Validation of 3D fluoroscopy for image-guidance registration in depth electrode implantation for medically refractory epilepsy.

BACKGROUND: Frame registration is a critical step to ensure accurate electrode placement in stereotactic procedures such as stereoelectroencephalography (SEEG) and is routinely done by merging a computed tomography (CT) scan with the preoperative magnetic resonance (MR) examination. Three-dimensional fluoroscopy (XT) has emerged as a method for intraoperative electrode verification following electrode implantation and more recently has been proposed as a registration method with several advantages. METHODS: We compared the accuracy of SEEG electrode placement by frame registration with CT and XT imaging by analyzing the Euclidean distance between planned and post-implantation trajectories of the SEEG electrodes to calculate the error in both the entry (EP) and target (TP) points. Other variables included radiation dose, efficiency, and complications. RESULTS: Twenty-seven patients (13 CT and 14 XT) underwent placement of SEEG electrodes (319 in total). The mean EP and TP errors for the CT group were 2.3 mm and 3.3 mm, respectively, and 1.9 mm and 2.9 mm for the XT group, with no statistical difference (p = 0.75 and p = 0.246). The time to first electrode placement was similar (XT, 82 ± 10 min; CT, 84 ± 22 min; p = 0.858) and the average radiation exposure with XT (234 ± 55 mGy*cm) was significantly lower than CT (1245 ± 123 mGy*cm) (p < 0.0001). Four complications were documented with equal incidence in both groups. CONCLUSIONS: The use of XT as a method for registration resulted in similar implantation accuracy compared with CT. Advantages of XT are the substantial reduction in radiation dose and the elimination of the need to transfer the patient out of the room which may have an impact on patient safety and OR efficiency.

The accuracy of 3D fluoroscopy (XT) vs computed tomography (CT) registration in deep brain stimulation (DBS) surgery.

BACKGROUND: Stereotactic registration is the most critical step ensuring accuracy in deep brain stimulation (DBS) surgery. 3D fluoroscopy (XT) is emerging as an alternative to CT. XT has been shown to be safe and effective for intraoperative confirmation of lead position following implantation. However, there is a lack of studies evaluating the suitability of XT to be used for the more crucial step of registration and its capability of being merged to a preoperative MRI. This is the first study comparing accuracy, efficiency, and radiation exposure of XT- vs CT-based stereotactic registration and XT/MRI merging in deep brain stimulation. METHODS: Mean absolute differences and Euclidean distance between planned (adjusted for intraoperative testing) and actual lead trajectories were calculated for accuracy of implantation. The radiation dose from each scan was recorded as the dose length product (DLP). Efficiency was measured as the time between the patient entering the operating room and the initial skin incision. A one-way ANOVA compared these parameters between patients that had either CT- or XT-based registration. RESULTS: Forty-one patients underwent DBS surgery-25 in the CT group and 16 in the XT group. The mean absolute difference between CT and XT was not statistically significant in the x (p = 0.331), y (p = 0.951), or z (p = 0.807) directions. The Euclidean distance between patient groups did not differ significantly (p = 0.874). The average radiation exposure with XT (220.0 ± 0.1 mGy*cm) was significantly lower than CT (1269.3 ± 112.9 mGy*cm) (p < 0.001). There was no significant difference in registration time between CT (107.8 ± 23.1 min) and XT (106.0 ± 18.2 min) (p = 0.518). CONCLUSION: XT-based frame registration was shown to result in similar implantation accuracy and significantly less radiation exposure compared with CT. Our results surprisingly showed no significant difference in registration time, but this may be due to a learning curve effect.

Attitudes Toward and Management of Fibromyalgia: A National Survey of Canadian Rheumatologists and Critical Appraisal of Guidelines.

BACKGROUND: Canadian rheumatologists' attitudes toward and management of fibromyalgia remain uncertain. OBJECTIVE: The aim of this study was to explore management strategies and attitudes of Canadian rheumatologists toward fibromyalgia and concordance with guideline recommendations. METHODS: We administered a 17-item cross-sectional survey to Canadian rheumatologists and explored the concordance between respondents' management practices with the 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia. RESULTS: Among 331 Canadian rheumatologists who were approached, 140 returned the survey for a 42% response rate. The majority felt that fibromyalgia was a useful clinical diagnosis (110/138 [80%]) but was divided as to whether fibromyalgia was objectively defined (75/138 [54%]) or a psychosocial condition (42/138 [30%]) or could result in an inability to work (37/138 [27%]). Contrary to guideline recommendations, most (82/134 [61%]) endorsed that tender points were useful for diagnosis. Half endorsed potentially refusing consultations with fibromyalgia patients, and only 42% (59/139) agreed that there were effective therapies for this syndrome. Consistent with the guideline, most respondents managed fibromyalgia with education, exercise therapy, antidepressants, and nonnarcotic analgesics (≥89% for all); however, fewer than half agreed that any of these modalities were effective (endorsement ranged from 9% to 47%). Assessment of the 2012 guideline revealed a number of important limitations. CONCLUSIONS: Canadian rheumatologists largely do not provide primary care for fibromyalgia. Most adhere to guideline recommendations for management of fibromyalgia, but few endorse these interventions as effective. Further research, including updating of the 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia, is required to inform this disconnect.

hace1 Influences zebrafish cardiac development via ROS-dependent mechanisms.

BACKGROUND: In this study, we reveal a previously undescribed role of the HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) tumor suppressor protein in normal vertebrate heart development using the zebrafish (Danio rerio) model. We examined the link between the cardiac phenotypes associated with hace1 loss of function to the expression of the Rho small family GTPase, rac1, which is a known target of HACE1 and promotes ROS production via its interaction with NADPH oxidase holoenzymes. RESULTS: We demonstrate that loss of hace1 in zebrafish via morpholino knockdown results in cardiac deformities, specifically a looping defect, where the heart is either tubular or "inverted". Whole-mount in situ hybridization of cardiac markers shows distinct abnormalities in ventricular morphology and atrioventricular valve formation in the hearts of these morphants, as well as increased expression of rac1. Importantly, this phenotype appears to be directly related to Nox enzyme-dependent ROS production, as both genetic inhibition by nox1 and nox2 morpholinos or pharmacologic rescue using ROS scavenging agents restores normal cardiac structure. CONCLUSIONS: Our study demonstrates that HACE1 is critical in the normal development and proper function of the vertebrate heart via a ROS-dependent mechanism. Developmental Dynamics 247:289-303, 2018. © 2017 Wiley Periodicals, Inc.

Strategies to mitigate dissociative and psychotomimetic effects of ketamine in the treatment of major depressive episodes: a narrative review.

Objectives Replicated evidence has demonstrated that ketamine exerts rapid-acting and potent antidepressant effects. Notwithstanding, its promise to mitigate depressive symptoms and suicidality in antidepressant-resistant populations, several limitations and safety concerns accompany ketamine including, but not limited to, the potential for abuse and psychotomimetic/dissociative experiences. The focus of the current narrative review is to synthesise available evidence of strategies that may mitigate and fully prevent treatment-emergent psychotomimetic and dissociative effects associated with ketamine administration. Methods PubMed, Google Scholar and ClinicalTrials.gov were searched for relevant articles. Results Potential avenues investigated to minimise psychotomimetic effects associated with ketamine administration include the following: (1) altering dosing and infusion rates; (2) route of administration; (3) enantiomer choice; (4) co-administration with mood stabilisers of antipsychotics; and (5) use of alternative N-methyl-d-aspartate (NMDA)-modulating agents. Emerging evidence indicates that dissociative experiences can be significantly mitigated by using an intranasal route of administration, lower dosages, or use of alternative NMDA-modulating agents, namely lanicemine (AZD6765) and GLYX-13. Conclusions Currently, intranasal administration presents as the most promising strategy to mitigate dissociative and psychotomimetic effects; however, studies of strategies to mitigate the adverse events of ketamine are limited in number and quality and thus further investigation is still needed.

Single-incision laparoscopic cholecystectomy at community hospitals in Honolulu, Hawai'i: a case series.

This study aims to demonstrate the feasibility of implementing single-incision laparoscopic cholecystectomy in a community hospital setting. Minimally invasive surgical approaches for cholecystectomy achieve equivalent outcomes to the open surgical approach with less post-operative pain, improved cosmesis, shorter hospital stays, and decreased complications. Surgeons are attempting to reduce incisional trauma further by decreasing the number of incisions. A retrospective chart review was conducted for demographics, operating time, blood loss, conversion rate, length of stay, and presence of operative complications on patients undergoing single-incision laparoscopic cholecystectomy at two community hospitals between 2008 and 2011. One hundred and three patients (79 females and 24 males) underwent single-incision laparoscopic cholecystectomy. The mean age was 49.8 years (range 18-88). Ninety-six patients (93.2%) underwent elective procedures while 7 patients (6.8%) underwent urgent procedures. The mean operating time was 89.7 (± 28.3) minutes and the average blood loss was 33.7 (± 27.4) milliliters. Ninety-five (92.2%) of the procedures were successfully completed with a single-incision approach and 8 (7.8%) were converted to a multi-incisional approach, while none were converted to an open approach. The median length of stay was 4.75 hours. The post-operative complication rate was 7.4% (7/95) and included four superficial wound infections, one bile leak, one acute renal failure, and one urinary tract infection. These outcomes for single-incision laparoscopic cholecystectomy are comparable to other case series reported in the literature, and this retrospective review illustrates that single-incision laparoscopic cholecystectomy is feasible in a community setting.

Predictions of hydration free energies from all-atom molecular dynamics simulations.

Here, we computed the aqueous solvation (hydration) free energies of 52 small drug-like molecules using an all-atom force field in explicit water. This differs from previous studies in that (1) this was a blind test (in an event called SAMPL sponsored by OpenEye Software) and (2) the test compounds were considerably more challenging than have been used in the past in typical solvation tests of all-atom models. Overall, we found good correlations with experimental values which were subsequently made available, but the variances are large compared to those in previous tests. We tested several different charge models and found that several standard charge models performed relatively well. We found that hypervalent sulfur and phosphorus compounds are not well handled using current force field parameters and suggest several other possible systematic errors. Overall, blind tests like these appear to provide significant opportunities for improving force fields and solvent models.

Small molecule hydration free energies in explicit solvent: An extensive test of fixed-charge atomistic simulations.

Using molecular dynamics free energy simulations with TIP3P explicit solvent, we compute the hydration free energies of 504 neutral small organic molecules and compare them to experiments. We find, first, good general agreement between the simulations and the experiments, with an RMS error of 1.24 kcal/mol over the whole set (i.e., about 2 kT) and a correlation coefficient of 0.89. Second, we use an automated procedure to identify systematic errors for some classes of compounds, and suggest some improvements to the force field. We find that alkyne hydration free energies are particularly poorly predicted due to problems with a Lennard-Jones well depth, and find that an alternate choice for this well depth largely rectifies the situation. Third, we study the non-polar component of hydration free energies - that is, the part that is not due to electrostatics. While we find that repulsive and attractive components of the non-polar part both scale roughly with surface area (or volume) of the solute, the total non-polar free energy does not scale with the solute surface area or volume, because it is a small difference between large components and is dominated by the deviations from the trend. While the methods used here are not new, this is a more extensive test than previous explicit solvent studies, and the size of the test set allows identification of systematic problems with force field parameters for particular classes of compounds. We believe that the computed free energies and components will be valuable to others in future development of force fields and solvation models.

Predicting small-molecule solvation free energies: an informal blind test for computational chemistry.

Experimental data on the transfer of small molecules between vacuum and water are relatively sparse. This makes it difficult to assess whether computational methods are truly predictive of this important quantity or merely good at explaining what has been seen. To explore this, a prospective test was performed of two different methods for estimating solvation free energies: an implicit solvent approach based on the Poisson-Boltzmann equation and an explicit solvent approach using alchemical free energy calculations. For a set of 17 small molecules, root mean square errors from experiment were between 1.3 and 2.6 kcal/mol, with the explicit solvent free energy approach yielding somewhat greater accuracy but at greater computational expense. Insights from outliers and suggestions for future prospective challenges of this kind are presented.

Surface plasmon-quantum dot coupling from arrays of nanoholes.

The coupling of semiconductor quantum dots (QDs) to the surface plasmon (SP) modes of nanohole arrays in a metal film was demonstrated for the first time, showing enhancement in the spontaneous emission by 2 orders of magnitude. The SP-enhanced transmission resonances of the nanohole arrays were tuned around the photoluminescence (PL) peak of polystyrene-b-poly(acrylic acid) (PS-b-PAA)-stabilized cadmium sulfide (CdS) quantum dots (QDs) in contact with the arrays. As a result the overall PL from the SP-QD system was enhanced by 2 orders of magnitude, even after excluding the enhanced transmission of the nanohole array without the QDs. The maximum enhancement occurred when the resonance from the nanohole array matched the QD PL spectrum. Time-resolved PL measurements were used to estimate the relative contribution of different physical mechanisms to the enhanced spontaneous emission. The increased spontaneous emission in the SP-QD system is promising for prospective plasmonic light-emitting devices incorporating QDs.