Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK.

Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections. Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.

Feasibility and preliminary efficacy of a parent-mediated sexual education curriculum for youth with autism spectrum disorders.

Youth with autism spectrum disorder can face social-communication challenges related to sexuality, dating, and friendships. The purpose of this study was to assess the feasibility, acceptability, and preliminary efficacy of the Supporting Teens with Autism on Relationships program. In total, 84 youth with autism spectrum disorder aged 9 to 18 and their parents participated in this study; two groups received the Supporting Teens with Autism on Relationships program (interventionist-led parent group vs parent self-guided), while an attentional control group received a substance abuse prevention program that included instruction in problem-solving and social skills. Feasibility and acceptability of the Supporting Teens with Autism on Relationships program was high overall. The Supporting Teens with Autism on Relationships program was effective in increasing parent and youth knowledge of sexuality, while the attentional control was not. There was preliminary support for improvement in parenting efficacy related to discussing sexuality with their children. Gains were seen among completers regardless of whether the parent received support from a facilitator. Implications and future directions are discussed.

Epidemiology, management, and outcomes of sustained ventricular arrhythmias after continuous-flow left ventricular assist device implantation.

BACKGROUND: Left ventricular assist devices (LVADs) are pivotal treatment options for patients with end-stage heart failure. Despite robust left ventricular unloading, the right ventricle remains unsupported and susceptible to hemodynamic perturbations from ventricular arrhythmias (VAs). Little is known about the epidemiology, management, resource use, and outcomes of sustained VAs in continuous-flow LVAD patients. METHODS: We reviewed data from all consecutive patients receiving a continuous-flow LVAD at the University of North Carolina from January 2006 to February 2011. Patient demographics, pharmacotherapies, resource use, and outcomes were recorded. Descriptive statistics were generated, and multivariable logistic regression was used to assess the independent association of clinical variables on the development of postimplantation VAs. RESULTS: Of 61 patients, 26 (43%) had sustained VAs after LVAD. Most were male (65%), had history of hypertension (65%), and had nonischemic cardiomyopathy (62%). Patients with VAs after LVAD more often had preimplant VAs (62% vs 14%, P < .01), prior implantable cardioverter-defibrillator (92% vs 71%, P = .04), and history of implantable cardioverter-defibrillator discharge (38% vs 11%, P < .01). Although length of stay was similar, those with postimplant VAs had greater rehospitalization rates, greater antiarrhythmic drug use, and frequently required external defibrillation. Using multivariable logistic regression, only history of prior VA was associated with postimplant arrhythmias (odds ratio 13.7, P < .001). CONCLUSIONS: Ventricular arrhythmias in LVAD patients are common, often refractory to conservative therapy, and associated with frequent rehospitalization. Post-LVAD VAs, however, did not significantly impact survival or transplantation rates. Arrhythmia burden should be considered before LVAD placement, and future study should focus on the impact of VAs on quality of life.

Visual signals bias auditory targets in azimuth and depth.

In the psychophysical phenomenon visual bias, an accurately localized irrelevant signal, such as a light, impairs localization of a spatially discrepant target, such as a sound, when the two stimuli are perceived as unified. Many studies have demonstrated visual bias in azimuth, but none have tested directly or found this effect in depth. The current study was able to produce over 90% bias in azimuth and somewhat less (83%) bias in depth. A maximum likelihood estimate can predict bias by the variance in the localization of each unimodal signal in each dimension in space.

Integration of on-chip peristaltic pumps and injection valves with microchip electrophoresis and electrochemical detection.

A microfluidic approach that integrates peristaltic pumping from an on-chip reservoir with injection valves, microchip electrophoresis and electrochemical detection is described. Fabrication and operation of both the peristaltic pumps and injection valves were optimized to ensure efficient pumping and discrete injections. The final device uses the peristaltic pumps to continuously direct sample from a reservoir containing a mixture of analytes to injection valves that are coupled with microchip electrophoresis and amperometric detection. The separation and direct detection of dopamine and norepinephrine were possible with this approach and the utility of the device was demonstrated by monitoring the stimulated release of these neurotransmitters from a layer of cells introduced into the microchip. It is also shown that this pumping/reservoir approach can be expanded to multiple reservoirs and pumps, where one reservoir can be addressed individually or multiple reservoirs sampled simultaneously.

Integration of serpentine channels for microchip electrophoresis with a palladium decoupler and electrochemical detection.

Although it has been shown that microchip electrophoresis (MCE) with electrochemical detection can be used to separate and detect electroactive species, there is a need to increase the separation performance of these devices so that complex mixtures can be routinely analyzed. Previous work in the MCE has demonstrated that increasing the separation channel length leads to an increase in resolution between closely eluting analytes. This paper details the use of lengthened serpentine microchannels for MCE and electrochemical detection where a palladium decoupler is used to ground the separation voltage so that the working electrodes remain in the fluidic network. In this work, palladium electrodepositions were used to increase the decoupler surface area and more efficiently dissipate hydrogen produced at the decoupler. Dopamine and norepinephrine, which only differ in structure by a hydroxyl group, were used as model analytes. It was found that increasing the separation channel length led to improvements in both the resolution and the number of theoretical plates for these analytes. The use of a bilayer valving device, where PDMS-based valves are utilized for the injection process, along with serpentine microchannels and amperometric detection resulted in a multianalyte separation and an average of 28 700 theoretical plates. It was also shown that the increased channel length is beneficial when separating and detecting analytes from a high ionic strength matrix. This was demonstrated by monitoring the stimulated release of neurotransmitters from a confluent layer of PC 12 cells.

Use of the Jarvik 2000 continuous flow left ventricular assist device for acute myocardial infarction and cardiogenic shock.

Several strategies for circulatory support have been successfully utilized as bridges to recovery or transplantation after acute myocardial infarction and cardiogenic shock. We report the novel use of a continuous flow left ventricular assist device (LVAD) for successful recovery and bridging to transplantation in a patient who had massive anterior wall myocardial infarction.