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The article investigates the effectiveness of a fitness program with elements of sports dancing for older preschool children. Research methods - scientific literature analysis, anthropometric, physiological, pedagogical research methods, methods of mathematical statistics. The effectiveness of the developed program was evaluated in a pedagogical experiment, the duration of which was 9 months. The research was carried out on the basis of the sports dance club "Supadans", Kiev. The study involved 46 older preschool children. In the course of the study, the dynamics of indicators of the state of the biogeometric profile of posture was studied. The proposed means had the maximum effect for such indicators of the state of the biogeometric profile of posture as the angle of inclination of the head, the angle at the knee joint, the triangle of the waist and the position of the feet. It is worth noting that it was for these indicators that a statistically significant (p

A microfluidic approach to seeded crystallization has been demonstrated using abacavir hemisulfate, a nucleoside analog reverse transcriptase inhibitor, in droplet reactors to control polymorphism and produce particles with a low particle size distribution. Two techniques are introduced: (1) the first technique involves an emulsion system consisting of a dispersed phase solvent and a continuous phase, which holds slight solubility of the dispersed phase solvent. The dispersed phase contains both a dissolved active pharmaceutical ingredient (API) and seeds of the desired polymorph. While the continuous phase enables solvent extraction, the negligible solubility of the API allows for growth of seeds inside droplets via extraction and subsequent API saturation. This technique demonstrates the ability to crystallize the API in spherical agglomerates via slow extraction of droplets. (2) The second technique utilizes a combined dispersed phase by joining in-flow a seed suspension stream with a supersaturated active pharmaceutical ingredient (API) stream. The combined dispersed phase is emulsified in a continuous phase for which the dispersed phase solvent and the API are both insoluble - droplets are incubated at temperatures below their saturation limit to induce crystal growth. Decreasing the concentration of seeds in its input stream resulted in a decreased number of crystals per droplet, increase in crystal size, and decrease in PSD. Temperature cycling was utilized as a proof of concept to demonstrate the ability to reduce the number of seeds per droplet where the optimal goal is to obtain a single seed per droplet for all droplets. Utilizing this approach in conjunction with the ability to produce monodispersed droplet reactors allows for enhanced control of particle size distribution (PSD) by precisely controlling the available mass for each individual seed crystal. The development of this technique as a proof-of-concept for crystallization can be expanded to manufacturing scales in a continuous manner using parallelized droplet generators and flow reactors to precisely control the temperature and crystal growth kinetics of individual droplets.

23 paginas.-- 10 figuras.-- 6 tablas.-- 88 referencias.-- Supporting information Additional Supporting Information may be found in the online version of this article at the publisher’s web-site: http://dx.doi.org/10.1111/1462-2920.13380

Since 2005, a serious emerging disease called fairway patch has occurred on the fairways, tees and green surrounds of a number of golf courses in New South Wales, Queensland, Victoria and Western Australia. It occurs most commonly on couch or bermudagrass (Cynodon dactylon) but has also been found on kikuyu (Pennisetum clandestinum) fairways at one golf course in Sydney. The disease begins as small patches (5–10 cm diam.) of yellow to tan-coloured grass. The patches enlarge into tan-coloured rings up to 1 m in diameter, which often coalesce to form unsightly brown networks of dead and dying grass. The patches are present all the year round but are most pronounced from late spring to late autumn. Fungal isolation from diseased roots and pathogenicity tests have proven that a slow-growing (ca. 2 mm/day on PDA at 25 °C), dark, septate, non-sporulating fungus is the cause of fairway patch. Phylogenetic analysis of the pathogen’s rDNA ITS and partial 28S sequences has shown that it is a new taxon and is described as Phialocephala bamuru P.T.W. Wong & C. Dong sp. nov. It belongs to a heterogeneous clade that includes Phialocephala, Acephala, Vibrissea, Phaeomollisia and Mollisia spp., but, as it is phylogenetically closest to Phialocephala spp. (94–95 % ITS affinities), it has been described as a Phialocephala species although it has not been shown to produce spores in culture. Research is continuing to study the biology and ecology of this ectotrophic root-infecting fungal pathogen and develop practical strategies to manage the disease.

With a dismal 5-year survival rate of only 8%, pancreatic cancer still remains a very lethal disease. As with most cancers, pancreatic cancer is treated with different combinations of chemotherapeutic drugs which result in side effects and potential drug resistance leading in many cases to the unfortunate demise of the patient. Over recent years, a number of therapies have been developed against numerous molecular targets in cancers. Kinase inhibitors and monoclonal antibodies have been shown to target numerous kinases, growth factor receptors, and cell signaling pathways. This can lead to effects on tumor cell growth, angiogenesis, apoptosis, and the microenvironment. Most recent findings are very promising as they relate to the use of immunotherapy to treat certain cancers. Immune checkpoint inhibitors and cancer vaccines are currently being investigated. In this review, we will highlight some novel molecular targeted strategies that are being used or considered as potential therapeutics to treat patients with pancreatic cancer.

Background: Risk assessment in node-negative (N0) breast cancer patients (pts) is routinely performed by established clinico-pathological algorithms (CP) (Schmidt et al. Ann Oncol 2009). ASCO guidelines also recommend invasion markers uPA/PAI-1 (UP; Harris et al. JCO 2007). The prospective randomized multicenter NNBC 3-Europe trial had two questions: 1) Does UP compared to the CP algorithm improve identification of low-risk node-negative breast cancer patients? 2) Does addition of taxanes to adjuvant chemotherapy improve DFS probability in high-risk node-negative breast cancer? Data are mature to report on the second question only. Methods: Between 2002 and 2009, 4,147 node-negative breast cancer pts were recruited. Risk assessment was performed by CP (43 %) or by UP (57 %). High-risk pts were randomized to receive FE100C*3-Doc*3 (FEC-D) versus FE100C*6 (FEC) as adjuvant chemotherapy. Primary endpoint was disease-free survival probability (DFS). It was planned to accrue 2,572 pts allowing detection of 4% reduction in recurrence probability at 5 years with a power of 80 % at a level of α=0.05 (LogRank) after a minimum observation time of 2.5 years for every recruited patient. Results: In the intent-to-treat population (ITT, n=2,541), 1,286 high-risk pts received FEC-D, and 1,255 received FEC. In July 2012, 90.8 % of patients had reached the minimum observation time – median follow-up was 43.8, and 44.4 months. Main patients' characteristics were distributed similarly between the two chemotherapy arms: median age was 53 yrs, 37.4 % of pts were premenopausal, median tumor size was 1.90 cm, grade 3 was seen in 53.8 %, hormone receptor status was negative in 30.1 % and HER2 was overexpressed in 20.0 %. Mastectomy was performed in 11 %. All planned courses of FEC-D were given in 84.4 %, of FEC in 91.4 % (p < 0.0001). DFS after 2.5 yrs was for FEC-D 97.5 % (+/− 0.45 %) and for FEC 97.3 % (+/− 0.47 %). Overall-survival probability (OS) after 2.5 yrs was 99.0 % (+/− 0.29 %) for FEC-D and 99.5 % (+/− 0.20 %) for FEC. The survival differences between the two arms were not statistically significant. Per-protocol analysis did not reveal any additional results. Conclusions: Use of taxanes does not further reduce the rate of early recurrences and led to significantly more treatment discontinuation. Today, with adequate adjuvant chemotherapy even high-risk node-negative breast cancer patients have an excellent prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-13.

Dans le developpement des cancers, la tumorigenese est une etape essentielle ou un processus a l’origine moleculaire et cellulaire devient tissulaire et surtout clinique. Cette etape est rendue possible par la mise en place et le developpement d’interactions entre les cellules epitheliales transformees et leur microenvironnement stromal tissulaire. Les cellules stromales recrutees et activees sont les myofibroblastes, les macrophages type M2, les cellules precurseurs medullaires et cellules inflammatoires. Le stroma, via ces cellules activees, devient un partenaire actif du developpement tumoral. La proliferation des cellules tumorales est limitee par les conditions de normoxie. Une proliferation rapide entraine le phenomene d’hypoxie cellulaire rendant les cellules tumorales capables de secreter des molecules chimioattractantes et activatrices telle, entre autres, l’adrenomedulline (AM). Les consequences sont: l’attraction dans l’environnement des cellules tumorales hypoxiques de cellules activees capables d’interactions cooperatives. Ces interactions entre myofibroblastes, macrophages, cellules inflammatoires et cellules epitheliales cancereuses concourent a activer en cascade des proproteases en proteases actives, des profacteurs de croissance en facteurs de croissance actifs. Cascade d’activation ou les activateurs du plasminogene type urokinase jouent un role d’origine plaquettaire ou cellulaire, jouent un role fondamental par la mise en route d’une boucle d’activation permanente du plasminogene en plasmine. Le stroma active prend le relais du relargage plaquettaire d’uPA par la secretion de pro-uPA qui peut etre active apres liaison a son recepteur specifique uPAR exprime a la surface des cellules tumorales. Toutes ces molecules activees interagissent avec les cellules endotheliales et pericytaires pour destabiliser les capillaires tissulaires et etablir une neoangiogenese. Cette neoangiogenese en constant remaniement compense en partie l’hypoxie intratumorale entrainee par la croissance tumorale rapide. Mais celle-ci est indispensable pour le phenomene metastatique. L’ensemble de ces interactions n’est qu’un detournement du processus physiologique observe lors de la reparation tissulaire, processus limite dans le temps et termine par la cicatrisation alors que les interactions entre cellules cancereuses et microenvironnement n’ont pas de blocage physiologique. Une meilleure connaissance de ces processus cellulaires et moleculaires peut se traduire a court ou moyen terme par le developpement et l’association de nouvelles therapies ciblees.

Background: Currently, the usefulness of conventional markers for breast carcinoma is limited to assess individual outcome. A statistical model was developed to improve the prognostic accuracy using multiple conventional and emerging prognostic biomarkers. Methods: A total of 305 node-negative breast carcinomas who underwent surgery (+/− radiotherapy) but no adjuvant treatment was selected. Putative prognosis factors including age, tumor size, ER, PR, SBR grading, urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and thymidine kinase (TK) were evaluated. The developed model was internally validated using Harrell's concordance index and calibrated. An external validation of the new model is warranted. Results: Age (p Conclusion: A nomogram can be used to predict probability survival curves for individual breast cancer patients and the effect of treatment options can be evaluated using these models. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-29.

A viral aetiology is one recently evocated theory behind the physiopathology of breast cancer (BC) (Glaser et al, 2004; de Villiers et al, 2005; zur Hausen, 2009). Even though, the mechanistic aspects of cancer induction by infectious agents sound multiples, that is, immunosuppressive, linked to animal–human transmission, direct or indirect oncogenic, there are epidemiological evidences of pathogens involvement in human cancer (zur Hausen, 2009). Among the putative viruses observed in BC tissue, the presence of the Epstein-Barr virus (EBV), a γ-herpes virus, has been reported in a number of studies (Bonnet et al, 1999; Fina et al, 2001; Glaser et al, 2004). The implication of EBV in carcinogenesis associated with other cancers, such as Burkitt's lymphoma, undifferentiated nasopharyngeal carcinoma, as well as Hodgkin's disease, has been well documented (zur Hausen, 1991). However, the presence and implication of EBV in BC remains controversial. The use of conventional technical approaches (in situ hybridisation, immunochemistry and standard PCR) for its detection may explain the conflicting results. Some groups have failed to detect EBV (Chang et al, 1992; Gaffey et al, 1993; Lespagnard et al, 1995; Chu et al, 1998; Glaser et al, 1998; Dadmanesh et al, 2001; Deshpande et al, 2002; Herrmann and Niedobitek, 2003; Perrigoue et al, 2005), whereas results from others show discrepancy and depended on the methodology used. For instance, although Murray et al (2003)could detect EBV nuclear antigen-1 by immunochemistry using 2B4-1 monoclonal antibody, they failed to detect the EBV genome by quantitative PCR. The reasons behind these apparently conflicting results remain to be clarified; however, technical limitations of the assays, dissimilarities in the archival materials and heterogeneity among cluster cells contaminated by the EBV genome may be same. Moreover, EBV positivity has been linked to the presence of latently infected lymphocytes in the tumours (Horiuchi et al, 1994; Brink et al, 2000) thus, questioning the role of EBV in BC (Chu et al, 2001). However, in accordance with other groups (Labrecque et al, 1995; Luqmani and Shousha, 1995; Bonnet et al, 1999; Chu et al, 2001; Huang et al, 2003; Preciado et al, 2005; Arbach et al, 2006; Perkins et al, 2006; Tsai et al, 2007), we have shown the presence of EBV genetic information in a subset of BC tissue with a specific localisation in the epithelial malignant cells (Fina et al, 2001). Currently, real-time PCR (RT–PCR is increasingly being used for both research and clinical applications. For BC in particular, the detection of HER2 gene amplification has been validated by comparison with conventional methods, such as FISH (Lamy et al, 2006). Analysis using RT–PCR might also help to clearly identify the presence of EBV in BC. However, the use of whole tissue can result in the risk of contamination and this risk has been corrected with the introduction of laser-assisted microdissection (Fina et al, 2001). In studies on formalin-fixed sections, micro- and macro-dissected breast tumours have been tested for the presence of multiple regions of the EBV genome with few actually uncovering the viral sequence (McCall et al, 2001; Thorne et al, 2005). Interestingly, by in situ hybridisation using a (35)S-labelled riboprobe for Epstein-Barr encoded RNA 1 and a laser capture microdissection on frozen samples, combined with quantitative PCR (Q-PCR), we showed that EBV localisation was restricted to certain tumour epithelial cell clusters (Fina et al, 2001). In accordance with our findings, Arbach et al (2006) observed that viral load is variable between tumours and is heterogeneously distributed among morphologically identical tumour cells, some clusters containing high genome numbers compared with others negative for EBV genome within the same specimen. In the present study, we hypothesised that EBV-infected BC cells might behave differently in comparison to those negative for EBV. In order to test this, we sought to (i) measure the frequency of EBV positivity using RT–PCR and (ii) to compare the biological phenotype of EBV-negative and EBV-positive tumours.

Les proteases jouent un role crucial dans la reparation tissulaire et le processus de croissance et invasivite tumorale. Cependant sur le plan physiopathologique, la quasi totalite de ces enzymes proteolytiques sont secretees sous forme de proproteases inactives. A l’exception de la cathepsine D qui est capable de s’autoactiver, l’ensemble des autres proteases sont activees par un mecanisme commun a partir de la plasmine, elle-meme derivant de la transformation du plasminogene, pro molecule ubiquitaire. uPA est l’initiateur de la transformation activatrice du plasminogene en plasmine. Son recepteur specifique uPAR est un recepteur de surface extra membranaire, sans domaine transmembranaire ni relie a des voies de transduction du signal intracellulaires. uPAR est cependant capable de s’heterodimeriser avec d’autres molecules membranaires (recepteurs des facteurs de croissance, molecules d’adhesion cellulaire....). Ces molecules transmembranaires, apres heterodimerisation avec uPAR, activent les voies de transduction du signal qui leur sont associees. uPAR est indispensable pour l’activation de uPA, mais egalement pour la mobilisation cellulaire en association avec le complexe integrines αvβ3. L’heterodimerisation uPAR - αvβ3 se fait au front anterieur des lamellipodes des cellules mobilisables (cellules epitheliales cancereuses EMT positives, cellules endotheliales activees, macrophages associes aux tumeurs, neofibroblastes...). PAI1, inhibiteur actif de l’activite uPA, a un role complexe dans la tumorigenese