Evaluation of the usage of incisional liposomal bupivacaine as a local anaesthetic for dogs undergoing limb amputation.

BACKGROUND: Bupivacaine lioposomal suspension has recently emerged in the veterinary field for local analgesia. OBJECTIVE: To describe the extra-label administration of bupivacaine liposomal suspension at the incision site of dogs undergoing limb amputation and characterize any complications. STUDY DESIGN: Nonblinded retrospective study. ANIMALS: Client-owned dogs undergoing limb amputation from 2016 to 2020. METHODS: Medical records of dogs undergoing limb amputation with concurrent use of long-acting liposomal bupivacaine suspension were reviewed for incisional complications, adverse effects, hospitalization length, and time to alimentation. Data were compared to a control group (CG) of dogs who underwent a limb amputation procedure without concurrent use of liposomal bupivacaine suspension. RESULTS: Forty-six dogs were included in the liposomal bupivacaine group (LBG) and 44 cases in the CG. The CG had 15 incidences of incisional complications (34%) compared to 6 within the LBG (13%). Four dogs required revisional surgery in the CG (9%) whereas none of the dogs required revisional surgery in the LBG. Time from surgery to discharge was statistically higher in the CG compared to the LBG (p = 0.025). First time to alimentation was statistically higher in the CG (p value = 0.0002). The total number of rechecks needed postoperatively revealed the CG having a statistically significant increase in recheck evaluations (p = 0.001). CONCLUSIONS: Extra-label administration of liposomal bupivacaine suspension was well-tolerated in dogs undergoing limb amputation. Liposomal bupivacaine usage did not increase incisional complication rates and its use allowed for a quicker time to discharge. CLINICAL SIGNIFICANCE: Surgeons should consider inclusion of extra-label administration of liposomal bupivacaine in analgesic regimens for dogs undergoing limb amputation.

Anorexia and the hippocampus: A case report.

Eating disorders have been shown to be associated with epilepsy, typically associated with the temporal lobe and usually of non-dominant hemisphere origin. We report the case of a 56-year-old woman with drug resistant epilepsy, localized to the dominant left hippocampus. She experienced an increasing frequency of seizures over a two-year period associated with loss of appetite and substantial weight loss independent of antiseizure medication changes. Extensive workup eliminated gastrointestinal and paraneoplastic etiologies. There was no history of psychiatric illness, including anorexia nervosa. Pre-surgical workup showed mesial temporal sclerosis on MRI and video-EEG was consistent with ipsilateral medial temporal seizure onset. The patient underwent laser interstitial ablation of the left amygdala and hippocampus, which resulted in a cessation of seizures. Within 24 h of the laser ablation, her appetite returned to normal and, within 8 months she regained 26 lbs. To our knowledge, this is the first case report of a patient with dominant temporal lobe epilepsy with anorexia that was temporally associated with escalating seizure frequency and stopped with treatment and cessation of seizures, suggesting a causal and pathogenic relationship.

Effects of footwear with different longitudinal bending stiffness on biomechanical characteristics and muscular mechanics of lower limbs in adolescent runners.

Background: Running shoes with carbon plates have been identified to have positive effects on improving running performance from a biomechanical perspective. However, the specific difference between the effects of carbon plates with different longitudinal bending stiffness (LBS)on biomechanical characteristics and muscular mechanics of lower limbs in adolescent runners remains unclear. This study aimed to identify the difference in biomechanical characteristics and muscular mechanics in lower limbs during running stance phases between wearing shoes with low longitudinal bending stiffness (Llbs) and high longitudinal bending stiffness (Hlbs) carbon plates in adolescent runners. Methods: 10 male adolescent runners with a habit of daily running exercise (age: 13.5 ± 0.6 years; height: 166.3 ± 1.9 cm; bodyweight: 50.8 ± 3.1 kg; foot length: 25.4 ± 0.2 cm) were recruited and asked to conduct two times of tests by wearing shoes with Llbs and Hlbs carbon plates in a randomized order. Paired t-test and statistical parametric mapping (SPM) analysis were used to identify the difference in biomechanical characteristics and muscular mechanics in lower limbs during running stance phases. Result: Under the condition of wearing shoes with Hlbs, the time of foot contact significantly increased, whereas the range of motion (ROM) of hip and metatarsophalangeal (MTP) in the sagittal plane significantly reduced as well as the peak moment of ankle joint in the sagittal plane. The activations of vastus medialis, vastus lateralis, flexor digitorum brevis (flex dig brevis), and flexor hallucis longus (flex hall long) significantly increased under the condition of wearing shoes with Hlbs. According to the results of the SPM analysis, the joint angles (hip, ankle, and MTP), the net joint moments (knee, ankle, and MTP), and the muscle forces (gluteus maximus and tibialis anterior) were significant difference during the running stance phase between conditions of wearing shoes with Hlbs and Llbs. Conclusion: Running shoes with Llb carbon plates are appropriate for adolescent runners due to the advantages of biomechanical characteristics and muscular mechanics.

TRPV6 Regulation by Cis-22a and Cholesterol.

The highly calcium-selective transient receptor potential vanilloid-type channel TRPV6 is important for epithelial Ca2+ transport. Proper regulation of the inherently constitutively active TRPV6 channels is intricate in preserving Ca2+ homeostasis, whereby structural and functional data suggest that lipids hold an essential role. Altered expression levels or specific TRPV6 mutations may lead to diseases, hence, TRPV6 represents an interesting target for pharmacological modulation. Recent cryo-EM data identified that the specific TRPV6 blocker cis-22a binds, apart from the pore, to a site within the tetrameric channel that largely matches a lipid binding pocket, LBS-2. Therein, cis-22a may replace a lipid such as cholesterol that is bound in the open state. Based on site-directed mutagenesis and functional recordings, we identified and characterized a series of residues within LBS-2 that are essential for TRPV6 inhibition by cis-22a. Additionally, we investigated the modulatory potential of diverse cholesterol depletion efforts on TRPV6 activity. While LBS-2 mutants exhibited altered maximum currents, slow Ca2+-dependent inactivation (SCDI) as well as less inhibition by cis-22a, TRPV6 activity was resistant to cholesterol depletion. Hence, lipids other than cholesterol may predominate TRPV6 regulation when the channel is expressed in HEK293 cells.

A Vehicle Trajectory Privacy Preservation Method Based on Caching and Dummy Locations in the Internet of Vehicles.

In the internet of vehicles (IoVs), vehicle users should provide location information continuously when they want to acquire continuous location-based services (LBS), which may disclose the vehicle trajectory privacy. To solve the vehicle trajectory privacy leakage problem in the continuous LBS, we propose a vehicle trajectory privacy preservation method based on caching and dummy locations, abbreviated as TPPCD, in IoVs. In the proposed method, when a vehicle user wants to acquire a continuous LBS, the dummy locations-based location privacy preservation method under road constraint is used. Moreover, the cache is deployed at the roadside unit (RSU) to reduce the information interaction between vehicle users covered by the RSU and the LBS server. Two cache update mechanisms, the active cache update mechanism based on data popularity and the passive cache update mechanism based on dummy locations, are designed to protect location privacy and improve the cache hit rate. The performance analysis and simulation results show that the proposed vehicle trajectory privacy preservation method can resist the long-term statistical attack (LSA) and location correlation attack (LCA) from inferring the vehicle trajectory at the LBS server and protect vehicle trajectory privacy effectively. In addition, the proposed cache update mechanisms achieve a high cache hit rate.

A New Homotetramer Hemoglobin in the Pulmonary Surfactant of Plateau Zokors (Myospalax Baileyi).

The plateau zokor (Myospalax baileyi) is a native species to the Qinghai-Tibetan Plateau, inhabiting hypoxia and hypercapnia sealed subterranean burrows that pose several unique physiological challenges. In this study, we observed a novel heme-containing protein in the pulmonary surfactant (PS) of plateau zokor, identified the encoding gene of the protein, predicted its origination and structure, verified its expression in alveolar epithelial cells, and determined the protein's affinity to oxygen and its effect on the oxygen-dissolving capability in the PS of plateau zokors. The protein is an unusual homotetramer hemoglobin consisting of four γ-like subunits, and the subunit is encoded by a paralog gene of γ, that is γ-like. The divergence time of γ-like from γ is estimated by the molecular clock to be about 2.45 Mya. The generation of γ-like in plateau zokors might well relate to long-time stress of the high land hypoxia. Unlike γ, the γ-like has a hypoxia response element (HRE) and a lung tissue-specific enhancer in its upstream region, and it is expressed specifically in lung tissues and up-regulated by hypoxia. The protein is named as γ4-like which is expressed specifically in Alveolar epithelial type II (ATII) cells and secreted into the alveolar cavities through the osmiophilic multilamellar body (LBs). The γ4-like has a higher affinity to oxygen, and that increases significantly oxygen-dissolving capability in the PS of plateau zokors by its oxygenation function, which might be beneficial for the plateau zokors to obtain oxygen from the severe hypoxia environments by facilitating oxygen diffusion from alveoli to blood.

Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells.

Parkinson's disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson's disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear. Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein preformed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson's disease and other synucleinopathies.

A Constrained Kalman Filter for Wi-Fi-Based Indoor Localization with Flexible Space Organization.

This paper presents a constrained Kalman filter for Wi-Fi-based indoor localization. The contribution of this work is to introduce constraints on the object speed and to provide a numerically optimized form for fast computation. The proposed approach is suitable to flexible space organization, as in warehouses, and when objects can be spun around, for example barcode readers in a hand. We experimented with the proposed technique using a robot and three devices, on five different journeys, in a 6000 m2 warehouse equipped with six Wi-Fi access points. The results highlight that the proposed approach provides a 19% improvement in localization accuracy.

Examining the Human Activity-Intensity Change at Different Stages of the COVID-19 Pandemic across Chinese Working, Residential and Entertainment Areas.

The COVID-19 pandemic has already resulted in more than 6 million deaths worldwide as of December 2022. The COVID-19 has also been greatly affecting the activity of the human population in China and the world. It remains unclear how the human activity-intensity changes have been affected by the COVID-19 spread in China at its different stages along with the lockdown and relaxation policies. We used four days of Location-based services data from Tencent across China to capture the real-time changes in human activity intensity in three stages of COVID-19-namely, during the lockdown, at the first stage of work resuming and at the stage of total work resuming-and observed the changes in different land use categories. We applied the mean decrease Gini (MDG) approach in random forest to examine how these changes are influenced by land attributes, relying on the CART algorithm in Python. This approach was also compared with Geographically Weighted Regression (GWR). Our analysis revealed that the human activity intensity decreased by 22-35%, 9-16% and 6-15%, respectively, in relation to the normal conditions before the spread of COVID-19 during the three periods. The human activity intensity associated with commercial sites, sports facilities/gyms and tourism experienced the relatively largest contraction during the lockdown. During the relaxations of restrictions, government institutions showed a 13.89% rise in intensity at the first stage of work resuming, which was the highest rate among all the working sectors. Furthermore, the GDP and road junction density were more influenced by the change in human activity intensity for all land use categories. The bus stop density was importantly associated with mixed-use land recovery during the relaxing stages, while the coefficient of density of population in entertainment land were relatively higher at these two stages. This study aims to provide additional support to investigate the human activity changes due to the spread of COVID-19 at different stages across different sectors.

Are Lysosomes Potential Therapeutic Targets for Parkinson's Disease?

Parkinson´s Disease (PD) is the second most common neurodegenerative disorder, affecting ~2-3% of the population over 65 years old. In addition to progressive degeneration of nigrostriatal neurons, the histopathological feature of PD is the accumulation of misfolded α-synuclein protein in abnormal cytoplasmatic inclusions, known as Lewy Bodies (LBs). Recently, Genome-Wide Association Studies (GWAS) have indicated a clear association of variants within several lysosomal genes with risk for PD. Newly evolving data have been shedding light on the relationship between lysosomal dysfunction and alpha-synuclein aggregation. Defects in lysosomal enzymes could lead to the insufficient clearance of neurotoxic protein materials, possibly leading to selective degeneration of dopaminergic neurons. Specific modulation of lysosomal pathways and their components could be considered a novel opportunity for therapeutic intervention for PD. The purpose of this review is to illustrate lysosomal biology and describe the role of lysosomal dysfunction in PD pathogenesis. Finally, the most promising novel therapeutic approaches designed to modulate lysosomal activity, as a potential disease-modifying treatment for PD will be highlighted.

MobChain: Three-Way Collusion Resistance in Witness-Oriented Location Proof Systems Using Distributed Consensus.

Smart devices have accentuated the importance of geolocation information. Geolocation identification using smart devices has paved the path for incentive-based location-based services (LBS). However, a user's full control over a smart device can allow tampering of the location proof. Witness-oriented location proof systems (LPS) have emerged to resist the generation of false proofs and mitigate collusion attacks. However, witness-oriented LPS are still susceptible to three-way collusion attacks (involving the user, location authority, and the witness). To overcome the threat of three-way collusion in existing schemes, we introduce a decentralized consensus protocol called MobChain in this paper. In this scheme the selection of a witness and location authority is achieved through a distributed consensus of nodes in an underlying P2P network that establishes a private blockchain. The persistent provenance data over the blockchain provides strong security guarantees; as a result, the forging and manipulation of location becomes impractical. MobChain provides secure location provenance architecture, relying on decentralized decision making for the selection of participants of the protocol thereby addressing the three-way collusion problem. Our prototype implementation and comparison with the state-of-the-art solutions show that MobChain is computationally efficient and highly available while improving the security of LPS.

Significant Geo-Social Group Discovery over Location-Based Social Network.

Geo-social community detection over location-based social networks combining both location and social factors to generate useful computational results has attracted increasing interest from both industrial and academic communities. In this paper, we formulate a novel community model, termed geo-social group (GSG), to enforce both spatial and social factors to generate significant computational patterns and to investigate the problem of community detection over location-based social networks. Specifically, GSG detection aims to extract all group-venue clusters, where users are similar to each other in the same group and they are located in a minimum covering circle (MCC) for which the radius is no greater than a distance threshold γ. Then, we present a GSGD algorithm following a three-step paradigm to enumerate all qualified GSGs in a large network. We propose effective optimization techniques to efficiently enumerate all communities in a network. Furthermore, we extend a significant GSG detection problem to top-k geo-social group (TkGSG) mining. Rather than extracting all qualified GSGs in a network, TkGSG aims to return k feasibility groups to guarantee the diversity. We prove the hardness of computing the TkGSGs. Nevertheless, we propose the effective greedy approach with a guaranteed approximation ratio of 1-1/e. Extensive empirical studies on real and synthetic networks show the superiority of our algorithm when compared with existing methods and demonstrate the effectiveness of our new community model and the efficiency of our optimization techniques.

Virtual Pseudonym-Changing and Dynamic Grouping Policy for Privacy Preservation in VANETs.

Location privacy is a critical problem in the vehicular communication networks. Vehicles broadcast their road status information to other entities in the network through beacon messages to inform other entities in the network. The beacon message content consists of the vehicle ID, speed, direction, position, and other information. An adversary could use vehicle identity and positioning information to determine vehicle driver behavior and identity at different visited location spots. A pseudonym can be used instead of the vehicle ID to help in the vehicle location privacy. These pseudonyms should be changed in appropriate way to produce uncertainty for any adversary attempting to identify a vehicle at different locations. In the existing research literature, pseudonyms are changed during silent mode between neighbors. However, the use of a short silent period and the visibility of pseudonyms of direct neighbors provides a mechanism for an adversary to determine the identity of a target vehicle at specific locations. Moreover, privacy is provided to the driver, only within the RSU range; outside it, there is no privacy protection. In this research, we address the problem of location privacy in a highway scenario, where vehicles are traveling at high speeds with diverse traffic density. We propose a Dynamic Grouping and Virtual Pseudonym-Changing (DGVP) scheme for vehicle location privacy. Dynamic groups are formed based on similar status vehicles and cooperatively change pseudonyms. In the case of low traffic density, we use a virtual pseudonym update process. We formally present the model and specify the scheme through High-Level Petri Nets (HLPN). The simulation results indicate that the proposed method improves the anonymity set size and entropy, provides lower traceability, reduces impact on vehicular network applications, and has lower computation cost compared to existing research work.

Prevalence and risk factors of strongyloidiasis among schoolchildren in Sabach Sanjal and Upper Badibou districts in the North Bank East Region of The Gambia.

BACKGROUND: Strongyloidiasis is a parasitic disease that mainly affects humans and is caused by a roundworm called Strongyloides stercoralis. It is endemic in humid tropical regions that include Africa, Latin America and Southern Asia. Among the public health important soil-transmitted helminths (STHs) classified as neglected tropical diseases, S. stercoralis is the most neglected. A study of schistosomiasis and STHs mapping was conducted and S. stercoralis larvae were detected using the utilized diagnostic method; thus, this current study described the prevalence and risk factors of S. stercoralis infection in districts of Sabach Sanjal and Upper Badibou in The Gambia. METHODS: The cross-sectional study enrolled 851 schoolchildren, ages 7 to 14 years old. The participants were enrolled from 17 schools in Sabach Sanjal and Upper Badibou Districts. The WHO random sampling technique n/50 (25 boys and 25 girls) was used. Stool samples were collected from each participant and Kato-Katz smear method was used to screen for S. stercoralis infection. RESULTS: Out of the total 851 pupils, 76 pupils (8.9%) were positive for S. stercoralis infection. The mean age of infected persons was 10.1 years (±2.2). The prevalence of infection was higher among females (9.2%) than males (8.7%). Rates of infection for age categories 7-10 years and 11-14 years were 12.4% and 4.2%, respectively. Rates of infection by districts were 12.3% for Sabach Sanjal and 7.1% for Upper Badibou. Schoolchildren from Sabach Sanjal were 1.6 times more likely to have strongyloidiasis compared to those from Upper Badibou (aOR = 1.64, p-value = 0.058). Schoolchildren aged 7-10 years were 3.2 times more likely to have strongyloidiasis infection compared to the 11-14-year-olds (aOR = 3.20, p-value <0.001). Schoolchildren who 'sometimes' have water or tissue after defaecation have more infection rate compared to those who 'always' have water or tissue after defaecation. However, this difference was not statistically significant (aOR = 1.36, p-value = 0.308). CONCLUSION: The study revealed the prevalence of strongyloidiasis in Sabach Sanjal and Upper Badibou districts of The Gambia. Kato-Katz technique might be inadequate for detecting S. stercoralis; thus, more studies are needed to determine the true prevalence of the disease in these two districts through the combined use of highly sensitive techniques such as Baermann, Koga Agar Culture and polymerase chain reaction.

Construction of Hybrid Dual Radio Frequency RSSI (HDRF-RSSI) Fingerprint Database and Indoor Location Method.

Radio frequency communication technology has not only greatly improved public network service, but also developed a new technological route for indoor navigation service. However, there is a gap between the precision and accuracy of indoor navigation services provided by indoor navigation service and the expectation of the public. This study proposed a method for constructing a hybrid dual frequency received signal strength indicator (HDRF-RSSI) fingerprint library, which is different from the traditional RSSI fingerprint library constructing method in indoor space using 2.4G radio frequency (RF) under the same Wi-Fi infrastructure condition. The proposed method combined 2.4G RF and 5G RF on the same access point (AP) device to construct a HDRF-RSSI fingerprint library, thereby doubling the fingerprint dimension of each reference point (RP). Experimental results show that the feature discriminability of HDRF-RSSI fingerprinting is 18.1% higher than 2.4G RF RSSI fingerprinting. Moreover, the hybrid radio frequency fingerprinting model, training loss function, and location evaluation algorithm based on the machine learning method were designed, so as to avoid limitation that transmission point (TP) and AP must be visible in the positioning method. In order to verify the effect of the proposed HDRF-RSSI fingerprint library construction method and the location evaluation algorithm, dual RF RSSI fingerprint data was collected to construct a fingerprint library in the experimental scene, which was trained using the proposed method. Several comparative experiments were designed to compare the positioning performance indicators such as precision and accuracy. Experimental results demonstrate that compared with the existing machine learning method based on Wi-Fi 2.4G RF RSSI fingerprint, the machine learning method combining Wi-Fi 5G RF RSSI vector and the original 2.4G RF RSSI vector can effectively improve the precision and accuracy of indoor positioning of the smart phone.

How does navigation system behavior influence human behavior?

Navigation systems are ubiquitous tools to assist wayfinders of the mobile information society with various navigational tasks. Whenever such systems assist with self-localization and path planning, they reduce human effort for navigating. Automated navigation assistance benefits navigation performance, but research seems to show that it negatively affects attention to environment properties, spatial knowledge acquisition, and retention of spatial information. Very little is known about how to design navigation systems for pedestrian navigation that increase both navigation performance and spatial knowledge acquisition. To this end, we empirically tested participants (N = 64) using four different navigation system behaviors (between-subject design). Two cognitive processes with varying levels of automation, self-localization and allocation of attention, define navigation system behaviors: either the system automatically executes one of the processes (high level of automation), or the system leaves the decision of when and where to execute the process to the navigator (low level of automation). In two experimental phases, we applied a novel empirical framework for evaluating spatial knowledge acquisition in a real-world outdoor urban environment. First, participants followed a route assisted by a navigation system and, simultaneously, incidentally acquired spatial knowledge. Second, participants reversed the route using the spatial knowledge acquired during the assisted phase, this time without the aid of the navigation system. Results of the route-following phase did not reveal differences in navigation performance across groups using different navigation system behaviors. However, participants using systems with higher levels of automation seemed not to acquire enough spatial knowledge to reverse the route without navigation errors. Furthermore, employing novel methods to analyze mobile eye tracking data revealed distinct patterns of human gaze behavior over time and space. We thus can demonstrate how to increase spatial knowledge acquisition without harming navigation performance when using navigation systems, and how to influence human navigation behavior with varying navigation system behavior. Thus, we provide key findings for the design of intelligent automated navigation systems in real-world scenarios.

Efficient AoA-Based Wireless Indoor Localization for Hospital Outpatients Using Mobile Devices.

The motivation of this work is to help outpatients find their corresponding departments or clinics, thus, it needs to provide indoor positioning services with a room-level accuracy. Unlike wireless outdoor localization that is dominated by the global positioning system (GPS), wireless indoor localization is still an open issue. Many different schemes are being developed to meet the increasing demand for indoor localization services. In this paper, we investigated the AoA-based wireless indoor localization for outpatients' wayfinding in a hospital, where Wi-Fi access points (APs) are deployed, in line, on the ceiling. The target position can be determined by a mobile device, like a smartphone, through an efficient geometric calculation with two known APs coordinates and the angles of the incident radios. All possible positions in which the target may appear have been comprehensively investigated, and the corresponding solutions were proven to be the same. Experimental results show that localization error was less than 2.5 m, about 80% of the time, which can satisfy the outpatients' requirements for wayfinding.

Nucleic Acid Delivery System by the Combination of Lipid bubbles and Ultrasound.

BACKGROUND: RNA interference (RNAi)-based therapy has gained attention because of its potent genesilencing effect and high specificity. However, the efficient delivery of nucleic acids to the target site is a major challenge to the clinical implementation. Recently, ultrasound-mediated gene delivery systems have been developed and attracted interest due to its safety and site-specificity. By the combination with contrast agents, called microbubbles, not only the delivery effects but also the imaging effects are significantly enhanced. We developed lipid bubbles (LBs) entrapping an ultrasound contrast gas to enhance the efficacy of ultrasound-mediated delivery and imaging. In this review, we summarize ultrasound-mediated nucleic acid delivery systems and discuss the possibility of combining LBs and ultrasound for RNAi-based therapies. METHODS: We prepared polyethylene glycol-modified liposomes and entrapped an echo-contrast gas within the liposomes. Small interfering RNA (siRNA) were transfected into cells and muscles using LBs and ultrasound. Moreover, we also developed nucleic acid-loaded LBs using cholesterol-conjugated siRNA or positively-charged lipid for an efficient systemic delivery of siRNA and microRNA. The usability of LBs for RNA delivery system was evaluated by the silencing effects of target genes and the therapeutic effects on ischemia hind limb. RESULTS: A combination of LBs and therapeutic ultrasound was able to enhance the gene silencing effects by siRNA. Nucleic acid-loaded LBs were able to efficiently deliver siRNA or microRNA by systemic administration. A combination of LBs and diagnostic ultrasound also enhanced the imaging efficiency. Using a hindlimb ischemia mouse model, microRNA-loaded LBs could lead to increased angiogenic factors and improved blood flow. CONCLUSION: Ultrasound technology is widely used in clinical settings not only for diagnosis but also for therapy. Ultrasonic devices are being actively developed. Computer-controlled ultrasound systems can provide precise exposure to the target site. The combination of precise ultrasound exposure and LBs might be useful for target site-specific nucleic acids delivery, and holds potential to be developed into a beneficial therapeutic and diagnostic system for various diseases.