Efficacy and risks in the use of human stem cells in the treatment of children with cerebral palsy

Cerebral palsy (CP), depending on disease severity, can result in diminished quality of life not only from decreased function but from societal stigmatization. Coordinating various care provider appointments, expense of short-term treatments, difficulty navigating transportation, and relying on caregivers can complicate patient and family lives. The costs of CP are substantial on the healthcare system, with one managed Medicaid database averaged across 15 U.S states finding the average annual Medicaid costs for children with CP to be 15 times higher than children without CP and averaged to $22, 383 United States dollar (USD) compared to$1,358 USD respectively (Pulgar et al., 2019). Cost effective treatment and effective prevention strategies are increasingly warranted for the CP population. Due to the varying manifestations associated with CP, a standardized treatment for this condition is challenging. Current treatments may enhance quality of life and temporarily reduce pain or discomfort, but they do not cure CP. While perinatal prevention strategies potentially provide the greatest chance to prevent CP from occurring and should be the focus of health care policy, financial barriers remain especially with strained health care budgets. While cure remains elusive, focus on treatments and prevention strategies to limit disease impact is paramount. In the last decade some attention has turned to the use of stem cell treatments in children and adolescents with CP to provide more impactful outcomes with earlier intervention potentially limiting the devastating musculoskeletal effects seen with severe disease. While primarily results from clinical trials both nationally and internationally suggest stem cell treatment increases gross motor function in children and adolescents, questions remain whether these treatments provide clinically meaningful improvement compared to traditional therapies. The goal of this thesis is to discuss the current pharmaceuticals and non- pharmaceutical treatments with rehabilitative therapies that are historically used to reduce severity of secondary manifestations associated with CP in children. Human stem cell clinical trials for CP will be reviewed to assess efficacy and risks as this treatment is translated into clinical practice for children. In addition to stem cell treatment, public health practices of prevention during prenatal visits will be reviewed as it is an encouraging method to reduce preterm births which are a risk factor for CP development

Complications Using Bioabsorbable Cross-Pin Femoral Fixation: A Case Report and Review of the Literature

The use of bioabsorbable cross-pin transcondylar fixation has remained a viable option for femoral fixation in anterior cruciate ligament reconstruction. Although numerous biomechanical studies have demonstrated high fixation strength and minimal slippage with use of this method of fixation, there have been increasing reports of a variety of clinical complications associated with these implants. We reviewed the literature for all complications associated with the Bio-TransFix implant and present a case report of a patient status after ACL reconstruction using Bio-TransFix cross-pin femoral fixation with iliotibial band friction syndrome from a broken cross-pin four month post-operatively

Determining the Completeness of the Nimbus Meteorological Data Archive

NASA launched the Nimbus series of meteorological satellites in the 1960s and 70s. These satellites carried instruments for making observations of the Earth in the visible, infrared, ultraviolet, and microwave wavelengths. The original data archive consisted of a combination of digital data written to 7-track computer tapes and on various film media. Many of these data sets are now being migrated from the old media to the GES DISC modern online archive. The process involves recovering the digital data files from tape as well as scanning images of the data from film strips. Some of the challenges of archiving the Nimbus data include the lack of any metadata from these old data sets. Metadata standards and self-describing data files did not exist at that time, and files were written on now obsolete hardware systems and outdated file formats. This requires creating metadata by reading the contents of the old data files. Some digital data files were corrupted over time, or were possibly improperly copied at the time of creation. Thus there are data gaps in the collections. The film strips were stored in boxes and are now being scanned as JPEG-2000 images. The only information describing these images is what was written on them when they were originally created, and sometimes this information is incomplete or missing. We have the ability to cross-reference the scanned images against the digital data files to determine which of these best represents the data set from the various missions, or to see how complete the data sets are. In this presentation we compared data files and scanned images from the Nimbus-2 High-Resolution Infrared Radiometer (HRIR) for September 1966 to determine whether the data and images are properly archived with correct metadata

Is Race a Risk Factor for the Development of Renal Artery Stenosis?

Atherosclerotic renal artery disease is a common cause of hypertension and chronic kidney disease that may progress into end stage renal failure if not diagnosed and treated early. Renal artery stenosis (RAS) has been shown to be an independent risk factor for mortality in patients with coronary artery disease. We sought to determine whether race is an independent risk factor for developing RAS. A retrospective study was conducted including 324 patients with resistant hypertension who underwent renal angiography with or without coronary angiography. In univariate analysis, Caucasian race was associated with significant risk of RAS (OR = 2.3, P = .01). However, this association was no longer significant after correcting for additional clinical variables in a multivariate model (OR = 1.5, P = .07). There was a strong association between smoking and RAS (OR 2.0, P = .02). We conclude that traditional risk factors, especially smoking, rather than race, are the most important predictors of RAS development

Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress. Histone deacetylase (HDAC) activity is reduced in cells of cigarette smokers, and low concentrations of theophylline can increase HDAC activity. We measured the effect of theophylline on HDAC activity and inflammatory gene expression in alveolar macrophages (AM) from patients with COPD. AM from normal smokers showed a decrease in HDAC activity compared with normal control subjects, and this was further reduced in COPD patients (51% decrease, P < 0.01). COPD AMs also showed increased basal release of IL-8 and TNF-α, which was poorly suppressed by dexamethasone. Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A. Therefore, theophylline might restore steroid responsiveness in COPD patients

Structure-function relationships at the human spinal disc-vertebra interface.

Damage at the intervertebral disc-vertebra interface associates with back pain and disc herniation. However, the structural and biomechanical properties of the disc-vertebra interface remain underexplored. We sought to measure mechanical properties and failure mechanisms, quantify architectural features, and assess structure-function relationships at this vulnerable location. Vertebra-disc-vertebra specimens from human cadaver thoracic spines were scanned with micro-computed tomography (μCT), surface speckle-coated, and loaded to failure in uniaxial tension. Digital image correlation (DIC) was used to calculate local surface strains. Failure surfaces were scanned using scanning electron microscopy (SEM), and adjacent sagittal slices were analyzed with histology and SEM. Seventy-one percent of specimens failed initially at the cartilage endplate-bone interface of the inner annulus region. Histology and SEM both indicated a lack of structural integration between the cartilage endplate (CEP) and bone. The interface failure strength was increased in samples with higher trabecular bone volume fraction in the vertebral endplates. Furthermore, failure strength decreased with degeneration, and in discs with thicker CEPs. Our findings indicate that poor structural connectivity between the CEP and vertebra may explain the structural weakness at this region, and provide insight into structural features that may contribute to risk for disc-vertebra interface injury. The disc-vertebra interface is the site of failure in the majority of herniation injuries. Here we show new structure-function relationships at this interface that may motivate the development of diagnostics, prevention strategies, and treatments to improve the prognosis for many low back pain patients with disc-vertebra interface injuries. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:192-201, 2018

Recovering Nimbus Era Observations at the NASA GES DISC

Between 1964 and 1978, NASA launched a series of seven Nimbus meteorological satellites which provided Earth observations for 30 years. These satellites, carrying a total of 33 instruments to observe the Earth at visible, infrared, ultraviolet, and microwave wavelengths, revolutionized weather forecasting, provided early observations of ocean color and atmospheric ozone, and prototyped location-based search and rescue capabilities. The Nimbus series paved the way for a number of currently operational systems such as the EOS (Earth Observation System) Terra, Aqua, and Aura platforms. The original data archive includes both magnetic tapes and film media. These media are well past their expected end of life, placing at risk valuable data that are critical to extending the history of Earth observations back in time. GES DISC (Goddard Earth Sciences Data and Information Services Center) has been incorporating these data into a modern online archive by recovering the digital data files from the tapes, and scanning images of the data from film strips. The digital data products were written on obsolete hardware systems in outdated file formats, and in the absence of metadata standards at that time, were often written in proprietary file structures. Through a tedious and laborious process, oft-corrupted data are recovered, and incomplete metadata and documentation are reconstructed

Data Recovery Effort of Nimbus Era Observations by the NASA GES DISC

NASA launched seven Nimbus meteorological satellites in the 1960s and 70s. These satellites carried instruments for making observations of the Earth in the visible, infrared, ultraviolet, and microwave wavelengths. The original data archive consisted of a combination of magnetic tapes and various film media. As these media are well past their expected end of life, the valuable data they contain are now being migrated to the GES DISC modern online archive. The process involves recovering the digital data files from the tapes as well as scanning images of the data from film strips. This presentation will address the status and challenges of recovering the Nimbus data. The old data products were written on now obsolete hardware systems and outdated file formats. They lack any metadata standards and each product is often written in its own proprietary file structure. This requires creating metadata by reading the contents of the old data files. The job is tedious and laborious, as documentation may be incomplete, data files and tapes are sometimes corrupted, or were improperly copied at the time they were created

Multilayer scaffolds in orthopaedic tissue engineering

Abstract Purpose The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Methods Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. Results In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Conclusions Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future

NASA Earth Science Data Rescue Efforts

Historically, at the end of a NASA mission, earth and space science data were stored at NASA's National Space Science Data Center (NSSDC). The original data archive consisted of both magnetic tapes and film media. As data storage technology improved, data from later missions were stored on disks and platters and higher capacity magnetic media for online accessibility. To conserve physical space at NASA archive sites and to meet disaster recovery guidelines, historical data originally stored on magnetic tapes and film were moved to the Federal Archives and Record Center (FRC) as a temporary holding area until its long-term value was determined by NASA. All records at the FRC are controlled by the NASA Records Retention Schedule (NRRS) which determines the disposal date for each record. On that date, responsible NASA parties are notified that all scheduled records should be reviewed and assessed to determine if they continue to hold significant historical, scientific or administrative value. For Earth Science data records being held at FRC, the Earth Science Data and Information System (ESDIS) Project office is the party responsible for making the value assessment that determines which records warrant preservation and which are ready for proper disposal according to NASA guidelines. Once the data's long-term value is determined, ESDIS takes definitive steps to preserve this data for future discovery and access. Deteriorating media containing historic data of value are recalled from FRC and brought back to ESDIS. Through a tedious, laborious process, digital data are recovered and restored to modern formats with improved metadata and documentation to aid discovery. The restored digital products are then incorporated into our modern online archive, and made immediately accessible to the public. In this paper, we will discuss how we identify data-at-risk, ways to minimize data loss, how we plan for recovery, how we delegate recovery activities to our archive facilities, and how we make recovered data more accessible