Purpose
The aim was to quantify the postural alignment of asymptomatic elderly, in comparison to a reference population, searching for possible invariants and compensatory mechanisms.
Methods
41 ...volunteers (49–76 years old) underwent bi-planar X-rays with 3D reconstructions of the spine and pelvis. Alignment parameters were compared with those of a reference group of asymptomatic subjects younger than 40 years old, with a particular focus on center of acoustic meati (CAM) and odontoid (OD) with regard to hip axis (HA). Possible markers of compensation were also investigated.
Results
No significant difference among groups appeared for CAM-HA and OD-HA parameters. Twenty four percent of elders had an abnormally high SVA value and twenty seven percent had an abnormal global spine inclination. Increased pelvic tilt and cervical lordosis allowed maintaining the head above the pelvis.
Conclusions
CAM-HA and OD-HA appeared quasi-invariant even in asymptomatic elderly. Some subjects exhibited alteration of spine alignment, compensated at the pelvis and cervical regions.
Increasing evidence suggests that synaptic functions of the amyloid precursor protein (APP), which is key to Alzheimer pathogenesis, may be carried out by its secreted ectodomain (APPs). The specific ...roles of APPsα and APPsβ fragments, generated by non‐amyloidogenic or amyloidogenic APP processing, respectively, remain however unclear. Here, we expressed APPsα or APPsβ in the adult brain of conditional double knockout mice (cDKO) lacking APP and the related APLP2. APPsα efficiently rescued deficits in spine density, synaptic plasticity (LTP and PPF), and spatial reference memory of cDKO mice. In contrast, APPsβ failed to show any detectable effects on synaptic plasticity and spine density. The C‐terminal 16 amino acids of APPsα (lacking in APPsβ) proved sufficient to facilitate LTP in a mechanism that depends on functional nicotinic α7‐nAChRs. Further, APPsα showed high‐affinity, allosteric potentiation of heterologously expressed α7‐nAChRs in oocytes. Collectively, we identified α7‐nAChRs as a crucial physiological receptor specific for APPsα and show distinct in vivo roles for APPsα versus APPsβ. This implies that reduced levels of APPsα that might occur during Alzheimer pathogenesis cannot be compensated by APPsβ.
Synopsis
Increasing evidence suggests that the synaptic functions of the amyloid precursor protein (APP), that is key to Alzheimer (AD) pathogenesis, may be carried out by its secreted ectodomain. Here, using AAV mediated intracranial expression, we studied the specific in vivo roles of APPs fragments generated by non‐amyloidogenic or amyloidogenic APP processing.
APPsα, but not APPsβ, efficiently rescued deficits in spine density, synaptic plasticity and spatial memory of mice lacking both APP and APLP2 (cDKO).
The C‐terminal 16 amino acids of APPsα (lacking in APPsβ) facilitate LTP to the same extent as APPsα.
This activity of APPsα involves the α7‐nAChR as a crucial physiological receptor specific for APPsα.
APPsα potentiates α7‐nAChRs expressed in oocytes and functions as an allosteric positive modulator
Reduced levels of APPsα that may occur during Alzheimer pathogenesis cannot be compensated by APPsβ.
Synaptotrophic defects in mouse brains lacking amyloid precursor protein (APP) expression can be selectively rescued by the non‐amyloidogenic APPsα fragment, for which α7‐nAChRs may constitute a physiological receptor.
Abstract
Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and ...evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = −0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis.
Synapses are pivotal sites of plasticity and memory formation. Consequently, synapses are energy consumption hotspots susceptible to dysfunction when their energy supplies are perturbed. Mitochondria ...are stabilized near synapses via the cytoskeleton and provide the local energy required for synaptic plasticity. However, the mechanisms that tether and stabilize mitochondria to support synaptic plasticity are unknown. We identified proteins exclusively tethering mitochondria to actin near postsynaptic spines. We find that VAP, the vesicle-associated membrane protein-associated protein implicated in amyotrophic lateral sclerosis, stabilizes mitochondria via actin near the spines. To test if the VAP-dependent stable mitochondrial compartments can locally support synaptic plasticity, we used two-photon glutamate uncaging for spine plasticity induction and investigated the induced and adjacent uninduced spines. We find VAP functions as a spatial stabilizer of mitochondrial compartments for up to ~60 min and as a spatial ruler determining the ~30 μm dendritic segment supported during synaptic plasticity.
MRI T2 mapping sequences quantitatively assess tissue health and depict early degenerative changes in musculoskeletal (MSK) tissues like cartilage and intervertebral discs (IVDs) but require long ...acquisition times. In MSK imaging, small features in cartilage and IVDs are crucial for diagnoses and must be preserved when reconstructing accelerated data. To these ends, we propose region of interest-specific postprocessing of accelerated acquisitions: a recurrent UNet deep learning architecture that provides T2 maps in knee cartilage, hip cartilage, and lumbar spine IVDs from accelerated T2-prepared snapshot gradient-echo acquisitions, optimizing for cartilage and IVD performance with a multi-component loss function that most heavily penalizes errors in those regions. Quantification errors in knee and hip cartilage were under 10% and 9% from acceleration factors R = 2 through 10, respectively, with bias for both under 3 ms for most of R = 2 through 12. In IVDs, mean quantification errors were under 12% from R = 2 through 6. A Gray Level Co-Occurrence Matrix-based scheme showed knee and hip pipelines outperformed state-of-the-art models, retaining smooth textures for most R and sharper ones through moderate R. Our methodology yields robust T2 maps while offering new approaches for optimizing and evaluating reconstruction algorithms to facilitate better preservation of small, clinically relevant features.
Cervical spine disorders in children are relatively uncommon; therefore, paradigms for surgical and nonsurgical clinical management are not well established. The purpose of this study was to bring ...together an international, multidisciplinary group of pediatric cervical spine experts to build consensus via a modified Delphi approach regarding the clinical management of children with cervical spine disorders and those undergoing cervical spine stabilization surgery.
A modified Delphi method was used to identify consensus statements for the management of children with cervical spine disorders requiring stabilization. A survey of current practices, supplemented by a literature review, was electronically distributed to 17 neurosurgeons and orthopedic surgeons experienced with the clinical management of pediatric cervical spine disorders. Subsequently, 52 summary statements were formulated and distributed to the group. Statements that reached near consensus or that were of particular interest were then discussed during an in-person meeting to attain further consensus. Consensus was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree).
Forty-five consensus-driven statements were identified, with all participants willing to incorporate them into their practice. For children with cervical spine disorders and/or stabilization, consensus statements were divided into the following categories: A) preoperative planning (12 statements); B) radiographic thresholds of instability (4); C) intraoperative/perioperative management (15); D) postoperative care (11); and E) nonoperative management (3). Several important statements reaching consensus included the following recommendations: 1) to obtain pre-positioning baseline signals with intraoperative neuromonitoring; 2) to use rigid instrumentation when technically feasible; 3) to provide postoperative external immobilization for 6-12 weeks with a rigid cervical collar rather than halo vest immobilization; and 4) to continue clinical postoperative follow-up at least until anatomical cervical spine maturity was reached. In addition, preoperative radiographic thresholds for instability that reached consensus included the following: 1) translational motion ≥ 5 mm at C1-2 (excluding patients with Down syndrome) or ≥ 4 mm in the subaxial spine; 2) dynamic angulation in the subaxial spine ≥ 10°; and 3) abnormal motion and T2 signal change on MRI seen at the same level.
In this study, the authors have demonstrated that a multidisciplinary, international group of pediatric cervical spine experts was able to reach consensus on 45 statements regarding the management of pediatric cervical spine disorders and stabilization. Further study is required to determine if implementation of these practices can lead to reduced complications and improved outcomes for children.
Chronic low back pain (cLBP) affects millions of Americans and costs billions. Studies suggest a link between cLBP and joint hypermobility.
We conducted cross-sectional primary analyses of joint ...hypermobility and cLBP, lumbar spine osteoarthritis (OA), and lumbar facet joint OA (FOA) in 3 large studies-the Generalized Osteoarthritis Study, Genetics of Generalized Osteoarthritis Study, and Johnston County Osteoarthritis Project (total n = 5072). Associations of joint hypermobility and Beighton trunk flexion with cLBP and lumbar OA were estimated using separate adjusted logistic regression models. Adjusted pooled odds ratios (pORs) and 95% confidence intervals (CIs) were then summarized-using random effect univariate, multivariate crude, and adjusted models-and heterogeneity was determined (I
statistic).
In univariate models, hypermobility was associated with symptomatic FOA (pOR = 0.64 95% CI 0.44, 0.93) but this result was not found in the multivariate models. In multivariate adjusted models, hypermobility was not significantly associated with cLBP and lumbar OA, but trunk flexion was inversely associated with cLBP (pOR = 0.40 95% 0.26, 0.62), spine OA (pOR = 0.66 95% CI 0.50, 0.87), symptomatic spine OA (pOR = 0.39 95% CI 0.28, 0.53), and symptomatic FOA (pOR = 0.53 95% CI 0.37, 0.77). Generally, between-study heterogeneity was moderate-high.
Hypermobility was not associated with cLBP or lumbar OA. The inverse association of trunk flexion with cLBP and lumbar OA may indicate a role for a flexible spine in avoiding or managing these conditions.
Abstract
Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated ...with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies. These models help our understanding of the disease process, but are limited as they do not come close to replicating the complexities that exist with an in Vivo model. Animal models have been developed to help us gain further understanding of the degenerative cascade of IVD degeneration In Vivo and test experimental treatment modalities to either prevent or reverse the process of DDD. Many modalities for treatment of DDD have been developed including therapeutic protein injections, stem cell injections, gene therapy, and tissue engineering. These interventions have had promising outcomes in animal models. Several of these modalities have been attempted in human trials, with early outcomes having promising results. Further, increasing our understanding of the degenerative process is essential to the development of new therapeutic interventions and the optimization of existing treatment protocols. Despite limited data, biological therapies are a promising treatment modality for DDD that could impact our future management of low back pain.
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