Feeding the Dragon. An Eschatological Motif in Medieval Europe

This book consists of six original essays concerning two popular eschatological motifs of medieval Europe: the devouring devil, especially in the guise of a dragon, and the zoomorphic mouth of hell, arguably a distinctive English adaptation of the anthropomorphic mouth of hell of classical antiquity. Over a time span ranging from late antiquity to the late Middle Ages and stretching across three languages, Latin, Old English, and Old Norse, the topos of the devouring demonic monster, a veritable commonplace across cultures and ages, is investigated in a variety of texts, including the Holy Scripture, homiletic and hagiographic works by authors such as Augustine of Hippo, Gregory the Great, and Ælfric of Eynsham, and apocryphal writings, e.g. the Seven Heavens Apocryphon and the Gospel of Nicodemus, especially its latter section, the Descensus Christi ad inferos. By detailing the creative interaction of a wide range of influences and the various practices of appropriation and adaptation of a vast stock of source material, both ultimate and intermediate, the contributions afford relevant case studies of the densely interlingual and intertextual modes of textual production, transmission, and reception in the European Middle Ages. Advancing our understanding of the cultural and textual networks of the period, this book will prove an important resource for anyone interested in the dynamic process of mediation between past and present, pagan and Christian, orthodoxy and apocrypha, exotic and local that makes up medieval literary and figurative culture

Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis

Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients. We investigated whether siponimod, in addition to its peripheral immune modulation, may exert direct neuroprotective effects in the central nervous system (CNS) of mice with chronic progressive EAE

Factors affecting choice of open surgical techniques in elbow stiffness.

We analyzed the clinical outcomes of stiff elbow open treatment to assess factors affecting the choice of surgical procedures in a consecutive series of patients followed up prospectively. MATERIALS AND METHODS: Forty-one patients, mean aged 48 years, were evaluated. Elbow stiffness was caused by post-traumatic osteoarthritis in 32 patients, primary osteoarthritis in seven and rheumatoid arthritis in two. Stiffness was classified as mixed and extrinsic in 28 and 13 cases, respectively. Seventeen ulno-humeral arthroplasties (UHA), seven UHA with radiocapitellar replacement, six UHA with radial head replacement, ten total elbow replacement and one UHA with anconeus interposition were performed. Mayo Elbow Performance Score (MEPS), modified-American Shoulder and Elbow Surgeons (m-ASES) and Q-DASH scores were used for the pre- and post-operative evaluation. RESULTS: Mean follow-up was 25 months. The average increase in MEPS and m-ASES was 45 and 41, respectively. The average decrease in Q-DASH and the average increase in m-ASES pain were 43 and 21, respectively. The mean increase in flection, extension, pronation and supination was 29°, 25°, 18° and 17°, respectively. All the differences were statistically significant. CONCLUSIONS: Strictly customized open surgery of elbow stiffness, by taking into account the clinical value of each patient's pathoanatomical conditions, yields satisfactory functional results in majority of cases. In particular, the degree and site of elbow cartilage wear proved to be the factors affecting the choice of treatment most. Treatment should be aimed at removing the causes of pain and at recovering range of motion.We analyzed the clinical outcomes of stiff elbow open treatment to assess factors affecting the choice of surgical procedures in a consecutive series of patients followed up prospectively. MATERIALS AND METHODS: Forty-one patients, mean aged 48 years, were evaluated. Elbow stiffness was caused by post-traumatic osteoarthritis in 32 patients, primary osteoarthritis in seven and rheumatoid arthritis in two. Stiffness was classified as mixed and extrinsic in 28 and 13 cases, respectively. Seventeen ulno-humeral arthroplasties (UHA), seven UHA with radiocapitellar replacement, six UHA with radial head replacement, ten total elbow replacement and one UHA with anconeus interposition were performed. Mayo Elbow Performance Score (MEPS), modified-American Shoulder and Elbow Surgeons (m-ASES) and Q-DASH scores were used for the pre- and post-operative evaluation. RESULTS: Mean follow-up was 25 months. The average increase in MEPS and m-ASES was 45 and 41, respectively. The average decrease in Q

Critical time period for recovery of functional range of motion after surgical treatment of complex elbow instability: prospective study on 76 patients.

Complex elbow instability (CEI) is one of the most troublesome pathologies that orthopaedic surgeons have to face. One of the key requirements regarding the CEI surgical treatment is an early rehabilitation programme to avoid the elbow stiffness caused by a long period of immobilisation. Although this is well known, no study has ever examined how, and to what extent, the functional range of motion (ROM) is recovered during the various stages of a prompt rehabilitation. Our aims were: (1) to prospectively analyse the pattern of ROM recovery in a series of patients with CEI who underwent early rehabilitation and (2) to identify the period of time during rehabilitation in which the greatest degree of motion recovery is obtained. Materials and methods A total of 76 patients (78 elbows) with CEI were followed up for 2 years. All the patients underwent anatomical and stable ostheosynthesis of all the fractures, radial head replacement in Mason III fractures, ligament injuries reconstruction and early rehabilitation that started 2 days after surgery. Two surgeons evaluated the ROM with a hand-held goniometer every 3 weeks for the first 3 months, then at 6, 12 and 24 months after surgery. Results At the 3-week follow-up, the mean flexion (F), extension (E), pronation (P) and supination (S) were 113, 29, 60 and 62, respectively. At the 6-week and 9-week follow-up, F, E, P and S were 119, 23, 70 and 69 and 123, 24, 72 and 71, respectively. At the 3-month follow-up, these values were 131, 18, 76 and 72, while at the 6-month follow-up they were 136, 15, 79 and 77, respectively. Thereafter, the ROM improvement was not significant. Discussion This study shows that the first 6 months represent the critical rehabilitation period to obtain a functional elbow; indeed, 70% of the patients recovered functional ROM between the third and sixth month, though the recovery of flexion proved to be slower than that of the other elbow movements. Thereafter, improvement continued, though at a lower rate, until the end of the first year, when approximately 80% of the patients had recovered the functional ROM. Conclusions Following CEI surgical treatment, a rehabilitation programme needs to be started promptly and continued for at least 6 months because a significant improvement of ROM occurs prevalently in this period, which should be considered the critical time period to obtain a functional elbow in a majority of patient

Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis

Microglia is increasingly recognized to play a crucial role in the pathogenesis of psychiatric diseases. In particular, microglia may be the cellular link between inflammation and behavioral alterations: by releasing a number of soluble factors, among which pro-inflammatory cytokines, that can regulate synaptic activity, thereby leading to perturbation of behavior. In multiple sclerosis (MS), the most common neuroinflammatory disorder affecting young adults, microglia activation and dysfunction may account for mood symptoms, like depression and anxiety, that are often diagnosed in patients even in the absence of motor disability. Behavioral studies in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, have shown that emotional changes occur early in the disease and in correlation to inflammatory mediator and neurotransmitter level alterations. However, such studies lack a full and comprehensive analysis of the role played by microglia in EAE-behavioral syndrome. We review the experimental studies addressing behavioral symptoms in EAE, and propose the study of neuron-glia interaction as a powerful but still poorly explored tool to investigate the burden of microglia in mood alterations associated to MS

A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum

The N-palmitoylethanolamine (PEA) is an endogenous member of the endocannabinoid system (ECS) with several biological functions, including a neuromodulatory activity in the central nervous system. To shed light on the neuronal function of PEA, we investigated its involvement in the control of both excitatory and inhibitory transmission in the murine striatum, a brain region strongly modulated by the ECS. By means of electrophysiological recordings, we showed that PEA modulates inhibitory synaptic transmission, through activation of GPR55 receptors, promoting a transient increase of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency. The subsequently rundown effect on sIPSC frequency was secondary to the delayed stimulation of presynaptic cannabinoid CB1 receptors (CB1Rs) by the endocannabinoid 2-AG, whose synthesis was stimulated by PEA on postsynaptic neurons. Our results indicate that PEA, acting on GPR55, enhances GABA transmission in the striatum, and triggers a parallel synthesis of 2-AG at the postsynaptic site, that in turn acts in a retrograde manner to inhibit GABA release through the stimulation of presynaptic CB1Rs. This electrophysiological study identifies a previously unrecognized function of PEA and of GPR55, demonstrating that GABAergic transmission is under the control of this compound and revealing that PEA modulates the release of the endocannabinoid 2-AG

Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis

Multiple sclerosis (MS) has long been regarded as a chronic inflammatory disease of the white matter that leads to demyelination and eventually to neurodegeneration. In the past decade, several aspects of MS pathogenesis have been challenged, and degenerative changes of the grey matter, which are independent of demyelination, have become a topic of interest. CNS inflammation in MS and experimental autoimmune encephalomyelitis (EAE; a disease model used to study MS in rodents) causes a marked imbalance between GABAergic and glutamatergic transmission, and a loss of synapses, all of which leads to a diffuse 'synaptopathy'. Altered synaptic transmission can occur early in MS and EAE, independently of demyelination and axonal loss, and subsequently causes excitotoxic damage. Inflammation-driven synaptic abnormalities are emerging as a prominent pathogenic mechanism in MS-importantly, they are potentially reversible and, therefore, represent attractive therapeutic targets. In this Review, we focus on the connection between inflammation and synaptopathy in MS and EAE, which sheds light not only on the pathophysiology of MS but also on that of primary neurodegenerative disorders in which inflammatory processes contribute to disease progression