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Background Annual flu vaccination is recommended for children with rheumatic diseases. We investigated the cellular and humoral immune response and safety in pediatric patients that received inactivated influenza vaccines. Methods This is a comparative study of in 41 children with juvenile idiopathic arthritis (JIA) receiving influenza vaccination while being treated with methotrexate (MTX) or biological therapy. The influenza vaccination was administered as a single dose of trivalent influenza vaccine (TIV). Serological tests to monitor seroconversion and seroprotection were performed at baseline and at 4 as well as 12 weeks after vaccination. Results In all of the 41 children with JIA and the 22 healthy children seroconversion and seroprotection were observed for Influenza A. For Influenza B, no adequate seroconversion rates were not detected in any of the groups studied. No significant differences were observed in lymphocyte subpopulations when analysing time points and groups simultaneously. There were no relapses or cases of influenza infection after the vaccination. Our findings do not suggest non-specific immune activation following vaccination based on the distribution and quantity of the lymphocyte subsets that were investigated. Conclusion The present study demonstrates adequate seroprotection rates against influenza A in immunosuppressed children with JIA. The trivalent vaccine had good immunogenicity and was safe to use in both JIA treatment groups.

Brain metastases are life‐threatening complications of triple‐negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo and in vitro techniques and human samples, here we show that pericytes play crucial role in the development of metastatic brain tumors by directly influencing key steps of the development of the disease. Brain pericytes had a prompt chemoattractant effect on breast cancer cells and established direct contacts with them. By secreting high amounts of extracellular matrix proteins, pericytes enhanced adhesion of both melanoma and triple‐negative cancer cells, which might be particularly important in the exclusive perivascular growth of these tumor cells. In addition, pericytes secreted insulin‐like growth factor 2 (IGF2), which had a very significant pro‐proliferative effect on mammary carcinoma, but not on melanoma cells. By inhibiting IGF2 signaling using silencing or picropodophyllin (PPP), we could block the proliferation‐increasing effect of pericytes on breast cancer cells. Administration of PPP (a blood–brain barrier‐permeable substance) significantly decreased the size of brain tumors in mice inoculated with triple‐negative breast cancer cells. Taken together, our results indicate that brain pericytes have significant pro‐metastatic features, especially in breast cancer. Our study underlines the importance of targeting pericytes and the IGF axis as potential strategies in brain metastatic diseases. Here, we show that brain pericytes have significant pro‐metastatic features, especially in breast cancer. Brain pericytes enhanced adhesion of tumor cells to support their exclusive perivascular growth. Pericytes also secreted IGF2 to promote proliferation of cancer cells. By blocking the IGF axis, the proliferation increasing effect of brain pericytes could be inhibited both in vitro and in vivo.

The comparison of human related communication skills of socialized canids may help to understand the evolution and the epigenesis of gesture comprehension in humans. To reconcile previously contradicting views on the origin of dogs' outstanding performance in utilizing human gestures, we suggest that dog-wolf differences should be studied in a more complex way. We present data both on the performance and the behaviour of dogs and wolves of different ages in a two-way object choice test. Characteristic behavioural differences showed that for wolves it took longer to establish eye contact with the pointing experimenter, they struggled more with the handler, and pups also bit her more before focusing on the human's signal. The performance of similarly hand-reared 8-week-old dogs and wolves did not differ in utilizing the simpler proximal momentary pointing. However, when tested with the distal momentary pointing, 4-month-old pet dogs outperformed the same aged hand reared wolves. Thus early and intensive socialisation does not diminish differences between young dogs and wolves in behaviour and performance. Socialised adult wolves performed similarly well as dogs in this task without pretraining. The success of adult wolves was accompanied with increased willingness to cooperate. Thus, we provide evidence for the first time that socialised adult wolves are as successful in relying on distal momentary pointing as adult pet dogs. However, the delayed emergence of utilising human distal momentary pointing in wolves shows that these wild canines react to a lesser degree to intensive socialisation in contrast to dogs, which are able to control agonistic behaviours and inhibition of actions in a food related task early in development. We suggest a \"synergistic\" hypothesis, claiming that positive feedback processes (both evolutionary and epigenetic) have increased the readiness of dogs to attend to humans, providing the basis for dog-human communication.

Therapeutic resistance of cerebral secondary tumours largely depends on unique aspects linked to the neurovascular unit, especially cerebral endothelial cells and astrocytes. By using advanced microscopy techniques, here we explored novel mechanisms related to the neurovascular unit during extravasation and proliferation of triple negative breast cancer cells in the brain. Metastatic mammary carcinoma cells arrested and elongated within one hour in cerebral microvessels, but their number decreased by almost 80% in the first two days. Interestingly, malignant cells induced vasoconstriction and development of intraluminal endothelial plugs, which isolated invading cells from the circulation. During diapedesis – which usually took place on day four and five after inoculation of the tumour cells – continuity of cerebral endothelial tight junctions remained intact, indicating migration of cancer cells through the transcellular pathway. In addition, metastatic cells induced formation of multiluminal vessels and claudin-5-positive endothelial blebs. However, even severe endothelial blebbing could be reversed and the vessel morphology was restored shortly after the tumour cells completed transendothelial migration. Similar to neuro-inflammatory leukocytes, tumour cells migrated not only through the endothelial layer, but through the glia limitans perivascularis as well. Nevertheless, along with the growth of metastatic lesions by co-option of pre-existing capillaries, astrocytes and astrocyte end-feet were gradually expelled from the vessels to the border of the tumour. Taken together, we identified previously unknown mechanisms involved in the reaction of brain resident cells to invading breast cancer cells. Our results contribute to a better understanding of the complex cross-talk between tumour cells and host cells in the brain, which is essential for the identification of new therapeutic targets in this devastating disease.

Fenton reactions with metal complexes of substituted porphyrins and hydrogen peroxide are useful tools for the mineralization of environmentally dangerous substances. In the homogeneous phase, autooxidation of the prophyrin ring may also occur. Covalent binding of porphyrins to a solid support may increase the lifetime of the catalysts and might change its activity. In this study, highly water-insoluble copper and iron complexes of 5,10,15,20-tetrakis(4-aminophenyl)porphyrin were synthesized and bonded covalently to a very hydrophilic silica aerogel matrix prepared by co-gelation of the propyl triethoxysilyl-functionalized porphyrin complex precursors with tetramethoxysilane, followed by a supercritical carbon dioxide drying. In contrast to the insoluble nature of the porphyrin complexes, the as-prepared aerogel catalysts were highly compatible with the aqueous phase. Their catalytic activities were tested in the mineralization reaction of phenol, 3-chlorophenol, and 2,4-dichlorophenol with hydrogen peroxide. The results show that both aerogels catalyzed the oxidation of phenol and chlorophenols to harmless short-chained carboxylic acids under neutral conditions. In batch experiments, and also in a miniature continuous-flow tubular reactor, the aerogel catalysts gradually reduced their activity, due to the slow oxidation of the porphyrin ring. However, the rate and extent of the degradation was moderate and did not exclude the possibility that the as-prepared catalysts, as well as their more stable derivatives, might find practical applications in environment protection.

Proper functioning of the nervous system is largely dependent on the precise regulation of the neuronal environment. By shielding the central nervous system (CNS) from potentially harmful substances, the blood-brain barrier (BBB) has an indispensable role in this process. The BBB is a specialized system of endothelial cells lining brain microvessels, which – supported by pericytes and glial cells – form a selective barrier between the blood and the neural tissue. Under abnormal conditions, permeability of the BBB may increase, which may either trigger or aggravate the disease. Since CNS disorders – at least in their initial phase – usually do not involve the whole brain and spinal cord, but are localized to a certain region, our aim was to understand whether the BBB is regionally heterogeneous at the molecular level. By using bioinformatics tools, we analyzed expression levels of genes specific to cerebral endothelial cells, pericytes or astrocytes in different brain territories. Our results revealed regional heterogeneities in the expression of BBB-associated genes in both human and mouse. Expression pattern of efflux transporters – which have a major role in blocking passage of therapeutic agents through the BBB – proved to be diverse both among brain regions and between mouse and human. Our results indicate that: (1) in silico database analyses are suitable for group-based studies on gene functions, overcoming the limitations of single-gene analyses; (2) high-throughput tests should always be validated using other methods; (3) when using animal models, inter-species differences have to be always considered; (4) when comparing different brain regions, the BBB is heterogeneous at the molecular level, and this might have clinical significance.