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Abstract The flexion relaxation phenomenon (FRP) is characterized by the reduction of paraspinal muscle activity at maximum trunk flexion. FRP is reported to be altered (persistence of spinal muscle activity) in more than half of nonspecific chronic low back pain (NSCLBP) patients. Little is known about how the multi-segmental spine affects FRP. The aim of this observational study was to investigate the relationship between FRP and kinematic parameters of the multi-segmental spine in NSCLBP patients. Forty NSCLBP patients and thirty-five asymptomatic participants performed a standing maximal trunk flexion task. Surface electromyography was recorded along the erector spinae longissimus. The kinematics of the spine were assessed using a 3D motion analysis system. The investigated spinal segments were upper thoracic, lower thoracic, thoracolumbar, upper lumbar, lower lumbar, and lumbopelvic. Upper lumbar ROM, anterior sagittal inclination of the upper lumbar relative to the lower lumbar in the upright position, and ROM of the upper lumbar relative to the lower lumbar during full trunk flexion were significantly correlated with the flexion relaxation ratio (Rho 0.42 to 0.58, p

Molecular carriers represent an increasingly common strategy in the field of nanopore sensing to use secondary molecules to selectively report on the presence of target analytes in solution, allowing for sensitive assays of otherwise hard-to-detect molecules such as small, weakly-charged proteins. However, existing carrier designs can often introduce drawbacks to nanopore experiments including higher levels of cost/complexity and carrier-pore interactions that lead to ambiguous signals and elevated clogging rates. In this work, we present a simple method of carrier production based on sticky-ended DNA molecules that emphasizes ease-of-synthesis and compatibility with nanopore sensing and analysis. In particular, our method incorporates the ability to flexibly control the length of the DNA carriers produced, enhancing the multiplexing potential of this carrier system through the separable nanopore signals they could generate for distinct targets. A proof-of-concept nanopore experiment is also presented, involving carriers produced by our method with multiple lengths and attached to DNA nanostructure targets, in order to validate the capabilities of the system. As the breadth of applications for nanopore sensors continues to expand, the availability of tools such as those presented here to help translate the outcomes of these applications into robust nanopore signals will be of major importance.

The posterior minimally invasive spine surgery (MISS) approach—or the paraspinal muscle approach—for posterior spinal fusion and segmental instrumentation in adolescent idiopathic scoliosis (AIS) was first reported in 2011. It is less invasive than the traditionally used open posterior midline approach, which is associated with significant morbidity, including denervation of the paraspinal muscles, significant blood loss, and a large midline skin incision. The literature suggests that the MISS approach, though technically challenging and with a longer operative time, provides similar levels of deformity correction, lower intraoperative blood loss, shorter hospital stays, better pain outcomes, and a faster return to sports than the open posterior midline approach. Correction maintenance and fusion rates also seem to be equivalent for both approaches. This narrative review presents the results of relevant publications reporting on spinal segmental instrumentation using pedicle screws and posterior spinal fusion as part of an MISS approach. It then compares them with the results of the traditional open posterior midline approach for treating AIS. It specifically examines perioperative morbidity and radiological and clinical outcomes with a minimal follow-up length of 2 years (range 2–9 years).

The concentration of a biomarker in solution can be determined by counting single molecules. Here the authors report a digital immunoassay scheme with solid-state nanopore readout to quantify a target protein and use this to measure thyroid-stimulating hormone from human serum.

(1) Background: Adolescent Idiopathic Scoliosis (AIS) is a three-dimensional (3D) spine deformity. The Cobb angle, evaluated with 2D radiography, is the gold standard to determine curve severity. The primary aim of this study was to evaluate the 3D spinal evaluation with rasterstereography in patients with AIS. The hypothesis was that rasterstereography reached higher accuracy than the gold standard 2D radiography. The second aim was to compare rasterstereography with 3D radiography. The hypothesis was that the rasterstereographic evaluation of patients with severe major scoliosis curves is closer to 3D radiography compared to the gold standard (2D radiography). (2) Methods: This is a prospective comparative study of a consecutive series of 53 patients, with the scoliosis curve evaluated with two 3D methods and the gold standard (2D radiography). (3) Results: The hypothesis that rasterstereography reached higher accuracy than the gold standard 2D radiography was validated for all curves. Even if all curves were highly correlated, both rasterstereography and 2D radiography scoliosis evaluation were underestimated for moderate/severe curves compared to 3D radiography. (4) Conclusions: The rasterstereographic evaluation of major curve scoliosis is not accurate enough to replace 2D radiography for moderate/severe curves. A longitudinal follow-up should be assessed in future studies to define the sensitivity of the detection of a significant change in the scoliotic mild and moderate curve (

The flexion relaxation phenomenon (FRP) is characterized by the reduction of paraspinal muscle activity at maximum trunk flexion. FRP is reported to be altered (persistence of spinal muscle activity) in more than half of nonspecific chronic low back pain (NSCLBP) patients. Little is known about how the multi-segmental spine affects FRP. The aim of this observational study was to investigate the relationship between FRP and kinematic parameters of the multi-segmental spine in NSCLBP patients. Forty NSCLBP patients and thirty-five asymptomatic participants performed a standing maximal trunk flexion task. Surface electromyography was recorded along the erector spinae longissimus. The kinematics of the spine were assessed using a 3D motion analysis system. The investigated spinal segments were upper thoracic, lower thoracic, thoracolumbar, upper lumbar, lower lumbar, and lumbopelvic. Upper lumbar ROM, anterior sagittal inclination of the upper lumbar relative to the lower lumbar in the upright position, and ROM of the upper lumbar relative to the lower lumbar during full trunk flexion were significantly correlated with the flexion relaxation ratio (Rho 0.42 to 0.58, p < 0.006). The relative position and movement of the upper lumbar segment seem to play an important role in the presence or absence of FRP in NSCLBP patients. [ABSTRACT FROM AUTHOR]

Abstract Serum neurofilament light chain (NfL) is emerging as an important biomarker in multiple sclerosis (MS). Our objective was to evaluate the prognostic value of serum NfL levels obtained close to the time of MS onset with long-term clinical outcomes. In this prospective cohort study, we identified patients with serum collected within 5 years of first MS symptom onset (baseline) with more than 15 years of routine clinical follow-up. Levels of serum NfL were quantified in patients and matched controls using digital immunoassay (SiMoA HD-1 Analyzer, Quanterix). Sixty-seven patients had a median follow-up of 18.9 years (range 15.0–27.0). The median serum NfL level in patient baseline samples was 10.1 pg/mL, 38.5% higher than median levels in 37 controls (7.26 pg/mL, p = 0.004). Baseline NfL level was most helpful as a sensitive predictive marker to rule out progression; patients with levels less 7.62 pg/mL were 4.3 times less likely to develop an EDSS score of ≥ 4 (p = 0.001) and 7.1 times less likely to develop progressive MS (p = 0.054). Patients with the highest NfL levels (3rd-tertile, > 13.2 pg/mL) progressed most rapidly with an EDSS annual rate of 0.16 (p = 0.004), remaining significant after adjustment for sex, age, and disease-modifying treatment (p = 0.022). This study demonstrates that baseline sNfL is associated with long term clinical disease progression. sNfL may be a sensitive marker of subsequent poor clinical outcomes.

Abstract Objective Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as ‘pseudoatrophy’, related to reduced inflammation. Treatment‐related neurotoxicity may be contributory. We sought objective evidence of post‐IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. Methods Sera were collected from 22 MS patients pre‐ and post‐IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single‐molecule assay. Results Pre‐IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12‐month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). Interpretation There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.

Intrinsic gait variability (GV), i.e., fluctuations in the regularity of gait patterns between repetitive cycles, is inherent to the sensorimotor system and influenced by factors such as age and pathology. Increased GV is associated with gait impairments in individuals with cerebral palsy (CP) and has been mainly studied based on spatiotemporal parameters. The present study aimed to describe kinematic GV in young people with CP and its associations with clinical impairments [i.e., passive range of motion (pROM), muscle weakness, reduced selective motor control (selectivity), and spasticity]. This retrospective study included 177 participants with CP (age range 5–25 years; Gross Motor Function Classification System I-III) representing 289 clinical gait analyses [n = 172 for unilateral CP (uCP) vs. 117 for bilateral CP (bCP)]. As variability metrics, Root Mean Square Deviation (RMSD) for nine lower-limb kinematic parameters and Gait Standard Deviation (GaitSD) – as composite score of the kinematic parameters – were computed for the affected (unilateral = uCP) and most affected side (bilateral = bCP), respectively, as defined by clinical scores. GaitSD was then computed for the non/less-affected side for between leg comparisons. Uni- and multivariate linear regressions were subsequently performed on GaitSD of the affected/most affected side with all clinical impairments (composite scores) as independent variables. Highest RMSD were found in the transverse plane (hip, pelvis), for distal joints in the sagittal plane (knee, ankle) and for foot progression. GaitSD was not different between uCP and bCP (affected/most affected side) but higher in the non-affected vs. affected side in uCP. GaitSD was associated with age (p < 0.001), gait deviation index (GDI) (p < 0.05), muscle weakness (p < 0.001), selectivity (p < 0.05), and pROM (p < 0.001). After adjustment for age and GDI, GaitSD remained associated with muscle weakness (uCP: p = 0.003, bCP: p < 0.001) and selectivity (bCP: p = 0.024). Kinematic GV can be expressed as global indicator of variability (GaitSD) in young people with CP given the strong correlation of RMSD for lower-limb kinematic parameters. In terms of asymmetry, increased variability of the non-affected vs. affected side may indicate contralateral compensation mechanisms in uCP. Notably muscle weakness (uCP, bCP) and selectivity (bCP) – but not spasticity – were associated with GaitSD. Further studies need to explore the clinical relevance of kinematic GV in CP to support the interpretation of clinical gait analyses and therapeutic decision-making.