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Characterizing a labor pain–related neural signature is a key prerequisite for devising optimized pharmacologic and nonpharmacologic labor pain relief methods. The aim of this study was to describe the neural basis of labor pain and to provide a brief summary of how epidural anesthesia may affect pain–related neuronal activity during labor. Possible future directions are also highlighted. By taking advantage of functional magnetic resonance imaging, brain activation maps and functional neural networks of women during labor that have been recently characterized were compared between pregnant women who received epidural anesthesia and those who did not. In the subgroup of women who did not receive epidural anesthesia, labor–related pain elicited activations in a distributed brain network that included regions within the primary somatosensory cortex (postcentral gyrus and left parietal operculum cortex) and within the traditional pain network (lentiform nucleus, insula, and anterior cingulate gyrus). The activation maps of women who had been administered epidural anesthesia were found to be different—especially with respect to the postcentral gyrus, the insula, and the anterior cingulate gyrus. Parturients who received epidural anesthesia were also compared with those who did not in terms of functional connectivity from selected sensory and affective regions. When analyzing women who did not receive epidural anesthesia, marked bilateral connections from the postcentral gyrus to the superior parietal lobule, supplementary motor area, precentral gyrus, and the right anterior supramarginal gyrus were observed. In contrast, women who received epidural anesthesia showed fewer connections from the postcentral gyrus—being limited to the superior parietal lobule and supplementary motor area. Importantly, one of the most noticeable effects of epidural anesthesia was observed in the anterior cingulate cortex—a primary region that modulates pain perception. The increased outgoing connectivity from the anterior cingulate cortex in women who received epidural anesthesia indicates that the cognitive control exerted by this area might play a major role in the relief from labor pain. These findings not only affirmed the existence of a brain signature for pain experienced during labor, but they also showed that this signature can be altered by the administration of epidural anesthesia. This finding raises a question about the extent to which the cingulo-frontal cortex may exert top-down influences to gate women's experiences of labor-related pain. Because the anterior cingulate cortex is also involved in the processing and modulation of emotional content, such as fear and anxiety, a related question is about the extent to which the use of epidural anesthesia can affect different components of pain perception. Finally, inhibition of anterior cingulate cortex neurons may represent a potential new therapeutic target for alleviating labor-associated pain. [ABSTRACT FROM AUTHOR]

Background & Aims: Tumor-initiating cells are a subset of tumor cells with the ability to form new tumors; however, they account for less than 0.001% of the cells in colorectal or other types of tumors. Mesenchymal stem cells (MSCs) integrate into the colorectal tumor stroma; we investigated their involvement in tumor initiation. Methods: Human colorectal cancer cells, MSCs, and a mixture of both cell types were injected subcutaneously into immunodeficient mice. We compared the ability of each injection to form tumors and investigated the signaling pathway involved in tumor initiation. Results: A small number (≤10) of unsorted, CD133–, CD166−, epithelial cell adhesion molecule–(EpCAM–), or CD133–/CD166−/EpCAM– colorectal cancer cells, when mixed with otherwise nontumorigenic MSCs, formed tumors in mice. Secretion of interleukin (IL)-6 by MSCs increased the expression of CD133 and activation of Janus kinase 2–signal transducer and activator of transcription 3 (STAT3) in the cancer cells, and promoted sphere and tumor formation. An antibody against IL-6 or lentiviral-mediated transduction of an interfering RNA against IL-6 in MSCs or STAT3 in cancer cells prevented the ability of MSCs to promote sphere formation and tumor initiation. Conclusions: IL-6, secreted by MSCs, signals through STAT3 to increase the numbers of colorectal tumor-initiating cells and promote tumor formation. Reagents developed to disrupt this process might be developed to treat patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Hypertension, which might contribute the white matter hyperintensities (Alber et al., 2019), is related to a higher risk of mild cognitive impairment (MCI) (Reitz et al., 2007). Studies used diffusion tensor imaging to reveal white matter lesions. In this cross‐sectional study, we used fixel‐based analysis to investigate the influence of hypertension for white matter differences in patients with MCI. Method: The study protocol complied with the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board. 80 patients with MCI (39 men and 41 girls; mean age: 68.33±7.92 years; 41 patients with hypertension), and 55 healthy control (HC, 30 boys and 25 girls; mean age: 62.02±6.99 years; 14 participants with hypertension) were recruited. MRI was performed with a 3T MR750 scanner (GE Medical Systems, Milwaukee, WI). Diffusion‐weighted images were acquired using a spin‐echo echo‐planar‐imaging sequence with TR/TE/ = 4000 ms/103.5 ms, with along 64 non‐collinear directions using b‐values of 0 and 1000 s/mm2. FBA was performed by MRtrix3 (https://github.com/MRtrix3/mrtrix3) following the recommended procedures (Raffelt et al., 2017). Fixel‐based metric, which included fiber density (FD), fiber bundle cross‐section (FC), and FDC (multiplying FD and FC) was calculated. Statistical analyses of the image were performed with the code fixelcfestat in MRtrix3 with A FWE‐corrected p < 0.05 (Nichols and Holmes, 2002). Result: The white matter difference between HC and patients with MCI with /without hypertension was performed by the comparisons of FBA metrics. In the status without hypertension, patients with MCI reduced in FC and FDC predominantly in the posterior limb and retrolenticular part of internal capsule, superior and posterior corona radiate, when compared with HC. In the status with hypertension, patients with MCI reduced in FC and FDC predominantly in the superior cerebellar peduncle, posterior limb and retrolenticular part of internal capsule, and posterior corona radiate, when compared with HC. Conclusion: This study provided a thorough fixel‐based metrics of white matter differences in patients with MCI and HC with new evidence of FD, FC, and FDC, which helped to clarify the pathological changes influenced by hypertension for specific white matter regions. [ABSTRACT FROM AUTHOR]