Purpose This longitudinal study aimed to disentangle the impact of chemotherapy on fatigue and hypothetically associated functional brain network alterations. Methods In total, 34 breast cancer patients treated with chemotherapy (BCC +), 32 patients not treated with chemotherapy (BCC −), and 35 non-cancer controls (NC) were included. Fatigue was assessed using the EORTC QLQ-C30 fatigue subscale at two time points: baseline (T1) and six months after completion of chemotherapy or matched intervals (T2). Participants also underwent resting-state functional magnetic resonance imaging (rsfMRI). An atlas spanning 90 cortical and subcortical brain regions was used to extract time series, after which Pearson correlation coefficients were calculated to construct a brain network per participant per timepoint. Network measures of local segregation and global integration were compared between groups and timepoints and correlated with fatigue. Results As expected, fatigue increased over time in the BCC + group (p = 0.025) leading to higher fatigue compared to NC at T2 (p = 0.023). Meanwhile, fatigue decreased from T1 to T2 in the BCC − group (p = 0.013). The BCC + group had significantly lower local efficiency than NC at T2 (p = 0.033), while a negative correlation was seen between fatigue and local efficiency across timepoints and all participants (T1 rho = − 0.274, p = 0.006; T2 rho = − 0.207, p = 0.039). Conclusion Although greater fatigue and lower local functional network segregation co-occur in breast cancer patients after chemotherapy, the relationship between the two generalized across participant subgroups, suggesting that local efficiency is a general neural correlate of fatigue.

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Aims Glioblastomas are high‐grade brain tumours that are characterised by the accumulation of brain‐resident microglia and peripheral macrophages. Recruitment of these myeloid cells can be facilitated by CCR2/CCL2 signalling. Besides the well‐known CCR2+ macrophages, we have identified microglia expressing CCR2 in glioma tissues. Thus, we investigated how Ccr2‐deficiency of one of the myeloid cell populations affects the other population and tumour biology. Methods We generated four chimeric groups to analyse single and combined Ccr2‐deficiency of microglia and macrophages. On day 21 after tumour cell implantation (GL261), we conducted flow cytometry, immunofluorescence and real‐time polymerase chain reaction analyses. Tumour volume and metabolism were determined by magnetic resonance imaging and magnetic resonance spectroscopy. Moreover, in vitro studies were performed with primary microglia and bone marrow‐derived macrophages. Results We demonstrated reduced infiltration of macrophages and microglia depending on the lack of Ccr2. However, the total number of myeloid cells remained constant except for the animals with dual Ccr2‐knockout. Both microglia and macrophages with Ccr2‐deficiency showed impaired expression of proinflammatory molecules and altered phagocytic activity. Despite the altered immunologic phenotype caused by Ccr2‐deficiency, glioma progression and metabolism were hardly affected. Alterations were detected solely in apoptosis and proliferation of tumours from animals with specific Ccr2‐deficient microglia, whereas vessel stability was increased in mice with Ccr2‐knockout in both cell populations. Conclusion These results indicate that microglia and macrophages provide a homoeostatic balance within glioma tissue and compensate for the lack of the corresponding counterpart. Moreover, we identified that the CCR2/CCL2 axis is involved in the immunologic function of microglia and macrophages beyond its relevance for migration.

Many women with breast cancer suffer from a decline in memory and executive function, particularly after treatment with chemotherapy. Recent neuroimaging studies suggest that changes in network dynamics are fundamental in decline in these cognitive functions. This has, however, not yet been investigated in breast cancer patients. Using resting state functional magnetic resonance imaging, we prospectively investigated whether changes in dynamic functional connectivity were associated with changes in memory and executive function. We examined 34 breast cancer patients that received chemotherapy, 32 patients that did not receive chemotherapy, and 35 no-cancer controls. All participants were assessed prior to treatment and six months after completion of chemotherapy, or at similar intervals for the other groups. To assess memory and executive function, we used the Hopkins Verbal Learning Test – Immediate Recall and the Trail Making Test B, respectively. Using a sliding window approach, we then evaluated dynamic functional connectivity of resting state networks supporting memory and executive function, i.e. the default mode network and frontoparietal network, respectively. Next, we directly investigated the association between cognitive performance and dynamic functional connectivity. We found no group differences in cognitive performance or connectivity measures. The association between dynamic functional connectivity of the default mode network and memory differed significantly across groups. This was not the case for the frontoparietal network and executive function. This suggests that cancer and chemotherapy alter the role of dynamic functional connectivity in memory function. Further implications of these findings are discussed.

Background:The aim of the study was to demonstrate the efficacy of human muscle stem cells (MuSCs) isolated using innovative technology in restoring internal urinary sphincter function in a preclinical animal model. Methods:Colonies of pure human MuSCs were obtained from muscle biopsy specimens. Athymic rats were subjected to internal urethral sphincter damage by electrocauterization. Five days after injury, 2 × 10 5 muscle stem cells or medium as control were injected into the area of sphincter damage (n = 5 in each group). Peak bladder pressure and rise in pressure were chosen as outcome measures. To repeatedly obtain the necessary pressure values, telemetry sensors had been implanted into the rat bladders 10 days prior to injury.Results: There was a highly significant improvement in the ability to build up peak pressure as well as a pressure rise in animals that had received muscle stem cells as compared to control (p = 0.007) 3 weeks after the cells had been injected. Only minimal histologic evidence of scarring was observed in treated rats. Conclusion:Primary human muscle stem cells obtained using innovative technology functionally restore internal urethral sphincter function after injury. Translation into use in clinical settings is foreseeable.