Effectiveness and tolerability of pegylated interferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust Study

Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community-based trial evaluating the sustained virological response. Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 mu g/kg/wk) and weight. based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91(41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community-based clinical practice. (Ada gastroenterol. belg., 2010, 73, 5-11)

Pauli graphs, Riemann hypothesis, Goldbach pairs

Let consider the Pauli group $\mathcal{P}_q=$ with unitary quantum generators $X$ (shift) and $Z$ (clock) acting on the vectors of the $q$-dimensional Hilbert space via $X|s> =|s+1>$ and $Z|s> =\omega^s |s>$, with $\omega=\exp(2i\pi/q)$. It has been found that the number of maximal mutually commuting sets within $\mathcal{P}_q$ is controlled by the Dedekind psi function $\psi(q)=q \prod_{p|q}(1+\frac{1}{p})$ (with $p$ a prime) \cite{Planat2011} and that there exists a specific inequality $\frac{\psi (q)}{q}>e^{\gamma}\log \log q$, involving the Euler constant $\gamma \sim 0.577$, that is only satisfied at specific low dimensions $q \in \mathcal {A}=\{2,3,4,5,6,8,10,12,18,30\}$. The set $\mathcal{A}$ is closely related to the set $\mathcal{A} \cup \{1,24\}$ of integers that are totally Goldbach, i.e. that consist of all primes $p2$) is equivalent to Riemann hypothesis. Introducing the Hardy-Littlewood function $R(q)=2 C_2 \prod_{p|n}\frac{p-1}{p-2}$ (with $C_2 \sim 0.660$ the twin prime constant), that is used for estimating the number $g(q) \sim R(q) \frac{q}{\ln^2 q}$ of Goldbach pairs, one shows that the new inequality $\frac{R(N_r)}{\log \log N_r} \gtrapprox e^{\gamma}$ is also equivalent to Riemann hypothesis. In this paper, these number theoretical properties are discusssed in the context of the qudit commutation structure.Comment: 11 page

English-speaking Three-year-olds in a Spanish Language Immersion Program

Foreign language immersion programs, wherein the regular school curriculum is taught through the foreign language, have become increasingly widespread in recent years. Although there have been a plethora of studies reporting on second language immersion programs involving school-age programs, there is a dearth of information describing such programs for preschoolers. The purpose of this study was to observe and describe an immersion program for three-year-olds, particularly with respect to specific features of early stages of the language acquisition process. The primary area of interest was to determine the existence of and features of a silent period for these children. Secondary goals included analyzing the kinds of speech that emerged in the early stages of language acquisition, to whom it was directed, and the circumstances under which it was produced; discovering when and how the children manifest bilingual awareness; and ascertaining what strategies were used by them for comprehension. Using a qualitative case study approach, eight monolingual three-year-olds attending a Spanish-language immersion school were observed using participant observation methodology for a total of 98.35 hours between September 6, 1994 and March 17, 1995. Classroom observation was supplemented by questionnaires completed by the children\u27s parents, and by interviews of parents. The data generated revealed that although there is wide variation in the amount of speech produced by the children and when it was produced, there was no silent period for most children. These results are inconsistent with the literature which generally assumes that such a period exists. The study also revealed that although language mixing occurred, it appeared to be a function of language dominance and did not reflect mixing in the input. Children used a variety of strategies to make sense of the Spanish surrounding them, the most important of which was attending to context clues. Finally, all the children manifested bilingual awareness at the same time they began to produce Spanish utterances

CELLS MEDIATING SPECIFIC IN VITRO CYTOTOXICITY : I. DETECTION OF RECEPTOR-BEARING LYMPHOCYTES

Spleen cells from mice immunized with allogeneic tumor cells are incubated on different fibroblast monolayers. The nonadsorbed cells are tested for cytotoxicity against 51Cr-labeled target cells. The cytotoxicity of nonadsorbed cells is much lower after incubation on fibroblasts syngeneic to the immunizing tumor cells than after incubation on fibroblasts syngeneic to the immune cells. This specific decrease of cytotoxic activity depends on the duration and temperature of incubation on monolayers. After incubation the monolayers are trypsinized and pure populations of adsorbed lymphocytes isolated by density gradient fractionation. The cytotoxicity of such trypsin-eluted, gradient-purified lymphocytes is much higher when these lymphocytes are isolated from fibroblasts syngeneic to the immunizing tumor cells than when they are isolated from fibroblasts syngeneic to the immune cells. These experiments demonstrate specific adsorption of immune cells onto fibroblasts carrying the immunizing antigens, and thus prove the existence of specific receptors at the surface of these immune cells. Spleen cells from mice immunized with two types of allogeneic tumor cells bearing different H-2 antigen alleles are incubated on different fibroblast monolayers. The results of such experiments show a differential specific adsorption pattern, suggesting independent adsorption of two populations of immune cells bearing receptors directed against either one or the other immunizing H-2 antigen. The existence of at least a majority of cells, each of which is homogeneous as to the specificity of its receptors, makes it likely that specific receptors are synthetized by the cells that bear them. The role of specific receptor-bearing cells in the killing process is discussed

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines

In the present study, we investigated the possible combined anticancer ability of bee venom (BV) and cisplatin towards two pairs of tumour cell lines: parental cervical carcinoma HeLa cells and their cisplatin-resistant HeLa CK subline, as well as laryngeal carcinoma HEp-2 cells and their cisplatin-resistant CK2 subline. Additionally, we identified several peptides of BV in the BV sample used in the course of the study and determined the exact concentration of MEL. BV applied alone in concentrations of 30 to 60 μg ml-1 displayed dose-dependent cytotoxicity against all cell lines tested. Cisplatin-resistant cervical carcinoma cells were more sensitive to BV than their parental cell lines (IC50 values were 52.50 μg ml-1 for HeLa vs. 47.64 μg ml-1 for HeLa CK cells), whereas opposite results were obtained for cisplatin-resistant laryngeal carcinoma cells (IC50 values were 51.98 μg ml-1 for HEp-2 vs. > 60.00 μg ml-1 for CK2 cells). Treatment with BV alone induced a necrotic type of cell death, as shown by characteristic morphological features, fast staining with ethidium-bromide and a lack of cleavage of apoptotic marker poly (ADP-ribose) polymerase (PARP) on Western blot. Combined treatment of BV and cisplatin induced an additive and/or weak synergistic effect towards tested cell lines, suggesting that BV could enhance the killing effect of selected cells when combined with cisplatin. Therefore, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. Our results suggest that combined treatment with BV could be useful from the point of minimizing the cisplatin concentration during chemotherapy, consequently reducing and/or postponing the development of cisplatin resistance