A nationwide study on topography and efficacy of the stroke treatment network in the Czech republic

The SITS (Safe Implementation of Thrombolysis in Stroke)-EAST project was launched in 2007 to support evidence-based stroke treatments, including thrombolytic treatments (TLTs), in Central and Eastern Europe. The aim of this study was to detail the topography, efficacy, and specific characteristics of stroke centers in the Czech Republic (CZ), the country with the highest rate of TLT. The nationwide study was performed between September and November 2007 through a questionnaire sent to all centers registered in SITS. The questionnaire contained 25 questions addressing how centers met recommendations for primary and comprehensive stroke centers in 2006. Center characteristics predicting the number of TLTs were identified by multiple regression analysis. Altogether, data were obtained from 42 centers (88% response rate) with the following characteristics [median (min–max)]: catchment area population 150,000 (90,000–750,000); number of strokes/year 420 (150–1,589); number of TLTs 7.5 (2–45); number of physicians specialized in stroke 3 (1–7). Centers treated 4.3% of the patients with ischemic strokes with tissue plasminogen activator. A stroke unit was present in 32 (78%) departments. Rescue interventional therapies were performed in 11 (26%). Financial problems restricted TLT in 14 (35%) centers. Fourteen factors were associated with the number of TLTs in univariate regression analysis, but in multiple regression analysis, only the catchment area population (p < 0.001), >3 physicians specialized in stroke (p < 0.001), and the presence of an acute interventional program (p < 0.006) remained significant. This study provides the fundamental stroke treatment network data that are essential for certification and further SITS-EAST TLT expansion.     

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

With 2 to 3% of the worldwide population chronically infected, hepatitis C virus (HCV) infection continues to be a major health care burden. Unfortunately, current interferon-based treatment options are not effective in all patients and are associated with significant side effects. Consequently, there is an ongoing need to identify and develop new anti-HCV therapies. Toward this goal, we previously developed a cell-based HCV infection assay for antiviral compound screening based on a low-multiplicity-of-infection approach that uniquely allows for the identification of antiviral compounds that target cell culture-derived HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we report the screening of the NCI Diversity Set II library, containing 1,974 synthesized chemical compounds, and the identification of compounds with specific anti-HCV activity. In combination with toxicity counterscreening, we identified 30 hits from the compound library, 13 of which showed reproducible and dose-dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic concentration [CC₅₀]/50% effective concentration [EC₅₀]) of greater than 6. Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as infectious HCVcc-based assembly and secretion analysis, we determined that different compounds within this group of candidate inhibitors target different steps of viral infection. The compounds identified not only will serve as biological probes to study and further dissect the biology of viral infection but also should facilitate the development of new anti-HCV therapeutic treatments.     

SPECT-CT visualization and biopsy of sentinel lymph nodes in patients with stage IAB–IIA cervical cancer

Annals of Nuclear Medicine - To evaluate the diagnostic accuracy of sentinel lymph node (SLN) biopsy and to determine clinical significance of preoperative single-photon emission computed...     

High prevalence of cestodes in Artemia spp. throughout the annual cycle: relationship with abundance of avian final hosts

Brine shrimp, Artemia spp., act as intermediate hosts for a range of cestode species that use waterbirds as their final hosts. These parasites can have marked influences on shrimp behavior and fecundity, generating the potential for cascading effects in hypersaline food webs. We present the first comprehensive study of the temporal dynamics of cestode parasites in natural populations of brine shrimp throughout the annual cycle. Over a 12-month period, clonal Artemia parthenogenetica were sampled in the Odiel marshes in Huelva, and the sexual Artemia salina was sampled in the Salinas de Cerrillos in Almería. Throughout the year, 4–45 % of A. parthenogenetica were infected with cestodes (mean species richness?=?0.26), compared to 27–72 % of A. salina (mean species richness?=?0.64). Ten cestode species were recorded. Male and female A. salina showed similar levels of parasitism. The most prevalent and abundant cestodes were those infecting the most abundant final hosts, especially the Greater Flamingo Phoenicopterus ruber. In particular, the flamingo parasite Flamingolepis liguloides had a prevalence of up to 43 % in A. parthenogenetica and 63.5 % in A. salina in a given month. Although there was strong seasonal variation in prevalence, abundance, and intensity of cestode infections, seasonal changes in bird counts were weak predictors of the dynamics of cestode infections. However, infection levels of Confluaria podicipina in A. parthenogenetica were positively correlated with the number of their black-necked grebe Podiceps nigricollis hosts. Similarly, infection levels of Anomotaenia tringae and Anomotaenia microphallos in A. salina were correlated with the number of shorebird hosts present the month before. Correlated seasonal transmission structured the cestode community, leading to more multiple infections than expected by chance.     

Boronate–dextran: An acid-responsive biodegradable polymer for drug delivery

Stimuli-responsive drug carriers have great potential to deliver bioactive materials on demand and to a specific location within the human body. Acid-responsive drug carriers can specifically release their payload in the acidic microenvironments of tumors or in the endosomal or lysosomal compartments within a cell. Here we describe an approach to functionalize vicinal diols of dextran with hydrophobic boronate esters in order to produce a water insoluble boronate dextran polymer (B-Dex), which spontaneously forms acid-responsive nanoparticles in water. We show the encapsulation of a hydrophobic anticancer drug doxorubicin into the particles. Hydrolysis of the boronate esters under mild acidic conditions recovers the hydrophilic hydroxyl groups of the dextran and disrupts the particles into water soluble fragments thereby leading to a pH-responsive release of the drug. According to dynamic light scattering (DLS) and UV/Vis spectroscopy, mild acidic conditions (pH 5.0) lead to a three-fold increase in the degradation of the particles and a four-fold increase in the release of the drug compared to the behavior of particles at pH 7.4. In vitro tests in Hela cells show no toxicity of the empty B-Dex nanoparticles, while the toxicity of doxorubicin-loaded B-Dex nanoparticles is comparable to that of the doxorubicin·HCl drug. Confocal fluorescence microscopy reveals that 100% of the Hela cells uptake doxorubicin-loaded B-Dex nanoparticles with a preferential accumulation of the nanoparticles in the cytoplasm.     

High-risk human papillomavirus DNA in paraaortic lymph nodes in advanced stages of cervical carcinoma

BackgroundParaaortic lymph nodes represent the second level in the lymphatic spread of cervical cancer. Recent studies have confirmed the association of HPV DNA in pelvic lymph nodes in early-stage disease with metastatic involvement and a less favourable prognosis.ObjectiveThe aim of our study was to detect 13 high-risk genotypes of HPV in paraaortic nodes harvested from patients with FIGO IB2–IIIB tumours and correlate findings with histopathology.Study designThe study involved patients with advanced cervical cancer who had undergone low paraaortic lymphadenectomy. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Patients with non-HPV related cancers were used as a control group.ResultsThe study involved 24 cervical cancer patients. High-risk HPV DNA was found in the primary tumour of all cases and in PALN in 16 (67%) cases. The most frequent genotype was HPV 16, both in the tumour and in the paraaortic lymph nodes (83% and 54%, respectively). Metastatic involvement of paraaortic lymph nodes was identified in 8 cases (33%), which all were also HPV DNA positive. No HPV DNA was detected in PALN in any of 22 control group cases.ConclusionsUsing the cytobrush technique, the presence of at least one HR HPV genotype in the primary tumour was identified in all the patients. The metastatically involved paraaortic lymph nodes always contained the DNA of at least one HPV genotype present in the primary tumour. Determination of clinical significance of HR HPV DNA presence in histologically negative lymph nodes requires further follow-up of the cohort.     

Statistical evaluation of coherence estimated from optimally beamformed signals

In this paper we investigate a situation where we want to perform a coherence analysis of two signal sources, one of which is measured directly, and the other is measured through a sensor array affected by noise. To extract the latter signal, we suggest the use of the optimal beamforming with reference. We note, however, that this approach results in a coherence estimate that is noticeably biased, and cannot be evaluated by the known statistical tests. We therefore derive a new statistical test, that allows the evaluation of the biased coherence estimate. We illustrate the applicability of our methodology on the coherence analysis of EEG and EMG signals. We note that the suggested approach has several advantages over the surface Laplacian, which is a spatial filter commonly used in the EEG–EMG coherence analysis.     

Immunohistochemical study of jejunal graft mucosa cell populations during the initial adaptation phase in the host body in rats

The character of the changes in cell populations within the jejunal graft mucosa during the initial adaptation phase in the host body was investigated. 24 adult male Wistar rats underwent intestinal heterotopic allotransplantation. Aorto-aortal and porto-caval anastomoses were performed using the end-to-side microsurgery technique. Graft tissues were compared to the intestinal tissues of the recipients. This study demonstrates that: (1) Distinct injury to the graft mucosa 1 h after transplantation was accompanied by significant reduction in numbers of epithelial secretory cell populations. The injury was more intense in the mesenteric portion. Six hours after transplantation the graft mucosa was covered by a continuous epithelium, but the number of goblet and Paneth cells was found to be less than 30% of that in the recipient epithelium. (2) In comparison with recipients, myeloperoxidase-positive cell numbers increased significantly in the graft mucosa 1 h after transplantation. In the epithelial layer, denudation and destruction of villi was associated with a significant reduction in intraepithelial lymphocyte numbers. A significant decrease in mucosal mast cell numbers was detected 6 h after transplantation. They attained only 10% of the number found in the recipients. (3) Time-dependent changes in the graft mucosa revealed that CD163-positive cells increased significantly in the graft mucosa during 6 h after transplantation and reached the level found in the recipients. In contrast, the myeloperoxidase-positive cell population significantly decreased in the graft mucosa within the initial 6 h.