Anatomy of Soft Tissues of the Spinal Canal

Background and Objectives. Important issues regarding the spread of solutions in the epidural space and the anatomy of the site of action of spinal and epidural injections are unresolved. However, the detailed anatomy of the spinal canal has been incompletely determined. We therefore examined the microscopic anatomy of the spinal canal soft tissues, including relationships to the canal walls. Methods. Whole mounts were prepared of decalcified vertebral columns with undisturbed contents from three adult humans. Similar material was prepared from a macaque and baboon immediately on death to control for artifact of tissue change after death. Other tissues examined included nerve root and proximal spinal nerve complex and dorsal epidural fat obtained during surgery. Slides were examined by light microscopy at magnifications of 10-40×. Results. There is no fibrous tissue in the epidural space. The epidural fat is composed of uniform cells enclosed in a fine membrane. The dorsal fat is only attached to the canal wall in the dorsal midline and is often tenuously attached to the dura. The dura is joined to the canal wall only ventrally at the discs. Veins are evident predominantly in the ventral epidural space. Nerve roots are composed of multiple fascicles which disperse as they approach the dorsal root ganglion. An envelope of arachnoid encloses the roots near the site of exit from the dura. Conclusions. These features of the fat explain its semifluid consistency. Lack of substantial attachments to the dura facilitate movement of the dura relative to the canal wall and allow distribution of injected solution. Fibrous barriers are an unlikely explanation for asymmetric epidural anesthesia, but the midline fat could impede solution spread. Details of nerve-root structure and their envelope of pia-arachnoid membrane may be relevant to anesthetic action

Divorce and Health: Does Educational Attainment Matter?

This study examines the relationship between divorce and women’s health, looking at whether the negative effects of divorce on health remain controlling for one’s educational attainment. Using data from the 2011 cycle of the Canadian GSS, a logistic regression was conducted to examine the relationship between divorce and health controlling for educational attainment. First, it was hypothesized that divorced women are more likely to report poor health than women who are married, single, or widowed. As expected, being divorced increased the odds of poor health. The second hypothesis was that controlling for educational attainment would reduce the negative consequences of divorce on health. The findings do not support this hypothesis as the negative health effects of divorce remain controlling for education. This suggests that the relationship between divorce and health is quite complex and requires an in-depth analysis of other variables that could be involved

Astrophysical Effects of Scalar Dark Matter Miniclusters

We model the formation, evolution and astrophysical effects of dark compact Scalar Miniclusters (``ScaMs''). These objects arise when a scalar field, with an axion-like or Higgs-like potential, undergoes a second order phase transition below the QCD scale. Such a scalar field may couple too weakly to the standard model to be detectable directly through particle interactions, but may still be detectable by gravitational effects, such as lensing and baryon accretion by large, gravitationally bound miniclusters. The masses of these objects are shown to be constrained by the Ly$\alpha$ power spectrum to be less than $\sim 10^4 M_\odot$, but they may be as light as classical axion miniclusters, of the order of $10^{-12} M_\odot$. We simulate the formation and nonlinear gravitational collapse of these objects around matter-radiation equality using an N-body code, estimate their gravitational lensing properties, and assess the feasibility of studying them using current and future lensing experiments. Future MACHO-type variability surveys of many background sources can reveal either high-amplification, strong lensing events, or measure density profiles directly via weak-lensing variability, depending on ScaM parameters and survey depth. However, ScaMs, due to their low internal densities, are unlikely to be responsible for apparent MACHO events already detected in the Galactic halo. A simple estimate is made of parameters that would give rise to early structure formation; in principle, early stellar collapse could be triggered by ScaMs as early as recombination, and significantly affect cosmic reionization.Comment: 13 pages, 12 figures. Replaced to reflect published versio

The Statistics of Subtypes: A Proposed Study Investigating Statistical Learning Across Subtypes of Dyslexia

Current research regarding dyslexia and its subtypes is inconsistent. There are discrepancies in the literature surrounding the causes and manifestations of dyslexia. Furthermore, there is very little research concerning the role of statistical learning in differentiating between subtypes of dyslexia. The purpose of the proposed study is to quantify the differences in statistical learning ability across three subtypes of dyslexia (i.e., phonological dyslexia, surface dyslexia, and deep dyslexia). It is predicted that participants with a dyslexia diagnosis of any subtype will be worse at using statistics to find word boundaries than control participants. Additionally, it is hypothesized that participants with surface dyslexia will express the highest capacity for statistical learning among the three subtypes. Finally, it is hypothesized that participants belonging to the deep dyslexia subgroup will express the lowest capacity for statistical learning. Participants from each of the four treatments (i.e., phonological dyslexia, surface dyslexia, deep dyslexia, and control) will be exposed to the same auditory nonsense word stream. After finishing the listening phase, all participants will complete a forced-choice recognition task. The task will be to indicate which of the two sound strings sounds most like a word from the nonsense language. If the results of this study show that there are differences in statistical learning ability between different subtypes of dyslexia, treatments and interventions can be tailored more appropriately to individuals belonging to each subtype. Additionally, it will be possible to highlight early risk factors that can help with early identification of dyslexia in children

The Stain of a Criminal Label: Post-Release Stigmatization and its Effects on Reintegration and Recidivism Among Ex-Offenders

The successful reintegration of ex-offenders into the community is a primary factor in reducing recidivism and protecting the public. However, successful reintegration is often hard to come by. Prior research has examined the ways in which the stigmatic labelling of ex-offenders disrupts their successful re-entry into the community. Further, studies have shown that the stigmatic labelling of ex-offenders by the community plays a prominent role in offender recidivism. The present study examines this prior research and explores how gender, age, race/ethnicity, and class determine the extent of stigmatization that offenders experience. I conclude that some marginalized groups, such as women, Blacks, young offenders, and those from working class backgrounds tend to be more negatively impacted by stigmatic labelling. Therefore, these marginalized groups are more at risk of becoming reincarcerated or facing further legal sanctions. It is suggested that to combat recidivism, social programs should be prioritized to assist ex-offenders in coping with stigmatization. Furthermore, to combat the unequal distribution of stigmatic labelling on marginalized groups, specialized community programs should be made available to address the unique needs of these populations. In addition, community-based sanctions should be implemented whenever appropriate to help combat the effects of stigmatic labelling imposed on ex-offenders upon re-entry. Future research directions are also discussed

Association of Neural Inflammation with Hyperalgesia Following Spinal Nerve Ligation

Aim:To explain the variability in the behavioral response after spinal nerve ligation by investigating the relation between the development of neuropathic pain and the expression of inflammatory indicators, in dorsal root ganglia (DRG) and the spinal nerve. Methods: Ninety-six male Sprague-Dawley rats were randomly assigned to the modified spinal nerve ligation, sham, and control group. Testing for pain-related behavior identified rats that successfully developed neuropathic pain (responders) and those which did not (non-responders). The extent of neuroinflammation in the two groups was assessed by immunohistochemical staining of dorsal root ganglions glial fibrillary acid protein (GFAP), and rat C3 complement receptor (OX-42). Results: GFAP and OX-42 immunopositive cell density in the DRG and spinal nerve was significantly higher in hyperalgesic animals. DRG cell density was 3.96±0.68 cells/2500 μm2 in GFAP responders’ group, compared with 2.76±0.75 cells/2500 μm2 in non-responders’ group (Mann-Whitney U test, Z=-3.956, P<0.001). OX-42 density was 7.71±1.03 cells/2500 μm2in responders and 4.75±1.76 cells/2500 μm2 in non responders (Mann-Whitney U test, Z=-2.572, P=0.01). Hyperalgesic behavior progressively increased during the testing period, although immunopositive cell density peaked on the fourth day post-injury and progressively decreased afterwards. Conclusion:Our study suggests that inflammation has a decisive role in initiating neuropathic pain. Also, this study confirms that, for the sake of selecting appropriate subjects for mechanistic study, it is necessary to discriminate between experimental subjects that develop pain completely and those that do not

Consensus Statement of the International Summit on Intellectual Disability and Dementia on Valuing the Perspectives of Persons with Intellectual Disability

The International Summit on Intellectual Disability and Dementia held in Scotland in 2016 covered a range of issues related to dementia and intellectual disability, including the dearth of personal reflections of persons with intellectual disability affected by dementia. This paper reflects on this deficiency and explores some of the personal perspectives gleaned from the literature, from Summit attendees, and from the experiences of persons with intellectual disability recorded or scribed in advance of the two-day Summit meeting. Omission of the perspectives of persons with intellectual disability in both policy and practice limits understanding of the experience of dementia. It leads to an overreliance on proxy reporting; something considered by the Summit to be a backwards step in person-centred work. The Summit recognised that the perspectives of persons with intellectual disability must be considered whenever interventions and supports are discussed with planning required at an earlier stage for advance directives that guide medical treatment, and for advice or counselling around relationships, the continuity of social networks, and when securing dementia-friendly housing. Systemic recommendations included reinforcing the value of the involvement of persons with intellectual disability in (a) research alongside removing barriers to inclusion posed by institutional/ethics review boards, (b) planning groups that establish services and supports for dementia, and (c) peer support efforts that help adults with intellectual disability who are affected by dementia (either directly or indirectly). Practice recommendations included (a) valuing personal perspectives in decision-making, (b) enabling peer-to-peer support models, (c) supporting choice in community dwelling arrangements, and (d) wider availability of materials for persons with intellectual disability that would promote understanding of dementia

Differential expression of CaMKII isoforms and overall kinase activity in rat dorsal root ganglia after injury.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) decodes neuronal activity by translating cytoplasmic Ca(2+) signals into kinase activity that regulates neuronal functions including excitability, gene expression, and synaptic transmission. Four genes lead to developmental and differential expression of CaMKII isoforms (α, β, γ, δ). We determined mRNA levels of these isoforms in the dorsal root ganglia (DRG) of adult rats with and without nerve injury in order to determine if differential expression of CaMKII isoforms may contribute to functional differences that follow injury. DRG neurons express mRNA for all four isoforms, and the relative abundance of CaMKII isoforms was γ>α>β=δ, based on the CT values. Following ligation of the 5th lumbar (L5) spinal nerve (SNL), the β isoform did not change, but mRNA levels of both the γ and α isoforms were reduced in the directly injured L5 neurons, and the α isoform was reduced in L4 neurons, compared to their contemporary controls. In contrast, expression of the δ isoform mRNA increased in L5 neurons. CaMKII protein decreased following nerve injury in both L4 and L5 populations. Total CaMKII activity measured under saturating Ca(2+)/CaM conditions was decreased in both L4 and L5 populations, while autonomous CaMKII activity determined in the absence of Ca(2+) was selectively reduced in axotomized L5 neurons 21days after injury. Thus, loss of CaMKII signaling in sensory neurons after peripheral nerve injury may contribute to neuronal dysfunction and pain

Lentiviral gene transfer into the dorsal root ganglion of adult rats

<p>Abstract</p> <p>Background</p> <p>Lentivector-mediated gene delivery into the dorsal root ganglion (DRG) is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. In this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the requirements for efficient transduction into neuronal cells <it>in vitro </it>and adult rat DRG <it>in vivo</it>.</p> <p>Results</p> <p><it>In vitro</it>, lentivectors expressing enhanced green fluorescent protein (EGFP) under control of the human elongation factor 1α (EF1α) promoter and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV-G) envelope exhibited the best performance in the transfer of EGFP into an immortalized DRG sensory neuron cell line at low multiplicities of infection (MOIs), and into primary cultured DRG neurons at higher MOIs. <it>In vivo</it>, injection of either first or second-generation EF1α-EGFP lentivectors directly into adult rat DRGs led to transduction rates of 19 ± 9% and 20 ± 8% EGFP-positive DRG neurons, respectively, detected at 4 weeks post injection. Transduced cells included a full range of neuronal phenotypes, including myelinated neurons as well as both non-peptidergic and peptidergic nociceptive unmyelinated neurons.</p> <p>Conclusion</p> <p>VSV-G pseudotyped lentivectors containing the human elongation factor 1α (EF1α)-EGFP expression cassette demonstrated relatively efficient transduction to sensory neurons following direct injection into the DRG. These results clearly show the potential of lentivectors as a viable system for delivering target genes into DRGs to explore basic mechanisms of neuropathic pain, with the potential for future clinical use in treating chronic pain.</p