Primary Cutaneous Large B-Cell Lymphoma, Leg Type, Localized on the Dorsum

Primary cutaneous large B-cell lymphoma, leg-type (PCLBCL-LT), is a large B-cell lymphoma primarily involving the skin. It is distinguished from the other 3 subsets of this lymphoproliferative disorder by its immunohistopathological features, configuring confluent sheets of medium-sized to large B lymphocytes with round nuclei provided with evident nucleoli, resembling centroblasts or immunoblasts, which express Bcl-6, Bcl-2. Prevalently appearing on the lower limbs, as a single or multicentric and frequently ulcerated skin nodule or plaque, PCLBCL-LT has a worse prognosis than the other large B-cell lymphomas. Moreover, the age of onset is delayed (7th decade) compared to those of the other 3 subtypes (6th decade); it presents a slight female predominance (2:1), and a higher percentage of positivity to Bcl-2. We present a 52-year-old man who showed a 2-year standing, non-ulcerated, round, 4 cm in diameter, red plaque, medially located on the dorsum. After biopsy the diagnosis of PCLBCL-LT was made on histopathological and immunohistochemical studies, the latter showing positivity to CD20, Bcl-2, and Bcl-6. After treatment with radiotherapy the patient has shown a 4.4-year follow-up free of disease

Is the astronomical forcing a reliable and unique pacemaker for climate? A conceptual model study

There is evidence that ice age cycles are paced by astronomical forcing, suggesting some kind of synchronisation phenomenon. Here, we identify the type of such synchronisation and explore systematically its uniqueness and robustness using a simple paleoclimate model akin to the van der Pol relaxation oscillator and dynamical system theory. As the insolation is quite a complex quasiperiodic signal involving different frequencies, the traditional concepts used to define synchronisation to periodic forcing are no longer applicable. Instead, we explore a different concept of generalised synchronisation in terms of (coexisting) synchronised solutions for the forced system, their basins of attraction and instabilities. We propose a clustering technique to compute the number of synchronised solutions, each of which corresponds to a different paleoclimate history. In this way, we uncover multistable synchronisation (reminiscent of phase- or frequency-locking to individual periodic components of astronomical forcing) at low forcing strength, and monostable or unique synchronisation at stronger forcing. In the multistable regime, different initial conditions may lead to different paleoclimate histories. To study their robustness, we analyse Lyapunov exponents that quantify the rate of convergence towards each synchronised solution (local stability), and basins of attraction that indicate critical levels of external perturbations (global stability). We find that even though synchronised solutions are stable on a long term, there exist short episodes of desynchronisation where nearby climate trajectories diverge temporarily (for about 50 kyr). (...)Comment: 22 pages, 18 figure

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging

Good Manufacturing Practices-Grade Preformed Ossicular Prostheses From Banked Bone Via Computer Numerically Controlled Micromilling

Objectives: The aim of this study was the fabrication of ossicular replacement prostheses (ORPs) from decellularized banked cortical bone via computer numerically controlled (CNC) ultraprecision micromilling, in order to obtain preformed clinical-grade tissue products, reproducing shape, size, and details perfectly comparable to those of synthetic devices. Methods: Banked femoral compact bone was used to fabricate partial and total ORPs via CNC micromilling according to Good Manufacturing Practices procedures. Drawings of ORPs with different shapes and sizes were uploaded to the computer interface, and different surface-finish parameters were tested. The obtained products underwent dimensional, weight, and surface characterizations. A histologic analysis was pursued to compare the bone matrix compactness of the produced ORPs to that of the ear ossicles. Results: Banked-bone ORPs were produced with high dimensional accuracy. Partial ORP weights averaged (±SD) 31.2 ± 0.6 mg, and total ORP weights averaged 69.3 ± 0.7 mg. The best-finish mode allowed microscale or nanoscale roughness free from machinery textures to be obtained. Finally, the histologic analysis confirmed that the extracellular matrix compactness of the produced ORPs was suitable for ossicular chain replacement. Conclusions: This study assesses the fabrication feasibility of novel banked-bone ORPs of extremely high dimensional accuracy. Such devices are aimed at combining the most favorable aspects of both synthetic (reproducibility, convenience, and biosafety) and biological replacements (total biocompatibility)

P-635 The impact of force-degraded variants of recombinant human follicle stimulating hormone alfa (r-hFSH alfa) on in-vitro and in-vivo biological activity

Study question: Can an in-vitro bioassay assess the potency of r-hFSH-alfa force-degraded variants with similar ability to the in-vivo rat bioassay described in EU Pharmacopoeia (EU-Pharm 2285) ? Summary answer: The in-vitro bioassay showed similar ability to the in-vivo bioassay for estimating the impact of r-hFSH-alfa variants, resulting from process-related modifications, on biological activity