Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N), interleukin (IL)-18, and IL-1β in NPCs were upregulated, and the number of propidium iodide (PI)-positive cells was also increased, which was able to be alleviated by pretreatment with melatonin. The protective effect of melatonin on pyroptosis was blunted by both the melatonin receptor antagonist luzindole and the nuclear factor erythroid 2–related factor 2 (Nrf2) inhibitor ML385. In addition, the expression of the transcription factor Nrf2 was up- or downregulated when the melatonin receptor was activated or blocked by melatonin or luzindole, respectively. Conclusion. Melatonin protects NPCs against reactive oxygen species-induced pyroptosis by upregulating the transcription factor Nrf2 via melatonin receptors. Cite this article: Bone Joint Res 2023;12(3):202–211

Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

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This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

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To systematically evaluate whether bracing can effectively achieve curve regression in patients with adolescent idiopathic scoliosis (AIS), and to identify any predictors of curve regression after bracing.

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CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

This prospective study of 136 children with progressive infantile scoliosis treated under the age of four years, and followed up for nine years, shows that the scoliosis can be reversed by harnessing the vigorous growth of the infant to early treatment by serial corrective plaster jackets. In 94 children (group 1), who were referred and treated in the early stages of progression, at a mean age of one year seven months (6 to 48 months) and with a mean Cobb angle of 32° (11° to 65°), the scoliosis resolved by a mean age of three years and six months. They needed no further treatment and went on to lead a normal life. At the last follow-up, their mean age was 11 years and two months (1 year 10 months to 25 years 2 months), 23 (24.5%) were at Risser stages 4 and 5 and 13 girls were post-menarchal. In 42 children (group 2), who were referred late at a mean age of two years and six months (11 to 48 months) and with a mean Cobb angle of 52° (23° to 92°), treatment could only reduce but not reverse the deformity. At the last follow-up, at a mean age of ten years and four months (1 year 9 months to 22 years 1 month), eight children (19%) were at Risser stages 4 and 5 and five girls were post-menarchal. Fifteen children (35.7%) had undergone spinal fusion, as may all the rest eventually

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The aim of the study was to determine if there was a direct correlation between the pain and disability experienced by patients and size of their disc prolapse, measured by the disc’s cross-sectional area on T2 axial MRI scans.

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The aim of this study was to assess the ability of morphological spinal parameters to predict the outcome of bracing in patients with adolescent idiopathic scoliosis (AIS) and to establish a novel supine correction index (SCI) for guiding bracing treatment.

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The outcome following the development of neurological complications after corrective surgery for scoliosis varies from full recovery to a permanent deficit. This study aimed to assess the prognosis and recovery of major neurological deficits in these patients, and to determine the risk factors for non-recovery, at a minimum follow-up of two years.

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Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

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To describe the clinical, radiological, and functional outcomes in patients with isolated congenital thoracolumbar kyphosis who were treated with three-column osteotomy by posterior-only approach.

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Spinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy.

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Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs).

A total of 39 HIV-infected adults with spinal tuberculosis underwent anterior spinal decompression for neurological deficit. Fresh-frozen allografts were used in 38 patients. Antituberculous drugs were prescribed for 18 months, but antiretroviral therapy was not used. Six patients died within two years of surgery. Neurological recovery and allograft incorporation were observed at follow-up at a mean of 38 months, although the CD4/CD8 ratios were reversed in all patients. Adequate preoperative nutritional support and compliance with antituberculous treatment are essential in ensuring a satisfactory outcome

Lateral oblique radiographs are considered important for the identification of spondylolytic lesions, but these projections will give a clear view only when the radiological beam is in the plane of the defect. We studied the variation in orientation of spondylolytic lesions on CT scans of 34 patients with 69 defects. There was a wide variation of angle: only 32% of defects were orientated within 15° of the 45° lateral oblique plane. Lateral oblique radiographs should not be considered as the definitive investigation for spondylolysis. We suggest that CT scans with reverse gantry angle are now more appropriate than oblique radiography for the assessment of spondylolysis. Variation in the angle of the defect may also need consideration when direct repair is being planned

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To determine the effectiveness of prone traction radiographs in predicting postoperative slip distance, slip angle, changes in disc height, and lordosis after surgery for degenerative spondylolisthesis of the lumbar spine.

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The direct posterior approach with subperiosteal dissection of the paraspinal muscles from the vertebrae is considered to be the standard approach for the surgical treatment of adolescent idiopathic scoliosis (AIS). We investigated whether or not a minimally-invasive surgery (MIS) technique could offer improved results.

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It is uncertain whether instrumented spinal fixation in nonambulatory children with neuromuscular scoliosis should finish at L5 or be extended to the pelvis. Pelvic fixation has been shown to be associated with up to 30% complication rates, but is regarded by some as the standard for correction of deformity in these conditions. The incidence of failure when comparing the most caudal level of instrumentation, either L5 or the pelvis, using all-pedicle screw instrumentation has not previously been reported. In this retrospective study, we compared nonambulatory patients undergoing surgery at two centres: one that routinely instrumented to L5 and the other to the pelvis.

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The aim of this study was to explore the prognostic factors for postoperative neurological recovery and survival in patients with complete paralysis due to neoplastic epidural spinal cord compression.

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The aim of this study was to determine the influence of pelvic parameters on the tendency of patients with adolescent idiopathic scoliosis (AIS) to develop flatback deformity (thoracic hypokyphosis and lumbar hypolordosis) and its effect on quality-of-life outcomes.

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To address the natural history of severe post-tuberculous (TB) kyphosis, with focus upon the long-term neurological outcome, occurrence of restrictive lung disease, and the effect on life expectancy.

The widespread use of MRI has revolutionised the diagnostic process for spinal disorders. A typical protocol for spinal MRI includes T1 and T2 weighted sequences in both axial and sagittal planes. While such an imaging protocol is appropriate to detect pathological processes in the vast majority of patients, a number of additional sequences and advanced techniques are emerging. The purpose of the article is to discuss both established techniques that are gaining popularity in the field of spinal imaging and to introduce some of the more novel ‘advanced’ MRI sequences with examples to highlight their potential uses.

Cite this article: Bone Joint J 2015;97-B:1683–92.

Acute angulation at the thoracolumbar junction with segmental subluxation of the spine occurring at the level above an anteriorly hypoplastic vertebra in otherwise normal children is a rare condition described as infantile developmental thoracolumbar kyphosis. Three patient series with total of 18 children have been reported in the literature. We report five children who presented with thoracolumbar kyphosis and discuss the treatment algorithm. We reviewed the medical records and spinal imaging at initial clinical presentation and at minimum two-year follow-up. The mean age at presentation was eight months (two to 12). All five children had L2 anterior vertebral body hypoplasia. The kyphosis improved spontaneously in three children kept under monitoring. In contrast, the deformity was progressive in two patients who were treated with bracing. The kyphosis and segmental subluxation corrected at latest follow-up (mean age 52 months; 48 to 60) in all patients with near complete reconstitution of the anomalous vertebra. The deformity and radiological imaging on a young child can cause anxiety to both parents and treating physicians. Diagnostic workup and treatment algorithm in the management of infantile developmental thoracolumbar kyphosis is proposed. Observation is indicated for non-progressive kyphosis and bracing if there is evidence of kyphosis and segmental subluxation deterioration beyond walking age. Surgical stabilisation of the spine can be reserved for severe progressive deformities unresponsive to conservative treatment.

Cite this article: Bone Joint J 2015;97-B:982–7.

We assessed the frequency and causes of neurological deterioration in 59 patients with spinal cord injury on whom reports were prepared for clinical negligence litigation. In those who deteriorated neurologically we assessed the causes of the change in neurology and whether that neurological deterioration was potentially preventable. In all 27 patients (46%) changed neurologically, 20 patients (74% of those who deteriorated) had no primary neurological deficit. Of those who deteriorated, 13 (48%) became Frankel A. Neurological deterioration occurred in 23 of 38 patients (61%) with unstable fractures and/or dislocations; all 23 patients probably deteriorated either because of failures to immobilise the spine or because of inappropriate removal of spinal immobilisation. Of the 27 patients who altered neurologically, neurological deterioration was, probably, avoidable in 25 (excess movement in 23 patients with unstable injuries, failure to evacuate an epidural haematoma in one patient and over-distraction following manipulation of the cervical spine in one patient). If existing guidelines and standards for the management of actual or potential spinal cord injury had been followed, neurological deterioration would have been prevented in 25 of the 27 patients (93%) who experienced a deterioration in their neurological status.

Cite this article: Bone Joint J 2015;97-B:527–31.

Back pain is a common symptom in children and adolescents. Here we review the important causes, of which defects and stress reactions of the pars interarticularis are the most common identifiable problems. More serious pathology, including malignancy and infection, needs to be excluded when there is associated systemic illness. Clinical evaluation and management may be difficult and always requires a thorough history and physical examination. Diagnostic imaging is obtained when symptoms are persistent or severe. Imaging is used to reassure the patient, relatives and carers, and to guide management.

Cite this article: Bone Joint J 2014;96-B:717–23.

We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration.

There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration.

Cite this article: Bone Joint J 2013;95-B:1239–43.

The revised Tokuhashi, Tomita and modified Bauer scores are commonly used to make difficult decisions in the management of patients presenting with spinal metastases. A prospective cohort study of 199 consecutive patients presenting with spinal metastases, treated with either surgery and/or radiotherapy, was used to compare the three systems. Cox regression, Nagelkerke’s R² and Harrell’s concordance were used to compare the systems and find their best predictive items. The three systems were equally good in terms of overall prognostic performance. Their most predictive items were used to develop the Oswestry Spinal Risk Index (OSRI), which has a similar concordance, but a larger coefficient of determination than any of these three scores. A bootstrap procedure was used to internally validate this score and determine its prediction optimism.

The OSRI is a simple summation of two elements: primary tumour pathology (PTP) and general condition (GC): OSRI = PTP + (2 – GC).

This simple score can predict life expectancy accurately in patients presenting with spinal metastases. It will be helpful in making difficult clinical decisions without the delay of extensive investigations.

Cite this article: Bone Joint J 2013;95-B:210–16.

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.

Objectives

In order to elucidate the influence of sympathetic nerves on lumbar radiculopathy, we investigated whether sympathectomy attenuated pain behaviour and altered the electrical properties of the dorsal root ganglion (DRG) neurons in a rat model of lumbar root constriction.

A number of causes have been advanced to explain the destructive discovertebral (Andersson) lesions that occur in ankylosing spondylitis, and various treatments have been proposed, depending on the presumed cause. The purpose of this study was to identify the causes of these lesions by defining their clinical and radiological characteristics.

We retrospectively reviewed 622 patients with ankylosing spondylitis. In all, 33 patients (5.3%) had these lesions, affecting 100 spinal segments. Inflammatory lesions were found in 91 segments of 24 patients (3.9%) and traumatic lesions in nine segments of nine patients (1.4%). The inflammatory lesions were associated with recent-onset disease; a low modified Stoke ankylosing spondylitis spine score (mSASSS) due to incomplete bony ankylosis between vertebral bodies; multiple lesions; inflammatory changes on MRI; reversal of the inflammatory changes and central bony ankylosis at follow-up; and a good response to anti-inflammatory drugs. Traumatic lesions were associated with prolonged disease duration; a high mSASSS due to complete bony ankylosis between vertebral bodies; a previous history of trauma; single lesions; nonunion of fractures of the posterior column; acute kyphoscoliotic deformity with the lesion at the apex; instability, and the need for operative treatment due to that instability.

It is essential to distinguish between inflammatory and traumatic Andersson lesions, as the former respond to medical treatment whereas the latter require surgery.

The presacral retroperitoneal approach for axial lumbar interbody fusion (presacral ALIF) is not widely reported, particularly with regard to the mid-term outcome. This prospective study describes the clinical outcomes, complications and rates of fusion at a follow-up of two years for 26 patients who underwent this minimally invasive technique along with further stabilisation using pedicle screws. The fusion was single-level at the L5-S1 spinal segment in 17 patients and two-level at L4–5 and L5-S1 in the other nine. The visual analogue scale for pain and Oswestry Disability Index scores were recorded pre-operatively and during the 24-month study period. The evaluation of fusion was by thin-cut CT scans at six and 12 months, and flexion-extension plain radiographs at six, 12 and 24 months. Significant reductions in pain and disability occurred as early as three weeks postoperatively and were maintained. Fusion was achieved in 22 of 24 patients (92%) at 12 months and in 23 patients (96%) at 24 months. One patient (4%) with a pseudarthrosis underwent successful revision by augmentation of the posterolateral fusion mass through a standard open midline approach.

There were no severe adverse events associated with presacral ALIF, which in this series demonstrated clinical outcomes and fusion rates comparable with those of reports of other methods of interbody fusion.

We investigated the safety and efficacy of treating osteoporotic vertebral compression fractures with an intravertebral cleft by balloon kyphoplasty. Our study included 27 patients who were treated in this way. The mean follow-up was 38.2 months (24 to 54). The anterior and middle heights of the vertebral body and the kyphotic angle were measured on standing lateral radiographs before surgery, one day after surgery, and at final follow-up. Leakage of cement was determined by CT scans. A visual analogue scale and the Oswestry disability index were chosen to evaluate pain and functional activity. Statistically significant improvements were found between the pre- and post-operative assessments (p < 0.05) but not between the post-operative and final follow-up assessments (p > 0.05). Asymptomatic leakage of cement into the paravertebral vein occurred in one patient, as did leakage into the intervertebral disc in another patient.

We suggest that balloon kyphoplasty is a safe and effective minimally invasive procedure for the treatment of osteoporotic vertebral compression fractures with an intravertebral cleft.

Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes.

These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS.

Segmental vessel ligation during anterior spinal surgery has been associated with paraplegia. However, the incidence and risk factors for this devastating complication are debated.

We reviewed 346 consecutive paediatric and adolescent patients ranging in age from three to 18 years who underwent surgery for anterior spinal deformity through a thoracic or thoracoabdominal approach, during which 2651 segmental vessels were ligated. There were 173 patients with idiopathic scoliosis, 80 with congenital scoliosis or kyphosis, 43 with neuromuscular and 31 with syndromic scoliosis, 12 with a scoliosis associated with intraspinal abnormalities, and seven with a kyphosis.

There was only one neurological complication, which occurred in a patient with a 127° congenital thoracic scoliosis due to a unilateral unsegmented bar with contralateral hemivertebrae at the same level associated with a thoracic diastematomyelia and tethered cord. This patient was operated upon early in the series, when intra-operative spinal cord monitoring was not available.

Intra-operative spinal cord monitoring with the use of somatosensory evoked potentials alone or with motor evoked potentials was performed in 331 patients. This showed no evidence of signal change after ligation of the segmental vessels.

In our experience, unilateral segmental vessel ligation carries no risk of neurological damage to the spinal cord unless performed in patients with complex congenital spinal deformities occurring primarily in the thoracic spine and associated with intraspinal anomalies at the same level, where the vascular supply to the cord may be abnormal.

Low back injuries account for the greatest loss of playing time for professional fast bowlers in cricket. Previous radiological studies have shown a high prevalence of degeneration of the lumbar discs and stress injuries of the pars interarticularis in elite junior fast bowlers. We have examined MRI appearance of the lumbar spines of 36 asymptomatic professional fast bowlers and 17 active control subjects. The fast bowlers had a relatively high prevalence of multi-level degeneration of the lumbar discs and a unique pattern of stress lesions of the pars interarticularis on the non-dominant side. The systems which have been used to classify the MR appearance of the lumbar discs and pars were found to be reliable. However, the relationship between the radiological findings, pain and dysfunction remains unclear.