Bezold's abscess, an uncommon complication of otitis media and cholesteatoma: a case report.

Background: Mastoiditis frequently occurs in children as they are more susceptible to middle ear infections, but infrequently occurs in adults. A rare complication that results from mastoiditis and an obstructing cholesteatoma is a Bezold's abscess, of which there are less than 100 reported cases in literature to date.

Case Presentation: Here, we present a case of a 72-year-old Caucasian man who has had no history of prior ear infections and was found to have a cholesteatoma and advanced acute coalescent mastoiditis complicated by a Bezold's abscess.

Expanding the dimensionality of bis(tetrazolyl)alkane-based Fe(II) coordination polymers by the application of dinitrile coligands.

Reactions between 1,2-di(tetrazol-2-yl)ethane (ebtz), 1,6-di(tetrazol-2-yl)hexane (hbtz) or 1,1'-di(tetrazol-1-yl)methane (1ditz) and Fe(BF) in the presence of adiponitrile (ADN), glutaronitrile (GLN) or suberonitrile (SUN) resulted in the formation of coordination polymers [Fe(μ-ebtz)(μ-ADN)](BF) (1), [Fe(μ-hbtz)(μ-ADN)](BF) (2), [Fe(μ-1ditz)(GLN)](BF)·GLN (3) and [Fe(μ-1ditz)(μ-SUN)](BF)·SUN (4). It was established that the application of dinitriles allows an increase in the dimensionality of the ebtz and hbtz based systems while maintaining the structure of the polymeric units characteristic of previously studied mononitrile based analogues. In 3 and 4, regardless of the type of dinitrile coligand, the motif of 2D polymeric layers constituted by 1ditz molecules remains preserved.

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.

Synergic Effect of Phthalide Lactones and Fluconazole and Its New Analogues as a Factor Limiting the Use of Azole Drugs against Candidiasis.

The resistance of and other pathogenic yeasts to azole antifungal drugs has increased rapidly in recent years and is a significant problem in clinical therapy. The current state of pharmacological knowledge precludes the withdrawal of azole drugs, as no other active substances have yet been developed that could effectively replace them. Therefore, one of the anti-yeast strategies may be therapies that can rely on the synergistic action of natural compounds and azoles, limiting the use of azole drugs against candidiasis.

Comprehensive studies on building a scalable downstream process for mRNAs to enable mRNA therapeutics.

In recent years, mRNA-based therapeutics have been a fast-growing new class of biologics that can, in principle, encode any protein(s) directly in patients to treat various diseases. mRNA vaccines have been proven to work efficiently, have high potency, and can be rapidly developed and deployed, which is critical for a quick responses in the case of a pandemic. Such agile development is enabled by rapid synthesis of RNA in vitro using recombinant enzymes rather than relying on lengthy and complex cell culture processes.

Insurance lesions: Does a second lesion make a difference?

Introduction: In radiofrequency ablation procedures for cardiac arrhythmia, the efficacy of creating repeated lesions at the same location ("insurance lesions") remains poorly studied. We assessed the effect of type of tissue, power, and time on the resulting lesion geometry during such multiple ablation procedures.

Methods: A custom ex vivo ablation model was used to assess lesion formation.

Spatiotemporal Studies of the One-Dimensional Coordination Polymer [Fe(ebtz) (C H CN) ](BF ) : Tug of War between the Nitrile Reorientation Versus Crystal Lattice as a Tool for Tuning the Spin Crossover Properties*.

Reaction of 1,2-di(tetrazol-2-yl)ethane (ebtz) with Fe(BF ) ⋅6 H O in different nitriles yields one-dimensional coordination polymers [Fe(ebtz) (RCN) ](BF ) ⋅nRCN (n=2 for R=CH (1) and n=0 for R=C H (2) C H (3), C H (4), CH Cl (5)) exhibiting spin crossover (SCO). SCO in 1 and 3-5 is complete and occurs above 160 K. In 2, it is shifted to lower temperatures and is accompanied by wide hysteresis (T =78 K, T =123 K) and proceeds extremely slowly.

Two ways of spin crossover in an iron(ii) coordination polymer associated with conformational changes of a bridging ligand.

1,4-Di(1-ethyl-1,2,3-triazol-5-yl)butane (bbtre) was prepared by lithiation of 1-ethyl-1,2,3-triazole, followed by alkylation with 1,4-dibromobutane. The ligand bbtre forms a three-dimensional network with Fe(ii), [Fe(bbtre)3](ClO4)2·2CH3CN, that exhibits thermally induced spin crossover (SCO). A change of temperature or change of spin state results in various types of structural transformation, leading to different structures that are stable in strictly defined temperature ranges.

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.

Prognostic gene expression signature for high-grade serous ovarian cancer.

Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.

Cell entry of a host-targeting protein of oomycetes requires gp96.

The animal-pathogenic oomycete Saprolegnia parasitica causes serious losses in aquaculture by infecting and killing freshwater fish. Like plant-pathogenic oomycetes, S. parasitica employs similar infection structures and secretes effector proteins that translocate into host cells to manipulate the host.

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.

Patients And Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time.

Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.

Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer.

Design, Setting, And Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium.

Deubiquitinating Enzyme USP9X Suppresses Tumor Growth via LATS Kinase and Core Components of the Hippo Pathway.

The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway.

MRTF/SRF dependent transcriptional regulation of TAZ in breast cancer cells.

Dysregulation of Hippo pathway results in activation of transcriptional co-activators YAP/TAZ in breast cancer. Previously, we showed that overexpression of TAZ in breast cancer promotes cell migration, invasion and tumorigenesis. Here, we show that upregulation of TAZ in breast cancers could also be due to dysregulation of TAZ transcription.

Cytotoxic drug-induced, p53-mediated upregulation of caspase-8 in tumor cells.

Apoptosis resistance is crucially involved in cancer development and progression, represents the leading cause for failure of anticancer therapy and is caused, for example, by downregulation of proapoptotic intracellular signaling molecules such as caspase-8. We found that the cytotoxic drugs methotrexate (MTX) and 5-fluorouracil (5-FU) were both able to sensitize resistant tumor cells for induction of apoptosis by p53-mediated upregulation of caspase-8. Increase in caspase-8 messenger RNA and protein expression disabled tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced proliferation and restored sensitivity toward TRAIL-induced apoptosis which was inhibited by transfection of p53 decoy oligonucleotides, p53 shRNA and caspase-8 shRNA.

Tumor necrosis factor-related apoptosis-inducing ligand-mediated proliferation of tumor cells with receptor-proximal apoptosis defects.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might represent a future cytotoxic drug to treat cancer as it induces apoptosis in tumor cells without toxicity in animal trials. We recently described that in contrast to apoptosis, TRAIL mediates tumor cell survival and proliferation in certain tumor cells. Here we studied the effect of TRAIL on 18 cell lines and 53 primary leukemia cells and classified these tumor cells into four groups: TRAIL, anti-DR4 or anti-DR5 induced apoptosis in group A cells, whereas they had no effect on group 0 cells and mediated proliferation in group P cells.

Losses at 3p common deletion sites in subtypes of kidney tumours: histopathological correlations.

Deletions of the short arm of chromosome 3 (3p) have been recognized as characteristic features of clear cell renal cell carcinomas (clear cell RCC). We analysed 55 clear-cell RCCs and 30 non-clear-cell kidney tumours (10 papillary and 7 chromophobic RCCs, 11 oncocytomas and 2 collecting duct carcinomas) in loss of heterozygosity (LOH) studies using microsatellite markers for previously observed regions of common deletions on 3p in kidney tumours (3p25, 3p21.3, 3p14.

Loss of heterozygosity at the familial RCC t(3;8) locus in most clear cell renal carcinomas.

Previously, we had observed that more than 80% of clear cell renal carcinomas (RCCs) exhibited loss of heterozygosity (LOH) between the microsatellite markers D3S1285 (in 3p14.1) and D3S1295 (in 3p21.1), a region which includes the protein tyrosine phosphatase gamma locus (PTPRG locus, PTP gamma gene) and the 3p14.

Abnormalities of chromosome 5q correlate with morphologic features of better prognosis in clear cell renal carcinomas.

Aberrations of the long arm of chromosome 5 (5q) were studied in 79 clear cell renal carcinomas (clear cell RCC) by LOH (loss of heterozygosity) method, using microsatellite markers D5S107, CRTL1, LNS-CA, IL-9.RP1, CFS1R and GeneScan analysis software. Alterations of chromosome 5q were detected in 42% of cases.

Common regions of deletion in chromosome regions 3p12 and 3p14.2 in primary clear cell renal carcinomas.

Nearly all clear cell renal cell carcinomas (RCCs) exhibit loss of alleles on the short arm of chromosome 3. Loss and mutation at the von Hippel-Lindau (VHL) gene at 3p25 probably occurs in most RCCs and, since the VHL gene was recently cloned, data on VHL involvement in RCCs is accumulating. However, the region 3p14-p12, a region that contains the familial RCC-associated t(3;8)(p14.