Use, and acceptability, of digital health technologies in musculoskeletal physical therapy: A survey of physical therapists and patients.

OBJECTIVES: Determine (a) frequency of digital health use to obtain/record clinical information (pre-COVID-19); (b) willingness to use digital technologies among physical therapists and patients with musculoskeletal conditions. METHODS: 102 physical therapists, and 103 patients were recruited in Australia. An electronic survey ascertained (a) demographic/clinical characteristics, (b) frequency of methods to obtain and record clinical information; (c) willingness to use digital technologies to support musculoskeletal care. RESULTS: Physical therapists mostly used non-digital methods to obtain subjective (e.g., face-to-face questioning, n = 98; 96.1%) and objective information (e.g., visual estimation, n = 95; 93.1%). The top three digital health technologies most frequently used by therapists: photo-based image capture (n = 19; 18.6%), accessing information logged/tracked by patients into a mobile app (n = 14; 13.7%), and electronic systems to capture subjective information that the patient fills in (n = 13; 12.7%). The top three technologies used by patients: activity trackers (n = 27; 26.2%), logging/tracking health information on mobile apps or websites (n = 12; 11.7%), and entering information on a computer (n = 12; 7.8%). Physical therapists were most willing to use technologies for: receiving diagnostic imaging results (n = 99; 97.1%), scheduling appointments (n = 92; 90.2%) and capturing diagnostic results (n = 92; 90.2%). Patients were most willing to use technologies for receiving notifications about health test results (n = 91; 88.4%), looking up health information (n = 83; 80.6%) and receiving personalised alerts/reminders (n = 80; 77.7%). CONCLUSIONS: Physical therapists and patients infrequently use digital health technologies to support musculoskeletal care, but expressed some willingness to consider using them for select functions.

Luminance Mechanisms of White Organic Light-Emitting Devices Fabricated Utilizing a Charge Generation Layer with a Light-Emitting Function.

The luminance mechanisms of the white organic light-emitting devices (WOLEDs) with a charge generation layer (CGL) consisting of a tungsten oxide layer and a 5,6,11,12-tetraphenyltetracene (rubrene) doped N,N',-bis-(1-naphthyl)-N,N'-diphenyl1-1'-biphenyl-4,4'-diamine (NPB) layer were investigated. Current densities and luminances of the WOLEDs increased with increasing a rubrene doping concentration because the formation of excitons in the rubrene-doped NPB layer increased due to the more exciton trapping in rubrene molecules and the delay of the electron injection due to the insertion of the litium qunolate layer. The yellow light emitted from the rubrene-doped NPB layer in the CGL combined with the blue light from the main emitting layer of the WOLEDs, resulting in the emission of the white light. The ratio between the yellow and the blue color peak intensities of the electroluminescence spectra for the WOLEDs was controlled by the rubrene doping concentration. The Commission Internationale de l'Eclairage coordinates of the fabricated WOLED were (0.31, 0.42) at 740.7 cd/m2, indicative of white emission color.

Novel and enhanced anti-melanoma DNA vaccine targeting the tyrosinase protein inhibits myeloid-derived suppressor cells and tumor growth in a syngeneic prophylactic and therapeutic murine model.

Melanoma is the most deadly type of skin cancer, constituting annually ∼ 75% of all cutaneous cancer-related deaths due to metastatic spread. Currently, because of metastatic spread, there are no effective treatment options for late-stage metastatic melanoma patients. Studies over the past two decades have provided insight into several complex molecular mechanisms as to how these malignancies evade immunological control, indicating the importance of immune escape or suppression for tumor survival. Thus, it is essential to develop innovative cancer strategies and address immune obstacles with the goal of generating more effective immunotherapies. One important area of study is to further elucidate the role and significance of myeloid-derived suppressor cells (MDSCs) in the maintenance of the tumor microenvironment. These cells possess a remarkable ability to suppress immune responses and, as such, facilitate tumor growth. Thus, MDSCs represent an important new target for preventing tumor progression and escape from immune control. In this study, we investigated the role of MDSCs in immune suppression of T cells in an antigen-specific B16 melanoma murine system utilizing a novel synthetic tyrosinase (Tyr) DNA vaccine therapy in both prophylactic and therapeutic models. This Tyr vaccine induced a robust and broad immune response, including directing CD8 T-cell infiltration into tumor sites. The vaccine also reduced the number of MDSCs in the tumor microenvironment through the downregulation of monocyte chemoattractant protein 1, interleukin-10, CXCL5 and arginase II, factors important for MDSC expansion. This novel synthetic DNA vaccine significantly reduced the melanoma tumor burden and increased survival in vivo, due likely, in part, to the facilitation of a change in the tumor microenvironment through MDSC suppression.

Hydrodynamic immunization leads to poor CD8 T-cell expansion, low frequency of memory CTLs and ineffective antiviral protection.

Hepatotropic pathogens, such as hepatitis B (HBV) and hepatitis C (HCV), often escape cellular immune clearance resulting in chronic infection. As HBV and HCV infections are the most common causes of hepatocellular carcinoma (HCC), prevention of these infections is believed to be key to the prevention of HCC. It is believed that an effective immune therapy must induce strong cytotonic T lymphocytes (CTLs) that can migrate into the liver, where they can clear infected hepatocytes. Here, we compared the induction of CD8 T cells by two different DNA immunization methods for T-cell differentiation, function, memory programming and their distribution within relevant tissues in a highly controlled fashion. We used hydrodynamic tail vein injection of plasmid to establish liver-specific LCMV-gp antigen (Ag) transient expression, and studied CD8 T cells induced using the P14 transgenic mouse model. CD8 T cells from this group exhibited unique and limited expansion, memory differentiation, polyfunctionality and cytotoxicity compared with T cells generated in intramuscularly immunized mice. This difference in liver-generated expansion resulted in lower memory CD8 T-cell frequency, leading to reduced protection against lethal viral challenge. These data show an unusual induction of naive CD8 T cells contributed to the lower frequency of Ag-specific CTLs observed after immunization in the liver, suggesting that limited priming in liver compared with peripheral tissues is responsible for this outcome.

Color stability of white organic light emitting devices with a color conversion layer utilizing CdSe/ZnS quantum dots and phosphors dispersed in polymethylmethacrylate.

White organic light-emitting devices (WOLEDs) were fabricated by combining a blue emitting organic light-emitting devices (OLEDs) and a color conversion layer made of yttrium aluminum garnet phosphors and CdSe/ZnS quantum dots (QDs) embedded into polymethylmethacrylate. When the ratio of phosphors and QDs changed, a good color balance was achieved at a ratio of 1:5, and the maximum luminance of 18.21 cd/m2 was obtained. As the applied voltage varied from 12 to 16 V, Commission Internationale de l'Eclairage coordinates shifted only slightly from (0.32, 0.34) to (0.30, 0.33), indicating a good color stability.

Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver.

The prevalence of hepatitis B virus (HBV) infection in Asia and sub-Sahara Africa is alarming. With quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, the need for a prophylactic or therapeutic vaccination approach that can effectively induce protective responses against the different genotypes of HBV is more important than ever. Such a strategy will require both the induction of a strong antigen-specific immune response and the subsequent deployment of immune response towards the liver. Here, we assessed the ability of a synthetic DNA vaccine encoding a recombinant consensus plasmid from genotype A through E of the HBV core antigen (HBcAg), to drive immunity in the liver. Intramuscular vaccination induced both strong antigen-specific T cell and high titer antibody responses systematically and in the liver. Furthermore, immunized mice showed strong cytotoxic responses that eliminate adoptively transferred HBV-coated target cells. Importantly, vaccine-induced immune responses provided protection from HBcAg plasmid-based liver transfection in a hydrodynamic liver transfection model. These data provide important insight into the generation of peripheral immune responses that are recruited to the liver-an approach that can be beneficial in the search for vaccines or immune-therapies to liver disease.

Effects of the mixing ratio of the CaAl12O19:mn and Zn2SiO4:mn color-conversion layer on the color tunable emissions of white organic light-emitting devices.

The optical properties of white organic light-emitting devices (WOLEDs) fabricated utilizing a CaAl12O19:Mn and Zn2SiO4:Mn phosphor layer were investigated. X-ray diffraction patterns for CaAl12O19:Mn and Zn2SiO4:Mn phosphors showed that Mn ions in the CaAl12O19:Mn phosphors were completely substituted into Ca ions and that Mn ions in the Zn2SiO4:Mn phosphors were completely substituted into Zn ions. Field emission scanning electron microscopy images showed that the size of the CaAl12O19:Mn phosphor was approximately between 0.1 and 3 microm, and that the size of the Zn2SiO4:Mn phosphor was smaller than 7 microm. The color coordinates of the electroluminescence spectra for WOLEDs with phosphor thicknesses of 0.25 and 0.35 mm shifted to the white emission side because the generated blue light from the blue OLEDs combined with the red and green lights was converted by the CaAl12O19:Mn and the Zn2SiO4:Mn phosphor down-conversion layers.

The role of inhibitor of DNA-binding (Id1) in hyperproliferation of keratinocytes: the pathological basis for middle ear cholesteatoma from chronic otitis media.

OBJECTIVES: A hallmark of cholesteatoma is hyperproliferation of keratinocytes with abundant production of keratins in the middle ear under chronic inflammatory conditions. However, little is known about the driving force of cellular proliferation and keratin production of cholesteatomal matrix. The purpose of this study was to investigate the cellular proliferation and keratin production of keratinocytes under the influence of Id1, a candidate transcription factor to cell proliferation. MATERIALS AND METHODS: Keratinocytes were transfected with Id1 and the responses of keratinocytes to Id1 were studied by using cellular and molecular biologic methods. RESULTS: Id1 positively contributed to the cell cycle progression and negatively to the p16(Ink4a) downregulation via the nuclear factor-kappa B (NF-κB)/cyclin D1 pathway. Id1 significantly increased the promoter activity of NF-κB which, in turn, up-regulated the expression of cyclin D1 and keratin 10 in keratinocytes. Specific NF-κB inhibitors (pyrrolidine dithiocarbamate, PDTC), or dominant-negative inhibitor (I kappa B alpha mutant, IκBαM) abrogated the Id1-induced cell proliferation and keratin 10 production whereas p65, a subunit of the NF-κB heterodimer and an enhancer of the NF-κB activity, strengthened the Id1-induced cell proliferation and keratin 10 production. CONCLUSIONS: Id1 contributed to hyperproliferation of keratinocytes via enhancement of cell cycle progression, removal of cell cycle inhibition, and simultaneously increased keratin production.

GJB2 mutations and additional disabilities in a pediatric cochlear implant population.

BACKGROUND: Children with severe to profound sensorineural hearing loss due to GJB2 mutations have often been deemed good cochlear implant candidates. Studies on children with GJB2 mutations and cochlear implants have typically excluded children with additional disabilities. OBJECTIVE: To investigate the presence of additional disabilities among children with and without GJB2 mutations in a cochlear implant population. METHODS: A retrospective chart review was performed of children with non-syndromic sensorineural hearing loss (SNHL) who received a cochlear implant between 1993 and 2004. RESULTS: Among 108 children within the cochlear implant database; 46 patients met the inclusion criteria of idiopathic non-syndromic hearing loss. Sixteen children had GJB2 mutations, 12 were GJB2 negative, and 17 did not receive GJB2 testing but had no other identifiable etiology or risk factor contributing to hearing loss. The proportion of children with additional disabilities that would affect either pre-operative assessments or post-operative results in the GJB2 positive group was 44% compared to 33% of children in the GJB2 negative. Additional disabilities were present in 41% of the children who did not receive GJB2 testing. The disabilities in the GJB2 positive group included specific learning disability, apraxia, epileptiform aphasia, attention deficit disorder, global developmental delay, and gross motor delay. The GJB2 negative and those children not receiving GJB2 testing had motor delays, language delay, autism, specific learning disability, and attention deficit disorder. The proportion of children with at least 6 months CI use who relied on oral communication was 62% in the GJB2 positive group, 66% in the GJB2 negative group, and 38% in the untested group. A majority of the genetic alleles were 35delG (81%) and 10 of 16 (63%) patients with GJB2 mutations were homozygous 35delG. The rate of developmental diagnoses was similar in patients with homozygous GJB2 compared to compound heterozygous genotypes. CONCLUSIONS: The presence of biallelic GJB2 mutations does not rule out non-hearing related disorders that can have an effect on speech, language and learning. Forty-four percent of children with GJB2 mutations had other conditions that could directly affect pre-implant evaluation and post-implant performance. This rate is similar to the reported prevalence among the overall population of children with hearing loss. All children should have a comprehensive evaluation of development and behavior regardless of the etiology of hearing loss.

Developmental expression of aquaporin 2 in the mouse inner ear.

OBJECTIVES: The maintenance of endolymph homeostasis is critical for the inner ear to perform its functions of hearing and maintaining balance. The identification and cloning of aquaporins (a family of water channel proteins) has allowed the study of a novel cellular mechanism potentially involved in endolymph homeostasis. The objective of the present study was to define the developmental temporal and spatial expression pattern of aquaporin 2 (Aqp2) in the developing mouse inner ear. STUDY DESIGN: A systematic immunohistochemical study of Aqp2 protein expression was performed on embryonic mouse inner ears ranging from embryonic day 10 (otocyst stage) to embryonic day 18 (just before birth). METHODS: Serial cryosections of embryonic mouse inner ears were used for immunohistochemical experiments. A rabbit polyclonal antisera raised against a synthetic Aqp2 peptide was used with a standard nickel intensified 3,3-diaminobenzidine reaction protocol for immunolocalization of Aqp2 in tissue sections. RESULTS: Aquaporin 2 is expressed diffusely in the early otocyst, then becomes progressively restricted as the inner ear matures. During early cochlear duct formation (embryonic days 12 and 13), expression of Aqp2 is homogeneous; later, it becomes restricted to specific regions of the endolymphatic compartment (embryonic days 15 and 18). Similar restriction of expression patterns could be noted for the vestibular structures. Endolymphatic duct and sac and stria vascularis expression of Aqp2 was noted to occur fairly late during development but demonstrated a distinct pattern of immunolabeling. CONCLUSIONS: Aquaporin 2 shows an early and specific pattern of expression in the developing mouse inner ear, suggesting a significant role for this water channel protein in the development of endolymph homeostasis and meriting further functional studies of Aqp2 in the inner ear.

Selective indications for the management of extensive anterior epitympanic cholesteatoma via combined transmastoid/middle fossa approach.

OBJECTIVES/HYPOTHESIS: Cholesteatoma that is present in the anterior epitympanic space may extend medially along the supralabyrinthine route to the geniculate ganglion, labyrinth, and cochlea and medially toward Kawase's triangle and the anterior petrous apex. Superiorly it may erode into the middle fossa. Contemporary microsurgical techniques allow for optimal management of these lesions with minimal morbidity, provided that the irregular and complex osteology of the petrous base is understood. The objective of the study was to review the relevant regional anatomy, pathobiology, and current algorithm used in treatment of this select patient population using a combined transmastoid/middle fossa (TM/MF) approach. METHODS: A retrospective review was performed of all clinical and radiographic data from patients undergoing combined TM/MF management of extensive anterior epitympanic cholesteatoma between July 1984 and June 1998. Data from physical examinations, preoperative imaging studies, and operative findings and other relevant data were tabulated and analyzed for patients undergoing TM/MF management of cholesteatoma. RESULTS: Of 488 patients with cholesteatoma treated by the otological service between 1984 and 1998, 11 patients underwent TM/MF exposure and removal of anterior epitympanic cholesteatoma. Total cholesteatoma removal was accomplished in six patients. In three patients, because of facial nerve involvement, labyrinthine fistulae, or internal carotid artery involvement, open-cavity surgery was performed. In two patients, residual or recurrent cholesteatoma was exteriorized at "second-look" procedures. In this small cohort of patients the majority had extension to the arcuate eminence, geniculate ganglion, or Kawase's triangle or had "blue-lining" of the cochlea or labyrinth. To a lesser degree, the middle ear and mastoid contents were involved. Further facial nerve dysfunction or sensorineural hearing loss was not noted after surgery. CONCLUSIONS: Selective TM/MF removal of cholesteatoma provides an optimal route for removing complex cholesteatoma in patients with intact sensorineural function and medial cholesteatoma extension.

The effect of transient balloon occlusion of the mitral valve on left atrial appendage blood flow velocity and spontaneous echo contrast.

BACKGROUND: Spontaneous echo contrast (SEC) is a phenomenon that is commonly seen in areas of blood stasis. It is a slowly moving, cloud-like swirling pattern of "smoke" or increased echogenicity recorded on echocardiography. SEC is commonly seen in the left atrium of patients with mitral stenosis or atrial fibrillation. The presence of SEC has been shown to be a marker of increased thromboembolic risk. HYPOTHESIS: By using transesophageal echocardiography during percutaneous balloon mitral valvotomy (PBMV), the study investigated the relationship between SEC and varying left atrial appendage (LAA) blood flow velocity in the human heart. METHODS: Thirty-five patients with rheumatic mitral stenosis underwent percutaneous balloon mitral valvotomy with intraoperative transesophageal echocardiography monitoring. We alternatively measured LAA velocities and observed the left atrium for various grades of SEC (0 = none to 4 = severe) before and after each balloon inflation. RESULTS: Left atrial appendage maximal ejection velocity was reduced from 35 +/- 14 to 6 +/- 2 mm/s at peak balloon inflation and increased to 40 +/- 16 mm/s after balloon deflation. In comparison with the values before balloon inflation and after balloon deflation, LAA velocities were significantly lower (p < 0.001). New or increased SEC grade was observed during 54 of 61 (88%) inflations and unchanged in 7 (12%) inflations at peak balloon inflation. Spontaneous echo contrast became lower in grade after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%), and remained unchanged after 6 deflations (10%). The mean time to achieve maximal SEC grade (2.5 +/- 1.2 s) coincided with the mean time to trough LAA velocities (2.3 +/- 1.1 s) after balloon inflation. Upon deflation, the mean time to lowest SEC grade (2.9 +/- 1.8 s) coincided with mean time to achieve maximal LAA velocities (2.7 +/- 1.6 s). CONCLUSION: During balloon inflation, the severity of SEC was enhanced with corresponding reduction in LAA flow velocity. Upon balloon deflation, SEC lightens or disappears with increase in LAA flow velocity.

Acute intracranial hemorrhage caused by acupuncture.

A 44-year-old Chinese man developed severe occipital headache, nausea, and vomiting during acupuncture treatment of the posterior neck for chronic neck pain. Computed tomography of the head showed hemorrhage in the fourth, third, and lateral ventricles. A lumbar puncture confirmed the presence of blood. Magnetic resonance angiography with gadolinium did not reveal any saccular aneurysms or arteriovenous malformations. The patient's headache resolved over a period of 28 days without any neurological deficits. Acupuncture of the posterior neck can cause acute intracranial hemorrhage.

The effect of transient balloon occlusion of the mitral valve on left atrial appendage blood flow velocity and spontaneous echo contrast: a comparison in sinus rhythm and atrial fibrillation patients.

OBJECTIVE: To investigate the relationship between spontaneous echo contrast (SEC) and left atrial appendage (LAA) blood flow velocity using transesophageal echocardiography (TEE) during percutaneous balloon mitral valvotomy (PBMV) in patients with atrial fibrillation and sinus rhythm. METHODS: Thirty-five patients (21 in sinus rhythm and 14 in atrial fibrillation) with rheumatic mitral stenosis underwent PBMV with intraoperative transesophageal echocardiography monitoring. We measured LAA blood flow velocities and observed the left atrium for various grades of SEC (from 0 = none to 4 = severe), before and after each balloon inflation. RESULTS: Left atrial appendage maximal emptying velocity (LAA MEV) was reduced from 35 +/- 14 cm/s to 6 +/- 2 cm/s at peak balloon inflation and increased to 40 +/- 16 cm/s after balloon deflation. Comparison of the values before balloon inflation and after balloon deflation showed that LAA velocities were significantly lower (P < 0.001). During balloon inflation, both maximal emptying velocity (MEV) and maximal filling velocity (MFV) were significantly decreased, compared to those before inflation and after balloon deflation (P < 0.01). And both MEV and MFV were significantly higher after balloon deflation relative to those before balloon inflation. Patients with atrial fibrillation had significantly lower MEV and MFV before and during balloon inflation and after balloon deflation than patients with sinus rhythm. At peak balloon inflation, new or increased SEC grades were observed during 54 of 61 (88%) inflations and unchanged during 7 (12%) inflations. SEC grades were reduced after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%) and remained unchanged after 6 deflations (10%). At peak balloon inflation, left atrium spontaneous echo contrast (LASEC) grade 4 was observed during 14 of 27 (93%) inflations in the atrial fibrillation patients, significantly higher than in patients with sinus rhythm (8 of 34, 24%; P < 0.05). LASEC completely disappeared after 16 of 34 deflations (47%) in the patients with sinus rhythm, significantly higher than in the atrial fibrillation patients (2 of 27 deflations; P < 0.01). The mean time to achieve maximal SEC grade (2.5 +/- 1.2 s) correlated with the mean time to trough LAA velocities (2.3 +/- 1.1 s) after balloon inflation. Both the time to lowest LAA velocity and the time to highest LASEC were significantly longer in the patients with sinus rhythm than in the atrial fibrillation patients (2.6 +/- 1.1 s vs 1.7 +/- 1.0 s, P < 0.05 and 2.8 +/- 1.4 s vs 1.9 +/- 1.3 s, P < 0.05, respectively). Upon deflation, the mean time to lowest SEC grade (2.9 +/- 1.8 s) correlated with the mean time to achieve maximal LAA velocities (2.7 +/- 1.6 s). Both intervals are significantly shorter in the patients with sinus rhythm than in the atrial fibrillation patients (2.0 +/- 1.6 s vs 3.5 +/- 1.5 s, P < 0.01 and 2.2 +/- 1.7 s vs 3.6 +/- 1.6 s, P < 0.05). CONCLUSION: Reducing the blood flow velocity in the human left atrium by balloon occlusion of the mitral valve may enhance SEC, whereas restoring blood flow after balloon deflation would cause enhanced echogenic blood to disappear or decrease in both groups of patients. Patients with atrial fibrillation demonstrate more severe blood stagnation of the left atrial body and appendage during transient balloon inflation at mitral valve orifice and slower recovery from the stagnation, decreasing to a lesser extent after balloon deflation, when compared to patients with sinus rhythm.

Aspergillus mastoiditis in acquired immunodeficiency syndrome.

OBJECTIVE: This study aimed to analyze the clinical presentation, diagnosis, management, and results of treatment in a series of three patients with acquired immunodeficiency syndrome (AIDS) in whom Aspergillus mastoiditis developed. This study also aimed to compare these aspects of Aspergillus mastoiditis in patients with AIDS with three additional cases present in the current literature. A classification system for fungal infections of the ear and temporal bone is proposed. STUDY DESIGN: The study design was a retrospective case review. SETTING: The study was conducted at multiple tertiary referral centers. PATIENTS: Three individuals with diagnosed AIDS and mastoiditis resulting from culture-proven Aspergillus were studied. INTERVENTION: Patients were treated with both medical and surgical methods including local and systemic antimicrobial/antifungal agents and mastoidectomy. MAIN OUTCOME MEASURES: These measures included return of facial nerve function, control/resolution of disease, and survival. RESULTS: All three patients in this series initially presented with otalgia and otorrhea and intact facial nerve function. Facial nerve paresis developed in all patients between 5 and 12 weeks after initial symptoms. Paresis uniformly improved or resolved after mastoidectomy. Two patients treated with systemic antifungal therapy and prompt surgical debridement after development of facial palsy had full resolution of infection. One patient had full recovery of facial paresis and the other had partial recovery. The third patient was lost to follow-up after initial treatment with antimicrobials and surgery and died 3 months later without a clear etiology. CONCLUSIONS: Aspergillus mastoiditis is an unusual infection in patients with AIDS. Because of its rarity, fungal mastoiditis in immunocompromised individuals can result in a significant delay in diagnosis and treatment. The decision between conservative antimicrobial therapy and aggressive surgical treatment also can present a therapeutic challenge in the management of these life-threatening infections, especially in patients with existing immunodeficiency and illness. Early surgical debridement followed by antimicrobial therapy may be life preserving in this patient population.

Otx1 and Otx2 activities are required for the normal development of the mouse inner ear.

The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs.