Correlation of Early Outcomes and Intradiscal Interleukin-6 Expression in Lumbar Fusion Patients.

OBJECTIVE: To determine if there is correlation between intradiscal levels of interleukin-6 (IL-6) and early outcome measures in patients undergoing lumbar fusion for painful disc degeneration. METHODS: Intervertebral disc tissue was separated into annulus fibrosus/nucleus pulposus and cultured separately in vitro in serum-free medium (Opti-MEM). Conditioned media was collected after 48 hours. The concentration of IL-6 was quantified using enzyme-linked immunosorbent assay. Pearson correlation coefficients quantified relationships between IL-6 levels and pre- and postoperative visual analogue scale (VAS) back pain and Oswestry Disability Index (ODI), as well as change in VAS/ODI. RESULTS: Sixteen discs were harvested from 9 patients undergoing anterior lumbar interbody fusion (mean age, 47.4 years; range, 21-70 years). Mean preoperative and 6-month postoperative VAS were 8.1 and 3.7, respectively. Mean preoperative and postoperative ODI were 56.2 and 25.6, respectively. There were significant positive correlations between IL-6 expression and postoperative VAS (ρ = 0.38, p = 0.048) and ODI (ρ = 0.44, p = 0.02). No significant correlations were found between intradiscal IL-6 expression and preoperative VAS (ρ = -0.12, p = 0.54). Trends were seen associating IL-6 expression and change in VAS/ODI (ρ = -0.35 p = 0.067; ρ = -0.34, p = 0.08, respectively). A trend associated IL-6 and preoperative ODI (ρ = 0.36, p = 0.063). CONCLUSION: The direct association between IL-6 expression and VAS/ODI suggests patients with elevated intradiscal cytokine expression may have worse early outcomes than those with lower expression of IL-6 after surgery for symptomatic disc degeneration

An organ culture system to model early degenerative changes of the intervertebral disc

ABSTRACT: INTRODUCTION: Back pain, a significant source of morbidity in our society, is related to the degenerative changes of the intervertebral disc. At present, the treatment of disc disease consists of therapies that are aimed at symptomatic relief. This shortcoming stems in large part from our lack of understanding of the biochemical and molecular events that drive the disease process. The goal of this study is to develop a model of early disc degeneration using an organ culture. This approach is based on our previous studies that indicate that organ culture closely models molecular events that occur in vivo in an ex vivo setting. METHODS: To mimic a degenerative insult, discs were cultured under low oxygen tension in the presence of TNF-α, IL-1β and serum limiting conditions. RESULTS: Treatment resulted in compromised cell survival and changes in cellular morphology reminiscent of degeneration. There was strong suppression in the expression of matrix proteins including collagen types 1, 2, 6 and 9, proteoglycans, aggrecan and fibromodulin. Moreover, a strong induction in expression of catabolic matrix metalloproteinases (MMP) 3, 9 and 13 with a concomitant increase in aggrecan degradation was seen. An inductive effect on NGF expression was also noticed. Although similar, nucleus pulposus and annulus fibrosus tissues showed some differences in their response to the treatment. CONCLUSIONS: Results of this study show that perturbations in microenvironmental factors result in anatomical and gene expression change within the intervertebral disc that may ultimately compromise cell function and induce pathological deficits. This system would be a valuable screening tool to investigate interventional strategies aimed at restoring disc cell function

Oat cultivars developed at Nemchinovka and included into the State Register in recent years (a review)

The main trend in crop breeding is to increase productivity and improve grain quality indicators. The formation of high crop productivity requires cultivars with high potential for productivity and quality as well as with resistance to biotic and abiotic environmental factors. Successful solution of these and emerging breeding problems is possible only if appropriate source material is employed.Source material from the Vavilov Institute’s collection of plant genetic resources was used in crosses aimed at the development of oat cultivars. Its brief description is presented here.The results of the breeding work on oat cultivars at the Nemchinovka Federal Research Center from 2007 through 2017 are discussed. Descriptions are given to all ten developed oat cultivars with a detailed pedigree for each combination of crosses. Pedigree analysis has been performed, and its results show a limited number of parental forms for crosses. The problem of source material utilization in breeding practice and narrowing of the genetic base in the process of cultivar development is discussed

Inhibition of Neurogenic Inflammatory Pathways Associated with the Reduction in Discogenic Back Pain

Study Design Retrospective cohort study. Purpose This study aimed to determine whether the initiation of anti-calcitonin gene-related peptide (CGRP inhibitor) medication therapy for migraines was also associated with improvements in back/neck pain, mobility, and function in a patient population with comorbid degenerative spinal disease and migraine. Overview of Literature CGRP upregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, brain-derived neurotrophic factor, and nerve growth factor in spinal spondylotic disease, which results in disc degeneration and sensitization of nociceptive neurons. Although CGRP inhibitors can quell neurogenic inflammation in migraines, their off-site efficacy as a therapeutic target for discogenic back/neck pain conditions remains unknown. Methods All adult patients diagnosed with spinal spondylosis and migraine treated with CGRP inhibitors at a single academic institution between 2017 and 2020 were retrospectively identified. Patient demographic and medical data, follow-up duration, migraine severity and frequency, spinal pain, functional status, and mobility before and after the administration of CGRP inhibitors were collected. Paired univariate analysis was conducted to determine significant changes in spinal pain, headache severity, and headache frequency before and after the administration of CGRP inhibitors. The correlation between changes in the spinal pain score and functional or mobility improvement was assessed with Spearman’s rho. Results In total, 56 patients were included. The mean follow-up time after the administration of CGRP inhibitors was 123 days for spinal pain visits and 129 days for migraine visits. Back/neck pain decreased significantly (p<0.001) from 6.30 to 4.36 after starting CGRP inhibitor therapy for migraine control. As recorded in the spine follow-up notes, 25% of patients experienced a functional improvement in the activities of daily living, and 17.5% experienced mobility improvement while taking CGRP inhibitors. Change in back/neck pain moderately correlated (ρ=−0.430) with functional improvement but was not correlated with mobility improvement (ρ=−0.052). Conclusions Patients taking CGRP inhibitors for chronic migraines with comorbid degenerative spinal conditions experienced significant off-target reduction of back/neck pain

Inhibition of Neurogenic Inflammatory Pathways Associated with the Reduction in Discogenic Back Pain

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to determine whether the initiation of anti-calcitonin gene-related peptide (CGRP inhibitor) medication therapy for migraines was also associated with improvements in back/neck pain, mobility, and function in a patient population with comorbid degenerative spinal disease and migraine. OVERVIEW OF LITERATURE: CGRP upregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, brain-derived neurotrophic factor, and nerve growth factor in spinal spondylotic disease, which results in disc degeneration and sensitization of nociceptive neurons. Although CGRP inhibitors can quell neurogenic inflammation in migraines, their off-site efficacy as a therapeutic target for discogenic back/neck pain conditions remains unknown. METHODS: All adult patients diagnosed with spinal spondylosis and migraine treated with CGRP inhibitors at a single academic institution between 2017 and 2020 were retrospectively identified. Patient demographic and medical data, follow-up duration, migraine severity and frequency, spinal pain, functional status, and mobility before and after the administration of CGRP inhibitors were collected. Paired univariate analysis was conducted to determine significant changes in spinal pain, headache severity, and headache frequency before and after the administration of CGRP inhibitors. The correlation between changes in the spinal pain score and functional or mobility improvement was assessed with Spearman\u27s rho. RESULTS: In total, 56 patients were included. The mean follow-up time after the administration of CGRP inhibitors was 123 days for spinal pain visits and 129 days for migraine visits. Back/neck pain decreased significantly (p CONCLUSIONS: Patients taking CGRP inhibitors for chronic migraines with comorbid degenerative spinal conditions experienced significant off-target reduction of back/neck pain

Use of the technique of physiotherapy exercises after operative measures on the backbone including with use of metalwork

According to WHO data the degenerative dystrophic diseases of a backbone(DDDB) occur in 80% of the population and make up to 90% of all cases of chronic diseases [2,6,9,12,13,27]. Disks and meniskoida, bodies of vertebras, own mioligamentamy device of a backbone and its joints are exposed to degenerative dystrophic process. Owing to irritation of nervous structures of a backbone there are difficult neuroreflex not radicular syndromes wilh tonic, neirodystrophic, vegetovascular frustration [19,22,23]. Now in treatment of this pathology a certain progress due to introduction in clinical practice of new technologies and performance of minimum invasive operative measures is noted. However expeditious treatment of hernias, even at good short-term results, does not exclude preservation of neurodystrophic changes and also a disease recurrence as eliminates only a mechanical compression factor [5,8,10,27].The research objective consisted in development of a complex medical physical culture for patients with degenerative dystrophic diseases of lumbosacral department of a backbone after operative measures on a backbone including with use of metalwork.По данным ВОЗ дегенеративно-дистрофические заболевания позвоночника (ДДЗП) встречаются у 80 % населения и составляют до 90 % всех случаев хронических заболеваний [2,6,9,12,13,27]. Дегенеративно-дистрофическому процессу подвергаются диски и менискоиды, тела позвонков, собственный миолигамектарный аппарат позвоночника и его суставы. Вследствие раздражения нервных структур позвоночника возникают сложные нейрорефлекторные не корешковые синдромы с тоническими, нейродистрофическими, вегетативно-сосудистыми расстройствами [19,22,23]. В настоящее время в лечении данной патологии отмечается определенный прогресс за счет внедрения в клиническую практику новых технологий и выполнения минимально инвазивных оперативных вмешательств. Однако оперативное лечение грыж, даже при хороших непосредственных результатах, не исключает сохранения нейродистрофических изменений, а также рецидивов заболевания, так как устраняет только механический компрессионный фактор [5,8,10,27]. Цель исследования состояла в разработке комплекса лечебной физкультура для пациентов с дегенеративно-дистрофическим заболеваниями пояснично-крестцового отдела позвоночника после оперативных вмешательств на позвоночнике в том числе с применением металлоконструкций

The VLT-FLAMES Tarantula Survey II. R139 revealed as a massive binary system

We report the discovery that R139 in 30 Doradus is a massive spectroscopic binary system. Multi-epoch optical spectroscopy of R139 was obtained as part of the VLT-FLAMES Tarantula Survey, revealing a double-lined system. The two components are of similar spectral types; the primary exhibits strong C III λ4650 emission and is classified as an O6.5 Iafc supergiant, while the secondary is an O6 Iaf supergiant. The radial-velocity variations indicate a highly eccentric orbit with a period of 153.9 days. Photometry obtained with the Faulkes Telescope South shows no evidence for significant variability within an 18 month period. The orbital solution yields lower mass limits for the components of M1sin3i = 78 ± 8 M⊙ and M2sin3i = 66 ± 7 M⊙. As R139 appears to be the most massive binary system known to contain two evolved Of supergiants, it will provide an excellent test for atmospheric and evolutionary models

Functional and proteomic analysis of a full thickness filaggrin-deficient skin organoid model

Background: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail. Methods: Primary human keratinocytes and donor-matched primary fibroblasts from healthy individuals were used to create skin organoid models with and without siRNA-mediated knockdown of FLG. Biological replicate sets of organoids were assessed using histological, functional and biochemical measurements. Results: FLG knockdown leads to subtle changes in histology and ultrastructure including a reduction in thickness of the stratum corneum and smaller, less numerous keratohyalin granules. Immature organoids showed some limited evidence of barrier impairment with FLG knockdown, but the mature organoids showed no difference in transepidermal water loss, water content or dye penetration. There was no difference in epidermal ceramide content. Mass spectrometry proteomic analysis detected &gt;8000 proteins per sample. Gene ontology and pathway analyses identified an increase in transcriptional and translational activity but a reduction in proteins contributing to terminal differentiation, including caspase 14, dermokine, AKT1 and TGF-beta-1. Aspects of innate and adaptive immunity were represented in both the up-regulated and down-regulated protein groups, as was the term ‘axon guidance’. Conclusions: This work provides further evidence for keratinocyte-specific mechanisms contributing to immune and neurological, as well as structural, aspects of skin barrier dysfunction. Individuals with filaggrin deficiency may derive benefit from future therapies targeting keratinocyte-immune crosstalk and neurogenic pruritus

Polarizabilities and parity non-conservation in the Cs atom and limits on the deviation from the standard electroweak model

A semi-empirical calculation of the 6s - 7s Stark amplitude $\alpha$ in Cs has been performed using the most accurate measurements and calculations of the electromagnetic amplitudes available. This is then used to extract the parameters of the electroweak theory from experimental data. The results are: $\alpha = 269.0 (1.3) a_0^3$, weak charge of Cs $Q_W = -72.41(25)_{exp} (80)_{theor}$, deviation from the Standard model $S = -1.0(.3)_{exp} (1.0)_{theor}$ and limit on the mass of the extra Z-boson in SO(10) model $M_{Z_x} > 550 GeV$.Comment: 8 pages; submitted to Phys. Rev.