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Put together stoma reversal as well as hard working liver resection for anus metastatic cancer: An individual centre retrospective evaluation.
DNA double-strand break (DSB) is a serious type of DNA damage and is known to trigger multiple responses within cells. In the responses, novel relationships among DSB, DSB repair and transcription machineries are created. First, transcription is repressed if DSB occurs near or at the transcription site, termed DSB-induced transcriptional repression, which contributes to DSB repair with the aid of DNA damage-signaling pathways, ATM- or DNA-PKcs-signaling pathway. DSB-induced transcriptional repression is also regulated by transcriptional factors TLP1, NELF, and ENL, as well as chromatin remodeling and organizing factors ZMYND8, CDYL1, PBAF, and cohesin. Second, transcription and RNA promote DSB repair for genome integrity. Transcription factors such as LEDGF, SETD2, and transcriptionally active histone modification, H3K36, facilitate homologous recombination (HR) to overcome DSB. At transcriptional active sites, DNARNA hybrids, termed R-loops, which are formed by DSB, are processed by RAD52 and XPG leading to an activation of the HR pathway. Even in a transcriptionally inactive non-genic site, noncoding RNAs that are produced by RNA polymerase II, DICER, and DROSHA, help to recruit DSB repair proteins at the DSB sites. Third, transcriptional activation itself, however, can induce DSB. Transcriptional activation often generates specific DNA structures such as R-loops and topoisomerase-induced DSBs, which cause genotoxic stress and may lead to genome instability and consequently to cancer. Thus, transcription and DSB repair machineries interact and cooperate to prevent genome instability and cancer. This article is protected by copyright. All rights reserved.Metabolite diffusion measurable in humans in vivo with diffusion-weighted spectroscopy (DW-MRS) provides a window into the intracellular morphology and state of specific cell types. Anisotropic diffusion in white matter is governed by the microscopic properties of the individual cell types and their structural units (axons, soma, dendrites). However, anisotropy is also markedly affected by the macroscopic orientational distribution over the imaging voxel, particularly in DW-MRS, where the dimensions of the volume of interest (VOI) are much larger than those typically used in diffusion-weighted imaging. One way to address the confound of macroscopic structural features is to average the measurements acquired with uniformly distributed gradient directions to mimic a situation where fibers present in the VOI are orientationally uniformly distributed. This situation allows the extraction of relevant microstructural features such as transverse and longitudinal diffusivities within axons and the related microscopic fractional anisotropy. We present human DW-MRS data acquired at 7 T in two different white matter regions, processed and analyzed as described above, and find that intra-axonal diffusion of the neuronal metabolite N-acetyl aspartate is in good correspondence to simple model interpretations, such as multi-Gaussian diffusion from disperse fibers where the transverse diffusivity can be neglected. We also discuss the implications of our approach for current and future applications of DW-MRS for cell-specific measurements. © 2020 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.Adult coloring books have been shown to reduce anxiety in healthy students as well as oncology patients in hospital settings. Anxiety and stress can be a cause of concern in emergency department patients. No previous randomized controlled trials exist evaluating the use of therapeutic coloring in the emergency department. We provide critical analysis of the article, and summarize the social media discussion and a podcast in which the authors discuss their work. This article is protected by copyright. All rights reserved.Neuronal dysfunction and synaptic loss are major hallmarks of Alzheimer's disease (AD) which correlate with symptom severity. Impairment of the γ-aminobutyric acid (GABA)ergic inhibitory interneurons, which form around 20% of the total neuronal network, may be an early event contributing to neuronal circuit dysfunction in neurodegenerative diseases. This study examined the expression of two of the main classes of inhibitory interneurons, parvalbumin (PV) and somatostatin (SST) interneurons in the temporal cortex and hippocampus of AD and control cases, using immunohistochemistry. NSC-185 purchase We report a significant regional variation in the number of PV and SST interneurons with a higher number identified per mm2 in the temporal cortex compared to the hippocampus. Fewer SST interneurons, but not PV interneurons, were identified per mm2 in the temporal cortex of AD cases compared to control subjects. Our results support regional neuroanatomical effects on selective interneuron classes in AD, and suggest that impairment of the interneuronal circuit may contribute to neuronal dysfunction and cognitive decline in AD. © 2020 Japanese Society of Neuropathology.Pemetrexed (PEM) is a useful drug that can be combined with immune checkpoint blockade therapy for treatment of patients with advanced non-small-cell lung cancer (NSCLC). However, its effects on anti-cancer immunity, especially the sensitivity of NSCLC cells to cytotoxic immune cells, have not been fully investigated. In this study, we examined the effects of PEM on the sensitivity of human NSCLC cells to two different types of cytotoxic immune cells. Pre-treatment with PEM increased the sensitivity of two NSCLC cell lines, PC9 and A549, to activated T cells and natural killer (NK) cells, and decreased the expression of anti-apoptotic proteins, including XIAP and Mcl-1. In addition, PEM treatment increased the cell surface expression of PD-L1 on PC9 cells. PEM-induced upregulation of PD-L1 on PC9 cells was at least partially ascribed to activation of ERK and the NFκB pathway. On the other hand, PEM treatment increased the expression of UL16-binding proteins (ULBPs), ligands for the NKG2D NK receptor, on PC9 and A549 cells, as well as the induction of senescence. Although the addition of anti-PD-1 antibody showed no effect on the sensitivity of PEM-treated PC9 and A549 cells to activated T cells, that of anti-NKG2D antibody decreased the enhanced sensitivity of PEM-treated A549 cells to NK cells. These results indicate that PEM can effectively sensitize human NSCLC cells toward cytotoxic immune cells with modulating the expression of immune-regulatory molecules. This article is protected by copyright. All rights reserved.
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