Serial Magnetic Resonance Imagings of Multiple Brain Abscesses in a Patient with Pneumococcal Meningoencephalitis

We report a 43-yr-old man manifesting bacterial meningoencephalitis and multiple abscesses by Streptococcus pneumoniae. Serial magnetic resonance (MR) imagings and MR spectroscopy showed the evolution of multiple brain abscesses over 4 weeks: the enhanced rings became thicker and the dimension of whole lesions larger despite shrinkage of the ring-enhanced regions. These findings may be evidence of active inflammation working to sequestrate the lesion and protect the surrounding normal brain parenchyma from additional damage, even in the final stage of the brain abscess

Acupuncture and Moxibustion for Cancer-Related Fatigue: An Overview of Systematic Reviews and Meta-Analysis

Although acupuncture (AT) is used in the treatment of CRF, the evidence from different systematic reviews (SRs) of AT has not yet been comprehensively evaluated. Moxibustion, which is a treatment method that is well established within Traditional East Asian Medicine, applies the heat of burning herbs towards or onto special points on the skin. Commonly, the herb Artemisia vulgaris, is used. It has been used for palliative cancer care, as well as for CRF. The aim of this overview was to evaluate the efficacy of AT and moxibustion in the management of CRF. Eleven databases were searched through for studies that were published from their dates of inception to February 2022. The study selection, the data extraction, and the assessment were performed independently by two researchers. The methodological and report quality were assessed by using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool. The evidence quality was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Fifteen SRs on AT (n = 10) and moxibustion (n = 5) treatments for CRF were included, and they include 169 randomized controlled trials and 14,392 participants. All of the SRs that were evaluated by the AMASTAR-2 had more than one deficiency, and so all of the SRs were rated as either low or critically low. For the GRADE, 18 outcomes were rated as very-low-quality evidence, 13 as low-quality evidence, 3 as moderate-quality evidence, and 0 as high-quality evidence. Most of the SRs reached the potential benefits of AT for CRF. No serious adverse effects were identified. In conclusion, the evidence suggests that, despite the advantages of AT in terms of the improvement in and the safety of the treatment of CRF, the methodological quality of most of these studies is low, which limits our ability to draw definitive meanings. Further research of high quality is needed in order to confirm these findings.T.Y. Choi, L.A., J.H.J. and M.S.L. were supported by the Korea Institute of Oriental Medicine, Korea (KSN2021210). T.A. is the PI of an ongoing study that is funded by a grant from Pink Ribbon, which is a collaboration between The Norwegian Cancer Association and the Breast Cancer Society (Contract no.: 207697-2019). The funder had no role in the study design, the data collection and analysis, the decision to publish, or the preparation of the manuscript.publishedVersio

AKAP12 Mediates Barrier Functions of Fibrotic Scars during CNS Repair

The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process

A Case of Congenital Common Bile Duct Web Treated with Balloon Dilation under Endoscopic Retrograde Cholangiopancreatography in a Young Child

Web in common bile duct (CBD web) is very rare. It is usually asymptomatic and detected incidentally during surgery for other causes in adults. It can be congenital or acquired, however congenital CBD web is extremely rare. Currently, despite its invasiveness and complications, endoscopic retrograde cholangiopancreatography (ERCP) is considered as a useful diagnostic and therapeutic modality in children with hepatobiliary pancreatic diseases as in adults. Herein we report a case of congenital CBD web presenting with acute pancreatitis and choledocholithiasis in a 4-year-old girl which was diagnosed and treated using balloon dilation under ERCP. After balloon dilation of the web, a common pancreatobiliary channel was observed. To the best of our knowledge, a case of congenital CBD web with pancreatobiliary junctional abnormality treated using ERCP in a child has not been reported to date

Investigation of Enhanced Polygon Wall Boundary Model in PNU-MPS Method

With regard to demonstration of fluid flow, there are two descriptions which are Eulerian description and Lagrangian description. In the field of CFD (Computational Fluid Dynamics), a number of studies relevant to grid method based on Eulerian description have been conducted generally. However, when the grid method is employed to simulate flow field, it is inevitable to give consideration to convection term which generates severe numerical diffusion and fluctuation. To obtain the accuracy of solution, a different type of method based on Lagrangian description is come to the fore. Numerical approaches following Lagrangian description have been called meshfree or particle method. Even though particle method does not accompany convection term and fully satisfies conservation of mass, its studies have not been carried out extensively because it is difficult to implement the boundary conditions correctly due to insufficient number of particles in the vicinity of boundary. It affects directly the stability of flow field and accuracy in computation. In MPS (Moving Particle Semi-implicit) method [1], fixed-type of dummy particles are placed inside wall boundary. By placing extra particles as the wall, it seems to be not easy to satisfy the boundary condition for sharp-edged or extremely thin body configuration. In this study, the enhanced polygon wall boundary model, which was suggested originally by Mitsume et al. [2], is employed to the PNU-MPS (Pusan-National-University-modified MPS) method [3] to improve and stabilize the analysis of fluid flow with arbitrary-shaped body including sharp-edged body configuration without any additional particles. The developed simulation method, called as PNU-MPS-POLY, is adopted to the Couette flow and the lid-driven cavity flow with various corner angles. The present simulation results are validated through comparison with the analytic solutions, the experiments [4], and other simulation results [5,6]

Differential Genomic Imprinting and Expression of Imprinted microRNAs in Testes-Derived Male Germ-Line Stem Cells in Mouse

BACKGROUND: Testis-derived male germ-line stem (GS) cells, the in vitro counterpart of spermatogonial stem cells (SSC), can acquire multipotency under appropriate culture conditions to become multipotent adult germ-line stem (maGS) cells, which upon testicular transplantation, produce teratoma instead of initiating spermatogenesis. Consequently, a molecular marker that can distinguish GS cells from maGS cells would be of potential value in both clinical and experimental research settings. METHODS AND FINDINGS: Using mouse as a model system, here we show that, similar to sperm, expression of imprinted and paternally expressed miRNAs (miR-296-3p, miR-296-5p, miR-483) were consistently higher (P<0.001), while those of imprinted and maternally expressed miRNA (miR-127, miR-127-5p) were consistently lower (P<0.001) in GS cells than in control embryonic stem (ES) cells. DNA methylation analyses of imprinting control regions (ICR), that control the expression of all imprinted miRNAs in respective gene clusters (Gnas-Nespas DMR, Igf2-H19 ICR and Dlk1-Dio3 IG-DMR), confirmed that imprinted miRNAs were androgenetic in GS cells. On the other hand, DNA methylation of imprinted miRNA genes in maGS cells resembled those of ES cells but the expression pattern of the imprinted miRNAs was intermediate between those of GS and ES cells. The expression of imprinted miRNAs in GS and maGS cells were also altered during their in vitro differentiation and varied both with the differentiation stage and the miRNA. CONCLUSIONS: Our data suggest that GS cells have androgenetic DNA methylation and expression of imprinted miRNAs which changes to ES cell-like pattern upon their conversion to maGS cells. Differential genomic imprinting of imprinted miRNAs may thus, serve as epigenetic miRNA signature or molecular marker to distinguish GS cells from maGS cells

Acupuncture for managing cancer-related fatigue in breast cancer patients: A systematic review and meta-analysis

Breast cancer (BC) is the most common cancer in women and is a serious threat to women’s health. Cancer-related fatigue (CRF) is a distressing symptom in BC patients during and after chemotherapy or radiation therapy that severely affects quality of life (QoL). AT is widely used for fatigue management. However, the effect of AT on CRF is still uncertain. This study aimed to evaluate the efficacy and safety of AT in the management of CRF in patients with BC. Eleven databases were searched through June 2022. Two researchers independently performed the database search, study selection, data extraction, and risk of bias assessment. Study selection was performed based on predefined Participants, Intervention, Comparators, Outcomes, Study design (PICOS) criteria, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when reporting the results. A meta-analysis was performed according to the Cochrane systematic review method using RevMan 5.3. A total of 12 studies including a total of 1084 participants were included. The results showed that AT had a beneficial effect compared with sham AT (n = 256, SMD = −0.26, 95% CI [−0.51, −0.01], p = 0.04, I2 = 0%) and a long-term effect on fatigue score (n = 209, MD = −0.32, 95% CI [–0.59, −0.04], p = 0.02, I2 = 0%). Meta-analysis showed that AT had a beneficial effect compared with usual care (UC) on fatigue scores (n = 238, SMD = −0.39, 95% CI [−0.66 to −0.12], p = 0.005, I2 = 0%). Of the 12 articles, 3 articles were judged as having a low risk of bias in all domains and hence were of high quality. No serious adverse effects were identified. AT is an effective and safe treatment for CRF, and AT is more effective than sham AT or UC or wait-list control (WLC). Nevertheless, the methodological quality of most of these studies was low, and the included studies/sample sizes were small, so the ability to derive decisive implications was limited. Further research is needed to confirm these findings.publishedVersio

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug&apos;s reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity