Application of ERTS imagery to the study of residual kaolins

There are no author-identified significant results in this report

Targeting the Anti-Apoptotic Protein c-FLIP for Cancer Therapy

Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) is a major resistance factor and critical anti-apoptotic regulator that inhibits tumor necrosis factor-alpha (TNF-alpha), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. c-FLIP is expressed as long (c-FLIPL), short (c-FLIPS), and c-FLIPR splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 in a ligand-dependent and-independent fashion, which in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. Moreover, c-FLIPL and c-FLIPS are known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective signaling molecules. Upregulation of c-FLIP has been found in various tumor types, and its downregulation has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIPL in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIPL and c-FLIPS splice variants have been found, and efforts are underway to develop other c-FLIP-targeted cancer therapies. This review focuses on (1) the functional role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and drug resistance; (2) the molecular mechanisms that regulate c-FLIP expression; and (3) strategies to inhibit c-FLIP expression and function

Ecological comparison of the risks of mother-to-child transmission and clinical manifestations of congenital toxoplasmosis according to prenatal treatment protocol

We compared the relative risks of mother-to-child transmission of Toxoplasma gondii and clinical manifestations due to congenital toxoplasmosis associated with intensive prenatal treatment in Lyon and Austria, short term treatment in 51% of Dutch women, and no treatment in Danish women. For each cohort, relative risks were standardized for gestation at seroconversion. In total, 856 mother–child pairs were studied: 549 in Lyon, 133 in Austria, 123 in Denmark and 51 in The Netherlands. The relative risk for mother-to-child transmission compared to Lyon was 1·24 (95% CI: 0·88, 1·59) in Austria; 0·59 (0·41, 0·81) in Denmark; and 0·65 (0·37, 1·01) in The Netherlands. Relative risks for clinical manifestations compared with Lyon (adjusted for follow-up to age 3 years) were: Austria 0·19 (0·04, 0·51); Denmark 0·60 (0·13, 1·08); and The Netherlands 1·46 (0·51, 2·72). There was no clear evidence that the risk of transmission or of clinical manifestations was lowest in centres with the most intensive prenatal treatment

Ano-genital Granulomatosis and Crohn's Disease: A Case Series of Males Presenting with Genital Lymphoedema.

Background and Aims: Ano-genital granulomatosis is a rare chronic granulomatous condition of the skin that causes lymphoedema of the external genitalia. There is a reported association with Crohn's disease. Mechanisms of disease and optimal methods of treatment are poorly understood. Methods: A retrospective casenote review of 25 male patients with ano-genital granulomatosis presenting with genital lymphoedema was performed to determine the clinical and histopathological features of this condition and its relationship to intestinal Crohn's disease. Results: A combination of penile and scrotal oedema was reported at presentation in 80% of patients; 40% of patients had associated intestinal Crohn's disease. The average time from symptom onset to diagnosis was 52.7 months. Half of cutaneous biopsies contained non-caseating granulomas and 14% contained intralymphatic granulomas. In all, 72% of patients responded to oral steroids initially but recurrence was common. Complete or partial response was achieved in 60% of patients treated with azathioprine. Three of six patients responded to anti-tumour necrosis factor [TNF] therapy. A small proportion of patients required circumcision or de-bulking surgery for more debilitating disease. Conclusions: Ano-genital granulomatosis is a rare condition that presents with genital lymphoedema, and there is frequently a protracted delay in diagnosis. There is a very strong association with intestinal Crohn's disease. Genital lymphoedema associated with gastrointestinal symptoms should prompt careful evaluation to exclude both ano-genital granulomatosis and Crohn's disease

A Gas Generating System for Complex Gas Mixtures – Multifunctional Application in PTR Method Optimization and Downstream Methanol Synthesis

The multifunctional applicability of a gas mixing system is presented within the scope of Carbon2Chem® for the simulation of steel mill flue gases and their application in downstream processes. A special focus is set on the parallel operation of the gas mixing system to enable PTR-MS method optimization and methanol synthesis with simulated real gas matrices. Information is gathered for the design of downstream processes and their application, where methanol synthesis is chosen as a model reaction. A proof-of-principle study is presented where operation of a catalytic reactor setup in combination with the gas mixing system and a compressor generate reproducible results. The addition of potential trace components in methanol synthesis is exemplarily demonstrated using ammonia. With respect to the PTR-MS application, the dosing of two calibration gas standards, toluene and carbonyl sulfide, via the gas mixing system were analyzed in detail. The obtained results give insight into its applicability to simulate traces and enables the further development of analytical methods for the analysis of trace impurities in the ppb and ppt range in complex gas mixtures

Emerging targets for glioblastoma stem cell therapy

Glioblastoma multiforme (GBM), designated as World Health Organization (WHO) grade IV astrocytoma, is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations, including GBM stem cells (GSCs) which are believed to contribute to tumor recurrence following initial response to therapies. Emerging evidence demonstrates that GBM tumors are initiated from GSCs. The development and use of novel therapies including small molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of GSCs, immunotherapy, and non-coding microRNAs may provide better means of treating GBM. Identification and characterization of GSC-specific signaling pathways would be necessary to identify specific therapeutic targets which may lead to the development of more efficient therapies selectively targeting GSCs. Several signaling pathways including mTOR, AKT, maternal embryonic leucine zipper kinase (MELK), NOTCH1 and Wnt/β-catenin as well as expression of cancer stem cell markers CD133, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain GSC properties. Moreover, the data published in the Cancer Genome Atlas (TCGA) specifically demonstrated the activated PI3K/AKT/mTOR pathway in GBM tumorigenesis. Studying such pathways may help to understand GSC biology and lead to the development of potential therapeutic interventions to render them more sensitive to chemotherapy and radiation therapy. Furthemore, recent demonstration of dedifferentiation of GBM cell lines into CSC-like cells prove that any successful therapeutic agent or combination of drugs for GBM therapy must eliminate not only GSCs, but the differentiated GBM cells and the entire bulk of tumor cells

Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs

AbstractCancer stem cells (CSCs) or cancer initiating cells (CICs) maintain self-renewal and multilineage differentiation properties of various tumors, as well as the cellular heterogeneity consisting of several subpopulations within tumors. CSCs display the malignant phenotype, self-renewal ability, altered genomic stability, specific epigenetic signature, and most of the time can be phenotyped by cell surface markers (e.g., CD133, CD24, and CD44). Numerous studies support the concept that non-stem cancer cells (non-CSCs) are sensitive to cancer therapy while CSCs are relatively resistant to treatment. In glioblastoma stem cells (GSCs), there is clonal heterogeneity at the genetic level with distinct tumorigenic potential, and defined GSC marker expression resulting from clonal evolution which is likely to influence disease progression and response to treatment. Another level of complexity in glioblastoma multiforme (GBM) tumors is the dynamic equilibrium between GSCs and differentiated non-GSCs, and the potential for non-GSCs to revert (dedifferentiate) to GSCs due to epigenetic alteration which confers phenotypic plasticity to the tumor cell population. Moreover, exposure of the differentiated GBM cells to therapeutic doses of temozolomide (TMZ) or ionizing radiation (IR) increases the GSC pool both in vitro and in vivo. This review describes various subtypes of GBM, discusses the evolution of CSC models and epigenetic plasticity, as well as interconversion between GSCs and differentiated non-GSCs, and offers strategies to potentially eliminate GSCs

Chronic abdominal pain in inflammatory bowel disease: a practical guide

Pain is common in inflammatory bowel disease (IBD), yet many patients feel their pain is not addressed by healthcare professionals. Listening to a patient’s concerns about pain, assessing symptoms and acknowledging the impact these have on daily life remain crucial steps in addressing pain in IBD. While acute pain may be effectively controlled by pain medication, chronic pain is more complex and often pharmacological therapies, particularly opioids, are ineffective. Low-dose tricyclic antidepressants and psychological approaches, including cognitive–behavioural therapy, have shown some promise in offering effective pain management while lifestyle changes such as a trial of low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet in those with overlapping irritable bowel syndrome may also reduce pain. Patients benefit from a long-term, trusting relationship with their healthcare professional to allow a holistic approach combining pharmacological, psychological, lifestyle and dietary approaches to chronic pain. We present a practical review to facilitate management of chronic abdominal pain in IBD

Using clinical cases to guide healthcare.

Evidence-based practice (EBP) has been the gold standard in healthcare for nearly three centuries and aims to assist physicians in providing the safest and most effective healthcare for their patients. The well-established hierarchy of evidence lists systematic reviews and meta-analyses at the top however these methodologies are not always appropriate or possible and in these instances case-control studies, case series and case reports are utilised to support EBP. Case-control studies allow simultaneous study of multiple risk factors and can be performed rapidly and relatively cheaply. A recent example was during the Coronavirus pandemic where case-control studies were used to assess the efficacy of personal protective equipment for healthcare workers. Case series and case reports also play a role in EBP and are particularly useful to study rare diseases such as inflammatory bowel disease in transgender and gender non-conforming individuals. They are also vital in generating and disseminating early signals and encouraging further research. Whilst these methodologies have weaknesses, particularly with regards to bias and loss of patient confidentiality for rare pathologies, they have an important part to play in EBP and when appropriately utilised can significantly impact upon clinical practice

Impact of Size, Secondary Structure, and Counterions on the Binding of Small Ribonucleic Acids to Layered Double Hydroxide Nanoparticles

Use of ribonucleic acid (RNA) interference to regulate protein expression has become an important research topic and gene therapy tool, and therefore, finding suitable vehicles for delivery of small RNAs into cells is of crucial importance. Layered double metal hydroxides such as hydrotalcite (HT) have shown great promise as nonviral vectors for transport of deoxyribose nucleic acid (DNA), proteins, and drugs into cells, but the adsorption of RNAs to these materials has been little explored. In this study, the binding of small RNAs with different lengths and levels of secondary structure to HT nanoparticles has been analyzed and compared to results obtained with small DNAs in concurrent experiments. Initial experiments established the spectrophotometric properties of HT in aqueous solutions and determined that HT particles could be readily sedimented with near 100% efficiencies. Use of RNA+HT cosedimentation experiments as well as electrophoretic mobility shift assays demonstrated strong adsorption of RNA 25mers to HT, with twofold greater binding of single-stranded RNAs relative to double-stranded molecules. Strong affinities were also observed with ssRNA and dsRNA 54mers and with more complex transfer RNA molecules. Competition binding and RNA displacement experiments indicated that RNA-HT associations were strong and were only modestly affected by the presence of high concentrations of inorganic anions