Long-Term Satisfaction of Oral Sedation versus Standard-of-Care Intravenous Sedation for Ocular Surgery.

Purpose: Long-term patient satisfaction may influence patients' perspectives of the quality of care and their relationship with their providers. This is a follow up to a comparative effectiveness study investigating oral to intravenous sedation (OIV study). The OIV study found that oral sedation was noninferior in patient satisfaction to standard intravenous (IV) sedation for anterior segment and vitreoretinal surgeries. This study aims to determine if patient satisfaction with oral sedation remained noninferior long term. Patients and Methods: Patients were re-interviewed using the same satisfaction survey given during the OIV study. Statistical analysis involved t-tests for noninferiority of the long-term mean satisfaction score of oral and IV sedation. We also compared the original mean satisfaction score and the follow-up mean satisfaction score for each type of sedation and for both groups combined. Results: Participants were interviewed at a median of 1225.5 days (range 754-1675 days) from their surgery. The original mean satisfaction score was 5.26 ± 0.79 for the oral treatment group (n = 52) and 5.27 ± 0.64 for the intravenous treatment group (n = 46), demonstrating noninferiority with a difference in mean satisfaction score of 0.015 (p < 0.0001). The follow-up mean satisfaction score was 5.23 ± 0.90 for oral sedation and 5.60 ± 0.61 for IV sedation, with a difference in the mean satisfaction score of 0.371 (p = 0.2071). Satisfaction scores did not differ between the original mean satisfaction score and the follow-up mean satisfaction score for the oral treatment group alone (p = 0.8367), but scores in the intravenous treatment group increased longitudinally (p = 0.0004). Conclusion: In this study, long-term patient satisfaction with oral sedation was not noninferior to satisfaction with IV sedation, unlike our findings with short-term patient satisfaction in our original study. Patient satisfaction also remained unchanged over time for the oral treatment group, but patients in the intravenous treatment group reported higher long-term satisfaction with their anesthesia experience compared to the immediate post-operative period.

Diverse Research Teams and Underrepresented Groups in Clinical Studies.

Importance: Several ophthalmic diseases disproportionately affect racial and ethnic minority patients, yet most clinical trials struggle to enroll cohorts that are demographically representative of disease burden; some barriers to recruitment include time and transportation, language and cultural differences, and fear and mistrust of research due to historical abuses. Incorporating diversity within the research team has been proposed as a method to increase trust and improve engagement among potential study participants. Objective: To examine how demographic factors of potential research participants and personnel may be associated with patient consent rates to participate in prospective ophthalmic clinical studies. Design, Setting, and Participants: This retrospective cohort study included patients from an urban, academic hospital who were approached for consent to participate in prospective ophthalmic clinical studies conducted between January 2015 and December 2021. Main Outcomes and Measures: Multivariable logistic regression assessing associations between patient and research personnel demographics and rates of affirmative consent to participate was used. Results: In total, 1380 patients (mean [SD] age, 58.6 [14.9] years; 50.3% male) who were approached for consent to participate in 10 prospective ophthalmic clinical studies were included. Of prospective patients, 566 (43.5%) were Black; 327 (25.1%), Hispanic or Latino; 373 (28.6%), White; 36 (2.8%), other race and ethnicity; and 78 (5.8%) declined to answer. Black patients (odds ratio [OR], 0.32; 95% CI, 0.24-0.44; P < .001) and Hispanic or Latino patients (OR, 0.31; 95% CI, 0.20-0.47; P < .001) were less likely to consent compared with White patients. Patients with lower socioeconomic status were less likely to consent than patients with higher socioeconomic status (OR, 0.43; 95% CI, 0.33-0.53; P < .001). Concordance between patient and research staff race and ethnicity was associated with increased odds of affirmative consent (OR, 2.72; 95% CI, 1.99-3.73; P < .001). Conclusions and Relevance: In this cohort study, patients from underrepresented racial and ethnic groups and those with lower socioeconomic status were less likely to participate in ophthalmic clinical studies. Concordance of race and ethnicity between patients and research staff was associated with improved participant enrollment. These findings underscore the importance of increasing diversity in clinical research teams to improve racial and ethnic representation in clinical studies.

Miniaturized MR-compatible ultrasound system for real-time monitoring of acoustic effects in mice using high-resolution MRI.

Visualization of focused ultrasound in high spatial and temporal resolution is crucial for accurately and precisely targeting brain regions noninvasively. Magnetic resonance imaging (MRI) is the most widely used noninvasive tool for whole-brain imaging. However, focused ultrasound studies employing high-resolution (> 9.4 T) MRI in small animals are limited by the small size of the radiofrequency (RF) volume coil and the noise sensitivity of the image to external systems such as bulky ultrasound transducers. This technical note reports a miniaturized ultrasound transducer system packaged directly above a mouse brain for monitoring ultrasound-induced effects using high-resolution 9.4 T MRI. Our miniaturized system integrates MR-compatible materials with electromagnetic (EM) noise reduction techniques to demonstrate echo-planar imaging (EPI) signal changes in the mouse brain at various ultrasound acoustic intensities. The proposed ultrasound-MRI system will enable extensive research in the expanding field of ultrasound therapeutics.

Utility of In Vivo Confocal Microscopy in Diagnosis of Acanthamoeba Keratitis: A Comparison of Patient Outcomes.

PURPOSE: The aim of this study was to compare outcomes between cases of Acanthamoeba keratitis (AK) diagnosed and treated with or without the use of in vivo confocal microscopy (IVCM). METHODS: We performed a retrospective comparative case series of 26 eyes of 23 patients diagnosed with AK at the Massachusetts Eye and Ear Infirmary over a 5-year period. The characteristics of all identified cases were summarized. We compared the time from presentation to diagnosis of AK (primary outcome), visual acuity, and rates of therapeutic penetrating keratoplasty between eyes diagnosed by culture-only group (n = 8) and by IVCM to diagnose AK (n = 9) and later confirmed by culture (IVCM/C group). RESULTS: The diagnostic delay was significantly longer in the culture only group (25 ± 29 days) compared with the IVCM/C group (3 ± 3 days, P < 0.01). At 6 months, there was a significant difference in best-corrected visual acuity between the culture-only group (1.46 ± 1.07, n = 7) and the IVCM/C group (0.22 ± 0.22, n = 8), after adjusting for initial baseline visual acuity (P = 0.02). Therapeutic penetrating keratoplasty was performed in 50% of culture-only (n = 7) and 11% of IVCM/C group eyes (n = 9), but this was not statistically significant (P = 0.13). CONCLUSIONS: IVCM can expedite the diagnosis of AK, and its use as an adjunct tool in the diagnosis of AK may result in better patient outcomes compared with basing treatment decisions on corneal cultures alone.

General-Purpose Ultrasound Neuromodulation System for Chronic, Closed-Loop Preclinical Studies in Freely Behaving Rodents.

Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head-fixed, anesthesia-dependent, and acute, limiting clinical translatability. Here, this work reports a general-purpose ultrasound neuromodulation system for chronic, closed-loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact-free stimulation and simultaneous neural recording. Using the general-purpose system, it can be observed that state-dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption.

FPCB as an Acoustic Matching Layer for 1D Linear Ultrasound Transducer Arrays.

An acoustic matching layer is an essential component of an ultrasound transducer to achieve maximum ultrasound transmission efficiency. Here, we develop a flexible printed circuit board (FPCB) with a composite structure consisting of multiple polyimide and copper layers and demonstrate it as a novel acoustic matching layer. With a flexible substrate and robust ACF bonding, the FPCB not only serves as an acoustic matching layer between piezoelectric elements and the surrounding medium but also as a ground for the electrical connection between the transducer array elements and the folded substrate. A 1D linear ultrasound transducer array with the FPCB matching layer exhibits larger output pressure, wider -3dB bandwidth, and higher ultrasound beam intensity compared to that of an ultrasound transducer array with the alumina/epoxy matching layer, which is one of the most commonly applied composite matching layers. The enhanced transmission performance verifies that the proposed FPCB is an excellent matching layer for 1D linear ultrasound transducer arrays.

Oral Sedation is Non-Inferior to Intravenous Sedation for Cornea and Glaucoma Surgery: A Randomized Controlled Trial.

Purpose: To determine whether oral sedation is as safe and effective as IV sedation for ophthalmic surgeries other than cataract surgery, we tested whether patient satisfaction with oral triazolam was non-inferior to IV midazolam for cornea and glaucoma surgeries. Patients and Methods: Seventy-five cornea and 49 glaucoma surgery patients 18 years and older at Boston Medical Center (Boston, MA) were randomized within each study group (cornea or glaucoma) to receive oral triazolam + IV placebo, or oral placebo + IV midazolam before surgery in a double-masked fashion. Supplemental IV anesthesia was administered as needed during surgery. The primary outcome measure was patient satisfaction with anesthesia, compared between oral and IV sedation groups via t-test for non-inferiority, based on 70 cornea and 43 glaucoma subjects completing the study. Secondary outcome measures included surgeon and anesthesia provider satisfaction with anesthesia, rate of supplemental IV anesthesia, and incidence of adverse events and surgical complications. Results: Using an a priori non-inferiority margin of 0.5, initial oral sedation was non-inferior to initial IV sedation in cornea (n=70, p<0.001) and glaucoma (n=43, p=0.017) groups, even after excluding subjects administered supplemental IV anesthesia. There were no significant differences in anesthesia provider or surgeon satisfaction, intra-operative complications, adverse events, or supplemental anesthesia between groups, except for higher anesthesia provider satisfaction with oral sedation in an Ahmed or Baerveldt implant ± cataract surgery sub-group (p=0.04). Subjects receiving supplemental anesthesia included 6 oral (18.2%) and 5 IV (13.5%) in the cornea group (p=0.59), and 7 oral (29.2%) and 6 IV (31.6%) in the glaucoma group (p=0.50). Conclusion: Our results suggest that an initial dose of oral triazolam is equivalent to IV midazolam for non-cataract anterior segment surgeries. However, there was a relatively high need for supplemental IV anesthesia during some surgery types, particularly with glaucoma tube shunt implantation.

Descemet's membrane injury due to bullet shockwave trauma.

Purpose: To report a case of corneal edema associated with Descemet membrane (DM) damage likely due to shockwave trauma from a bullet passing by the eye. Observations: A 27-year-old man presented to the emergency department with pain, redness, and severely decreased vision in the left eye immediately following a gun assault. Examination of the eye revealed a temporal conjunctival laceration, corneal edema, hyphema, and vitreous hemorrhage. Bullets were found in the patient's left chest and axilla, and a laceration was present on the bridge of his nose, but no foreign bodies were found in or around the eyes. The intraocular hemorrhage and corneal edema gradually resolved, and it became apparent that there were DM irregularities that possibly represented micro-ruptures. After 7 months, uncorrected visual acuity improved to 20/25, and the cornea was free of edema but had persistent small focal areas of DM thickening and scarring. Conclusions and Importance: This case illustrates that DM and possibly endothelial cell damage can occur due to shockwave injury from high-speed projectiles. In our case of presumed small central DM micro-ruptures, the corneal edema resolved, and the vision significantly improved with topical therapy and observation, suggesting an overall good prognosis from such injuries.

Corneal Endothelial Cell Density in Normal Tension Glaucoma Compared to Healthy Controls.

The purpose of this study was to investigate corneal endothelial cell density (ECD) and morphology between normal tension glaucoma (NTG) and controls. A cross-sectional, single center study of 24 NTG and 26 age-matched healthy eyes were included. ECD, mean cell size (MCA) and coefficient of variance (CV) were analyzed, controlling for age and number and duration of concurrent glaucoma medications. NTG subjects had significantly lower ECD (2307 ± 514.7 vs. 2558 ± 278.5, p = 0.044) and larger MCA (458.3 ± 94.8 vs. 386.7 ± 57.3, p = 0.004), but no difference in CV compared to healthy subjects. NTG subjects stratified by number of glaucoma medications showed significant differences in ECD (p = 0.024) and MCA (p = 0.021), but no difference in CV. There were no significant differences in ECD, MCA or CV between subjects stratified by duration of glaucoma medication usage. After age-adjusting, there was no dose-dependent relationship between mean ECD or MCA and number of glaucoma medications. Post hoc analysis demonstrated only NTG subjects on three or more glaucoma medications had statistically significant differences in ECD (p = 0.032) and MCA (p = 0.037) compared to NTG subjects on two glaucoma medications. This study suggests that NTG is associated with lower corneal endothelial cell density and mean cell size.

Poor Correlation of Provider and Patient Satisfaction with Anesthesia in Ophthalmic Surgeries: A Secondary Analysis of a Clinical Trial.

Purpose: This secondary analysis of a clinical trial that measured surgeon, anesthesiologist, and patient satisfaction following ophthalmic surgery under monitored anesthesia care (MAC) with a benzodiazepine investigates the degree of association between patient satisfaction with anesthesia compared to surgeon and anesthesiologist satisfaction with anesthesia. Patients and Methods: Data from analogous 6-point surgeon satisfaction surveys and anesthesiologist satisfaction surveys were compared to data from a 6-point validated patient satisfaction survey collected from a clinical trial investigating satisfaction with different forms of benzodiazepine for patients undergoing cataract, retina, cornea, or glaucoma surgery. Relationships between measures were analyzed using Pearson's correlation coefficient, with further subgroup analysis based on language groups and single-question measures of satisfaction. Results: A total of 283 ophthalmic surgical cases were analyzed. Mean surgeon satisfaction was 5.27 (range, 1.33-6.00), mean anesthesiologist satisfaction was 5.12 (range, 1.17-6.00), and mean patient satisfaction was 5.28 (range, 2.58-6.00). The correlation between surgeon and patient satisfaction was 0.333 (p = 9.06e-9), while the correlation between anesthesiologist and patient satisfaction was 0.319 (p = 4.28e-8). There was no difference between English and non-English speaking patients in correlation between surgeon and patient satisfaction (p = 0.08) and anesthesiologist and patient satisfaction (p = 0.47). Conclusion: The data demonstrate a low level of association between patient satisfaction with anesthesia and provider satisfaction, even when patient language is taken into consideration. This suggests that providers are poor predictors of patient satisfaction with anesthesia and are unreliable judges of patient comfort perioperatively.

Calcium-Modified Silk Patch as a Next-Generation Ultrasound Coupling Medium.

There is an increasing interest in developing next-generation wearable ultrasound patch systems because of their wide range of applications, such as home healthcare systems and continuous monitoring systems for physiological conditions. A wearable ultrasound patch system requires a stable interface to the skin, an ultrasound coupling medium, a flexible transducer array, and miniaturized operating circuitries. In this study, we proposed a patch composed of calcium (Ca)-modified silk, which serves as both a stable interface and a coupling medium for ultrasound transducer arrays. The Ca-modified silk patch provided not only a stable and conformal interface between the epidermal ultrasound transducer and human skin with high adhesion but also offered acoustic impedance close to that of human skin. The Ca-modified silk patch was flexible and stretchable (∼400% strain) and could be attached to various materials. In addition, because the acoustic impedance of the Ca-modified silk patch was 2.15 MRayl, which was similar to that of human skin (1.99 MRayl), the ultrasound transmission loss of the proposed patch was relatively low (∼0.002 dB). We also verified the use of the Ca-modified silk patch in various ultrasound applications, including ultrasound imaging, ultrasound heating, and transcranial ultrasound stimulation for neuromodulation. The comparable performance of the Ca-modified patch to that of a commercial ultrasound gel and its durability against various environmental conditions confirmed that the Ca-modified silk patch could be a promising candidate as a coupling medium for next-generation ultrasound patch systems.

The impact of CT image parameters and skull heterogeneity modeling on the accuracy of transcranial focused ultrasound simulations.

Objective. Low-intensity transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation (NIBS) technique. TUS can reach deeper areas and target smaller regions in the brain than other NIBS techniques, but its application in humans is hampered by the lack of a straightforward and reliable procedure to predict the induced ultrasound exposure. Here, we examined how skull modeling affects computer simulations of TUS.Approach. We characterized the ultrasonic beam after transmission through a sheep skull with a hydrophone and performed computed tomography (CT) image-based simulations of the experimental setup. To study the skull model's impact, we varied: CT acquisition parameters (tube voltage, dose, filter sharpness), image interpolation, segmentation parameters, acoustic property maps (speed-of-sound, density, attenuation), and transducer-position mismatches. We compared the impact of modeling parameter changes on model predictions and on measurement agreement. Spatial-peak intensity and location, total power, and the Gamma metric (a measure for distribution differences) were used as quantitative criteria. Modeling-based sensitivity analysis was also performed for two human head models.Main results. Sheep skull attenuation assignment and transducer positioning had the most important impact on spatial peak intensity (overestimation up to 300%, respectively 30%), followed by filter sharpness and tube voltage (up to 20%), requiring calibration of the mapping functions. Positioning and skull-heterogeneity-structure strongly affected the intensity distribution (gamma tolerances exceeded in>80%, respectively>150%, of the focus-volume in water), necessitating image-based personalized modeling. Simulation results in human models consistently demonstrate a high sensitivity to the skull-heterogeneity model, attenuation tuning, and transducer shifts, the magnitude of which depends on the underlying skull structure complexity.Significance. Our study reveals the importance of properly modeling the skull-heterogeneity and its structure and of accurately reproducing the transducer position. The results raise red flags when translating modeling approaches among clinical sites without proper standardization and/or recalibration of the imaging and modeling parameters.

Thrombospondin 1 polymorphism associated with decreased expression and increased risk of pterygium.

PURPOSE: To assess the potential association of a thrombospondin 1 gene (THBS1) single-nucleotide polymorphism (rs1478604) with thrombospondin 1 (TSP-1) mRNA expression, as well as the risk of pterygium, in a pilot study. METHODS: DNA and RNA were isolated from peripheral blood samples collected from normal volunteer subjects (n = 39). In addition, DNA was isolated from conjunctival tissue samples collected during pterygium excision surgeries (n = 42). Relative expression of TSP-1 mRNA was measured by quantitative RT-PCR, and rs1478604 genotype was determined using a TaqMan SNP genotyping assay. Genotype frequencies were compared with mRNA expression and between pterygium samples and normal controls. RESULTS: Expression of TSP-1 mRNA was significantly lower in the peripheral blood of normal subjects who were homozygous for the C allele of rs1478604 (CC) compared to TT and CT genotypes (p = 0.004). When we compared rs1478604 genotypes between normal and pterygium patients, we found that the CC genotype was also associated with an increased risk of pterygium compared to TT (odds ratio (OR) = 5.39, 95% CI [1.26-22.99], p = 0.028), CT (OR = 7.86, 95% CI [1.92-32.17], p = 0.003), and combined CT and TT genotypes (OR = 6.67; 95% CI = [1.75-25.37]; p = 0.003). CONCLUSIONS: We found that the C allele of rs1478604 was associated with both lower TSP-1 expression and higher risk of pterygium, possibly implicating TSP-1 in the pathogenesis of pterygium.

Transducer modeling for accurate acoustic simulations of transcranial focused ultrasound stimulation.

OBJECTIVE: Low-intensity transcranial ultrasound stimulation (TUS) is emerging as a non-invasive brain stimulation technique with superior spatial resolution and the ability to reach deep brain areas. Medical image-based computational modeling could be an important tool for individualized TUS dose control and targeting optimization, but requires further validation. This study aims to assess the impact of the transducer model on the accuracy of the simulations. APPROACH: Using hydrophone measurements, the acoustic beam of a single-element focused transducer (SEFT) with a flat piezoelectric disc and an acoustic lens was characterized. The acoustic beam was assessed in a homogeneous water bath and after transmission through obstacles (3D-printed shapes and skull samples). The acoustic simulations employed the finite-difference time-domain method and were informed by computed tomography (CT) images of the obstacles. Transducer models of varying complexity were tested representing the SEFT either as a surface boundary condition with variable curvature or also accounting for its internal geometry. In addition, a back-propagated pressure distribution from the first measurement plane was used as source model. The simulations and measurements were quantitatively compared using key metrics for peak location, focus size, intensity and spatial distribution. MAIN RESULTS: While a surface boundary with an adapted, 'effective' curvature radius based on the specifications given by the manufacturer could reproduce the measured focus location and size in a homogeneous water bath, it regularly failed to accurately predict the beam after obstacle transmission. In contrast, models that were based on a one-time calibration to the homogeneous water bath measurements performed substantially better in all cases with obstacles. For one of the 3D-printed obstacles, the simulated intensities deviated substantially from the measured ones, irrespective of the transducer model. We attribute this finding to a standing wave effect, and further studies should clarify its relevance for accurate simulations of skull transmission. SIGNIFICANCE: Validated transducer models are important to ensure accurate simulations of the acoustic beam of SEFTs, in particular in the presence of obstacles such as the skull.

Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease.

Current pharmacological treatments for Parkinson's disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.

Multifunctional multi-shank neural probe for investigating and modulating long-range neural circuits in vivo.

Investigation and modulation of neural circuits in vivo at the cellular level are very important for studying functional connectivity in a brain. Recently, neural probes with stimulation capabilities have been introduced, and they provided an opportunity for studying neural activities at a specific region in the brain using various stimuli. However, previous methods have a limitation in dissecting long-range neural circuits due to inherent limitations on their designs. Moreover, the large size of the previously reported probes induces more significant tissue damage. Herein, we present a multifunctional multi-shank MEMS neural probe that is monolithically integrated with an optical waveguide for optical stimulation, microfluidic channels for drug delivery, and microelectrode arrays for recording neural signals from different regions at the cellular level. In this work, we successfully demonstrated the functionality of our probe by confirming and modulating the functional connectivity between the hippocampal CA3 and CA1 regions in vivo.

Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies.

BACKGROUND: Low-intensity transcranial focused ultrasound stimulation (TFUS) holds great promise as a highly focal technique for transcranial stimulation even for deep brain areas. Yet, knowledge about the safety of this novel technique is still limited. OBJECTIVE: To systematically review safety related aspects of TFUS. The review covers the mechanisms-of-action by which TFUS may cause adverse effects and the available data on the possible occurrence of such effects in animal and human studies. METHODS: Initial screening used key term searches in PubMed and bioRxiv, and a review of the literature lists of relevant papers. We included only studies where safety assessment was performed, and this results in 33 studies, both in humans and animals. RESULTS: Adverse effects of TFUS were very rare. At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood-brain barrier (BBB) opening. TFUS may also unintentionally affect long-term neural activity and behaviour. A variety of methods was used mainly in rodents to evaluate these adverse effects, including tissue staining, magnetic resonance imaging, temperature measurements and monitoring of neural activity and behaviour. In 30 studies, adverse effects were absent, even though at least one Food and Drug Administration (FDA) safety index was frequently exceeded. Two studies reported microhaemorrhages after long or relatively intense stimulation above safety limits. Another study reported BBB opening and neuronal damage in a control condition, which intentionally and substantially exceeded the safety limits. CONCLUSION: Most studies point towards a favourable safety profile of TFUS. Further investigations are warranted to establish a solid safety framework for the therapeutic window of TFUS to reliably avoid adverse effects while ensuring neural effectiveness. The comparability across studies should be improved by a more standardized reporting of TFUS parameters.

Patient Satisfaction with Oral versus Intravenous Sedation for Cataract Surgery: A Randomized Clinical Trial.

PURPOSE: To determine whether patient satisfaction with oral sedation is noninferior to intravenous sedation for cataract surgery. DESIGN: Prospective, randomized, double-masked clinical trial. PARTICIPANTS: A volunteer sample of patients 18 years or older from diverse backgrounds scheduled for cataract surgery. Patients who were allergic to benzodiazepines, older than 70 years with a failed delirium screening questionnaire, pregnant or nursing, using a medication inhibiting cytochrome 450 3A, or intoxicated on the day of surgery were excluded. METHODS: Patients were randomized to receive either oral triazolam with intravenous placebo or intravenous midazolam with oral placebo before surgery. MAIN OUTCOMES MEASURES: The primary outcome was patient satisfaction, measured by a survey administered on postoperative day 1. Secondary outcomes included surgeon and anesthesia provider satisfaction, need for supplemental anesthesia, and surgical complications. RESULTS: Among the 85 patients (42 men [49.4%]; mean age, 65.8 years; standard deviation, 9.5 years) completing the study, the mean satisfaction score was 5.34±0.63 (range, 3.75-6) in the oral sedation group and 5.40±0.52 (range, 4-6) in the intravenous group. With an a priori noninferiority margin of 0.5 and a difference in mean scores between the 2 groups of 0.06 (1-tailed 95% confidence interval [CI], -infinity to 0.27), our results demonstrate noninferiority of oral sedation with a P value of 0.0004. Surgeon and anesthesia provider satisfaction was similar between the 2 groups. Intraoperative complications occurred in 16.7% in the oral group and 9.3% in the intravenous group (difference, 7.4%; 95% CI, -6.9% to 21.6%; P = 0.31). The only major intraoperative complication-a posterior capsular tear-occurred in the intravenous group. Eight patients in the oral group (19.0%) and 3 in the intravenous group (7.0%) received supplemental intravenous sedation (difference, 12.1%; 95% CI, -2.0% to 26.2%; P = 0.097). CONCLUSIONS: The use of oral sedation in cataract surgery has been suggested as a cost- and space-saving measure, potentially allowing the transition of some patients from an operating to procedure room or office-based setting. We report the noninferiority of oral compared with intravenous sedation for cataract surgery in a diverse patient population in terms of patient satisfaction.

A Capacitive Micromachined Ultrasonic Transducer-Based Resonant Sensor Array for Portable Volatile Organic Compound Detection with Wireless Systems.

The development of portable volatile organic compound (VOC) sensors is essential for home healthcare and workplace safety because VOCs are environmental pollutants that may critically affect human health. Here, we report a compact and portable sensor platform based on a capacitive micromachined ultrasonic transducer (CMUT) array offering multiplex detection of various VOCs (toluene, acetone, ethanol, and methanol) using a single read-out system. Three CMUT resonant devices were functionalized with three different layers: (1) phenyl-selective peptide, (2) colloids of single-walled nanotubes and peptide, and (3) poly(styrene-co-allyl alcohol). As each device exhibited different sensitivities to the four VOCs, we performed principal component analysis to achieve selective detection of all four gases. For the simultaneous detection of VOCs using CMUT sensors, the changes in the resonant frequencies of three devices were monitored in real time, but using only a single oscillator through an electrically controlled relay to achieve compactness. In addition, by devising a wireless system, measurement results were transmitted to a smartphone to monitor the concentration of VOCs. We used multiple sensors to obtain a larger number of fingerprints for pattern recognition to enhance selectivity but interfaced these sensors with a single read-out circuit to minimize the footprint of the overall system. The compact CMUT-based sensor array based on a multiplex detection scheme is a promising sensor platform for portable VOC monitoring.

Miniature ultrasound ring array transducers for transcranial ultrasound neuromodulation of freely-moving small animals.

BACKGROUND: Current transcranial ultrasound stimulation for small animal in vivo experiment is limited to acute stimulation under anesthesia in stereotaxic fixation due to bulky and heavy curved transducers. METHODS: We developed a miniaturized ultrasound ring array transducer which is capable of invoking motor responses through neuromodulation of freely-moving awake mice. RESULTS: The developed transducer is a 32-element, 183-kHz ring array with a weight of 0.035 g (with PCB: 0.73 g), a diameter of 8.1 mm, a focal length of 2.3 mm, and lateral resolution of 2.75 mm. By developing an affixation scheme suitable for freely-moving animals, the transducer was successfully coupled to the mouse brain and induced motor responses in both affixed and awake states. CONCLUSION: Ultrasound neuromodulation of a freely-moving animal is now possible using the developed lightweight and compact system to conduct a versatile set of in vivo experiments.