Live Rabbits Research Articles

Blindness After Facial Filler Injections: The Role of Extravascular Hyaluronidase on Intravascular Hyaluronic Acid Embolism in the Rabbit Experimental Model.

Blindness caused by ophthalmic artery embolism is the most catastrophic complication of facial hyaluronic acid (HA) injections. Extravascular (retrobulbar) injection of hyaluronidase has been suggested as a salvage in this calamitous situation. However, the effectiveness of this treatment still lacks consensus. The aim of this study was to investigate the role of extravascular hyaluronidase in dissolving intravascular HA occlusion. Two different animal experiments were performed: (1) isolated rabbit abdominal aorta segments filled with HA were treated with extravascular immersion of highly concentrated hyaluronidase for 90 minutes, followed by gross observation, microscopic examination, particle size analysis, and immunohistochemical staining; and (2) live rabbit auricular arteries were first occluded with HA and then immediately treated with extravascular injection of hyaluronidase. The ears were then evaluated by gross observation, microscopic examination, and perfusion studies after 60 minutes and again after 90 minutes. The HA within the aorta segments showed no gross or microscopic changes after treatment with extravascular hyaluronidase. Hyaluronidase could only be detected in adventitia of the aortae, instead of in vascular smooth muscle, tunica intima, or vascular lumen. The occluded auricular arteries showed no reperfusion after extravascular injection of hyaluronidase. In this rabbit model, extravascular hyaluronidase was unable to penetrate into the arterial lumen of the isolated abdominal aorta or the live auricular artery of the rabbit to dissolve intravascular HA within a 90-minute time limit, thus casting doubt on whether extravascular (retrobulbar) hyaluronidase injection has a role in treating ophthalmic artery embolism caused by HA injections.

Evaluation of a simple off-the-shelf bi-layered vascular scaffold based on poly(L-lactide-co-ε-caprolactone)/silk fibroin in vitro and in vivo.

Purpose: In the field of small-caliber vascular scaffold research, excellent vascular remodeling is the key to ensuring anticoagulant function. We prepared an off-the-shelf bi-layered vascular scaffold with a dense inner layer and a loose outer layer and evaluated its remodeling capabilities by in vivo transplantation.Materials and Methods: Based on poly(L-lactide-co-ε-caprolactone) (PLCL), silk fibroin(SF), and heparin (Hep), PLCL/SF/Hep bi-layered scaffolds and PLCL/Hep bi-layered scaffolds were prepared by electrospinning. The inner layer was a PLCL/SF/Hep or PLCL/Hep nanofiber membrane, and the outer layer was PLCL/SF nano yarn. The in vitro tests included a hydrophilicity test, mechanical properties test, and blood and cell compatibility evaluation. The in vivo evaluation was conducted via single rabbit carotid artery replacement and subsequent examinations, including ultrasound imaging, immunoglobulin assays, and tissue section staining.Results: Compared to the PLCL/Hep nanofiber membrane, the hydrophilicity of the PLCL/SF/Hep nanofiber membrane was significantly improved. The mechanical strength met application requirements. Both the blood and cell compatibility were optimal. Most importantly, the PLCL/SF/Hep scaffolds maintained lumen patency for 3 months after carotid artery transplantation in live rabbits. At the same time, CD31 and α-SMA immunofluorescence staining confirmed bionic endothelial and smooth muscle layers remodeling.Conclusion: Using this hybrid strategy, PLCL and SF were combined to manufacture bi-layered small-caliber vascular scaffolds; these PLCL/SF/Hep scaffolds showed satisfactory vascular remodeling.

Influence of Clothing on Decomposition and Presence of Insects on Rabbit Carcasses.

The decomposition rate and insects attraction to carcasses are affected by a number of factors such as temperature, body mass, the presence of poisons, humidity, and insect activity. The present study was planned to investigate the influence of clothing on both the decomposition process and the presence of insects on rabbit carcasses. The study was performed in May 2016 and involved the use of 18 live mature rabbits (Oryctolagus cuniculus L.), which were euthanized by chloroform. Rabbit carcasses were divided into three replicates with six rabbits in each replicate. Rabbits in each replicate were further subdivided, so that three rabbits were wrapped with cloth, whereas the remaining three were left unclothed. Both clothed and unclothed carcasses reached the dry stage within 6 d. The results of this study showed that clothes neither affect the decomposition process nor the presence of insects (flies and beetles). The pattern of flies and beetles, however, did vary significantly in the different decomposition stages. In total, 2,849 insects, including 2,459 flies and 390 beetles, were collected and sorted during the decomposition process. Among the dominant species, flies were assigned to the families Calliphoridae and Muscidae, whereas beetles were assigned to the families Dermestidae and Histeridae. Lucilia sericata Meigen, Musca domestica L., Dermestes maculatus DeGeer, and Saprinus moyses Marseul were the most abundant species occurring on both the clothed and unclothed carcasses. In conclusion, this study emphasized that, the clothes have no effect when dealing with decay process and insect attraction to the carrions.

THE LIVE WEIGHT AND BODY MEASUREMENTS OF THE RABBIT CROSS «HYLA» IN VARIOUS PERIODS

THE LIVE WEIGHT AND BODY MEASUREMENTS OF THE RABBIT CROSS «HYLA» IN VARIOUS PERIODS

High-resolution, in vivo multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence microscopy imaging of rabbit retinal neovascularization

Photoacoustic microscopy (PAM) is an emerging imaging technology that can non-invasively visualize ocular structures in animal eyes. This report describes an integrated multimodality imaging system that combines PAM, optical coherence tomography (OCT), and fluorescence microscopy (FM) to evaluate angiogenesis in larger animal eyes. High-resolution in vivo imaging was performed in live rabbit eyes with vascular endothelial growth factor (VEGF)-induced retinal neovascularization (RNV). The results demonstrate that our multimodality imaging system can non-invasively visualize RNV in both albino and pigmented rabbits to determine retinal pathology using PAM and OCT and verify the leakage of neovascularization using FM and fluorescein dye. This work presents high-resolution visualization of angiogenesis in rabbits using a multimodality PAM, OCT, and FM system and may represent a major step toward the clinical translation of the technology.

Toxicological Analysis of Insects on the Corpse: a Valuable Source of Information in Forensic Investigations

Entomotoxicology as a subset of forensic entomology can be used by analysis of carcass feeding insects to detecting of drugs or toxins, as well as the cause and manner of death in cases of ante-mortem drugs intoxication. Morphine is one of the deacetylate metabolites of heroin. The aim of this study was to determine the presence and quantity of morphine in insects on the carcass and compare them with decomposing carcass. Field of this study was in Chalabeh District and toxicological tests were carried out at the Department of Forensic Toxicology, Legal Medicine Center, Kermanshah, Iran in 2017. Morphine was inoculated into live rabbit as experimental model at concentrations of 12.5, 25, 50mg/ml, similar to those normally encountered in human overdoses, then quality and quantity of morphine were determined in insects such as Chrysomya albiceps (as the first wave of insect succession on human cadavers) fed on carcass. Quantitative assessment at larvae showed that morphine was detected in all larvae (feeding and post feeding stage) fed on tissues from carcasses administered morphine, except for post-feeding larvae from R1 which received 12.5mg/ml dosage of morphine. Necrophagous insects are an indicator on the scene of crime and a potential source of information about the antemortem situation. Detection of drug in insects which is actually a reflection of the cause of death is possible.

Cone-beam CT reconstruction with gravity-induced motion

Fixed-gantry cone-beam computed tomography (CBCT), where the imaging hardware is fixed while the subject is continuously rotated 360° in the horizontal position, has implications for building compact and affordable fixed-gantry linear accelerators (linacs). Fixed-gantry imaging with a rotating subject presents a challenging image reconstruction problem where the gravity-induced motion is coupled to the subject’s rotation angle. This study is the first to investigate the feasibility of fixed-gantry CBCT using imaging data of three live rabbits in an ethics-approved study. A novel data-driven motion correction method that combines partial-view reconstruction and motion compensation was developed to overcome this challenge. Fixed-gantry CBCT scans of three live rabbits were acquired on a standard radiotherapy system with the imaging beam fixed and the rabbits continuously rotated using an in-house programmable rotation cradle. The reconstructed images of the thoracic region were validated against conventional CBCT scans acquired at different cradle rotation angles. Results showed that gravity-induced motion caused severe motion blur in all of the cases if unaccounted for. The proposed motion correction method yielded clinically usable image quality with <1 mm gravity-induced motion blur for rabbits that were securely immobilized on the rotation cradle. Shapes of the anatomic structures were correctly reconstructed with <0.5 mm accuracy. Translational motion accounted for the majority of gravity-induced motion. The motion-corrected reconstruction represented the time-averaged location of the thoracic region over a 360° rotation. The feasibility of fixed-gantry CBCT has been demonstrated. Future work involves the validation of imaging accuracy for human subjects, which will be useful for emerging compact fixed-gantry radiotherapy systems.

Ultrasonic through-tissue communication with video capabilities

The use of wireless implanted medical devices (IMDs), which communicate data wirelessly from sensors within the body to a receiver outside of the body, are gaining significant momentum in medical diagnosis and treatment procedures. Currently, radio frequency (RF) electromagnetic waves are the most frequently used communication method for wireless IMDs. However, there are various drawbacks of using RF electromagnetic waves in such applications such as high attenuation in the body and strictly regulated frequency spectrum, which consequently limit data rates of these devices. An alternative approach to RF transmission for IMDs uses ultrasonic waves, which experience lower attenuation in the body and have higher available bandwidth. In our work, we aim to demonstrate high data rate (>1.2 Mbps) through tissue communication using ultrasonic waves that will allow us to stream video with an IMD while actively controlling it inside the body. Initial experiments performed with 2mm biocompatible sonomicrometry transducers, where 2.4 Mbps data rate BER less than 5E-5 through water is achieved, demonstrating the capability of this method for high speed data transmission. Additional targets of this work include data transmission through beef liver and a live rabbit abdominal wall with high enough data rates capable of video streaming.The use of wireless implanted medical devices (IMDs), which communicate data wirelessly from sensors within the body to a receiver outside of the body, are gaining significant momentum in medical diagnosis and treatment procedures. Currently, radio frequency (RF) electromagnetic waves are the most frequently used communication method for wireless IMDs. However, there are various drawbacks of using RF electromagnetic waves in such applications such as high attenuation in the body and strictly regulated frequency spectrum, which consequently limit data rates of these devices. An alternative approach to RF transmission for IMDs uses ultrasonic waves, which experience lower attenuation in the body and have higher available bandwidth. In our work, we aim to demonstrate high data rate (>1.2 Mbps) through tissue communication using ultrasonic waves that will allow us to stream video with an IMD while actively controlling it inside the body. Initial experiments performed with 2mm biocompatible sonomicrometry tran...

An Outbreak of Rabbit Hemorrhagic Disease in Finland.

Rabbit hemorrhagic disease (RHD) was detected in European rabbits ( Oryctolagus cuniculus) for the first time ever in Finland in 2016. Reports of dead feral rabbits in Helsinki started to accumulate from April 2016. The Finnish Food Safety Authority Evira received the first animals in late April, and the main necropsy finding was severe, acute necrotizing hepatitis. Genetic material from RHD virus (RHDV) was detected in the liver and was further characterized as RHDV2. The Finnish virus did not group with RHDV strains from a concurrent outbreak in neighboring Sweden, suggesting another origin. The outbreak peaked in May and lasted until August, after which sightings of both live and dead rabbits became rare. No major outbreaks in domestic rabbits were observed, although infection in one pet rabbit was confirmed.

A CBCT study of the gravity-induced movement in rotating rabbits

Fixed-beam radiotherapy systems with subjects rotating about a longitudinal (horizontal) axis are subject to gravity-induced motion. Limited reports on the degree of this motion, and any deformation, has been reported previously. The purpose of this study is to quantify the degree of anatomical motion caused by rotating a subject around a longitudinal axis, using cone-beam CT (CBCT).In the current study, a purpose-made longitudinal rotating was aligned to a Varian TrueBeam kV imaging system. CBCT images of three live rabbits were acquired at fixed rotational offsets of the cradle. Rigid and deformable image registrations back to the original position were used to quantify the motion experienced by the subjects under rotation.In the rotation offset CBCTs, the mean magnitude of rigid translations was 5.7 ± 2.7 mm across all rabbits and all rotations. The translation motion was reproducible between multiple rotations within 2.1 mm, 1.1 mm, and 2.8 mm difference for rabbit 1, 2, and 3, respectively. The magnitude of the mean and absolute maximum deformation vectors were 0.2 ± 0.1 mm and 5.4 ± 2.0 mm respectively, indicating small residual deformations after rigid registration. In the non-rotated rabbit 4DCBCT, respiratory diaphragm motion up to 5 mm was observed, and the variation in respiratory motion as measured from a series of 4DCBCT scans acquired at each rotation position was small.The principle motion of the rotated subjects was rigid translational motion. The deformation of the anatomy under rotation was found to be similar in scale to normal respiratory motion. This indicates imaging and treatment of rotated subjects with fixed-beam systems can use rigid registration as the primary mode of motion estimation. While the scaling of deformation from rabbits to humans is uncertain, these proof-of-principle results indicate promise for fixed-beam treatment systems.

Abnormal scar identification with spherical-nucleic-acid technology.

The accurate diagnosis of scar type and severity relies on histopathology of biopsied tissue, which is invasive and time-consuming, causes discomfort and may exacerbate scarring. Here, we show that imaging nanoprobes for the live-cell detection of intracellular messenger RNA (mRNA) (also known as NanoFlares) enable measurements of the expression of connective tissue growth factor (CTGF) as a visual indicator of hypertrophic scars and keloids. During cell culture, NanoFlares enabled the distinction of hypertrophic and keloidal fibroblasts from normal fibroblasts, and the detection of changes in CTGF expression resulting from the regulatory effects of transforming growth factor-β (TGF-β) agonists and TGF-β antagonists. We also applied the NanoFlares topically to the skin of live mice and rabbits, and to ex vivo human skin models. Transepidermal penetration of the NanoFlares enabled the visual and spectroscopic quantification of underlying abnormal fibroblasts on the basis of CTGF mRNA expression. Our proof-of-concept studies of topically applied NanoFlare technology as a means of biopsy-free scar diagnosis may eventually inform therapeutic decisions on the basis of the mRNA-expression patterns of skin disorders.

Validation of a dynamic joint contracture measuring device in a live rabbit model of arthrofibrosis.

The current method of measuring arthrofibrosis in live rabbits is critically limited. Specifically, this method involves radioactive fluoroscopy, error-prone goniometric measurements, and static joint angle outcomes that fail to approximate the compliance of tissues surrounding the joint. This study aims to validate a novel method of capturing the compliance of contracted tissues surrounding the joint without the use of fluoroscopy or animal sacrifice. Surgically induced contractures of one-hundred and eight rabbits were measured using the current standard of contracture measurement (a pulley system) as well as a newly designed dynamic load cell (DLC) device. The DLC device was highly reliable when compared to the pulley system (r = 0.907, p < 0.001). Finally, the DLC device produced joint stiffness hysteresis curves capable of approximating the compliance of stiff joint tissues, ultimately calculating a mean joint stiffness of 1.57 ± 1.31 N · m · rad-1 (range, 0.33-6.37 N · m · rad-1 ). In conclusion, the DLC device represents a valid method for measuring joint contractures. Further, the DLC device notably improves current techniques by introducing the capacity to approximate the compliance of contracted tissues in living rabbits. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Novel Combination BMP7 and HGF Gene Therapy Instigates Selective Myofibroblast Apoptosis and Reduces Corneal Haze In Vivo.

PurposeWe tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.MethodsEighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n = 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n = 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n = 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. Gene therapy effects on corneal fibrosis and ocular safety were evaluated by slit-lamp microscope, stereo microscopes, quantitative real-time PCR, immunofluorescence, TUNEL, modified MacDonald-Shadduck scoring system, and Draize tests.ResultsPEI2-GNP–mediated BMP7+HGF gene therapy significantly decreased corneal fibrosis in live rabbits in vivo (Fantes scale was 0.6 in BMP7+HGF-treated eyes compared to 3.3 in −therapy group; P < 0.001). Corneas that received BMP7+HGF demonstrated significantly reduced mRNA levels of profibrotic genes: α-SMA (3.2-fold; P < 0.01), fibronectin (2.3-fold, P < 0.01), collagen I (2.1-fold, P < 0.01), collagen III (1.6-fold, P < 0.01), and collagen IV (1.9-fold, P < 0.01) compared to the −therapy corneas. Furthermore, BMP7+HGF-treated corneas showed significantly fewer myofibroblasts compared to the −therapy controls (83%; P < 0.001). The PEI2-GNP introduced >104 gene copies per microgram DNA of BMP7 and HGF genes. The recombinant HGF rendered apoptosis in corneal myofibroblasts but not in fibroblasts. Localized topical BMP7+HGF therapy showed no ocular toxicity.ConclusionsLocalized topical BMP7+HGF gene therapy treats corneal fibrosis and restores transparency in vivo mitigating excessive healing and rendering selective apoptosis in myofibroblasts.

Alizarin Red-S Protocol for Skeletal Staining during Fetal Period in Rabbit

Background: The main purpose of this study was to give detailed information on the staining protocol of Alizarin Red-S to detect the normal and abnormal skeleton of rabbit fetus. Methods: Eleven (9 females and 2 males) of adult rabbit weighing 3-3.5 kg were used. The female rabbits were left with buck to become pregnant then were classified into a treatment and a control group. The former group received oral doses of 400mg/kg of sodium valproate for 15 days starting from the 6th day after mating until 20th day of pregnancy, while the second received water in the same period. The pregnant rabbit was slaughtered at the 29th day of pregnancy. The live rabbit fetuses were collected. The staining protocol included fixation, dehydration, clearing, staining and preservation. The fetuses were examined under dissecting microscope and photos were taken for documentation. Results: The staining protocol made the rabbit fetuses to be clear enough to see their skeleton through the surrounding tissue. The axial skeleton including skull with mandible, vertebral column, ribs and sternum and the appendicular skeleton including the bones of the fore-and hindlimbs took the stain and became red in color. The macroscopic skeletal disorders of the fetuses of the treatment group were observed. The ossification centres were assessed. Conclusion: This protocol which depended on fixation by 95% ethanol, clearing by 1% potassium hydroxide and staining by 0.001 % Alizarin Red-S was effective in detecting normal and abnormal fetal skeletal morphology.

In Vivo Elasticity Mapping of Posterior Ocular Layers Using Acoustic Radiation Force Optical Coherence Elastography.

PurposeWe used acoustic radiation force optical coherence elastography (ARF-OCE) to map out the elasticity of retinal layers in healthy and diseased in vivo rabbit models for the first time.MethodsA healthy rabbit eye was proptosed and imaged using ARF-OCE, by measuring the tissue deformation after an acoustic force is applied. A diseased retinal inflammation model was used to observe the contrast before and after disease formation. Retinal histologic analysis was performed to identify layers of the retina corresponding with the optical images.ResultsThe general trend of the retinal layer elasticity is increasing stiffness from the ganglion side to the photoreceptor side, with the stiffest layer being the sclera. In a healthy rabbit model, the mechanical properties varied from 3 to 16 kPa for the five layers that were identified via optical imaging and histology (3.09 ± 0.46, 3.82 ± 0.88, 4.53 ± 0.74, 6.59 ± 2.27, 16.11 ± 5.13 kPa). In the diseased model, we have induced optical damage in a live rabbit and observed a change in the stiffness trend in its retina.ConclusionsHigh sensitivity elasticity maps can be obtained using the ARF-OCE system to differentiate different retinal layers. Subtle changes in the mechanical properties during the onset of diseases, such as retinal degeneration, can be measured and aid in early clinical diagnosis. This study validates our imaging system for the characterization of retinal elasticity for the detection of retinal diseases in vivo.

Ultrasonographic anatomy of the atlanto-occipital region and ultrasound-guided cerebrospinal fluid collection in rabbits (Oryctolagus cuniculus).

Cerebrospinal fluid analyses are important for diagnosis of neurologic problems in rabbits and for translational research projects using rabbits as models. Blind puncture of the cisterna magna is the current standard technique for sampling cerebrospinal fluid in this species. However, the complexity and small size of the cisterna magna and surrounding structures are limitations of this technique. Aims of this prospective, anatomic, pilot study were to (1) describe the normal anatomy of the atlanto-occipital region, (2) describe ultrasonographic anatomic landmarks, and (3) develop and evaluate a technique for ultrasound-guided puncture of the cisterna magna for cerebrospinal fluid sampling in rabbits. Thirty healthy rabbits were included and the study was conducted in three stages. Three rabbit cadavers were used for the first stage of the study. Then, the second stage was completed using 13 rabbit cadavers. Finally, the third stage was completed in 14 live rabbits. The ultrasound-guided puncture performed in 13 cadavers was successful at the first attempt in 10 cases, and at the second attempt in the remaining three cases. In the in vivo study, the ultrasound-guided puncture was successful in all 14 cases, without signs of complications. Findings supported the use of ultrasound-guided puncture of the cisterna magna as a safe technique that may be used routinely or when the sample of cerebrospinal fluid cannot be obtained with the blind technique in rabbits.

Longitudinal study on antimicrobial consumption and resistance in rabbit farming

Reliable indicators of antimicrobial consumption (AMC) measured with harmonised data and supported by indicators for antimicrobial resistance (AMR) at herd level are necessary to target antimicrobial misuse in food-producing animals. AMC data in 2010–2015 in 32 Italian industrial rabbit holdings weighted with semester production and standardised with animal daily doses (ADDs) were collected. Herd-level AMR against eight antimicrobials was assessed in Escherichia coli, Enterococcus faecalis and Enterococcus hirae collected in 2014–2015. Escherichia coli were assessed for mcr-1 and mcr-2 genes. To produce 1 kg of live rabbit, a mean of 71.8 ADDs was used. Overall AMC reduced over time (P < 0.05) owing to lowering consumption of tetracyclines (P < 0.05) and colistin (P < 0.01), but consumption of quinolones (P < 0.05), bacitracin (P < 0.01) and sulfonamides (P = 0.017) increased. All except one indicator E. coli were wild-type for cefotaxime, whereas 97% displayed reduced susceptibility to tetracyclines, 89% to trimethoprim, 63% to enrofloxacin, 24% to chloramphenicol and 21% to colistin. mcr-1 was detected in 50/320 E. coli isolates from 15/32 holdings; mcr-2 was not detected in 58 isolates with colistin MIC ≥ 2 mg/L. All 305 enterococci were wild-type for ampicillin, ciprofloxacin and vancomycin and displayed reduced tetracycline susceptibility. The mean antimicrobial resistance index (ARI) was 0.5 for E. coli and 0.3 for enterococci. ARI was significantly correlated with AMC at herd level for enterococci (P = 0.008) but not E. coli where high ARI levels were found in a few holdings with low AMC.

Anatomy and Surgical Approaches to the Rabbit Nasal Septum

The rabbit is the primary animal model used to investigate aspects of nasal surgery. Although several studies have used this model, none has provided a comprehensive analysis of the surgical anatomy and techniques used to gain access to the rabbit nasal fossae and septum. To describe and optimize the surgical anatomy and approach to the rabbit nasal vault and septal cartilage. In an ex vivo animal study conducted at an academic medical center, preliminary cadaveric dissections were performed on rabbit head specimens to establish familiarity with relevant anatomy and rehearse various approaches. Live Pasteurella-free New Zealand white rabbits (3.5-4.0 kg) were used to further develop this surgical technique developed here. Access of the nasal vault was gained through a midline nasal dorsum incision and creation of an osteoplastic flap with a drill. Submucosal resection was performed with preservation of the mucoperichondrium. All rabbits were monitored daily for 4 weeks in the postoperative period for signs of infection, pain, and complications. The study was conducted from June 1, 2014, to December 1, 2014. Surgical anatomy and techniques used to gain access to the rabbit nasal vault and harvest septal cartilage. Four Pasteurella-free New Zealand white rabbits (Western Organ Rabbit Co), ranging in age from 9 to 12 months and weighing between 3.5 and 4.0 kg, were used in this study. Initial dissections demonstrated the feasibility of harvesting septal cartilage while preserving the mucoperichondrial envelope. Access to the nasal vault through this 3-osteotomy approach allowed for maximal exposure to the nasal cavity bilaterally while maintaining the integrity of the mucoperichondrium following septal cartilage harvest. The maximum amount of bulk, en bloc, cartilage harvested was 1.0 × 2.5 cm. Following surgical dissection, all animals maintained adequate airway patency and support to midface structures. Furthermore, all specimens preserved the integrity of the mucoperichondrium, septum, vascular anatomy, and airway dynamics. No operative complications, postoperative airway compromise, or infections were observed. Access to the rabbit nasal vault and septal cartilage is feasible through a variety of surgical approaches and techniques. To date, this is the first study to meticulously document and review the surgical approaches to the rabbit nasal cavity. This approach describes a novel, 3-osteotomy method of accessing the nasal cavity bilaterally and successfully harvesting rabbit septal cartilage in a submucoperichondrial plane. The ability to preserve native anatomy and function allows for improved outcomes in translational and animal guided clinical research. NA.

Closed-loop control of circulating drug levels in live animals

Current methods of drug dosing rely on physical parameters (such as sex, age and weight) that do not account for genetic and physiological differences among individual patients. These differences can greatly affect how drugs are processed in the body and can result in ineffective underdosing or toxic overdosing. Here, we describe a generalizable closed-loop system consisting of a biosensor, controller and infusion pump, and a model of drug pharmacokinetics that continuously monitors and adjusts the concentration of a given drug in the body. As proof of concept, we demonstrate that the system can maintain the concentration of doxorubicin—a widely used chemotherapy drug—in live rabbits and rats at any desired set point and in real time, while automatically compensating for large pharmacokinetic differences among individual animals and stabilizing dramatic perturbations arising from acute drug–drug interactions. The feedback-loop system opens up the possibility of tightly controlled, patient-specific dosing of chemotherapeutics and other drugs within narrow therapeutic windows. A closed-loop control system measures and adjusts the concentration of a chemotherapeutic in real time and maintains it within a predefined therapeutic window in both rabbits and rats.

Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics

Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.