upright faces, and more right- than left-hemispheric activity. Compared to controls, participants with congenital prosopagnosia displayed a general decrease in brain activity, primarily over left occipitotemporal areas. This attenuation did not interact with familiarity or orientation.The study substantiates the finding of an early involvement of the left hemisphere in symptoms of prosopagnosia. This might be related to an efficient and overused featural processing strategy which serves as a compensation of impaired configural processing

Morphological and Behavioral Changes in the Pathogenesis of a Novel Mouse Model of Communicating Hydrocephalus

The Ro1 model of hydrocephalus represents an excellent model for studying the pathogenesis of hydrocephalus due to its complete penetrance and inducibility, enabling the investigation of the earliest cellular and histological changes in hydrocephalus prior to overt pathology. Hematoxylin and eosin staining, immunofluorescence and electron microscopy were used to characterize the histopathological events of hydrocephalus in this model. Additionally, a broad battery of behavioral tests was used to investigate behavioral changes in the Ro1 model of hydrocephalus. The earliest histological changes observed in this model were ventriculomegaly and disorganization of the ependymal lining of the aqueduct of Sylvius, which occurred concomitantly. Ventriculomegaly led to thinning of the ependyma, which was associated with periventricular edema and areas of the ventricular wall void of cilia and microvilli. Ependymal denudation was subsequent to severe ventriculomegaly, suggesting that it is an effect, rather than a cause, of hydrocephalus in the Ro1 model. Additionally, there was no closure of the aqueduct of Sylvius or any blockages within the ventricular system, even with severe ventriculomegaly, suggesting that the Ro1 model represents a model of communicating hydrocephalus. Interestingly, even with severe ventriculomegaly, there were no behavioral changes, suggesting that the brain is able to compensate for the structural changes that occur in the pathogenesis of hydrocephalus if the disorder progresses at a sufficiently slow rate

Discovery and Creation: Alternative Theories of Entrepreneurial Action

As oportunidades empreendedoras existem, independentemente, das percepções dos empreendedores, esperando apenas para serem descobertas? Ou, estas oportunidades são criadas pelas ações dos empreendedores? Duas teorias, internamente, consistentes com as oportunidades empreendedoras são: teoria da criação e teoria da descoberta- as quais serão descritas. Enquanto, será sempre possível, descrever a formação de uma oportunidade particular, como exemplo, de um processo da descoberta ou da criação de oportunidade, estas duas teorias têm implicações importantes para a eficácia de uma variedade ampla de ações empreendedoras em contextos diferentes. As implicações destas teorias para sete destas ações serão descritas, acompanhadas de uma discussão sobre algumas das implicações teóricas mais amplas destas duas teorias para os campos do empreendimento e do gerenciamento estratégico

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine