Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database

PURPOSE: To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.     

Clinical Supervision of Psychotherapy: Essential Ethics Issues for Supervisors and Supervisees

Clinical supervision is an essential aspect of every mental health professional's training. The importance of ensuring that supervision is provided competently, ethically, and legally is explained. The elements of the ethical practice of supervision are described and explained. Specific issues addressed include informed consent and the supervision contract, supervisor and supervisee competence, attention to issues of diversity and multicultural competence, boundaries and multiple relationships in the supervision relationship, documentation and record keeping by both supervisor and supervisee, evaluation and feedback, self‐care and the ongoing promotion of wellness, emergency coverage, and the ending of the supervision relationship. Additionally, the role of clinical supervisor as mentor, professional role model, and gatekeeper for the profession are discussed. Specific recommendations are provided for ethically and effectively conducting the supervision relationship and for addressing commonly arising dilemmas that supervisors and supervisees may confront.     

Biomolecule Delivery to Engineer the Cellular Microenvironment for Regenerative Medicine

To realize the potential of regenerative medicine, controlling the delivery of biomolecules in the cellular microenvironment is important as these factors control cell fate. Controlled delivery for tissue engineering and regenerative medicine often requires bioengineered materials and cells capable of spatiotemporal modulation of biomolecule release and presentation. This review discusses biomolecule delivery from the outside of the cell inwards through the delivery of soluble and insoluble biomolecules as well as from the inside of the cell outwards through gene transfer. Ex vivo and in vivo therapeutic strategies are discussed, as well as combination delivery of biomolecules, scaffolds, and cells. Various applications in regenerative medicine are highlighted including bone tissue engineering and wound healing.     

Copper is an endogenous modulator of neural circuit spontaneous activity

For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu⁺ sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.The foundation of cellular signal transduction relies on intricate chemical messenger systems that operate through the dynamic spatial and temporal regulation of elements, ions, and molecules. Nowhere is this concept better illustrated than in the brain, which extensively regulates fluxes of alkali and alkaline earth metals such as sodium, potassium, and calcium for a diverse array of signaling processes. Interestingly, the brain also accumulates among the highest levels of transition metals in the body (1–3), including redox-active copper. This high-redox metal load, in combination with the brain''s disproportionately active oxygen metabolism (4), makes this organ particularly susceptible to oxidative stress (4–6). As such, copper has been historically regarded as a tightly sequestered cofactor that must be buried within protein active sites to protect against reactive oxygen species generation and subsequent free radical damage chemistry. Indeed, elegant work continues to identify molecular players that maintain copper homeostasis in the brain (7, 8) and related organs (9–11), and loss of this strict regulation is implicated in neurotoxic stress (12–14) and a variety of neurodegenerative and neurodevelopmental disorders including Menkes (15, 16) and Wilson''s (17) diseases, familial amyotrophic lateral sclerosis (18, 19), Alzheimer''s (6, 14, 20–22) and Huntington''s (23, 24) diseases, and prion-mediated encephalopathies (14, 25, 26).Despite this long-held paradigm, emerging data also link pools of labile copper (defined as dynamic and loosely bound stores that undergo facile ligand exchange relative to static, tightly bound pools buried within protein active sites) to neurophysiology. Included are observations of ⁶⁴Cu efflux from stimulated neurons (12, 27), reversible trafficking of ATP7A from the perinuclear trans-Golgi to neuronal processes by NMDA receptor activation (12), effects of copper chelation on olfactory response to thiol odorants (28), and direct X-ray fluorescence imaging of copper translocation in neurons from somatic cell bodies to peripheral processes upon depolarization (29). Against this backdrop, we have initiated a program aimed at exploring the potential contributions of loosely bound forms of redox-active metals like copper in cell signaling. In this report, we identify a role for copper in the brain as a modulator of spontaneous activity, a fundamental property of developing neural circuits. The design and synthesis of Copper Fluor-3 (CF3), a fluorescent copper sensor based on a hydrophilic and tunable rhodol scaffold, along with Control Copper Fluor-3 (Ctrl-CF3), a matched control dye based on an identical fluorophore but lacking responsiveness to copper, enabled the visualization of loosely bound Cu⁺ in dissociated neurons and neural tissue by one- and two-photon microscopy. Disruption of Cu⁺ stores by acute application of a copper chelator or genetic knockdown of the copper ion channel CTR1 altered the spatiotemporal properties of spontaneous activity. In dissociated hippocampal cultures, these manipulations increased the correlation of spontaneous calcium transients, whereas in retina, both cell participation and frequency of correlated calcium transients increased.     

The Peculiar Epidemiology of Dracunculiasis in Chad

Dracunculiasis was rediscovered in Chad in 2010 after an apparent absence of 10 years. In April 2012 active village-based surveillance was initiated to determine where, when, and how transmission of the disease was occurring, and to implement interventions to interrupt it. The current epidemiologic pattern of the disease in Chad is unlike that seen previously in Chad or other endemic countries, i.e., no clustering of cases by village or association with a common water source, the average number of worms per person was small, and a large number of dogs were found to be infected. Molecular sequencing suggests these infections were all caused by Dracunculus medinensis. It appears that the infection in dogs is serving as the major driving force sustaining transmission in Chad, that an aberrant life cycle involving a paratenic host common to people and dogs is occurring, and that the cases in humans are sporadic and incidental.