No Effect of Hole Geometry in Microfracture for Talar Osteochondral Defects

Background

Débridement and bone marrow stimulation is an effective treatment option for patients with talar osteochondral defects. However, whether surgical factors affect the success of microfracture treatment of talar osteochondral defects is not well characterized.

Questions/purposes

We hypothesized (1) holes that reach deeper into the bone marrow-filled trabecular bone allow for more hyaline-like repair; and (2) a larger number of holes with a smaller diameter result in more solid integration of the repair tissue, less need for new bone formation, and higher fill of the defect.

Methods

Talar osteochondral defects that were 6 mm in diameter were drilled bilaterally in 16 goats (32 samples). In eight goats, one defect was treated by drilling six 0.45-mm diameter holes in the defect 2 mm deep; in the remaining eight goats, six 0.45-mm diameter holes were punctured to a depth of 4 mm. All contralateral defects were treated with three 1.1-mm diameter holes 3 mm deep, mimicking the clinical situation, as internal controls. After 24 weeks, histologic analyses were performed using Masson-Goldner/Safranin-O sections scored using a modified O’Driscoll histologic score (scale, 0–22) and analyzed for osteoid deposition. Before histology, repair tissue quality and defect fill were assessed by calculating the mean attenuation repair/healthy cartilage ratio on Equilibrium Partitioning of an Ionic Contrast agent (EPIC) micro-CT (μCT) scans. Differences were analyzed by paired comparison and Mann-Whitney U tests.

Results

Significant differences were not present between the 2-mm and 4-mm deep hole groups for the median O’Driscoll score (p = 0.31) and the median of the μCT attenuation repair/healthy cartilage ratios (p = 0.61), nor between the 0.45-mm diameter and the 1.1-mm diameter holes in defect fill (p = 0.33), osteoid (p = 0.89), or structural integrity (p = 0.80).

Conclusions

The results indicate that the geometry of microfracture holes does not influence cartilage healing in the caprine talus.

Clinical Relevance

Bone marrow stimulation technique does not appear to be improved by changing the depth or diameter of the holes.     

Convergent access to bis-1,2,4-triazinyl-2,2′-bipyridines (BTBPs) and 2,2′-bipyridines via a Pd-catalyzed Ullman-type reaction

Multidentate, soft-Lewis basic, complexant scaffolds have displayed significant potential in the discrete speciation of the minor actinides from the neutron-absorbing lanthanides resident in spent nuclear fuel. Efforts to devise convergent synthetic strategies to targets of interest to improve liquid–liquid separation outcomes continue, but significant challenges to improve solubility in process-relevant diluents to effectively define meaningful structure–activity relationships remain. In the current work, a synthetic method to achieve the challenging 2,2′-bipyridine bond of the bis-1,2,4-triazinyl-2,2′-bipyridine (BTBP) complexant class leveraging a Pd-catalyzed Ullman-type coupling is reported. This convergent strategy improves upon earlier work focused on linear synthetic access to the BTBP complexant moiety. Method optimization, relevant substrate scope and application, as well as a preliminary mechanistic interrogation are reported herein.

Access to functionalized BTBP complexants through a reductive coupling strategy decreases linearity of common synthetic strategies towards these relevant materials for separations.     

Neuropathic Pain Post Spinal Cord Injury Part 2: Systematic Review of Dorsal Root Entry Zone Procedure

Background:

Pharmacotherapy may not sufficiently reduce neuropathic pain in many individuals post spinal cord injury (SCI). The use of alternative therapies such as surgery may be effective in reducing neuropathic pain in these individuals. However, because of the invasive nature of surgery, it is important to examine the evidence for use of this treatment.

Objective:

The purpose of this study was to conduct a systematic review of published literature on the surgical treatment of neuropathic pain after SCI.

Methods:

MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles in which surgical treatment of pain after SCI was examined. Articles were restricted to the English language. Article selection was conducted by 2 independent reviewers with the following inclusion criteria: the subjects participated in a surgical intervention for neuropathic pain; at least 50% of the subjects had an SCI; at least 3 subjects had an SCI; and a definable intervention involving the dorsal root entry zone (DREZ) procedure was used to reduce pain. Data extracted included study design, study type, subject demographics, inclusion and exclusion criteria, sample size, outcome measures, and study results. Randomized controlled trials (RCTs) were assessed for quality using the Physiotherapy Evidence Database (PEDro) assessment scale. Levels of evidence were assigned to each intervention using a modified Sackett scale.

Results:

Eleven studies met the inclusion criteria. One study provided level 2 evidence, and the rest provided level 4 evidence. The DREZ procedure was shown to be more effective for segmental pain than for diffuse pain after SCI. Further, individuals with conus medullaris level injury were found to have a higher level of neuropathic pain relief than those with cervical, thoracic, or cauda equina injury.

Conclusions:

The studies demonstrated that the DREZ procedure may be effective in reducing segmental pain. Hence, DREZ may be important in treatment of neuropathic pain in individuals resistant to less invasive treatments. Because the studies lacked control conditions and examination of long-term effects, there is a need for larger trials with more stringent conditions.Key words: pain, spinal cord injury, surgical treatmentPain is a major cause of distress and disability in persons with spinal cord injury (SCI). It has been shown to lead to social isolation, unemployment, decreased function, decreased quality of life, depression, and even suicide.^1,2 More than 77% of individuals with an SCI indicated that pain interfered with one or more of their daily activities including sleep (40%), exercise (34.9%), and work (33.6%).² The International Association for the Study of Pain (IASP) defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory nervous system.”³ After an SCI, individuals often report the onset of chronic neuropathic pain caudal to the level of the lesion or at the same level within the associated spinal cord segment.⁴ Dijkers et al⁵ reported no difference in the prevalence of pain based on level or completeness.The reported incidence of neuropathic pain after SCI varies greatly among studies, but between 10% and 30% of patients with SCI experience pain severe enough to interfere with their activities of daily living^6,7 and may require surgical intervention to relieve persistent and refractory pain.^4,8 Unmanageable neuropathic pain occurs more often in individuals with conus medullaris and cauda equina lesions where damage also involves the peripheral nerve roots.⁸When pharmacological and other noninvasive treatments fail to reduce pain, surgical spinal cord stimulation and dorsal root entry zone (DREZ) ablation treatments, such as DREZ lesioning and microsurgical DREZotomy (MDT), can be considered as options for the management of refractory pain.⁹ Neurosurgical procedures to reduce neuropathic pain should be reserved for cases in which medical therapies have failed to sufficiently reduce pain.⁴ The risks associated with ablative surgeries can be significant for individuals with incomplete neurological deficits; therefore, DREZ ablation is generally only considered a treatment option when neuropathic pain is present after a complete SCI.⁸ The MDT procedure targets for ablation the nociceptive fibers in the lateral bundle of the dorsal rootlet, the deafferented neurons of the dorsal horn, and the medial portion of the Lissauer tract.^4,6 This systematic review was conducted to assess the effectiveness of DREZ ablation therapies in reducing neuropathic pain in individuals following SCI.     

Dual Language Learning Predicts Improved Executive Functioning in Youth with Autism

Journal of Autism and Developmental Disorders - Previous findings show executive functioning advantages associated with dual language learning (DLL) among neurotypical individuals, yet few studies...     

A native antibody-based mobility-shift technique (NAMOS-assay) to determine the stoichiometry of multiprotein complexes

Characterization of multiprotein complexes (MPCs) is an important step toward an integrative view of protein interaction networks and prerequisite for a molecular understanding of how a certain MPC functions. Here, we present a technique utilizing monoclonal subunit-specific antibodies for an electrophoretic immunoshift assay in Blue Native-gels (NAMOS-assay), which allows the determination of the stoichiometry of MPCs. First, we use the B cell antigen receptor as a model MPC whose stoichiometry is known, confirming the HC(2)LC(2)Igalpha/beta(1) stoichiometry. Second, we demonstrate that the digitonin-extracted T cell antigen receptor (TCR) extracted from T cells has a stoichiometry of alphabetaepsilon(2)gammadeltazeta(2). We then show that the NAMOS-assay does not require purified MPCs, since it can determine the stoichiometry of an MPC in cell lysates. The NAMOS-assay is also compatible with use of epitope tags appended to the protein of interest, as e.g. the widely used HA-tag, and anti-epitope antibodies for the assay. Given its general applicability, this method has a wide potential for MPC research.