Safety and efficacy of botox injection in alleviating post-operative pain and improving quality of life in lower extremity limb lengthening and deformity correction

<p>Abstract</p> <p>Background</p> <p>Distraction osteogenesis is the standard treatment for the management of lower limb length discrepancy of more than 3 cm and bone loss secondary to congenital anomalies, trauma or infection. This technique consists of an osteotomy of the bone to be lengthened, application of an external fixator, followed by gradual and controlled distraction of the bone ends. Although limb lengthening using the Ilizarov distraction osteogenesis principle yields excellent results in most cases, the technique has numerous problems and is not well tolerated by many children. The objective of the current study is to determine if Botulinum Toxin A (BTX-A), which is known to possess both analgesic and paralytic actions, can be used to alleviate post-operative pain and improve the functional outcome of children undergoing distraction osteogenesis.</p> <p>Methods/Design</p> <p>The study design consists of a multi centre, randomized, double-blinded, placebo-controlled trial. Patients between ages 5–21 years requiring limb lengthening or deformity correction using distraction will be recruited from 6 different sites (Shriners Hospital for Children in Montreal, Honolulu, Philadelphia and Portland as well as DuPont Hospital for Children in Wilmington, Delaware and Hospital for Sick Children in Toronto, Ont). Approximately 150 subjects will be recruited over 2 years and will be randomized to either receive 10 units per Kg of BTX-A or normal saline (control group) intraoperatively following the surgery. Functional outcome effects will be assessed using pain scores, medication dosages, range of motion, flexibility, strength, mobility function and quality of life of the patient. IRB approval was obtained from all sites and adverse reactions will be monitored vigorously and reported to IRB, FDA and Health Canada.</p> <p>Discussion</p> <p>BTX-A injection has been widely used world wide with no major side effects reported. However, to the best of our knowledge, this is the first time BTX-A is being used under the context of limb lengthening and deformity correction.</p> <p>Trial Registration</p> <p>NCT00412035</p

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

BACKGROUND: The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). METHODS: This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. RESULTS: Short-course TPT discontinuation was higher with 4R (31% vs 14%; P &lt; .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. CONCLUSIONS: TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations

Effect of Photolysis on Absorption and Fluorescence Spectra of Light-Absorbing Secondary Organic Aerosols

Excitation–emission matrices (EEMs) constructed from fluorescence measurements are increasingly used for the characterization of chromophoric dissolved organic matter (CDOM) and light-absorbing atmospheric organic aerosols known as brown carbon (BrC). There is a high uncertainty in the effect of BrC aerosols on climate because their optical properties depend on the amount of time they spent in the atmosphere. In order to aid in the quantification of BrC aerosols’ contribution to radiative forcing, we investigated the effect of solar radiation on the fluorescence, expressed as EEMs, and absorption spectra of the water-soluble fraction of BrC species formed by the high-NOx photooxidation of benzene, toluene, p-xylene, and naphthalene. The BrC samples were prepared in a smog chamber, extracted in water, and irradiated in a solar simulator at a fixed pH of 3, representative of aerosol liquid water, or at a fixed pH of 6, representative of cloudwater. Semicontinuous fluorescence and absorbance measurements were carried out during the irradiation at 20 min intervals for 44 h. The absorption coefficients depended on the solution pH, with the solutions at pH 6 absorbing stronger than solutions at pH 3. All samples underwent a decrease in absorption coefficient at all visible wavelengths, whereas fluorescence intensities showed both increases and decreases in different regions of the EEMs. Upon comparison with CDOM samples, the fluorescence intensity of all secondary organic aerosol (SOA) samples decreased in the region of the EEMs where the characteristic terrestrial humic-like C peak occurs. These experimental observations suggest that (i) this type of BrC will have different effects on climate depending on whether it ends up in an acidic or neutral environment; (ii) exposure to UV radiation will diminish the ability of this type of BrC to affect climate on a time scale of about a day; (iii) fluorescence by BrC compounds has a minimal effect on aerosol radiative forcing; (iv) photooxidized aromatics may be closely related, in terms of optical properties, to CDOM found in fresh waters

Transcriptional landscape of the prenatal human brain.

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development