Intrathecal Immunoglobulin Synthesis in MS—A Complete Reappraisal

Multiple sclerosis (MS) is characterized by the intrathecal synthesis (ITS) of immunoglobulins (Igs), which, although nonspecific, is the strongest biological marker. Since no specific target has been elucidated, this synthesis is considered to be disease‐irrelevant. We demonstrate that this synthesis provides pertinent information about the pathophysiological processes involved. Quantification of ITS is based on an approximation intrinsically underestimating its level and it remains constant in MS, albeit sometimes at a low level. B‐cell maturation seems to be initiated within the cervical lymph nodes and B‐cells traffic on both sides of the blood‐brain barrier by rounds of bidirectional traffic. During this process, they undergo somatic hypermutation, which is the hallmark of antigen‐driven antibody maturation, suggesting that most of the ITS is probably directed against as yet unknown targets. Alternatively, examining”non‐disease‐relevant” ITS in the light of meningeal tertiary lymphoid organs provides new insights into the pathophysiology of MS. Although no specific target has yet been identified in MS, recent developments in the search for targeted antigens point to non‐conventional antigens (posttranslationally modified proteins or oxidized products) of which a few are promising for future research

Plasma Exchange in Severe Attacks of Neuromyelitis Optica

Background. Neuromyelitis optica (NMO) attacks are poorly controlled by steroids and evolve in stepwise neurological impairments. Assuming the strong humoral response underlying NMO attacks, plasma exchange (PLEX) is an appropriate technique in severe NMO attacks. Objective. Presenting an up-to-date review of the literature of PLEX in NMO. Methods. We summarize the rationale of PLEX in relation with the physiology of NMO, the main technical aspects, and the available studies. Results. PLEX in severe attacks from myelitis or optic neuritis are associated with a better outcome, depending on PLEX delay (“time is cord and eyes”). NMO-IgG status has no influence. Finally, we build up an original concept linking the inner dynamic of the lesion, the timing of PLEX onset and the expected clinical results. Conclusion. PLEX is a safe and efficient add-on therapy in NMO, in synergy with steroids. Large therapeutic trials are required to definitely assess the procedure and define the time opportunity window

Au-delà du casque à cornes : Théodoric, monarque parfait et ami des poètes

Dans l’imaginaire populaire, le Romain voit le Barbare comme un être dépourvu de raffinement. Sidoine Apollinaire quant à lui n’était peut-être pas de cet avis. Le portrait qu'il dresse du personnage de Théodoric, roi des Wisigoths, dans ses lettres I, 2 et I, 11 ainsi que dans ses panégyriques impériaux, est de fait révélateur à bien des égards. Il témoigne en premier lieu d’un changement de mentalité envers les barbares de la part d’un aristocrate comme Sidoine, à une époque où disparaît le pouvoir impérial et où règnent des rois barbares. De plus, ce traitement de l’image des barbares interroge le mélange des genres dans l’Antiquité tardive. En cette période où la hiérarchie des genres est bouleversée, le panégyrique, grand genre par excellence, par sa forme et son sujet, se trouve parasité par l’épistolaire, qui se met chez Sidoine à assumer le rôle encomiastique, alors que les Panégyriques se font beaucoup nuancés et ironiques.In our collective mind, Romans were supposed to consider the Barbarians as unrefined being. Sidonius Apollinaris may not have shared this point of view. The portrait he draws of Theodoric, king of the Visigoths (in his letters 1,2, and 1,11 as in his imperial panegyrics), is indeed very instructive. It shows a change in the attitude of Romans towards Barbarians, in a time when imperial power disappears, replaced by Barbarian kings. Besides, it questions the concept of mixture of literary styles during Late Antiquity. In this period, the epistolary genre interferes with the panegyric, great genre par excellence, the first handling the encomiastic role, as the Panegyrics become more ironic and tempered

Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location

Фракционный СО2-лазер: новая терапевтическая системадля фотобиомодуляции ремоделирования кожи и продукциицитокинов при репарации

Eighteen female patients with the signs of photoageing underwent skin rejuvenation using a fractional CO2 laser (SmartXide DOT, DEKA M.E.L.A., Florence, Italy) with varying energy density (2.07, 2.77 and 4.15 J/cm2). Clinical efficacy of the said laser irradiation parameters was assessed in all of the subjects, and the skin cytokine profile was studied by using the immunohistochemistry technique based on skin tissue samples taken prior to the treatment, right after the treatment and in 3 and 30 days. There were significant improvements in the wrinkle and skin texture condition, and hyperpigmentation was reduced as a result of the treatment, which proves the efficacy of using the fractional CO2 laser for the skin photorejuvenation. The technique ensures good clinical results and is distinguished by a short rehabilitation period and excellent safety profile. In the course of the immunohistochemistry, a relation between the skin cytokine production, reepithelization and laser irradiation density was established.Восемнадцати женщинам добровольцам, имевшим признаки фотостарения, проведено омоложение кожи фракционным СО2-лазером (SmartXide DOT, DEKA M.E.L.A., Флоренция, Италия) с использованием различных показателей плотности энергии (2,07, 2,77 и 4,15 Дж/см2). У всех испытуемых оценена клиническая эффективность применения указанных параметров лазерного излучения, а также иммуногистохимическим методом изучен цитокиновый профиль кожи в биоптатах, взятых до лечения, сразу после лечения и спустя 3 и 30 дней. В результате лечения значительно улучшилось состояние морщин и текстуры кожи, уменьшилась гиперпигментация, что свидетельствует о высокой эффективности применения фракционного СО2-лазера для фотоомоложения кожи. Метод позволяет получить хорошие клинические результаты, характеризуется коротким реабилитационным периодом и отличным профилем безопасности. При иммуногистохимическом исследовании выявлена связь продукции цитокинов в коже с фазой реэпителизации и плотностью энергии лазерного облучения

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Cancellous bone and theropod dinosaur locomotion. Part II—a new approach to inferring posture and locomotor biomechanics in extinct tetrapod vertebrates

This paper is the second of a three-part series that investigates the architecture of cancellous bone in the main hindlimb bones of theropod dinosaurs, and uses cancellous bone architectural patterns to infer locomotor biomechanics in extinct non-avian species. Cancellous bone is widely known to be highly sensitive to its mechanical environment, and therefore has the potential to provide insight into locomotor biomechanics in extinct tetrapod vertebrates such as dinosaurs. Here in Part II, a new biomechanical modelling approach is outlined, one which mechanistically links cancellous bone architectural patterns with three-dimensional musculoskeletal and finite element modelling of the hindlimb. In particular, the architecture of cancellous bone is used to derive a single ‘characteristic posture’ for a given species—one in which bone continuum-level principal stresses best align with cancellous bone fabric—and thereby clarify hindlimb locomotor biomechanics. The quasi-static approach was validated for an extant theropod, the chicken, and is shown to provide a good estimate of limb posture at around mid-stance. It also provides reasonable predictions of bone loading mechanics, especially for the proximal hindlimb, and also provides a broadly accurate assessment of muscle recruitment insofar as limb stabilization is concerned. In addition to being useful for better understanding locomotor biomechanics in extant species, the approach hence provides a new avenue by which to analyse, test and refine palaeobiomechanical hypotheses, not just for extinct theropods, but potentially many other extinct tetrapod groups as well

Cancellous bone and theropod dinosaur locomotion. Part I—an examination of cancellous bone architecture in the hindlimb bones of theropods

This paper is the first of a three-part series that investigates the architecture of cancellous (‘spongy’) bone in the main hindlimb bones of theropod dinosaurs, and uses cancellous bone architectural patterns to infer locomotor biomechanics in extinct non-avian species. Cancellous bone is widely known to be highly sensitive to its mechanical environment, and has previously been used to infer locomotor biomechanics in extinct tetrapod vertebrates, especially primates. Despite great promise, cancellous bone architecture has remained little utilized for investigating locomotion in many other extinct vertebrate groups, such as dinosaurs. Documentation and quantification of architectural patterns across a whole bone, and across multiple bones, can provide much information on cancellous bone architectural patterns and variation across species. Additionally, this also lends itself to analysis of the musculoskeletal biomechanical factors involved in a direct, mechanistic fashion. On this premise, computed tomographic and image analysis techniques were used to describe and analyse the three-dimensional architecture of cancellous bone in the main hindlimb bones of theropod dinosaurs for the first time. A comprehensive survey across many extant and extinct species is produced, identifying several patterns of similarity and contrast between groups. For instance, more stemward non-avian theropods (e.g. ceratosaurs and tyrannosaurids) exhibit cancellous bone architectures more comparable to that present in humans, whereas species more closely related to birds (e.g. paravians) exhibit architectural patterns bearing greater similarity to those of extant birds. Many of the observed patterns may be linked to particular aspects of locomotor biomechanics, such as the degree of hip or knee flexion during stance and gait. A further important observation is the abundance of markedly oblique trabeculae in the diaphyses of the femur and tibia of birds, which in large species produces spiralling patterns along the endosteal surface. Not only do these observations provide new insight into theropod anatomy and behaviour, they also provide the foundation for mechanistic testing of locomotor hypotheses via musculoskeletal biomechanical modelling