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While much has been observed regarding hypothermia by way of environmental exposure, it is modern day medicine that deployed hypothermia as a therapeutic. From the early 1930s, when Temple Fay deployed "refrigeration" to treat pain, to the work of Wilfred Bigelow and Charles Drew, who utilized hypothermia in open heart surgery—the opportunities seemed endless. However, questions arose surrounding appropriate temperatures to achieve best outcomes and how to minimize adverse events, such as coagulopathy and infection. In the 1980s, hypothermia underwent a resurgence through Peter Safar's critical studies in large animals, which quickly translated into feasibility studies and the landmark trials of 2002 that paved the way for postcardiac arrest care as we currently know it. Through clinical and observational trials, modern‐day targeted temperature management continues to adapt, striving to improve patient outcomes. While hypothermia has come a long way from the writings of Hippocrates, the ideal therapy has not yet been defined, and more work is needed. While the history is long, there is more to be written and advances to be achieved as we optimize the neuroprotective effects of hypothermia for comatose survivors of cardiac arrest. [ABSTRACT FROM AUTHOR]

Background: Rats are a widely accepted preclinical model for evaluating intervertebral disc (IVD) degeneration and regeneration. IVD morphology is commonly assessed using histology, which forms the foundation for quantifying the state of IVD degeneration. IVD degeneration severity is evaluated using different grading systems that focus on distinct degenerative features. A standard grading system would facilitate more accurate comparison across laboratories and more robust comparisons of different models and interventions. Aims: This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models. Materials & Methods: This study involved a literature review, a survey of experts in the field, and a validation study using 25 slides that were scored by 15 graders from different international institutes to determine inter‐ and intra‐rater reliability. Results: A new IVD degeneration grading system was established and it consists of eight significant degenerative features, including nucleus pulposus (NP) shape, NP area, NP cell number, NP cell morphology, annulus fibrosus (AF) lamellar organization, AF tears/fissures/disruptions, NP‐AF border appearance, as well as endplate disruptions/microfractures and osteophyte/ossification. The validation study indicated this system was easily adopted, and able to discern different severities of degenerative changes from different rat IVD degeneration models with high reproducibility for both experienced and inexperienced graders. In addition, a widely‐accepted protocol for histological preparation of rat IVD samples based on the survey findings include paraffin embedding, sagittal orientation, section thickness < 10 μm, and staining using H&E and/or SO/FG to facilitate comparison across laboratories. Conclusion: The proposed histological preparation protocol and grading system provide a platform for more precise comparisons and more robust evaluation of rat IVD degeneration models and interventions across laboratories. [ABSTRACT FROM AUTHOR]

Background: The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Aims: The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. Materials and Methods: The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. Results: The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. Discussion: Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. Conclusion: This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing. [ABSTRACT FROM AUTHOR]

The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits. At 1‐, 2‐, 3‐, 4‐, and 6‐weeks, the expression of sclerostin and a variety of canonical and noncanonical Wnts signaling factors was measured by qRT‐PCR from tissue separately collected from the transverse processes, the Outer and Inner Zones of the fusion mass, and the adjancent paraspinal muscle. Immunohistochemistry for sclerostin protein was also performed. Sclerostin and many Wnt factors, especially Wnt3a and Wnt5a, were found to have distinct spatial and temporal expression patterns. For example, harvesting ICBG caused a significant increase in sclerostin expression. Furthermore, the paraspinal muscle immediately adjacent to the transplanted ICBG also had significant increases in sclerostin expression at 3 weeks, suggesting new potential mechanisms for pseudarthroses following spinal arthrodesis. The presented work is the first description of the spatial and temporal expression of sclerostin and Wnt signaling factors in the developing spine fusion, filling an important knowledge gap in the basic biology of spinal fusion and potentially aiding in the development of novel biologics to increase spinal fusion rates. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) is a public health dilemma as it is associated with low back and neck pain, a frequent reason for patients to visit the physician. During IDD, nucleus pulposus (NP), the central compartment of intervertebral disc (IVD) undergo degeneration. Stem cells have been adopted as a promising biological source to regenerate the IVD and restore its function. Here, we describe a simple, two‐step differentiation strategy using a cocktail of four factors (LDN, AGN, FGF, and CHIR) for efficient derivation of notochordal cells from human embryonic stem cells (hESCs). We employed a CRISPR/Cas9 based genome‐editing approach to knock‐in the mCherry reporter vector upstream of the 3′ untranslated region of the Noto gene in H9‐hESCs and monitored notochordal cell differentiation. Our data show that treatment of H9‐hESCs with the above‐mentioned four factors for 6 days successfully resulted in notochordal cells. These cells were characterized by morphology, immunostaining, and gene and protein expression analyses for established notochordal cell markers including FoxA2, SHH, and Brachyury. Additionally, pan‐genomic high‐throughput single cell RNA‐sequencing revealed an efficient and robust notochordal differentiation. We further identified a key regulatory network consisting of eight candidate genes encoding transcription factors including PAX6, GDF3, FOXD3, TDGF1, and SOX5, which are considered as potential drivers of notochordal differentiation. This is the first single cell transcriptomic analysis of notochordal cells derived from hESCs. The ability to efficiently obtain notochordal cells from pluripotent stem cells provides an additional tool to develop new cell‐based therapies for the treatment of IDD. [ABSTRACT FROM AUTHOR]

Here, we report on the analytical findings and their cultural implications of a multidisciplinary study of the pre‐Columbian Codex Fejérváry‐Mayer. Today conserved at the World Museum in Liverpool, it is one of the finest Mesoamerican codices among the few extant. Thanks to the exploitation of non‐invasive analytical methodologies accessible through the MOLAB European mobile facility, the study allowed us to disclose the chemical composition of the painting materials used in the codex, which have never been analysed before. The results are discussed and compared with the outcomes of previous studies on other Mesoamerican codices. [ABSTRACT FROM AUTHOR]

With the aim of deepening the knowledge on the behavior of cyclododecane (CDD) as a temporary consolidant agent for weathered stones, NMR longitudinal and transverse relaxation decays have been exploited to follow the distribution of cyclododecane solutions into porous matrices. By measuring as function of time the relaxation decay constants of CDD solutions dropped onto porous supports, it has been possible to differentiate the step encompassing the solvent evaporation, which determines the consolidant migration within the matrix, from that governing the consolidant sublimation, which is related to the consolidation effectiveness over time. [ABSTRACT FROM AUTHOR]

In order to realize a surface enhanced Raman spectroscopy (SERS) gel protocol with portable Raman instrumentation, this contribution oversees the optimization of a removable SERS active methylcellulose gel and the applicability of an innovative gelatin substrate. Analytical evaluations by non-invasive portable nuclear magnetic resonance (NMR) profilometry with regards to methylcellulose and gelatin film penetration and removal from an unvarnished painted surface and commercial dyed paper substrates have been carried out, respectively, following successful SERS measurements. Both gels have been specifically prepared in accordance to the substrate under exam so as to simultaneously permit sufficient surface interaction for Raman enhancements to be recorded with limited penetration into or subsequent damage on removal of the matrix under study. This work continues to bridge the gap towards non-invasive SERS measurements and in-situ SERS measurements. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Degeneration of the intervertebral disc (IVD) results in deterioration of the spinal motion segment and can lead to debilitating back pain. Given the established mitotic and anti-apoptotic effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a variety of cell types we postulated that rhPDGF-BB might delay disc cell degeneration through inhibition of apoptosis. To address this hypothesis, we treated human IVD cells isolated from five independent patients with rhPDGF-BB in monolayer and 3D pellet cultures. The anti-apoptotic potential, cell proliferative capacity, morphology/pellet differentiation, and gene expression of PDGF-treated IVD cells were evaluated via flow cytometry/immunohistochemistry, MTT assays, histology, and quantitative RT-PCR, respectively. We found that rhPDGF-BB treatment significantly inhibited cell apoptosis, increased cell proliferation and matrix production, and maintained mRNA expression of critical extracellular matrix genes. This study suggests two possible mechanisms for the anti-degenerative effects of rhPDGF-BB on human IVD cells. First, PDGF treatment strongly inhibited IVD cell apoptosis in 3D cultures. Second, rhPDGF-BB acts as an anabolic agent, promoting maintenance of IVD cell phenotype in 3D culture, based on the molecular and protein expression analysis. We speculate that rhPDGF-BB may be used as a biologic treatment to target early degenerative IVD disease in the future. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1181-1188, 2014. [ABSTRACT FROM AUTHOR]

In 1605, Roberto Antinori, prior of the Innocenti foundling hospital in Florence, commissioned marble busts of the first three Medici grand dukes for the hospital loggia. Several years later, he hired Bernardino Poccetti to fresco in the girls' refectory an ‘Istoria degl'Innocenti’, which included an idealized representation of the activities of the hospital under the watchful eyes of Cosimo II. The present study argues that these decorative projects worked together to shape an image of the grand dukes as ‘fathers’ of the foundlings of the Innocenti. In contrast to much of the scholarship on the grand dukes, which has focused on their use of visual imagery to achieve absolutist goals, I show how the image of Medici ‘fatherhood’ forged at the Innocenti, by articulating a construction of ruling authority in which the hospital and its young inmates played a constitutive role, served the interests of the hospital as much as it did those of the grand dukes. The paternal metaphor, which obligated the ‘fathers of the Innocenti’ to provide for their ‘children’, is elaborated most extensively in Poccetti's fresco, which represents Cosimo II as custodian of imperilled souls, supplier of nourishment, provider of education, and guardian of nubile chastity. [ABSTRACT FROM AUTHOR]

Background and purpose: Repeated episodes of hypoxia, hypercapnia and transient blood pressure elevation in obstructive sleep apnea syndrome (OSAS) may damage neutral structures and induce cerebral metabolic impairment. This study aimed to determine the impact of OSAS on cerebral metabolites measured by 1H magnetic resonance spectroscopy (1H -MRS). Methods: Twenty OSAS patients underwent standard overnight polysomnography and 1H-MRS separately. Proton volumes of interest (VOIs) were placed in frontal and midtemporal regions bilaterally. Results: Significantly lower values of the N-acetylaspartate (NAA)/creatine (Cr) ratio were found in frontal regions ( P < 0.004) compared with 20 age-matched control subjects. A significant increase in the myo-inositol (Ins)/Cr ratio was evident bilaterally in temporal and frontal regions ( P < 0.00002 and P < 0.04). Choline (Cho)/Cr ratio values were also significantly greater in temporal regions ( P < 0.00001). A significant negative correlation ( r = −0.51, P < 0.03) was found between the apnea-hypopnea index (AHI) and NAA/Cr ratio in the frontal regions of OSAS patients. Conclusions: Reduction in the NAA/Cr ratio in frontal regions of OSAS patients could be related to neural loss. Increase in the Cho/Cr ratio in temporal regions and Ins/Cr ratio in both frontal and temporal regions could be interpreted as evidence of membrane breakdown and reactive gliosis, respectively, consequent to repeated episodes of hypoxia in OSAS. [ABSTRACT FROM AUTHOR]

Although the molecular defect causing Becker muscular dystrophy (BMD) has been identified, the biochemical mechanisms that lead to muscle necrosis remain unclear. Exercise-related muscle metabolism in 9 mildly affected BMD patients was assessed by muscle 31-phosphorus magnetic resonance spectroscopy (31P MRS) during an incremental workload. Compared with normal controls, BMD patients showed deregulation of resting pH and intramuscular membrane breakdown. We also observed increased reliance upon anaerobic metabolism during sustained submaximal contraction and maintenance of oxidative function during recovery. Muscle Nerve, 2011 [ABSTRACT FROM AUTHOR]