Effect of Dexmedetomidine on Postoperative Renal Function in Patients Undergoing Cardiac Valve Surgery Under Cardiopulmonary Bypass: A Randomized Clinical Trial.

OBJECTIVE: The effect of dexmedetomidine on postoperative renal function was investigated in patients undergoing cardiac valve surgery under cardiopulmonary bypass (CPB). DESIGN: A randomized controlled trial. SETTING: University teaching, grade A tertiary hospital. PARTICIPANTS: A total of 70 patients scheduled to undergo cardiac valve replacement or valvuloplasty under CPB were eligible and randomly divided into groups D (n = 35) and C (n = 35) between January 2020 and March 2021. INTERVENTIONS: Patients in group D were administered 0.6 µg/kg/h of dexmedetomidine intravenously from 10 minutes before anesthesia induction to 6 hours after surgery; normal saline was used instead of dexmedetomidine in group C. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of acute kidney injury (AKI). Acute kidney injury was defined according to the Kidney Disease Improving Global Outcomes (2012). It was 22.86% and 48.57% in groups D and C, respectively (p = 0.025). The secondary outcomes were intraoperative hemodynamics and various indices in serum. Ten minutes before CPB (T1), 10 minutes after CPB (T2), and 30 minutes after CPB (T3), mean arterial pressure in group D was lower than that in group C, with statistical significance (74.94 ± 8.52 v 81.89 ± 13.66 mmHg, p=0.013; 62.83 ± 11.27 v 71.86 ± 7.89 mmHg, p < 0.001; 72.26 ± 8.75 v 78.57 ± 8.83 mmHg, p = 0.004). At T1, the heart rate in group D was significantly lower than in group C (80.89 ± 14.04 v 95.54 ± 12.53 bpm, p=0.022). The tumor necrosis factor α, interleukin-6, C-reactive protein, and cystatin C levels in group D were lower than those in group C after the surgery (T4) and 24 hours after surgery (T5), with statistical significance. The duration of mechanical ventilation, intensive-care-unit stay time, and hospital stay time in group D were significantly shorter than in group C. The incidences of tachycardia, hypertension, nausea, and vomiting in group D were similar to those in group C. CONCLUSIONS: Dexmedetomidine may be considered as a way to reduce the incidence and severity of postoperative AKI in patients undergoing cardiac valve surgery under cardiopulmonary bypass.

Hand-assisted laparoscopic resection versus total laparoscopic gastric surgery for primary gastric gastrointestinal stromal tumors (GISTs): an analysis from a high-volume institution.

BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) is technically feasible and associated with favorable outcomes. We compared the clinical efficacy of hand-assisted laparoscopic surgery (HLS) and total laparoscopic surgery (TLS) for gastric GISTs. METHODS: We retrospectively analyzed the clinical data of 69 consecutive patients diagnosed with a gastric GIST in a tertiary referral teaching hospital from December 2016 to December 2020. Surgical outcomes were compared between two groups. RESULTS: Fifty-three patients (TLS group: n = 36; HLS group: n = 17) were included. The mean age was 56.9 and 58.1 years in the TLS and HLS groups, respectively. The maximum tumor margin was significantly shorter in the HLS group than in the TLS group (2.3 ± 0.9. vs. 3.0 ± 0.8 cm; P = 0.004). The operative time of the HLS group was significantly shorter than that of the TLS group (70.6 ± 19.1 min vs. 134.4 ± 53.7 min; P < 0.001). The HLS group had less intraoperative blood loss, a shorter time to first flatus, and a shorter time to fluid diet than the TLS group (P < 0.05). No significant difference was found between the groups in the incidence or severity of complications within 30 days after surgery. Recurrence or metastasis occurred in four cases (HLS group; n = 1; TLS group; n = 3). CONCLUSIONS: This study demonstrated that compared with TLS, HLS for gastric GISTs has the advantages of simpler operation, shorter operative time, and faster postoperative recovery.

Association of functional variant in GDF1 promoter with risk of congenital heart disease and its regulation by Nkx2.5.

GDF1 plays an important role in left-right patterning and genetic mutations in the coding region of GDF1 are associated with congenital heart disease (CHD). However, the genetic variation in the promoter of GDF1 with sporadic CHD and its expression regulation is little known. The association of the genetic variation in GDF1 promoter with CHD was examined in two case-control studies, including 1084 cases and 1198 controls in the first study and 582 cases and 615 controls in the second study. We identified one single nucleotide polymorphism (SNP) rs181317402 and two novel genetic mutations located in the promoter region of GDF1. Analysis of combined samples revealed a significant association in genotype and allele frequencies of rs181317402 T/G polymorphism between CHD cases in overall or ventricular septal defects or Tetralogy of Fallot and the control group. rs181317402 allele G polymorphism was significantly associated with a decreased risk of CHD. Furthermore, luciferase assay, chromatin immunoprecipitation and DNA pulldown assay indicated that Nkx2.5 transactivated the expression of GDF1 by binding to the promoter of GDF1. Luciferase activity assay showed that rs181317402 allele G significantly increased the basal and Nkx2.5-mediated activity of GDF1 promoter, while the two genetic mutations had the opposite effect. rs181317402 TG genotype was associated with significantly increased mRNA level of GDF1 compared with TT genotype in 18 CHD individuals. Our results demonstrate for the first time that Nkx2.5 acts upstream of GDF1 and the genetic variants in GDF1 promoter may confer genetic susceptibility to sporadic CHD potentially by altering its expression.

Replication of a genome-wide association study on essential hypertension in Mongolians.

Replication of genome-wide significant association SNPs in independent populations is an essential approach for identifying gene-disease relationships. Therefore, we sought to investigate the top 21 SNPs (rs10507454, rs11897156, rs11897991, rs12325203, rs12541835, rs13395322, rs1525035, rs16936892, rs17010027, rs17045859, rs17136827, rs1866525, rs2045590, rs4547758, rs4655688, rs7107438, rs761353, rs8127139, rs9312305, rs9407874 and rs9865108) from a genome-wide association study of essential hypertension in Mongolians. This was a community-based case-control study involving 428 hypertensives and 638 normotensives from Kerqinzuoyihou Banner,Tongliao, Inner Mongolian Autonomous Region, China. Genotyping was conducted with Sequenom MassArray (®) SNP detection technology. Overall, there were no significant differences in the genotype distributions and allele frequencies between the cases and controls. There was a significant difference between the allele frequencies at locus rs17010027 in cases (high systolic blood pressure) and controls in female (p = .036). There were significant differences in the distribution of genotypes and the allele frequencies at locus rs10507454 between cases (high diastolic blood pressure) and controls (p = .019 and p = .022, respectively) especially in male (p = .009 and p = .011, respectively). rs17010027 is associated with high systolic blood pressure in female, and rs10507454 is associated with high diastolic blood pressure especially in male of this Mongolian population.

Acoustic Sensing and Ultrasonic Drug Delivery in Multimodal Theranostic Capsule Endoscopy.

Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work.

Piezoelectric micromachined ultrasound transducer (PMUT) arrays for integrated sensing, actuation and imaging.

Many applications of ultrasound for sensing, actuation and imaging require miniaturized and low power transducers and transducer arrays integrated with electronic systems. Piezoelectric micromachined ultrasound transducers (PMUTs), diaphragm-like thin film flexural transducers typically formed on silicon substrates, are a potential solution for integrated transducer arrays. This paper presents an overview of the current development status of PMUTs and a discussion of their suitability for miniaturized and integrated devices. The thin film piezoelectric materials required to functionalize these devices are discussed, followed by the microfabrication techniques used to create PMUT elements and the constraints the fabrication imposes on device design. Approaches for electrical interconnection and integration with on-chip electronics are discussed. Electrical and acoustic measurements from fabricated PMUT arrays with up to 320 diaphragm elements are presented. The PMUTs are shown to be broadband devices with an operating frequency which is tunable by tailoring the lateral dimensions of the flexural membrane or the thicknesses of the constituent layers. Finally, the outlook for future development of PMUT technology and the potential applications made feasible by integrated PMUT devices are discussed.

[Prevalence and risk factors of hypertension among community residents in Qiqihar].

OBJECTIVE: To evaluate the prevalence and potential risk factors of hypertension among community residents aged 18 years old and over in Qiqihar in 2014. METHODS: 5850 subjects aged ≥ 18 years old in three communities in Qiqihar were selected by random cluster sampling. The demographic information, personal health condition, living habits and the prevalence of hypertension using unified design questionnaire were surveyed. The height, weight, waist and hip circumference, and blood pressure levels were measured. RESULTS: The prevalence of hypertension was 26.56% among the survey, population while the standardized prevalence was 22.19%. Comparing with different demographic characteristics, physique and behavioral lifestyle, the age, gender, education, marital status, family history, BMI, WHR, smoking, alcohol consumption, exercise, and taste affected the occurrence of hypertension, and the difference was statistically significant (P < 0.001). After univariate logistic regression analysis, age, family history, BMI and alcohol consumption were related with hypertension (P < 0.05). CONCLUSION: The prevalence of hypertension among community residents aged ≥ 18 years old in Qiqihar is high.

Acoustic devices for particle and cell manipulation and sensing.

An emerging demand for the precise manipulation of cells and particles for applications in cell biology and analytical chemistry has driven rapid development of ultrasonic manipulation technology. Compared to the other manipulation technologies, such as magnetic tweezing, dielectrophoresis and optical tweezing, ultrasonic manipulation has shown potential in a variety of applications, with its advantages of versatile, inexpensive and easy integration into microfluidic systems, maintenance of cell viability, and generation of sufficient forces to handle particles, cells and their agglomerates. This article briefly reviews current practice and reports our development of various ultrasonic standing wave manipulation devices, including simple devices integrated with high frequency (>20 MHz) ultrasonic transducers for the investigation of biological cells and complex ultrasonic transducer array systems to explore the feasibility of electronically controlled 2-D and 3-D manipulation. Piezoelectric and passive materials, fabrication techniques, characterization methods and possible applications are discussed. The behavior and performance of the devices have been investigated and predicted with computer simulations, and verified experimentally. Issues met during development are highlighted and discussed. To assist long term practical adoption, approaches to low-cost, wafer level batch-production and commercialization potential are also addressed.

Distance Measurement of Contra-Rotating Rotor Blades with Ultrasonic Transducers.

Coaxial rotor helicopters have great potential in civilian and commercial uses, with many advantages, but challenges remain in the accurate measurement of rotor blades' distance to prevent blade collision. In this paper, a blade tip distance measurement method based on ultrasonic measurement window and phase triggering is proposed, and the triggering time of the transmitter is studied. Due to the complexity of the measured signal, bandpass filtering and a time-of-flight (TOF) estimation based on the power density of the received signal are utilised. The method is tested on an experimental test platform with a pair of 200 kHz ultrasonic transducers. The experimental results show that the maximum ranging error is less than 1.0% for the blade tip distance in a range of 100-1000 mm. Compared with the amplitude threshold method, the proposed TOF estimation method works well on the received signal with a low SNR and improves the ranging accuracy by about 5 mm when the blade tip distance is larger than 500 mm. This study provides a good reference for the accurate measurement of rotor blade tip distance, and gives a solution for ranging high-speed rotating objects.

Ultrasound-Mediated Ocular Drug Delivery: From Physics and Instrumentation to Future Directions.

Drug delivery to the anterior and posterior segments of the eye is impeded by anatomical and physiological barriers. Increasingly, the bioeffects produced by ultrasound are being proven effective for mitigating the impact of these barriers on ocular drug delivery, though there does not appear to be a consensus on the most appropriate system configuration and operating parameters for this application. In this review, the fundamental aspects of ultrasound physics most pertinent to drug delivery are presented; the primary phenomena responsible for increased drug delivery efficacy under ultrasound sonication are discussed; an overview of common ocular drug administration routes and the associated ocular barriers is also given before reviewing the current state of the art of ultrasound-mediated ocular drug delivery and its potential future directions.

Ultrasound Capsule Endoscopy With a Mechanically Scanning Micro-ultrasound: A Porcine Study.

Wireless capsule endoscopy has been used for the clinical examination of the gastrointestinal (GI) tract for two decades. However, most commercially available devices only utilise optical imaging to examine the GI wall surface. Using this sensing modality, pathology within the GI wall cannot be detected. Micro-ultrasound (µUS) using high-frequency (>20 MHz) ultrasound can provide a means of transmural or cross-sectional image of the GI tract. Depth of imaging is approximately 10 mm with a resolution of between 40-120 µm that is sufficient to differentiate between subsurface histologic layers of the various regions of the GI tract. Ultrasound capsule endoscopy (USCE) uses a capsule equipped with µUS transducers that are capable of imaging below the GI wall surface, offering thereby a complementary sensing technique to optical imaging capsule endoscopy. In this work, a USCE device integrated with a ∼30 MHz ultrasonic transducer was developed to capture a full 360° image of the lumen. The performance of the device was initially evaluated using a wire phantom, indicating an axial resolution of 69.0 µm and lateral resolution of 262.5 µm. Later, in vivo imaging performance was characterised in the oesophagus and small intestine of anaesthetized pigs. The reconstructed images demonstrate clear layer differentiation of the lumen wall. The tissue thicknesses measured from the B-scan images show good agreement with ex vivo images from the literature. The high-resolution ultrasound images in the in vivo porcine model achieved with this device is an encouraging preliminary step in the translation of these devices toward future clinical use.

Multi-Channel Signal-Generator ASIC for Acoustic Holograms.

A complementary metal-oxide-semiconductor (CMOS) application-specific integrated circuit (ASIC) has been developed to generate arbitrary, dynamic phase patterns for acoustic hologram applications. An experimental prototype has been fabricated to demonstrate phase shaping. It comprises a cascadable 1 ×9 array of identical, independently controlled signal generators implemented in a 0.35- [Formula: see text] minimum-feature-size process. It can individually control the phase of a square wave on each of the nine output pads. The footprint of the integrated circuit is [Formula: see text]. A 128-MHz clock frequency is used to produce outputs at 8 MHz with a phase resolution of 16 levels (4 bits) per channel. A 6 ×6 air-coupled matrix array ultrasonic transducer was built and driven by four ASICs, with the help of commercial buffer amplifiers, for the application demonstration. Acoustic pressure mapping and particle manipulation were performed. In addition, a 2 ×2 array piezoelectric micromachined ultrasonic transducer (PMUT) was connected and driven by four output channels of a single ASIC, demonstrating the flexibility of the ASIC to work with different transducers and the potential for direct integration of CMOS and PMUTs.

In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes.

Clinical endoscopy and colonoscopy are commonly used to investigate and diagnose disorders in the upper gastrointestinal tract and colon, respectively. However, examination of the anatomically remote small bowel with conventional endoscopy is challenging. This and advances in miniaturization led to the development of video capsule endoscopy (VCE) to allow small bowel examination in a noninvasive manner. Available since 2001, current capsule endoscopes are limited to viewing the mucosal surface only due to their reliance on optical imaging. To overcome this limitation with submucosal imaging, work is under way to implement microultrasound (µUS) imaging in the same form as VCE devices. This paper describes two prototype capsules, termed Sonocap and Thermocap, which were developed respectively to assess the quality of µUS imaging and the maximum power consumption that can be tolerated for such a system. The capsules were tested in vivo in the oesophagus and small bowel of porcine models. Results are presented in the form of µUS B-scans as well as safe temperature readings observed up to 100 mW in both biological regions. These results demonstrate that acoustic coupling and µUS imaging can be achieved in vivo in the lumen of the bowel and the maximum power consumption that is possible for miniature µUS systems.

Light sheet microscopy with acoustic sample confinement.

Contactless sample confinement would enable a whole host of new studies in developmental biology and neuroscience, in particular, when combined with long-term, wide-field optical imaging. To achieve this goal, we demonstrate a contactless acoustic gradient force trap for sample confinement in light sheet microscopy. Our approach allows the integration of real-time environmentally controlled experiments with wide-field low photo-toxic imaging, which we demonstrate on a variety of marine animal embryos and larvae. To illustrate the key advantages of our approach, we provide quantitative data for the dynamic response of the heartbeat of zebrafish larvae to verapamil and norepinephrine, which are known to affect cardiovascular function. Optical flow analysis allows us to explore the cardiac cycle of the zebrafish and determine the changes in contractile volume within the heart. Overcoming the restrictions of sample immobilisation and mounting can open up a broad range of studies, with real-time drug-based assays and biomechanical analyses.

Thin Film PZT-Based PMUT Arrays for Deterministic Particle Manipulation.

Lead zirconate titanate (PZT)-based piezoelectric micromachined ultrasonic transducers (PMUTs) for particle manipulation applications were designed, fabricated, characterized, and tested. The PMUTs had a diaphragm diameter of 60 [Formula: see text], a resonant frequency of ~8 MHz, and an operational bandwidth (BW) of 62.5%. Acoustic pressure output in water was 9.5 kPa at 7.5 mm distance from a PMUT element excited with a unipolar waveform at 5 Vpp . The element consisted of 20 diaphragms connected electrically in parallel. Particle trapping of 4 [Formula: see text] silica beads was shown to be possible with 5 Vpp unipolar excitation. Trapping of multiple beads by a single element and deterministic control of particles via acoustophoresis without the assistance of microfluidic flow were demonstrated. It was found that the particles move toward diaphragm areas of highest pressure, in agreement with literature and simulations. Unique bead patterns were generated at different driving frequencies and were formed at frequencies up to 60 MHz, much higher than the operational BW. Levitation planes were generated above the 30 MHz driving frequency.

Implementation of a PMN-PT piezocrystal-based focused array with geodesic faceted structure.

The higher performance of relaxor-based piezocrystals compared with piezoceramics is now well established, notably including improved gain-bandwidth product, and these materials have been adopted widely for biomedical ultrasound imaging. However, their use in other applications, for example as a source of focused ultrasound for targeted drug delivery, is hindered in several ways. One of the issues, which we consider here, is in shaping the material into the spherical geometries used widely in focused ultrasound. Unlike isotropic unpoled piezoceramics that can be shaped into a monolithic bowl then poled through the thickness, the anisotropic structure of piezocrystals make it impossible to machine the bulk crystalline material into a bowl without sacrificing performance. Instead, we report a novel faceted array, inspired by the geodesic dome structure in architecture, which utilizes flat piezocrystal material and maximizes fill factor. Aided by 3D printing, a prototype with f#≈ 1.2, containing 96 individually addressable elements was manufactured using 1-3 connectivity PMN-PT piezocrystal-epoxy composite. The fabrication process is presented and the array was connected to a 32-channel controller to shape and steer the beam for preliminary performance demonstration. At an operating frequency of 1MHz, a focusing gain around 30 was achieved and the side lobe intensities were all at levels below -12dB compared to main beam. We conclude that, by taking advantage of contemporary fabrication techniques and driving instrumentation, the geodesic array configuration is suitable for focused ultrasound devices made with piezocrystal.

Screen-printed ultrasonic 2-D matrix array transducers for microparticle manipulation.

This paper reports the development of a two-dimensional thick film lead zirconate titanate (PZT) ultrasonic transducer array, operating at frequency approximately 7.5MHz, to demonstrate the potential of this fabrication technique for microparticle manipulation. All layers of the array are screen-printed then sintered on an alumina substrate without any subsequent patterning processes. The thickness of the thick film PZT is 139±2µm, the element pitch of the array is 2.3mm, and the dimension of each individual PZT element is 2×2mm(2) with top electrode 1.7×1.7mm(2). The measured relative dielectric constant of the PZT is 2250±100 and the dielectric loss is 0.09±0.005 at 10kHz. Finite element analysis was used to predict the behaviour of the array and to optimise its configuration. Electrical impedance spectroscopy and laser vibrometry were used to characterise the array experimentally. The measured surface motion of a single element is on the order of tens of nanometres with a 10Vpeak continuous sinusoidal excitation. Particle manipulation experiments have been demonstrated with the array by manipulating Ø10µm polystyrene microspheres in degassed water. The simplified array fabrication process and the bulk production capability of screen-printing suggest potential for the commercialisation of multilayer planar resonant devices for ultrasonic particle manipulation.

Optically transparent piezoelectric transducer for ultrasonic particle manipulation.

We report an optically transparent ultrasonic device, consisting of indium-tin-oxide-coated lithium niobate (LNO), for use in particle manipulation. This device shows good transparency in the visible and near-infrared wavelengths and, acoustically, compares favorably with conventional prototype devices with silver electrodes.

Array-controlled ultrasonic manipulation of particles in planar acoustic resonator.

Ultrasonic particle manipulation tools have many promising applications in life sciences, expanding on the capabilities of current manipulation technologies. In this paper, the ultrasonic manipulation of particles and cells along a microfluidic channel with a piezoelectric array is demonstrated. An array integrated into a planar multilayer resonator structure drives particles toward the pressure nodal plane along the centerline of the channel, then toward the acoustic velocity maximum centered above the subset of elements that are active. Switching the active elements along the array moves trapped particles along the microfluidic channel. A 12-element 1-D array coupled to a rectangular capillary has been modeled and fabricated for experimental testing. The device has a 300-µm-thick channel for a half-wavelength resonance near 2.5 MHz, with 500 µm element pitch. Simulation and experiment confirm the expected trapping of particles at the center of the channel and above the set of active elements. Experiments demonstrated the feasibility of controlling the position of particles along the length of the channel by switching the active array elements.