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Journal of the American Academy of... Mar 2024Scheuermann kyphosis can be treated surgically to restore proper sagittal alignment. Thoracic curves >70° are typically indicated for surgical intervention. However,...
Scheuermann kyphosis can be treated surgically to restore proper sagittal alignment. Thoracic curves >70° are typically indicated for surgical intervention. However, patients who have reached their natural limit of compensatory lumbar hyperlordosis are at risk of accelerated degeneration. This can be determined by comparing lumbar lordosis on standing neutral radiographs and supine extension radiographs. Minimal additional lordosis in extension compared with neutral, abutment of the spinous processes, or greater lumbar lordosis standing than with attempted extension suggest the patient is maximally compensated. We present a case of an adolescent boy with Scheuermann kyphosis who had reached the limit of his hyperlordosis compensation reserve. He subsequently underwent a T4 to L2 posterior spinal fusion with T7 to T11 Ponte Smith-Petersen grade two osteotomies. He tolerated the procedure well with no intraoperative complications or neuromonitoring changes. The patient has continued to do well and progressed to normal activity at 5-month follow-up.
Topics: Adolescent; Male; Animals; Humans; Scheuermann Disease; Lordosis; Intraoperative Complications; Osteotomy; Spinal Fusion
PubMed: 38441155
DOI: 10.5435/JAAOSGlobal-D-23-00187 -
Bioconjugate Chemistry Aug 2023The targeted delivery of bioactive proteins, such as cytokines, for cancer immunotherapy approaches mostly relies on antibodies or antibody fragments. However, fusion...
The targeted delivery of bioactive proteins, such as cytokines, for cancer immunotherapy approaches mostly relies on antibodies or antibody fragments. However, fusion proteins may display low tissue penetration due to a large molecular size. Small molecule ligands with high affinity toward tumor-associated antigens provide a promising alternative for the selective delivery of cytokines to tumor lesions. We developed a one-pot procedure for the site-specific thiazolidine formation between an aldehyde bearing small molecule and the generated N-terminal cysteine of a bioactive protein. Thereby, neoleukin-2/15 (Neo-2/15), a computationally engineered interleukin-2 and -15 mimic, was chemically conjugated to acetazolamide plus, a potent carbonic anhydrase IX (CAIX) ligand. The conjugate retained the biological activity of Neo-2/15 and revealed its ability to accumulate in renal cell carcinoma (SK-RC-52) xenografts upon systemic intravenous administration. The results highlight the potential of small molecule targeting moieties to drive the accumulation of a protein cargo to the respective disease site while conserving the small construct size.
Topics: Humans; Cytokines; Antigens, Neoplasm; Carcinoma, Renal Cell; Acetazolamide; Kidney Neoplasms; Cell Line, Tumor
PubMed: 37462264
DOI: 10.1021/acs.bioconjchem.3c00194 -
Assistive Technology : the Official... Sep 2023The aim of this study was to determine the effects of the Milwaukee brace and thoracolumbosacral orthosis (TLSO) on head to pelvis sagittal alignment in adolescents with...
The aim of this study was to determine the effects of the Milwaukee brace and thoracolumbosacral orthosis (TLSO) on head to pelvis sagittal alignment in adolescents with Scheuermann's kyphosis (SK). A total of 52 adolescents with SK who were under brace treatment were studied. They underwent biplanar radiography of the head to pelvis (EOS Imaging, Paris, France) before and 6 months after the beginning of bracing. We measured T slope, neck tilt (NT), cervical sagittal vertical axis (cSVA), thoracic inlet angle (TIA), C-C lordosis, C-C lordosis, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), sagittal vertical axis (SVA) and T spinopelvic inclination (TSPi). There were no significant differences in baseline values of TIA, PT, SS, PI, SVA, TK, cSVA, NT and T slope between the two groups ( > 0.05). There were significant differences between the baseline and final measurements of T slope, cSVA, TK, LL, TSPi and TIA in both groups ( < 0.05). The results imply that brace treatment can significantly affect head to pelvis sagittal parameters of adolescents with SK. However, there are no significant differences in the values of head to pelvis sagittal parameters when comparing short-term effect of TLSO and the Milwaukee brace.
Topics: Humans; Adolescent; Lordosis; Scheuermann Disease; Pelvis; Sacrum; Neck
PubMed: 35882059
DOI: 10.1080/10400435.2022.2102092 -
SICOT-J 2024Scheuermann's disease is a diagnosis of hyperkyphosis commonly encountered in pediatric patients. Studies in animal models suggest an association with vitamin D...
INTRODUCTION
Scheuermann's disease is a diagnosis of hyperkyphosis commonly encountered in pediatric patients. Studies in animal models suggest an association with vitamin D deficiency, however, extensive studies have not been performed in humans. This study analyzes the role of vitamin D deficiency on unfavorable results in patients with Scheuermann's disease.
METHODS
The TriNetX database was utilized to perform a retrospective analysis. Patients in the United States aged 0-18 years with Scheuermann's disease were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes and categorized into those with and without a diagnosis of vitamin D deficiency. Comparison of patient groups depending on age, sex, ethnic origin, prior diagnosis of fibromyalgia, anxiety disorder, myositis, and major depressive disorder. Statistical analysis was conducted to identify the association between vitamin D levels and unfavorable results including pain, depression, suicide attempt, emergency department (ED) consult, hospitalization, and procedures on the spine or spinal cord.
RESULTS
In total, 11,277 patients were identified, 39% of whom had a concurrent diagnosis of scoliosis. A total of 1,024 (9.08%) were deficient in vitamin D. Patients with vitamin D deficiency had greater odds of pain (P < 0.0001), depression (P < 0.0001), suicide attempt (P = 0.0021), ED visits (P = 0.0246), and hospital admission (P < 0.0015). Conversely, patients with vitamin D deficiency had decreased odds of surgery on the spine or spinal cord (P = 0.0009).
CONCLUSION
Vitamin D deficiency is associated with an elevated risk of pain, depression, suicide attempts, ED visits, and hospitalization. Our analysis highlights the need for more research to study the effect of vitamin D on Scheuermann's disease.
LEVEL OF EVIDENCE
Level III, Prognostic.
PubMed: 38568088
DOI: 10.1051/sicotj/2024010 -
Spine Deformity Sep 2023The purpose of this study is to determine the incidence of intraoperative neuromonitoring (IONM) changes and postoperative neurologic deficit in patients with...
INTRODUCTION
The purpose of this study is to determine the incidence of intraoperative neuromonitoring (IONM) changes and postoperative neurologic deficit in patients with Scheuermann's Kyphosis (SK) undergoing posterior spinal fusion (PSF).
METHODS
Single-center, retrospective chart review of the clinical, surgical and IONM data (somatosensory evoked potential (SSEP) and neurogenic motor evoked potential (NMEP) or transcranial motor evoked potential (TcMEP)) from patients with SK undergoing PSF at our center from 1993 to 2021.
RESULTS
One hundred and four SK patients (mean 16.4 ± 1.9 years) underwent PSF with correction of kyphosis from mean 79.4 ± 10.8° to 35.4 ± 13.9°. MEP data were obtained using either NMEP in 34.6% of patients) or TcMEP in 65.4% of patients. Only 3.8% of cases had lower extremity (LE) IONM changes during surgery, with no postoperative neurologic deficits in those patients. IONM changes occurred more frequently in the upper extremities (UE) with 14 (13.4%) patients having changes in UE SSEPs. Patients with UE IONM changes had significantly longer surgical times (p = 0.0096) and higher number of levels fused (p = 0.003) compared to patients without changes. Their weight, but not BMI, was also significantly higher (p = 0.036). These UE IONM changes resolved with arm repositioning in all but one patient who had a postoperative UE neurapraxia that resolved by 6 weeks. There was 1 postoperative transient femoral nerve palsy without IONM changes thought to be due to patient positioning.
CONCLUSION
The incidence of critical LE IONM changes during PSF for SK is 3.4%, which is similar to that reported in AIS. UE IONM changes are significantly more common at 13.4%, revealing that these patients are vulnerable to malpositioning of the arms during surgery.
Topics: Humans; Scheuermann Disease; Spinal Fusion; Retrospective Studies; Upper Extremity; Lower Extremity
PubMed: 37074516
DOI: 10.1007/s43390-023-00688-9 -
Viruses Apr 2024This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To...
This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 () mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19.
Topics: Animals; Killer Cells, Natural; COVID-19; Mice; SARS-CoV-2; Disease Models, Animal; Mice, Inbred C57BL; DNA-Binding Proteins; Mice, Knockout; Humans; Lung; Angiotensin-Converting Enzyme 2; B-Lymphocytes; Female; T-Lymphocytes
PubMed: 38675952
DOI: 10.3390/v16040611 -
Journal of Microbiological Methods Nov 2023Genetic resistance is the most effective and eco-friendly approach to combat rice blast. The application of resistance genes may be facilitated by the availability of...
Genetic resistance is the most effective and eco-friendly approach to combat rice blast. The application of resistance genes may be facilitated by the availability of molecular markers that allow marker-assisted selection during the breeding process. The Pi1 gene, considered to be a broad-spectrum resistance gene, might contribute to enhancing resistance to rice blast, but it lacks a suitable marker that can be used. In this study, we investigated nucleotide polymorphism in the Pik locus and combined the SNAP protocol with the touch-up gradient amplification method to develop a SNAP marker. The Pi1 SNAP marker could distinguish Pi1 from Pik alleles, and when used for screening a germplasm bank and an F2 population, it consistently identified germplasms carrying the Pi1 gene. The P1 SNAP marker offers as advantages to involve only the presence/absence analysis of PCR amplicons resolved on an agarose gel.
Topics: Alleles; Disease Resistance; Genetic Markers; Oryza; Plant Diseases; Polymorphism, Genetic
PubMed: 37858898
DOI: 10.1016/j.mimet.2023.106845 -
BioRxiv : the Preprint Server For... Apr 2024The use of single-cell transcriptomic technologies that quantitively describe cell transcriptional phenotypes using single cell/nucleus RNA sequencing (scRNA-seq) is...
The use of single-cell transcriptomic technologies that quantitively describe cell transcriptional phenotypes using single cell/nucleus RNA sequencing (scRNA-seq) is revolutionizing our understanding of cell biology, leading to new insights in cell type identification, disease mechanisms, and drug development. The tremendous growth in scRNA-seq data has posed new challenges in efficiently characterizing data-driven cell types and identifying quantifiable marker genes for cell type classification. The use of machine learning and explainable artificial intelligence has emerged as an effective approach to study large-scale scRNA-seq data. NS-Forest is a random forest machine learning-based algorithm that aims to provide a scalable data-driven solution to identify minimum combinations of necessary and sufficient marker genes that capture cell type identity with maximum classification accuracy. Here, we describe the latest version, NS-Forest version 4.0 and its companion Python package (https://github.com/JCVenterInstitute/NSForest), with several enhancements, to select marker gene combinations that exhibit selective expression patterns among closely related cell types and more efficiently perform marker gene selection for large-scale scRNA-seq data atlases with millions of cells. By modularizing the final decision tree step, NS-Forest v4.0 can be used to compare the performance of user-defined marker genes with the NS-Forest computationally-derived marker genes based on the decision tree classifiers. To quantify how well the identified markers exhibit the desired pattern of being exclusively expressed at high levels within their target cell types, we introduce the On-Target Fraction metric that ranges from 0 to1, with a metric of 1 given to markers that are only expressed within their target cell types and not in cells of any other cell types. We have applied NS-Forest v4.0 on scRNA-seq datasets from three human organs, including the brain, kidney, and lung. We observe that NS-Forest v4.0 outperforms previous versions on its ability to identify markers with higher On-Target Fraction values for closely related cell types and outperforms other marker gene selection approaches on the classification performance with significantly higher F-beta scores.
PubMed: 38712147
DOI: 10.1101/2024.04.22.590194 -
Journal of Neuroinflammation Jun 2024Pediatric acute transverse myelitis (ATM) accounts for 20-30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical...
BACKGROUND
Pediatric acute transverse myelitis (ATM) accounts for 20-30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical presentation of a relapsing ADS such as multiple sclerosis (MS). B cells have been strongly implicated in the pathogenesis of adult MS. However, little is known about B cells in pediatric MS, and even less so in pediatric ATM. Our lab previously showed that plasmablasts (PB), the earliest B cell subtype producing antibody, are expanded in adult ATM, and that these PBs produce self-reactive antibodies that target neurons. The goal of this study was to examine PB frequency and phenotype, immunoglobulin selection, and B cell receptor reactivity in pediatric patients presenting with ATM to gain insight to B cell involvement in disease.
METHODS
We compared the PB frequency and phenotype of 5 pediatric ATM patients and 10 pediatric healthy controls (HC) and compared them to previously reported adult ATM patients using cytometric data. We purified bulk IgG from the plasma samples and cloned 20 recombinant human antibodies (rhAbs) from individual PBs isolated from the blood. Plasma-derived IgG and rhAb autoreactivity was measured by mean fluorescence intensity (MFI) in neurons and astrocytes of murine brain or spinal cord and primary human astrocytes. We determined the potential impact of these rhAbs on astrocyte health by measuring stress and apoptotic response.
RESULTS
We found that pediatric ATM patients had a reduced frequency of peripheral blood PB. Serum IgG autoreactivity to neurons in EAE spinal cord was similar in the pediatric ATM patients and HC. However, serum IgG autoreactivity to astrocytes in EAE spinal cord was reduced in pediatric ATM patients compared to pediatric HC. Astrocyte-binding strength of rhAbs cloned from PBs was dependent on somatic hypermutation accumulation in the pediatric ATM cohort, but not HC. A similar observation in predilection for astrocyte binding over neuron binding of individual antibodies cloned from PBs was made in EAE brain tissue. Finally, exposure of human primary astrocytes to these astrocyte-binding antibodies increased astrocytic stress but did not lead to apoptosis.
CONCLUSIONS
Discordance in humoral immune responses to astrocytes may distinguish pediatric ATM from HC.
Topics: Humans; Myelitis, Transverse; Animals; Female; Astrocytes; Child; Mice; Male; Adolescent; Plasma Cells; Autoantibodies; Mice, Inbred C57BL; Cells, Cultured; Child, Preschool; Immunoglobulin G; Spinal Cord
PubMed: 38915059
DOI: 10.1186/s12974-024-03127-2 -
Turkish Neurosurgery 2024To evaluate the quality of life of patients with postural kyphosis (PK) compared with those adolescent idiopathic scoliosis (AIS) and Scheuermann Kyphosis (SK). (Comparative Study)
Comparative Study
AIM
To evaluate the quality of life of patients with postural kyphosis (PK) compared with those adolescent idiopathic scoliosis (AIS) and Scheuermann Kyphosis (SK).
MATERIAL AND METHODS
Health-related quality of life (HRQoL) of adolescents with PK who were admitted to our clinic between January 2020 and June 2022 was compared with that of patients with AIS and SK who were admitted during the same period by using the Scoliosis Research Society-22 (SRS-22) questionnaire. All patients were asked to complete the SRS-22 questionnaire before the radiological evaluation. In the radiological evaluation, the sagittal and coronal deformities of the patients were measured.
RESULTS
In total, 126 patients with PK were compared with age and sex-matched AIS patients and 42 SK patients. The mean SRS-22 function score of the PK group was 4.72 ± 0.3 while it was 4.38 ± 0.6 (p=0.015) in SK patients and it was 4.34 ± 0.6 (p < 0.001) in AIS patients. The mean SRS-22 pain scores of PK patients was 4.18 ± 0.7. The mean pain score was 3.68 ± 0.8 (p=0.033) in the SK group and 3.6 ± 0.8 (p=0.010) in the AIS group. Adolescents with PK perceived less pain than those with AIS or SK. The scores for the other domains of SRS-22 revealed no differences.
CONCLUSION
HRQoL of patients with PK is reduced, similar to that of patients with common structural spine deformities. Recognizing the effects of PK on the HRQoL in adolescents can help physicians to treat these patients.
Topics: Humans; Quality of Life; Adolescent; Female; Male; Kyphosis; Cross-Sectional Studies; Scoliosis; Surveys and Questionnaires; Scheuermann Disease; Child
PubMed: 38650564
DOI: 10.5137/1019-5149.JTN.43440-23.2