Vancouver call for action to strengthen expertise in radiological protection worldwide.

Ionising radiation has been used for over a century for peaceful purposes, revolutionising health care and promoting well-being through its application in industry, science, and medicine. For almost as long, the International Commission on Radiological Protection (ICRP) has promoted understanding of health and environmental risks of ionising radiation and developed a protection system that enables the safe use of ionising radiation in justified and beneficial practices, providing protection from all sources of radiation. However, we are concerned that a shortage of investment in training, education, research, and infrastructure seen in many sectors and countries may compromise society's ability to properly manage radiation risks, leading to unjustified exposure to or unwarranted fear of radiation, impacting the physical, mental, and social well-being of our peoples. This could unduly limit the potential for research and development in new radiation technologies (healthcare, energy, and the environment) for beneficial purposes. ICRP therefore calls for action to strengthen expertise in radiological protection worldwide through: (1) National governments and funding agencies strengthening resources for radiological protection research allocated by governments and international organisations, (2) National research laboratories and other institutions launching and sustaining long-term research programmes, (3) Universities developing undergraduate and graduate university programmes and making students aware of job opportunities in radiation-related fields, (4) Using plain language when interacting with the public and decision makers about radiological protection, and (5) Fostering general awareness of proper uses of radiation and radiological protection through education and training of information multipliers. The draft call was discussed with international organisations in formal relations with ICRP in October 2022 at the European Radiation Protection Week in Estoril, Portugal, and the final call announced at the 6th International Symposium on the System of Radiological Protection of ICRP in November 2022 in Vancouver, Canada.

Perspectives on tolerability and reasonableness.

Judgements on tolerability and reasonableness are central to the optimisation of protection. There are currently several international developments regarding these key considerations which will contribute to the review and evolution of the system of radiological protection. The IRPA15 International Congress brought together the principal issues currently under discussion, and the outcome of these discussions is presented.

Summary of the 2021 ICRP workshop on the future of radiological protection.

The International Commission on Radiological Protection (ICRP) has embarked on a process to review and revise the current System of Radiological Protection ('the System'). To stimulate discussion, the ICRP published two open-access articles: one on aspects of the System that might require review, and another on research that might improve the scientific foundation of the System. Building on these articles, the ICRP organized a Workshop on the Future of Radiological Protection as an opportunity to engage in the review and revision of the System. This digital workshop took place from 14 October-3 November 2021 and included 20 live-streamed and 43 on-demand presentations. Approximately 1500 individuals from 100 countries participated. Based on the subjects covered by the presentations, this summary is organized into four broad areas: the scientific basis, concepts and application of the System; and the role of the ICRP. Some of the key topics that emerged included the following: classification of radiation-induced effects; adverse outcome pathway methodologies; better understanding of the dose-response relationship; holistic and reasonable approaches to optimization of protection; radiological protection of the environment; ethical basis of the System; clarity, consistency and communication of the System; application of the System in medicine and application of the principles of justification and optimization of protection.

Stress Impairs Intentional Memory Control through Altered Theta Oscillations in Lateral Parietal Cortex.

Accumulating evidence suggests that forgetting is not necessarily a passive process but that we can, to some extent, actively control what we remember and what we forget. Although this intentional control of memory has potentially far-reaching implications, the factors that influence our capacity to intentionally control our memory are largely unknown. Here, we tested whether acute stress may disrupt the intentional control of memory and, if so, through which neural mechanism. We exposed healthy men and women to a stress (n = 27) or control (n = 26) procedure before they aimed repeatedly to retrieve some previously learned cue-target pairs and to actively suppress others. While control participants showed reduced memory for suppressed compared with baseline pairs in a subsequent memory test, this suppression-induced forgetting was completely abolished after stress. Using magnetoencephalography (MEG), we show that the reduced ability to suppress memories after stress is associated with altered theta activity in the inferior temporal cortex when the control process (retrieval or suppression) is triggered and in the lateral parietal cortex when control is exerted, with the latter being directly correlated with the stress hormone cortisol. Moreover, the suppression-induced forgetting was linked to altered connectivity between the hippocampus and right dorsolateral prefrontal cortex (PFC), which in turn was negatively correlated to stress-induced cortisol increases. These findings provide novel insights into conditions under which our capacity to actively control our memory breaks down and may have considerable implications for stress-related psychopathologies, such as posttraumatic stress disorder (PTSD), that are characterized by unwanted memories of distressing events.SIGNIFICANCE STATEMENT It is typically assumed that forgetting is a passive process that can hardly be controlled. There is, however, evidence that we may actively control, to some extent, what we remember and what we forget. This intentional memory control has considerable implications for mental disorders in which patients suffer from unwanted (e.g., traumatic) memories. Here, we demonstrate that the capacity to intentionally control our memory breaks down after stress. Using magnetoencephalography (MEG), we show that this stress-induced memory control deficit is linked to altered activity in the lateral parietal cortex and the connectivity between the hippocampus and right prefrontal cortex (PFC). These findings provide novel insights into conditions under which memory control fails and are highly relevant in the context of stress-related psychopathologies.

Cav2.3 R-type calcium channels: from its discovery to pathogenic de novo CACNA1E variants: a historical perspective.

So-called pharmacoresistant (R-type) voltage-gated Ca2+ channels are structurally only partially characterized. Most of them are encoded by the CACNA1E gene and are expressed as different Cav2.3 splice variants (variant Cav2.3a to Cav2.3e or f) as the ion conducting subunit. So far, no inherited disease is known for the CACNA1E gene but recently spontaneous mutations leading to early death were identified, which will be brought into focus. In addition, a short historical overview may highlight the development to understand that upregulation during aging, easier activation by spontaneous mutations or lack of bioavailable inorganic cations (Zn2+ and Cu2+) may lead to similar pathologies caused by cellular overexcitation.

The diversity and evolution of odorant receptors in beetles (Coleoptera).

The insect odorant receptors (ORs) are amongst the largest gene families in insect genomes and the primary means by which insects recognize volatile compounds. The evolution of ORs is thus instrumental in explaining the chemical ecology of insects and as a model of evolutionary biology. However, although ORs have been described from numerous insect species, their analysis within and amongst the insect orders has been hindered by a combination of limited genomic information and a tendency of the OR family toward rapid divergence, gain, and loss. We addressed these issues in the insect order Coleoptera through a targeted genomic annotation effort that included 1181 ORs from one species of the sister order Strepsiptera and 10 species representing the four coleopteran suborders. The numbers of ORs in each species varied from hundreds to fewer than 10, but coleopteran ORs could nevertheless be represented within a scheme of nine monophyletic subfamilies. We observed many radiations and losses of genes amongst OR subfamilies, and the diversity of ORs appeared to parallel the host breadth of the study species. However, some small lineages of ORs persisted amongst many coleopteran families, suggesting receptors of key function that underlie the olfactory ecology of beetles.

Applying science to pressing conservation needs for penguins.

More than half of the world's 18 penguin species are declining. We, the Steering Committee of the International Union for Conservation of Nature Species Survival Commission Penguin Specialist Group, determined that the penguin species in most critical need of conservation action are African penguin (Spheniscus demersus), Galápagos penguin (Spheniscus mendiculus), and Yellow-eyed penguin (Megadyptes antipodes). Due to small or rapidly declining populations, these species require immediate scientific collaboration and policy intervention. We also used a pairwise-ranking approach to prioritize research and conservation needs for all penguins. Among the 12 cross-taxa research areas we identified, we ranked quantifying population trends, estimating demographic rates, forecasting environmental patterns of change, and improving the knowledge of fisheries interactions as the highest priorities. The highest ranked conservation needs were to enhance marine spatial planning, improve stakeholder engagement, and develop disaster-management and species-specific action plans. We concurred that, to improve the translation of science into effective conservation for penguins, the scientific community and funding bodies must recognize the importance of and support long-term research; research on and conservation of penguins must expand its focus to include the nonbreeding season and juvenile stage; marine reserves must be designed at ecologically appropriate spatial and temporal scales; and communication between scientists and decision makers must be improved with the help of individual scientists and interdisciplinary working groups.

Aplicación de Ciencia en las Necesidades de Conservación Urgentes para los Pingüinos. Resumen Más de la mitad de las 18 especies de pingüinos del mundo están disminuyendo. Nosotros, el Comité Directivo de la Unión Internacional para la Conservación de la Naturaleza, Grupo de Especialistas en Pingüinos, determinamos que las especies de pingüinos con necesidades críticas de conservación son el pingüino africano (Spheniscus demersus), el pingüino de las Galápagos (Spheniscus mendiculus) y el pingüino de ojos amarillos (Megadyptes antipodes). Debido a que sus poblaciones son pequeñas o están declinando rápidamente, estos pingüinos requieren colaboración científica e intervención política inmediatas. También utilizamos un método de clasificación por pares para priorizar las necesidades de investigación y conservación para todas las especies de pingüinos. Entre las 12 áreas de investigación que identificamos, las más prioritarias fueron: cuantificación de las tendencias poblacionales, estimación de las tasas demográficas, predicción de las patrones de cambio ambiental y mejora del conocimiento de las interacciones con pesquerías. Las mayores necesidades de conservación fueron: optimizar la planificación marina espacial, mejorar la colaboración de las partes interesadas y desarrollar planes de manejo de desastres y de acción para cada especie. Coincidimos en que, para mejorar la traducción de la ciencia en la conservación efectiva de los pingüinos, la comunidad científica y los organismos financiadores deben reconocer la importancia de la investigación a largo plazo y apoyarla; la investigación sobre pingüinos y su conservación debe expandir su enfoque para incluir la época no reproductiva y la etapa juvenil; las reservas marinas deben ser diseñadas a escalas espaciotemporales ecológicamente apropiadas; y la comunicación entre científicos y tomadores de decisiones debe mejorar con la ayuda de científicos individuales y grupos de trabajo interdisciplinario.

Flat Bands, Indirect Gaps, and Unconventional Spin-Wave Behavior Induced by a Periodic Dzyaloshinskii-Moriya Interaction.

Periodically patterned metamaterials are known for exhibiting wave properties similar to the ones observed in electronic band structures in crystal lattices. In particular, periodic ferromagnetic materials are characterized by the presence of bands and band gaps in their spin-wave spectrum at tunable GHz frequencies. Recently, the fabrication of magnets hosting Dzyaloshinskii-Moriya interactions has been pursued with high interest since properties, such as the stabilization of chiral spin textures and nonreciprocal spin-wave propagation, emerge from this antisymmetric exchange coupling. In this context, to further engineer the magnon band structure, we propose the implementation of magnonic crystals with periodic Dzyaloshinskii-Moriya interactions, which can be obtained, for instance, via patterning of periodic arrays of heavy metal wires on top of an ultrathin magnetic film. We demonstrate through theoretical calculations and micromagnetic simulations that such systems show an unusual evolution of the standing spin waves around the gaps. We also predict the emergence of indirect gaps and flat bands, effects that depend on the strength of the Dzyaloshinskii-Moriya interaction. Such phenomena, which have been previously observed in different systems, are observed here simultaneously, opening new routes towards engineered metamaterials for spin-wave-based devices.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases.

BACKGROUND: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. METHODS: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. RESULTS: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1­4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1­13) and dose per fraction (median: 18.5 Gy; range 3­37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. CONCLUSION: After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

Seasonal plasticity in photoprotection modulates UV-induced hsp gene expression in copepods from a clear lake.

Zooplankton from clear alpine lakes is exposed to stressful levels of solar UV radiation (UVR). As these pelagic organisms experience high UVR and large changes in solar radiation conditions between ice-free and ice-cover periods, they have evolved various strategies to minimize UVR exposure and damage. Here, we studied the relation between photoprotection levels (mycosporine-like amino acids, carotenoids), antioxidant capacities, and gene expression of heat shock proteins (hsps) as indicator of stress in the copepod Cyclops abyssorum tatricus during the course of a year. Expression of hsp60, hsp70, and hsp90 was measured in the field (baseline expression [BE]) and after UVR exposure in the laboratory. The BE differed among genes and seasons (hsp60: high during summer, hsp70 and hsp90: high during the ice-cover period). The gene expression of hsp70 was upregulated after exposure to UVR (up to 5.2-fold change), while hsp60 and hsp90 were only constitutively expressed. A strong seasonal pattern was found in the photoprotective compounds and antioxidant capacities, with highest levels during the ice-free period. The extent of upregulation of hsp70 gene expression increased with decreasing photoprotection levels and peaked 24 h post UVR exposure (9.6-fold change) at the time of lowest photoprotection (February). Our data suggest that hsp70 gene expression is modulated by seasonal plasticity in photoprotection. This ability of adequate stress response is essential for survival in highly variable ecosystems such as alpine lakes.

Polar methane accumulation and rainstorms on Titan from simulations of the methane cycle.

Titan has a methane cycle akin to Earth's water cycle. It has lakes in polar regions, preferentially in the north; dry low latitudes with fluvial features and occasional rainstorms; and tropospheric clouds mainly (so far) in southern middle latitudes and polar regions. Previous models have explained the low-latitude dryness as a result of atmospheric methane transport into middle and high latitudes. Hitherto, no model has explained why lakes are found only in polar regions and preferentially in the north; how low-latitude rainstorms arise; or why clouds cluster in southern middle and high latitudes. Here we report simulations with a three-dimensional atmospheric model coupled to a dynamic surface reservoir of methane. We find that methane is cold-trapped and accumulates in polar regions, preferentially in the north because the northern summer, at aphelion, is longer and has greater net precipitation than the southern summer. The net precipitation in polar regions is balanced in the annual mean by slow along-surface methane transport towards mid-latitudes, and subsequent evaporation. In low latitudes, rare but intense storms occur around the equinoxes, producing enough precipitation to carve surface features. Tropospheric clouds form primarily in middle and high latitudes of the summer hemisphere, which until recently has been the southern hemisphere. We predict that in the northern polar region, prominent clouds will form within about two (Earth) years and lake levels will rise over the next fifteen years.

GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice.

BACKGROUND: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown. METHODS: Ear thickness of wild-type (wt) and Sucnr1-deficient (Sucnr1-/- ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD). Results obtained in this system were contrasted with data generated using passive cutaneous anaphylaxis, ovalbumin-induced asthma and arthritis models. RESULTS: We found augmented ACD reactions in Sucnr1-/- mice. This observation correlated with increased mast cell activation in vitro and in vivo. However, exacerbated mast cell activation in Sucnr1-/- mice did not contribute to the enhancement of asthma or arthritis and seemed to be due to alterations during mast cell development as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. CONCLUSIONS: A deficiency in succinate sensing during mast cell development confers these cells with a hyperactive phenotype. Such a phenomenon does not translate into exacerbation of asthma or mast cell-dependent arthritis. On the contrary, the fact that Sucnr1-/- mice developed reduced arthritic disease, using two different in vivo models, indicates that GPR91 antagonists may have therapeutic potential for the treatment of allergic and autoimmune diseases.

3D quantitative assessment of response to fractionated stereotactic radiotherapy and single-session stereotactic radiosurgery of vestibular schwannoma.

OBJECTIVES: To determine clinical outcome of patients with vestibular schwannoma (VS) after treatment with fractionated stereotactic radiotherapy (FSRT) and single-session stereotactic radiosurgery (SRS) by using 3D quantitative response assessment on MRI. MATERIALS: This retrospective analysis included 162 patients who underwent radiation therapy for sporadic VS. Measurements on T1-weighted contrast-enhanced MRI (in 2-year post-therapy intervals: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12 years) were taken for total tumour volume (TTV) and enhancing tumour volume (ETV) based on a semi-automated technique. Patients were considered non-responders (NRs) if they required subsequent microsurgical resection or developed radiological progression and tumour-related symptoms. RESULTS: Median follow-up was 4.1 years (range: 0.4-12.0). TTV and ETV decreased for both the FSRT and SRS groups. However, only the FSRT group achieved significant tumour shrinkage (p < 0.015 for TTV, p < 0.005 for ETV over time). The 11 NRs showed proportionally greater TTV (median TTV pre-treatment: 0.61 cm(3), 8-10 years after: 1.77 cm(3)) and ETV despite radiation therapy compared to responders (median TTV pre-treatment: 1.06 cm(3); 10-12 years after: 0.81 cm(3); p = 0.001). CONCLUSION: 3D quantification of VS showed a significant decrease in TTV and ETV on FSRT-treated patients only. NR had significantly greater TTV and ETV over time. KEY POINTS: Only FSRT not GK-treated patients showed significant tumour shrinkage over time. Clinical non-responders showed significantly less tumour shrinkage when compared to responders. 3D volumetric assessment of vestibular schwannoma shows advantages over unidimensional techniques.

Comet assay: an essential tool in toxicological research.

The comet assay is a versatile, reliable, cost-efficient, and fast technique for detecting DNA damage and repair in any tissue. It is useable in almost any cell type and applicable to both eukaryotic and prokaryotic organisms. Instead of highlighting one of the numerous specific aspects of the comet assay, the present review aims at giving an overview about the evolution of this widely applicable method from the first description by Ostling and Johanson to the OECD Guideline 489 for the in vivo mammalian comet assay. In addition, methodical aspects and the influence of critical steps of the assay as well as the evaluation of results and improvements of the method are reviewed. Methodical aspects regarding oxidative DNA damage and repair are also addressed. An overview about the most recent works and relevant cutting-edge reviews based on the comet assay with special regard to, e.g., clinical applications, nanoparticles or environmental risk assessment concludes this review. Taken together, the presented overview raises expectations to further decades of successful applications and enhancements of this excellent method.

Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas.

OBJECTIVES: Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors. MATERIALS AND METHODS: This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS. RESULTS: In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient's age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13. CONCLUSION: Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs. CLINICAL RELEVANCE: The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.

[Benign recurring aseptic meningitis. What requires our attention?]. / Benigne rekurrierende aseptische Meningitis. Worauf muss man achten?

Benign recurrent aseptic meningitis (BRAM) or Mollaret's meningitis is a rare disease characterized by recurrent episodes of aseptic meningitis followed by spontaneous recovery. Disease courses over several years have been reported. In most cases, BRAM is caused by HSV-2, less frequently by other viruses or autoimmune diseases. In up to 10 %, the aetiology remains unclear. We present a case of idiopathic BRAM and discuss clinical findings, diagnosis and therapeutic options of this rare illness.

[Chronic cough, pleuritic chest pain, and night sweats in a 45­year-old female smoker]. / Chronischer Husten, atemabhängiger Thoraxschmerz und Nachtschweiß bei einer 45­jährigen Raucherin.

A 45-year-old woman presented with chronic cough, pleuritic chest pain, and night sweat. High-resolution computed tomography revealed multiple bilateral nodular lesions in a centrilobular distribution, primarily located in the upper and mid lung zones with relative sparing of the lung bases. No lymphadenopathy or pleural effusions were detected. Histological analysis confirmed the suspected diagnosis of pulmonary Langerhans cell histiocytosis. After smoking cessation the patient recovered completely.

Serum inflammatory factors and circulating immunosuppressive cells are predictive markers for efficacy of radiofrequency ablation in non-small-cell lung cancer.

In recent years, percutaneous radiofrequency ablation (RFA) has been developed as a new tool in the treatment of non-small-cell lung cancer (NSCLC) in non-surgical patients. There is growing evidence that RFA-mediated necrosis can modulate host immune responses. Here we analysed serum inflammatory factors as well as immunosuppressive cells in the peripheral blood to discover possible prognostic indicators. Peripheral blood and serum samples were collected before RFA and within 3 months after the treatment in a total of 12 patients. Inflammatory cytokines and growth factors were measured in serum by the Bio-Plex assay. Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs ) were evaluated in the peripheral blood via flow cytometry. In patients developing local or lymphogenic tumour relapse (n=4), we found an early significant increase in the concentration of tumour necrosis factor (TNF)-α as well as chemokine (C-C motif) ligand (CCL)-2 and CCL-4 compared to patients without relapse (n=4) and healthy donors (n=5). These changes were associated with an elevated activity of circulating MDSC indicated by an increased nitric oxide (NO) production in these cells. Elevated serum levels of TNF-α, CCL-2 and CCL-4 associated with an increased NO production in circulating MDSCs might be an early indicator of the incomplete RFA and subsequently a potential tumour relapse in NSCLC.

Spinal cord grey matter abnormalities are associated with secondary progression and physical disability in multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), pathological studies have identified substantial demyelination and neuronal loss in the spinal cord grey matter (GM). However, there has been limited in vivo investigation of cord GM abnormalities and their possible functional effects using MRI combined with clinical evaluation. METHODS: We recruited healthy controls (HC) and people with a clinically isolated syndrome (CIS), relapsing remitting (RR) and secondary progressive (SP) MS. All subjects had 3 T spinal cord MRI with measurement of cord cross-sectional area and diffusion tensor imaging metrics in the GM and posterior and lateral column white matter tracts using region of interest analysis. Physical disability was assessed using the expanded disability status scale (EDSS) and motor components of the MS functional composite scale. We calculated differences between MS and HC using a ANOVA and associations with disability using linear regression. RESULTS: 113 people were included in this study: 30 controls, 21 CIS, 33 RR and 29 SPMS. Spinal cord radial diffusivity (RD), fractional anisotropy and mean diffusivity in the GM and posterior columns were significantly more abnormal in SPMS than in RRMS. Spinal cord GM RD (ß=0.33, p<0.01) and cord area (ß=-0.45, p<0.01) were independently associated with EDSS (R(2)=0.77); spinal cord GM RD was also independently associated with a 9-hole peg test (ß=-0.33, p<0.01) and timed walk (ß=-0.20, p=0.04). CONCLUSIONS: The study findings suggest that pathological involvement of the spinal cord GM contributes significantly to physical disability in relapse-onset MS and SPMS in particular.