Macrophage phenotype impacts in vitro equine intrasynovial deep digital flexor tenocyte matrix metalloproteinase gene expression and secretion.

OBJECTIVE: To investigate matrix metalloproteinase (MMP) and their inhibitors tissue inhibitor matrix metalloproteinase (TIMP) gene expression and secretion during equine deep digital flexor tendon (DDFT) tenocyte and macrophage (undifferentiated, proinflammatory, and regulatory) co-culture. SAMPLE: Third passage DDF tenocytes and donor-matched macrophages differentiated from peripheral blood CD14+ monocytes from 5 healthy horses ages 9-11 years, euthanized for reasons unrelated to musculoskeletal conditions. METHODS: Passage 3 DDT tenocyte aggregate cultures were co-cultured with undifferentiated (control), proinflammatory (granulocyte-macrophage colony-stimulating factor; GM-CSF pretreated and lipopolysaccharide + interferon gamma-primed; LPS+IFN-γ) or regulatory (interleukin-4 and interleukin-10-primed; IL-4 + IL-10) macrophages in direct and transwell co-cultures for 72 hours. MMP-1, -2, -3, -9, -13, and TIMP -1, -2 mRNA were measured via real-time Polymerase Chain Reaction (rtPCR). Co-culture media MMP -3, -9, and TIMP -1, -2 concentrations were quantified via ELISA. RESULTS: Direct co-culture of DDF tenocytes with proinflammatory macrophages for 72 hours increased MMP-1, -3, and -13 mRNA levels whereas, MMP-9 mRNA levels decreased. Direct and transwell co-culture with proinflammatory and regulatory macrophages resulted in increased MMP-3 and decreased MMP-9 media concentrations. While direct co-culture with regulatory macrophages significantly increased TIMP-1 mRNA, overall, TIMP mRNA and culture media concentrations were largely unchanged. CLINICAL RELEVANCE: Cell-to-cell contact between DDF tenocytes and macrophages is not essential to induce MMP gene expression and secretion. Co-culture systems offer a viable in vitro platform to screen and evaluate immunomodulatory properties of therapies aimed at improving equine intrasynovial tendon healing.

Brain structure correlates with auditory function in children diagnosed with auditory neuropathy spectrum disorder.

INTRODUCTION: Auditory neuropathy spectrum disorder (ANSD) is a term for a collection of test results which indicate disruption of the auditory signal at some point along the neural pathway. This results in a spectrum of functional outcomes, ranging from reasonably normal hearing to profound hearing loss. This study assessed brain structure changes and behavioral correlates in children diagnosed with ANSD. METHODS: Seventeen children who had previously been diagnosed with ANSD were recruited to the study and underwent a battery of behavioral measures of hearing, language, and communication, along with structural MR imaging. Analysis of cortical thickness of temporal lobe structures was carried out using FreeSurfer. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. The control group comprised imaging data taken from a library of MRI scans from neurologically normal children. Control images were matched as closely as possible to the ANSD group for age and sex. RESULTS: Reductions in right temporal lobe cortical thickness were observed in children with ANSD compared to controls. Increases in medial diffusivity in areas including the corpus callosum and in the right occipital white matter were also seen in the group with ANSD compared to controls. Speech perception abilities, both in quiet and in noise, were correlated with cortical thickness measurements for several temporal lobe structures in children with ANSD, and relationships were also seen between diffusion metrics and measures of auditory function. CONCLUSION: This study shows that children with ANSD have structural brain differences compared to healthy controls. It also demonstrates associations between brain structure and behavioral hearing abilities in children diagnosed with ANSD. These results show that there is a potential for structural imaging to be used as a biomarker in this population with the possibility of predicting functional hearing outcome.

Use of an autoinflation device does not lead to a clinically meaningful change in hearing thresholds in children with otitis media with effusion.

DESIGN: The objective of this study was to establish whether autoinflation was an effective intervention in a paediatric audiology service. This was a pragmatic retrospective study with historical controls using a paired availability design. SETTING: The study took place at a single paediatric audiology service in England. PARTICIPANTS: All children seen in the clinic over a two-year period who were aged between 3 and 11 years and who had a type B tympanogram in at least one ear were included. The Otovent autoinflation device was available as a treatment option over the second year (Cohort B) but not the first (Cohort A). There were 976 children included in the study: Cohort A comprised 513 children, Cohort B comprised 463 children. MAIN OUTCOME MEASURES: The aims were to evaluate whether there was improvement in hearing thresholds following introduction of an autoinflation device, and whether there was a reduction in further audiology follow-ups, and in referrals to an ear, nose and throat specialist for consideration of ventilation tube insertion. RESULTS AND CONCLUSIONS: There was a statistically significant improvement in hearing thresholds in Cohort B compared to Cohort A, however the improvements were clinically minimal with small effect sizes. There was no significant difference in improvement of tympanometry results between the two cohorts. Significantly more children in Cohort B (autoinflation group) were referred to an ear, nose and throat specialist after their second appointment compared to Cohort A. It was feasible to introduce autoinflation into the care pathway, however there was no evidence of clinically meaningful improved outcomes for patients.

Treatment and outcome of eight horses with limb cellulitis and septic tendonitis or desmitis.

OBJECTIVE: To report the clinical features, treatment, and outcome in horses with cellulitis and concurrent septic tendonitis and/or desmitis. STUDY DESIGN: Short case series. METHODS: Medical records from 2000 to 2019 were reviewed, identifying horses with cellulitis and concurrent septic tendonitis and/or desmitis based on sonographic examination and positive bacterial culture. Signalment, ultrasonographic results, bacterial culture, treatment, duration of hospitalization, and complications were recorded. Long-term outcome data were obtained from follow-up examinations and/or telephone interviews. Successful outcome was defined as return to intended use. RESULTS: Eight horses met the inclusion criteria. All infections occurred in hindlimbs, with septic suspensory ligament in six of eight horses, and septic superficial digital flexor tendon in one of eight horses. Surgical debridement was performed in six of eight horses. All horses were treated with systemic and regional intravenous antimicrobials and were discharged from the hospital. Long-term follow-up was available in seven of eight horses. Of these, four horses returned to their intended athletic function, two horses returned to their intended function as a broodmare or pasture pet, and one horse is still rehabilitating. CONCLUSION: Septic tendonitis or desmitis is a rare but possible sequela of limb cellulitis. Based on the findings in this study, prognosis for return to athletic function is fair to good for horses diagnosed with cellulitis and concurrent septic tendonitis or desmitis.

White matter microstructural abnormalities in children with severe congenital hypothyroidism.

This study assessed white matter microstructural integrity and behavioral correlates for children with severe congenital hypothyroidism (CH) who were identified and treated early following newborn screening. Eighteen children with severe CH and 21 healthy controls underwent a battery of behavioral measures of hearing, language and communication, along with diffusion MR imaging. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. Microscopic diffusion anisotropy mapping based on the Spherical Mean Technique was also used to evaluate biologically specific metrics. Compared with age-matched controls, children with severe CH had poorer hearing and communication skills, albeit generally within normal limits. Children with severe CH had fractional anisotropy that was significantly lower in the cerebellum, bilateral thalami and right temporal lobe, and radial diffusivity that was significantly higher in the cerebellum and bilateral thalami. Microscopic fractional anisotropy and intra-neurite volume fraction were also significantly decreased, and transverse microscopic diffusivity was significantly increased, in the CH group in areas including the cerebellum, thalamus, occipital lobe, and corpus callosum, and in the white matter adjacent to sensorimotor cortex, particularly in the left hemisphere. Significant and widespread correlations were observed between behavioral measures and measures of white matter microstructural integrity in children with CH. The results indicate that children with severe CH who are identified through newborn screening may have significant brain white matter microstructural abnormalities despite early treatment.