Multivariate analysis of oestrogen receptor alpha, pS2, metallothionein and CD24 expression in invasive breast cancers

Determination of oestrogen receptor alpha (ER) represents at present the most important predictive factor in breast cancers. Data of ours and of other authors suggest that promising predictive/prognostic factors may also include pS2, metallothionein (MT) and CD24. Present study aimed at determining prognostic and predictive value of immunohistochemical determination of ER, pS2, MT, and CD24 expression in sections originating from 104 patients with breast cancer. An univariate and multivariate analysis was performed. Both univariate and multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24 (CD24c-m) represents a strong unfavourable prognostic factor in the entire group and in most of the subgroups of patients. In several subgroups of the patients also a prognostic value was demonstrated of elevated expression of pS2 and of membranous expression of CD24. Our studies demonstrated that all patients with good prognostic factors (higher ER and pS2 expressions, lower MT expression, CD24c-m negativity) survived total period of observation (103 months). The study documented that cytoplasmic-membranous expression of CD24 represented an extremely strong unfavourable prognostic factor in breast cancer. Examination of the entire panel of the studied proteins permitted to select a group of patients of an exceptionally good prognosis

EPIC 219217635: A Doubly Eclipsing Quadruple System Containing an Evolved Binary

We have discovered a doubly eclipsing, bound, quadruple star system in the field of K2 Campaign 7. EPIC 219217635 is a stellar image with $Kp = 12.7$ that contains an eclipsing binary (`EB') with $P_A = 3.59470$ d and a second EB with $P_B = 0.61825$ d. We have obtained followup radial-velocity (`RV') spectroscopy observations, adaptive optics imaging, as well as ground-based photometric observations. From our analysis of all the observations, we derive good estimates for a number of the system parameters. We conclude that (1) both binaries are bound in a quadruple star system; (2) a linear trend to the RV curve of binary A is found over a 2-year interval, corresponding to an acceleration, $\dot \gamma = 0.0024 \pm 0.0007$ cm s$^{-2}$; (3) small irregular variations are seen in the eclipse-timing variations (`ETVs') detected over the same interval; (4) the orbital separation of the quadruple system is probably in the range of 8-25 AU; and (5) the orbital planes of the two binaries must be inclined with respect to each other by at least 25$^\circ$. In addition, we find that binary B is evolved, and the cooler and currently less massive star has transferred much of its envelope to the currently more massive star. We have also demonstrated that the system is sufficiently bright that the eclipses can be followed using small ground-based telescopes, and that this system may be profitably studied over the next decade when the outer orbit of the quadruple is expected to manifest itself in the ETV and/or RV curves.Comment: Accepted for publication in MNRA

Determination of the Her-2/neu gene amplification status in cytologic breast cancer specimens using automated silver-enhanced in-situ hybridization (SISH)

Silver-enhanced in-situ hybridization (SISH) is an emerging tool for the determination of the Her-2/neu amplification status in breast cancer. SISH is technically comparable to fluorescence in-situ hybridization (FISH) but does not require a fluorescence microscope for its interpretation. Although recent studies on histologic evaluations of SISH are promising, we aimed to evaluate its performance on 71 cytologic breast cancer specimens with the new combined Her-2/Chr17 probe. Her-2/neu status as routinely determined by FISH was available for all patients. We found SISH signals in cytologic cell blocks and smear specimens easy to evaluate in most cases. Small numbers of tumor cells and difficulties in identifying tumor cells in lymphocyte-rich backgrounds were limiting factors. Her-2/neu status, as determined by Her-2/Chr17 SISH, was basically identical to the results of the corresponding FISH. The discrepancies were mainly owing to the heterogeneity of Her-2/neu amplification in the tumor tissue. Interobserver agreement for the SISH evaluation was high (kappa value: 0.972). We conclude that Her-2/Chr17 SISH is a useful and accurate method for the evaluation of the Her-2/neu gene amplification status in cytologic breast cancer specimens, particularly in metastatic breast cancer lesions. The advantages of signal permanency and bright-field microscopic result interpretation make this technique an attractive alternative to the current FISH-based gold standard

Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present

Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (–) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (–) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease. [Int Microbiol 2015; 18(1):1-12]Keywords: Mycobacterium tuberculosis · phenotiazines · thioridazine · tuberculosi

ASSESSING KINEMATICS AND KINETICS OF HIGH-SPEED RUNNING USING INERTIAL MOTION CAPTURE: A PRELIMINARY ANALYSIS

The purpose of this study was to determine whether inertial motion capture (IMC) in combination with musculoskeletal modeling is a suitable method to assess lower limb kinematics and kinetics during high-speed running. Optical motion capture (OMC), IMC and ground reaction forces (GRF) were used as input for musculoskeletal models. Kinematics showed excellent correlations (knee: ρ=0.98, rRMSE=21.0%, hip: ρ=0.95, rRMSE=18.5 %, ankle: ρ=0.93, rRMSE=46.6%). The ground reaction force predictions showed varying results (anteroposterior: ρ=0.77, rRMSE=33.4%, mediolateral: ρ=0.04, rRMSE=69.1%, vertical: ρ=0.78, rRMSE=25.7%). The examined IMC and musculoskeletal modeling approach was proven a useful alternative to OMC and force plates for outdoor measurements in high-speed running

EPIC 220204960: A Quadruple Star System Containing Two Strongly Interacting Eclipsing Binaries

We present a strongly interacting quadruple system associated with the K2 target EPIC 220204960. The K2 target itself is a Kp = 12.7 magnitude star at Teff ~ 6100 K which we designate as "B-N" (blue northerly image). The host of the quadruple system, however, is a Kp = 17 magnitude star with a composite M-star spectrum, which we designate as "R-S" (red southerly image). With a 3.2" separation and similar radial velocities and photometric distances, 'B-N' is likely physically associated with 'R-S', making this a quintuple system, but that is incidental to our main claim of a strongly interacting quadruple system in 'R-S'. The two binaries in 'R-S' have orbital periods of 13.27 d and 14.41 d, respectively, and each has an inclination angle of >89 degrees. From our analysis of radial velocity measurements, and of the photometric lightcurve, we conclude that all four stars are very similar with masses close to 0.4 Msun. Both of the binaries exhibit significant ETVs where those of the primary and secondary eclipses 'diverge' by 0.05 days over the course of the 80-day observations. Via a systematic set of numerical simulations of quadruple systems consisting of two interacting binaries, we conclude that the outer orbital period is very likely to be between 300 and 500 days. If sufficient time is devoted to RV studies of this faint target, the outer orbit should be measurable within a year.Comment: 20 pages, 18 figures, 7 tables; accepted for publication in MNRA

Phenothiazines as a solution for multidrug resistant tuberculosis:From the origin to present

Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (–) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (–) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease. [Int Microbiol 2015; 18(1):1-12]Keywords: Mycobacterium tuberculosis · phenotiazines · thioridazine · tuberculosi

Communicating effectiveness of intervention for chronic diseases: what single format can replace comprehensive information?

<p>Abstract</p> <p>Background</p> <p>There is uncertainty about how GPs should convey information about treatment effectiveness to their patients in the context of cardiovascular disease. Hence we study the concordance of decisions based on one of four single information formats for treatment effectiveness with subsequent decisions based on all four formats combined with a pictorial representation.</p> <p>Methods</p> <p>A randomized study comprising 1,169 subjects aged 40–59 in Odense, Denmark. Subjects were randomized to receive information in terms of absolute risk reduction (ARR), relative risk reduction (RRR), number needed to treat (NNT), or prolongation of life (POL) without heart attack, and were asked whether they would consent to treatment. Subsequently the same information was conveyed with all four formats jointly accompanied by a pictorial presentation of treatment effectiveness. Again, subjects should consider consent to treatment.</p> <p>Results</p> <p>After being informed about all four formats, 52%–79% of the respondents consented to treatment, depending on level of effectiveness and initial information format. Overall, ARR gave highest concordance, 94% (95% confidence interval (91%; 97%)) between initial and final decision, but ARR was not statistically superior to the other formats.</p> <p>Conclusion</p> <p>Decisions based on ARR had the best concordance with decisions based on all four formats and pictorial representation, but the difference in concordance between the four formats was small, and it is unclear whether respondents fully understood the information they received.</p

Identification of miR-21-5p and miR-210-3p serum levels as biomarkers for patients with papillary renal cell carcinoma: a multicenter analysis

BACKGROUND: Expression of circulating serum microRNAs has not been studied in a cohort of patients with papillary renal cell carcinoma (pRCC) so far. We hypothesized that miRNA deregulation in malignant tissue is reflected in serum and could be used for non-invasive diagnosis of pRCC as well as differentiation between type 1 and type 2 pRCC. METHODS: We selected 11 differentially regulated miRNAs from the Cancer Genome Atlas (TCGA) pRCC data set as potential serum validation candidates. Serum miRNA expression was determined by qRT-PCR in a total of 34 pRCC type 1, 33 pRCC type 2 and 33 control subjects of three german high-volume medical centers. RESULTS: Heatmap and principal component analysis showed that miRNA expression did not cluster the samples into distinct sample groups and that miRNA levels did not significantly discriminate healthy individuals from patients with pRCC, nor between patients with type 1 and type 2 pRCC. However, miR-21-5p levels were significantly increased in patients with advanced pRCC (>pT3, and/or pN+ and/or pM+) in comparison to localized pRCC. Moreover, adding the expression of miR-210-3p, which was significantly down-regulated in localized pRCC sera in comparison to healthy sera, additionally increased diagnostic accuracy in our study cohort. CONCLUSIONS: In our multicenter cohort, we were not able to identify a single miRNA serum marker for pRCC including its subclasses. However, our study revealed that miR-21-5p levels were elevated in advanced disease (with added diagnostic accuracy via addition of miR-210-3p expression), proposing these two miRs as potential biomarkers in pRCC