Foreign body responses in central nervous system mimic natural wound responses and alter biomaterial functions

Biomaterials hold promise for diverse therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo , or about how such responses influence biomaterial function. Here, we probed these factors using a platform of injectable hydrogels readily modified to present interfaces with different representative physiochemical properties to host cells. We show that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. Moreover, we found that the nature and intensity of CNS FBRs are determined by definable properties. For example, cationic, anionic or nonionic interfaces with CNS cells elicit quantifiably different levels of stromal cell infiltration, inflammation, neural damage and amyloid production. The nature and intensity of FBRs significantly influenced hydrogel resorption and molecular delivery functions. These results characterize specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications

Dynamics of bovine intramammary infections due to coagulase-negative staphylococci on four farms

The objectives of this study were to compare the impact of different coagulase-negative species (CNS) on udder health measured in terms of individual quarter milk somatic cell count (SCC) and duration of intramammary infection, and to get some insight into most likely routes of infection for different CNS species. This longitudinal observational study was performed on four farms that were sampled at 4-week intervals for a total of 12 visits each. Quarters infected with CNS were followed through time with milk samples being submitted for bacteriological culture and SCC determination. PCR amplification of the internal transcribed spacer region and sequencing of the sodA and rpoB genes were used for species allocation. Pulsed-field gel electrophoresis (PFGE) was performed to assess strain identity. The percentage of quarters affected per farm varied between 6 and 35%, with the most frequently isolated CNS species being Staphylococcus epidermidis, followed by Staph. simulans, Staph. chromogenes and Staph. haemolyticus. It was possible to follow 111 intramammary infections due to CNS through time. Duration of infection had a mean of 188 d and was not significantly different between CNS species. Geometric mean quarter SCC overall was 132 000 cells/ml and was also not significantly different between CNS species. Despite the possibility of a different epidemiology of infection, the impact in terms of udder health seems to be similar for different CNS species

Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases.

Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many ALK resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two ALK-rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in ALK-rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs

Primary CNS Lymphoma

Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system is an aggressive malignancy that exhibits unique biological features and characteristic clinical behaviour, with overall long-term survival rates of around 20–40 %. Clinical outcome has improved following the advent of chemoradiation protocols incorporating high-dose methotrexate in the mid-1980s, but disease relapse and adverse neurocognitive sequelae remain major clinical challenges. To address this, investigators have focused on improving drug therapy with novel cytotoxic combinations, monoclonal antibody therapy, and intensive chemotherapy consolidation approaches, in an attempt to improve disease control whilst reducing the requirement for whole-brain radiotherapy. Outcomes for patients that are older, immunocompromised, or have relapsed/refractory disease remain unsatisfactory and there is a paucity of clinical trial data to guide treatment of these groups. This review highlights recent advances in pathobiology, imaging, and clinical management of PCNSL and looks ahead to research priorities for this rare and challenging lymphoid malignancy

The knowledge domain of chain and network science

This editorial paper aims to provide a framework to categorise and evaluate the domain of Chain and Network Science (CNS), and to provide an envelope for the research and management agenda. The authors strongly feel that although considerable progress has been made over the past couple of years in the development of the CNS domain, a number of important and exciting challenges are still waiting to be tackled. This paper provides a definition of the object of study of CNS, its central problem area, the organisation and governance of chain and network co-operation, and the relationships between chain organisation and technology development, market dynamics, and the economy and society at large. It indicates relevant sources of knowledge among the various academic disciplines. It touches upon CNS problem solving by identifying areas for knowledge development and CNS tool construction

The multifaceted role of astrocytes in regulating myelination

Astrocytes are the major glial cell of the central nervous system (CNS), providing both metabolic and physical support to other neural cells. After injury, astrocytes become reactive and express a continuum of phenotypes which may be supportive or inhibitory to CNS repair. This review will focus on the ability of astrocytes to influence myelination in the context of specific secreted factors, cytokines and other neural cell targets within the CNS. In particular, we focus on how astrocytes provide energy and cholesterol to neurons, influence synaptogenesis, affect oligodendrocyte biology and instigate cross-talk between the many cellular components of the CNS

Influence of dimensionality on superconductivity in carbon nanotubes

We investigate the electronic instabilities in carbon nanotubes (CNs), looking for the break-down of the one dimensional Luttinger liquid regime due to the strong screening of the long-range part of the Coulomb repulsion. We show that such a breakdown is realized both in ultra-small single wall CNs and multi wall CNs, while a purely electronic mechanism could explain the superconductivity (SC) observed recently in ultra-small (diameter $\sim 0.4 nm$) single wall CNs ($T_c\sim 15 ^{o}K$) and entirely end-bonded multi-walled ones ($T_c\sim 12 ^{o}K$). We show that both the doping and the screening of long-range part of the electron-electron repulsion, needed to allow the SC phase, are related to the intrinsically 3D nature of the environment where the CNs operate.Comment: 5 pages, 3 figures, PACS: 71.10.Pm,74.50.+r,71.20.Tx, to appear in J. Phys. Cond. Ma