Background
To document the role of sub-clinical infections in disc disorders and investigate the existence of microbiome in intervertebral discs (IVD).
Methods
Genomic DNA from 24 lumbar IVDs 8—MRI ...normal discs (ND) from brain dead yet alive organ donors, 8—disc herniation (DH), 8—disc degeneration (DD) was subjected to 16SrRNA sequencing for profiling the diversity of human disc microbiome in health and disease. The disc microbiome was further compared to established human gut and skin microbiomes.
Results
All healthy MRI normal discs from brain dead yet alive organ donors also had a rich bacterial presence. A total of 424 different species (355-ND, 346-DD, and 322-DH) were detected, with 42.75% OTUs being classified at kingdom level, 44% at the phylum level, 22.62% at genus level, and 5.5% at species level. Varying biodiversity and abundance between healthy and diseased discs were documented with protective bacteria being abundant in normal discs, and putative pathogens abundant in DD and DH.
Propionibacterium acnes
had a similar but lower abundance to other pathogens in all three groups ND (3.07%), DD (3.88%), DH (1.56%). Fifty-eight bacteria were common between gut and IVD microbiomes, 29 between skin and IVD microbiomes, and six common to gut/skin/IVD.
Conclusion
Our study challenges the hitherto concept of sterility in healthy IVD and documented a microbiome even in MRI normal healthy discs. The varying abundance of bacteria between ND, DD, and DH documents ‘dysbiosis’ as a possible etiology of DD. Many known pathogens were identified in greater abundance than
Propionibacterium acnes,
and there was evidence for the presence of the gut/skin/spine microbiome axis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This was a retrospective study.
To analyze the surgical and neurological outcomes following surgical decompression in patients with aggressive vertebral hemangioma (AVH) presenting with neurological ...deficit and to determine whether a less extensive approach is appropriate.
AVHs are a rare subset of benign vascular tumors frequently presenting with neurological deficit because of spinal cord compression. Though the results of surgical management have improved over time, there is a lack of consensus on the ideal management in this group of patients.
Twenty-one patients who underwent surgery for AVH between 2009 and 2018 were analyzed. Demographic and clinical details of patients were retrieved from hospital information system. Imaging information (i.e., radiography, computed tomography, magnetic resonance imaging) of all patients was accessed and analyzed in picture archiving and communication system. Tumor staging was performed using Enneking and Weinstein-Boriani-Biagini classifications and Spinal Instability Neoplastic Score. At followup, neurological and radiological evaluations were performed.
Twenty-one patients (13 61.9% females and 8 38.1% males) were included with a mean age of 44.29 years (range, 14-72 years). All patients in the study had neurological deficit. Back pain was present in 80.9% of patients. Mean duration of symptoms was 4.6 months (range, 1 day to 10 months). Most common lesion location was thoracic spine (n=12), followed by thoracolumbar (D11- L2; n=7) and lumbar (n=2) regions. Ten patients had multiple level lesions. All patients underwent preoperative embolization. Nine patients underwent intralesional spondylectomy with reconstruction; another nine patients underwent stabilization, decompression, and vertebroplasty; three patients underwent decompression and stabilization. Neurology improved in all patients, and only one case of recurrence was noted in a mean follow-up of 55.78±25 months (range, 24-96 months).
In AVH, good clinical and neurological outcomes with low recurrence rates can be achieved using less extensive procedures, such as posterior instrumented decompression with vertebroplasty and intralesional tumor resection.
To better understand the neurotoxic effects of diverse hazards on the developing human nervous system, researchers and clinicians rely on data collected from a number of model species that develop ...and mature at varying rates. We review the methods commonly used to extrapolate the timing of brain development from experimental mammalian species to humans, including morphological comparisons, “rules of thumb” and “event-based” analyses. Most are unavoidably limited in range or detail, many are necessarily restricted to rat/human comparisons, and few can identify brain regions that develop at different rates. We suggest this issue is best addressed using “neuroinformatics”, an analysis that combines neuroscience, evolutionary science, statistical modeling and computer science. A current use of this approach relates numeric values assigned to 10 mammalian species and hundreds of empirically derived developing neural events, including specific evolutionary advances in primates. The result is an accessible, online resource (
http://www.translatingtime.net/) that can be used to equate dates in the neurodevelopmental literature across laboratory species to humans, predict neurodevelopmental events for which data are lacking in humans, and help to develop clinically relevant experimental models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the ...core matrisome of fetal NP's and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22-79), and 11 degenerated NP's was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP's. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in 'collagen biosynthesis' pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of 'tissue development'. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in 'negative regulation of cell death'. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This letter presents a novel non-iterative impedance based two-terminal fault location algorithm with unsynchronized terminals. The novelty of this method lies in the fact that it is non-iterative, ...does not require signal alignment, are independent of fault classification, suitable for both transposed and untransposed lines with distributed line model. Several results of simulations on standard and practical data of Power Grid Corporation of India Limited (PGCIL) are presented. The test results verifies the validity and accuracy of the developed fault location algorithm.
OBJECTIVE:High doses or prolonged exposure to ketamine increase neuronal apoptosis in the developing brain, although effects on neural stem progenitor cells remain unexplored. This study investigated ...dose- and time-dependent responses to ketamine on cell death and neurogenesis in cultured rat fetal cortical neural stem progenitor cells.
DESIGN:Laboratory-based study.
SETTING:University research laboratory.
SUBJECT:Sprague-Dawley rats.
INTERVENTIONS:Neural stem progenitor cells were isolated from the cortex of Sprague-Dawley rat fetuses on embryonic day 17. In dose-response experiments, cultured neural stem progenitor cells were exposed to different concentrations of ketamine (0–100 µM) for 24 hrs. In time-course experiments, neural stem progenitor cells cultures were exposed to 10 µM ketamine for different durations (0–48 hrs).
MEASUREMENTS AND MAIN RESULTS:Apoptosis and necrosis in neural stem progenitor cells were assessed using activated caspase-3 immunostaining and lactate dehydrogenase assays, respectively. Proliferative changes in neural stem progenitor cells were detected using bromo-deoxyuridine incorporation and Ki67 immunostaining. Neuronal differentiation was assessed using Tuj-1 immunostaining. Cultured neural stem progenitor cells were resistant to apoptosis and necrosis following all concentrations and durations of ketamine exposure tested. Ketamine inhibited proliferation with decreased numbers of bromo-deoxyuridine–positive cells following ketamine exposure to 100 µM for 24 hrs (p < .005) or 10 µM for 48 hrs (p < .01), and reduced numbers of Ki67-positive cells following exposure to ketamine concentration >10 µM for 24 hrs (p < .001) or at 10 µM for 48 hrs (p < .01). Ketamine enhanced neuronal differentiation, with all ketamine concentrations increasing Tuj-1-positive neurons (p < .001) after 24-hrs of exposure. This also occurred with all exposures to 10 µM ketamine for > 8 hrs (p < .001).
CONCLUSIONS:Clinically relevant concentrations of ketamine do not induce cell death in neural stem progenitor cells via apoptosis or necrosis. Ketamine alters the proliferation and increases the neuronal differentiation of neural stem progenitor cells isolated from the rat neocortex. These studies imply that ketamine exposure during fetal or neonatal life may alter neurogenesis and subsequent brain development.
CONTEXT Effective strategies to improve pain management in neonates require a clear understanding of the epidemiology and management of procedural pain. OBJECTIVE To report epidemiological data on ...neonatal pain collected from a geographically defined region, based on direct bedside observation of neonates. DESIGN, SETTING, AND PATIENTS Between September 2005 and January 2006, data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospectively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France (11.3 millions inhabitants) for the Epidemiology of Procedural Pain in Neonates (EPIPPAIN) study. MAIN OUTCOME MEASURE Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy. RESULTS The mean (SD) gestational age and intensive care unit stay were 33.0 (4.6) weeks and 8.4 (4.6) calendar days, respectively. Neonates experienced 60 969 first-attempt procedures, with 42 413 (69.6%) painful and 18 556 (30.4%) stressful procedures; 11 546 supplemental attempts were performed during procedures including 10 366 (89.8%) for painful and 1180 (10.2%) for stressful procedures. Each neonate experienced a median of 115 (range, 4-613) procedures during the study period and 16 (range, 0-62) procedures per day of hospitalization. Of these, each neonate experienced a median of 75 (range, 3-364) painful procedures during the study period and 10 (range, 0-51) painful procedures per day of hospitalization. Of the 42 413 painful procedures, 2.1% were performed with pharmacological-only therapy; 18.2% with nonpharmacological-only interventions, 20.8% with pharmacological, nonpharmacological, or both types of therapy; and 79.2% without specific analgesia, and 34.2% were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons. Prematurity, category of procedure, parental presence, surgery, daytime, and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia, whereas mechanical ventilation, noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia. CONCLUSION During neonatal intensive care in the Paris region, large numbers of painful and stressful procedures were performed, the majority of which were not accompanied by analgesia.
Purpose
To probe the pathophysiological basis of Modic change (MC) by multimodal imaging rather than by MRI alone.
Methods
Nineteen radiological signs found in mild infections and traumatic endplate ...fractures were identified by MRI and CT, and by elimination, three signs unique to infection and trauma were distilled. By ranking the Z score, radiological ‘Endplate Infection Probability Score’ (EIPS) was developed. The score’s ability to differentiate infection and traumatic endplate changes (EPC) was validated in a fresh set of 15 patients each, with documented infection and trauma. The EIPS, ESR, CRP, and Numeric Pain Rating Scale (NRS) were then compared between 115 patients with and 80 patients without MC.
Results
The EIPS had a confidence of 66.4%, 83% and, 100% for scores of 4, 5 and, 6, respectively, for end plate changes suggesting infection. The mean EIPS was 4.85 ± 1.94 in patients with Modic changes compared to − 0.66 ± 0.49 in patients without Modic changes (
p
< 0.001). Seventy-eight (67.64%) patients with MC had a score of 6, indicating high infection possibility. There was a difference in the NRS (
p
< 0.01), ESR (
p
= 0.05), CRP (
p
< 0.01), and type of pain (
p
< 0.01) between patients with and without MC.
Conclusion
Multimodal imaging showed many radiological signs not easily seen in MRI alone and thus missed in Modic classification. There were distinct radiological differences between EPCs of trauma and infection which allowed the development of an EIPS. The scores showed that 67.64% of our study patients with Modic changes had EPCs resembling infection rather than trauma suggesting the possibility of an infective aetiology and allowing us to propose an alternate theory of ‘Primary Endplatitis’.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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Co-amorphous drug delivery systems are evolving as a credible alternative to amorphous solid dispersions technology. In Co-amorphous systems (CAMs), a drug is stabilized in amorphous ...form using small molecular weight compounds called as co-formers. A wide variety of small molecular weight co-formers have been leveraged in the preparation of CAMs. The stability and supersaturation potential of prepared co-amorphous phases largely depend on the type of co-former employed in the CAMs. However, the rationality behind the co-former selection in co-amorphous systems is poorly understood and scarcely compiled in the literature. There are various facets to the rational selection of co-former for CAMs. In this context, the present review compiles various factors affecting the co-former selection. The factors have been broadly classified under Thermodynamic, Kinetic and Pharmacokinetic-Pharmacologically relevant parameters. In particular, the importance of Glass transition, Miscibility, Liquid-Liquid phase separation (LLPS), Crystallization inhibition has been deliberated in detail.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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