Neurofilament light chain as neuronal injury marker - What is needed to facilitate implementation in clinical laboratory practice?

Neurobiomarkers have attracted significant attention over the last ten years. One promising biomarker is the neurofilament light chain protein (NfL). Since the introduction of ultrasensitive assays, NfL has been developed into a widely used axonal damage marker of relevance to the diagnosis, prognostication, follow-up, and treatment monitoring of a range of neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. The marker is increasingly used clinically, as well as in clinical trials. Even if we have validated precise, sensitive, and specific assays for NfL quantification in both cerebrospinal fluid and blood, there are analytical, as well as pre- and post-analytical aspects of the total NfL testing process, including biomarker interpretation, to consider. Although the biomarker is already in use in specialised clinical laboratory settings, a more general use requires some further work. In this review, we provide brief basic information and opinions on NfL as a biomarker of axonal injury in neurological diseases and pinpoint additional work needed to facilitate biomarker implementation in clinical practice

Prevalence and Characteristics of Campylobacter Species Isolated from Gallbladder of Slaughtered Sheep in Van (Eastern) Turkey

To determine the prevalence of campylobacter species in gallbladder of sheep in Van, (Eastern) Turkey, a total of 220 gallbladder samples from healthy slaughtered sheep were examined bacteriologically in October 2000 and 2002. Of the 110 samples examined each year, 27 (24.6%) and 24 (21.8%) campylobacter strains were isolated, respectively. Of the 27 campylobacter strains isolated in the year 2000, 14 (51.9%) were identified as C. jejuni, 7 (25.9%) C. fetus, 3 (11.1%) C. coli and 3 (11.1%) C. lari. Similar results were obtained in the study performed in 2002, but C. lari could not be isolated. Growth and biochemical characteristics of all identified Campylobacter species with some exceptions were typical of each species. Six of 13 examined C. fetus strains grew well at both 25 °C and 42 °C in thioglycollate medium and on blood agar. C. jejuni strains differed from C. coli only by Na-hippurate hydrolysis test. Results of the present study revealed that C. jejuni is the most common campylobacter species isolated from gallbladders of sheep. The thermophilic campylobacters in significant proportions may cause contamination of carcass during slaughter and transmission of the food-borne pathogens to humans

Reflections on the Evolution of Smart Polymers

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Since Staudinger\u27s recognition that polymers were long chain molecules with covalent bonds between repeating units, the field has evolved tremendously. In addition to their many structural roles, polymers have been developed to exhibit “smart” stimuli-responsive behavior. This article will describe the evolution of selected classes of smart polymers including those responsive to changes in pH, temperature, light, and mechanical stimuli, as well as self-immolative polymers and their application in drug delivery, sensors, and actuators. It will also highlight key advancements in polymer chemistry that enabled rapid progress over the past ∼20 years. Whether the key achievements were predictable will be discussed, and the extent to which polymer science remains an independent science versus a service tool will be addressed. Finally, some possibilities for the evolution of the field over the next 20–30 years will be described

Realistic modelling of quantum point contacts subject to high magnetic fields and with current bias at out of linear response regime

The electron and current density distributions in the close proximity of quantum point contacts (QPCs) are investigated. A three dimensional Poisson equation is solved self-consistently to obtain the electron density and potential profile in the absence of an external magnetic field for gate and etching defined devices. We observe the surface charges and their apparent effect on the confinement potential, when considering the (deeply) etched QPCs. In the presence of an external magnetic field, we investigate the formation of the incompressible strips and their influence on the current distribution both in the linear response and out of linear response regime. A spatial asymmetry of the current carrying incompressible strips, induced by the large source drain voltages, is reported for such devices in the non-linear regime.Comment: 16 Pages, 9 Figures, submitted to PR

PCA-based lung motion model

Organ motion induced by respiration may cause clinically significant targeting errors and greatly degrade the effectiveness of conformal radiotherapy. It is therefore crucial to be able to model respiratory motion accurately. A recently proposed lung motion model based on principal component analysis (PCA) has been shown to be promising on a few patients. However, there is still a need to understand the underlying reason why it works. In this paper, we present a much deeper and detailed analysis of the PCA-based lung motion model. We provide the theoretical justification of the effectiveness of PCA in modeling lung motion. We also prove that under certain conditions, the PCA motion model is equivalent to 5D motion model, which is based on physiology and anatomy of the lung. The modeling power of PCA model was tested on clinical data and the average 3D error was found to be below 1 mm.Comment: 4 pages, 1 figure. submitted to International Conference on the use of Computers in Radiation Therapy 201

Food allergy alters jejunal circular muscle contractility and induces local inflammatory cytokine expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. This was tested in a mouse model.</p> <p>Methods</p> <p>Balb/c mice were epicutaneously sensitized with ovalbumin and challenged with 10 intragastric ovalbumin administrations every second day. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath with increasing concentrations of carbamylcholine chloride (carbachol). Smooth muscle layer thickness and mast cell protease-1 (MMCP-1) positive cell density were assayed histologically. Serum MMCP-1 and immunoglobulins were quantified by ELISA, and mRNA expressions of IFN-γ, IL-4, IL-6 and TGFβ-1 from jejunal and ileal tissue segments were analyzed with quantitative real-time PCR.</p> <p>Results</p> <p>Ovalbumin-specific serum IgE correlated with jejunal MMCP-1⁺cell density. In the allergic mice, higher concentrations of carbachol were required to reach submaximal muscular stimulation, particularly in preparations derived from mice with diarrhoea. Decreased sensitivity to carbachol was associated with increased expression of IL-4 and IL-6 mRNA in jejunum. Smooth muscle layer thickness, as well as mRNA of IFN-γ and TGF-β1 remained unchanged.</p> <p>Conclusion</p> <p>In this mouse model of food allergy, we demonstrated a decreased response to a muscarinic agonist, and increased levels of proinflammatory IL-6 and Th2-related IL-4, but not Th1-related IFN-γ mRNAs in jejunum. IgE levels in serum correlated with the number of jejunal MMCP-1⁺cells, and predicted diarrhoea. Overall, these changes may reflect a protective mechanism of the gut in food allergy.</p

Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

Cataloged from PDF version of article.Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism

Cholesteatoma of the concha bullosa: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cholesteatoma is a relatively common disease within the middle ear cavity, but rarely it manifests in the paranasal sinuses. There is, to the best of our knowledge, only one other published case of cholesteatoma inside the concha bullosa in the English language literature.</p> <p>Case presentation</p> <p>An 81-year-old Caucasian woman was admitted to our hospital complaining of nasal obstruction, headache and diplopia. After endoscopic and radiological evaluation a transnasal endoscopic approach was chosen. The diagnosis of cholesteatoma was established by histopathological evaluation of the mass inside the concha bullosa.</p> <p>Conclusion</p> <p>Although it is rarely seen, cholesteatoma should be considered in the differential diagnosis of slow-growing and destructive paranasal masses.</p

The relation of the pleural thickening in tuberculosis pleurisy with the activity of adenosine deaminase

Selvi, A. Kant, S. Arslan, M. Ozgel. Background: Residual pleural thickening (RPT) still occurs in most patients with tuberculosis pleurisy despite advances in the treatment of tuberculosis. The aim of this study was to evaluate the significance of RPT in tuberculosis pleurisy with the patients clinical findings, biochemical and microbiological properties of pleural effusion and with the total adenosine deaminase (ADA) and isoenzymes levels. Methods: 121 tuberculosis pleurisy patients were evaluated retrospectively. According to posteroanterior chest x-rays, the 63 (52%) cases with the thickness 2 mm or more in lower lateral hemithorax were grouped as I and the 58 (48%) cases without pleural thickness were grouped as II. The amount of pleural effusion was classified into small, medium or massive according to their chest x-rays. In both groups; sex, age, symptoms score, bacteriological and biochemical tests and ADA levels were recorded. Results: 81 (67%) male and 40 (33%) female, overall 121 patients were enrolled into the study. RPT was found higher in males (p=0.014) and the increase ran parallel with the amount of cigarette smoking (p=0.014). RPT was found to be lower in small effusions (p=0.001). The group with RPT, the serum albumin was found lower (p=0.002), pleural fluid total protein (p=0.047) and the ratio of pleural fluid protein to serum protein (p=0.002) were found higher. In group I, total ADA: 69.5±38.9 IU/L and ADA2: 41.3±31.6 IU/L were higher than the cases without RPT (p=0.032, p=0.017, respectively). Conclusions: We suggest that the immunological mechanisms are effective in the development of pleural thickening

Bis(2-{[3-methyl-4-(2,2,2-trifluoro­eth­oxy)-2-pyrid­yl]methyl­sulfan­yl}-1H,3H +-benzimidazolium) 2,5-dichloro-3,6-dioxocyclo­hexa-1,4-diene-1,4-diolate

The title salt, 2C16H15F3N3OS+·C6Cl2O4 2−, is composed of two independent cations of a lansoprazole {systematic name 2-([3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl)-1H-benzo[d]imidazole} inter­mediate and a dianion of chloranilic acid. In the cations of the lansoprazole inter­mediate, the dihedral angles between the least-squares planes of the pyridine and benzimidazole rings are 11.1 (6) and 13.1 (5)°, respectively. The dihedral angles between the mean plane of the benzene ring in the chloranilic acid dianion and the pryidine and benzimidazole rings of the two lansoprazole inter­mediate groups are 71.8 (1)/80.5 (7) and 74.2 (4)/74.8 (6)°. In addition to ionic bond inter­actions, the lansoprazole inter­mediate and chloranilic ions are connected by strong N—H⋯O hydrogen bonds, which produce a set of extended O—H⋯O—H⋯O—H chains along the b axis in the (011) plane. In addition, weak C—H⋯O, C—H⋯F, N—H⋯Cl and π–π [centroid–centroid distances = 3.5631 (15), 3.8187 (13), 3.7434 (17) and 3.842 (2) Å] inter­molecular inter­actions are observed, which contribute to crystal packing stability