Evaluation of MRSA-Screen, a simple anti-PBP 2a slide latex agglutination kit, for rapid detection of methicillin resistance in Staphylococcus aureus.

The MRSA-Screen test (Denka Seiken Co., Ltd., Tokyo, Japan), consisting of a slide latex agglutination kit that detects PBP 2a with a monoclonal antibody, was blindly compared to the oxacillin disk diffusion test, the oxacillin-salt agar screen, and PCR of the mecA gene for the detection of methicillin resistance in Staphylococcus aureus. A total of 120 methicillin-susceptible S. aureus (MSSA) and 80 methicillin-resistant S. aureus (MRSA) isolates, defined by the absence or presence of the mecA gene, respectively, were tested. The MRSA-Screen test, the oxacillin disk diffusion test, and the oxacillin-salt agar screening test showed sensitivities of 100, 61.3, and 82.5% and specificities of 99.2, 96.7, and 98.3%, respectively. We conclude that the MRSA-Screen is a very accurate, reliable, and fast test (15 min) for differentiation of MRSA from MSSA colonies on agar plates.

Construction and Quantitative Evaluation of a Dual Specific Promoter System for Monitoring the Expression Status of Stra8 and c-kit Genes.

Applications of genetic constructs with multiple promoters, which are fused with reporter genes and simultaneous monitoring of various events in cells, have gained special attention in recent years. Lentiviral vectors, with their distinctive characteristics, have been considered to monitor the developmental changes of cells in vitro. In this study, we constructed a novel lentiviral vector (FUM-M), containing two germ cell-specific promoters (Stra8 and c-kit), fused with ZsGreen and DsRed2 reporter genes, and evaluated its efficiency in different cells following treatments with retinoic acid and DMSO. Several cell lines (P19, GC-1 spg and HEK293T) were transduced with this vector, and functional capabilities of the promoters were verified by flow cytometry and quantitative RT-PCR. Our results indicate that FUM-M shows dynamic behavior in the presence and absence of extrinsic factors. A correlation was also observed between the function of promoters, present in the lentiviral construct and the endogenous level of the Stra8 and c-kit mRNAs in the cells. In conclusion, we recommend this strategy, which needs further optimization of the constructs, as a beneficial and practical way to screen chemical inducers involved in cellular differentiation toward germ-like cells.

Field testing of arsenic in groundwater samples of Bangladesh using a test kit based on lyophilized bioreporter bacteria.

A test kit based on living, lyophilized bacterial bioreporters emitting bioluminescence as a response to arsenite and arsenate was applied during a field campaign in six villages across Bangladesh. Bioreporter field measurements of arsenic in groundwater from tube wells were in satisfying agreement with the results of spectroscopic analyses of the same samples conducted in the lab. The practicability of the bioreporter test in terms of logistics and material requirements, suitability for high sample throughput, and waste disposal was much better than that of two commercial chemical test kits that were included as references. The campaigns furthermore demonstrated large local heterogeneity of arsenic in groundwater, underscoring the use of well switching as an effective remedy to avoid high arsenic exposure.

Validation of the NGM SElect(TM) kit

The Swiss national database was launched August 2000 based on the 10 SGM Plus loci. With the aim ofaddressing the needs of the next-generation European STR genotyping systems in Switzerland, wevalidated the NGM SElectTM kit. In this study, we present the results of forensic validation studiesincluding the following aspects: sensitivity, heterozygote peak height ratio calculations, performancewith simulated PCR inhibition, proficiency tests and Swiss population data.

KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours.

A recent randomized EORTC phase III trial, comparing two doses of imatinib in patients with advanced gastrointestinal stromal tumours (GISTs), reported dose dependency for progression-free survival. The current analysis of that study aimed to assess if tumour mutational status correlates with clinical response to imatinib. Pre-treatment samples of GISTs from 377 patients enrolled in phase III study were analyzed for mutations of KIT or PDGFRA by combination of D-HPLC and direct sequencing of tumour genomic DNA. Mutation types were correlated with patients' survival data. The presence of exon 9-activating mutations in KIT was the strongest adverse prognostic factor for response to imatinib, increasing the relative risk of progression by 171% (P<0.0001) and the relative risk of death by 190% (P<0.0001) when compared with KIT exon 11 mutants. Similarly, the relative risk of progression was increased by 108% (P<0.0001) and the relative risk of death by 76% (P=0.028) in patients without detectable KIT or PDGFRA mutations. In patients whose tumours expressed an exon 9 KIT oncoprotein, treatment with the high-dose regimen resulted in a significantly superior progression-free survival (P=0.0013), with a reduction of the relative risk of 61%. We conclude that tumour genotype is of major prognostic significance for progression-free survival and overall survival in patients treated with imatinib for advanced GISTs. Our findings suggest the need for differential treatment of patients with GISTs, with KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the drug.

Factors influencing the adoption of an innovation: an examination of the uptake of the Canadian Heart Health Kit (HHK)

BACKGROUND: There is an emerging knowledge base on the effectiveness of strategies to close the knowledge-practice gap. However, less is known about how attributes of an innovation and other contextual and situational factors facilitate and impede an innovation's adoption. The Healthy Heart Kit (HHK) is a risk management and patient education resource for the prevention of cardiovascular disease (CVD) and promotion of cardiovascular health. Although previous studies have demonstrated the HHK's content validity and practical utility, no published study has examined physicians' uptake of the HHK and factors that shape its adoption. OBJECTIVES: Conceptually informed by Rogers' Diffusion of Innovation theory, and Theory of Planned Behaviour, this study had two objectives: (1) to determine if specific attributes of the HHK as well as contextual and situational factors are associated with physicians' intention and actual usage of the HHK kit; and (2), to determine if any contextual and situational factors are associated with individual or environmental barriers that prevent the uptake of the HHK among those physicians who do not plan to use the kit. METHODS: A sample of 153 physicians who responded to an invitation letter sent to all family physicians in the province of Alberta, Canada were recruited for the study. Participating physicians were sent a HHK, and two months later a study questionnaire assessed primary factors on the physicians' clinical practice, attributes of the HHK (relative advantage, compatibility, complexity, trialability, observability), confidence and control using the HHK, barriers to use, and individual attributes. All measures were used in path analysis, employing a causal model based on Rogers' Diffusion of Innovations Theory and Theory of Planned Behaviour. RESULTS: 115 physicians (follow up rate of 75%) completed the questionnaire. Use of the HHK was associated with intention to use the HHK, relative advantage, and years of experience. Relative advantage and the observability of the HHK benefits were also significantly associated with physicians' intention to use the HHK. Physicians working in solo medical practices reported experiencing more individual and environmental barriers to using the HHK. CONCLUSION: The results of this study suggest that future information innovations must demonstrate an advantage over current resources and the research evidence supporting the innovation must be clearly visible. Findings also suggest that the innovation adoption process has a social element, and collegial interactions and discussions may facilitate that process. These results could be valuable for knowledge translation researchers and health promotion developers in future innovation adoption planning.

Construction and Quantitative Evaluation of a Dual Specific Promoter System for Monitoring the Expression Status of Stra8 and c-kit Genes.

Applications of genetic constructs with multiple promoters, which are fused with reporter genes and simultaneous monitoring of various events in cells, have gained special attention in recent years. Lentiviral vectors, with their distinctive characteristics, have been considered to monitor the developmental changes of cells in vitro. In this study, we constructed a novel lentiviral vector (FUM-M), containing two germ cell-specific promoters (Stra8 and c-kit), fused with ZsGreen and DsRed2 reporter genes, and evaluated its efficiency in different cells following treatments with retinoic acid and DMSO. Several cell lines (P19, GC-1 spg and HEK293T) were transduced with this vector, and functional capabilities of the promoters were verified by flow cytometry and quantitative RT-PCR. Our results indicate that FUM-M shows dynamic behavior in the presence and absence of extrinsic factors. A correlation was also observed between the function of promoters, present in the lentiviral construct and the endogenous level of the Stra8 and c-kit mRNAs in the cells. In conclusion, we recommend this strategy, which needs further optimization of the constructs, as a beneficial and practical way to screen chemical inducers involved in cellular differentiation toward germ-like cells.

Adoption of the Healthy Heart Kit by Alberta family physicians

OBJECTIVE: The Healthy Heart Kit (HHK) is a risk management and patient education kit for the prevention of cardiovascular disease (CVD) and the promotion of CV health. There are currently no published data examining predictors of HHK use by physicians. The main objective of this study was to examine the association between physicians' characteristics (socio-demographic, cognitive, and behavioural) and the use of the HHK. METHODS: All registered family physicians in Alberta (n=3068) were invited to participate in the "Healthy Heart Kit" Study. Consenting physicians (n=153) received the Kit and were requested to use it for two months. At the end of this period, a questionnaire collected data on the frequency of Kit use by physicians, as well as socio-demographic, cognitive, and behavioural variables pertaining to the physicians. RESULTS: The questionnaire was returned by 115 physicians (follow-up rate = 75%). On a scale ranging from 0 to 100, the mean score of Kit use was 61 [SD=26]. A multiple linear regression showed that "agreement with the Kit" and the degree of "confidence in using the Kit" was strongly associated with Kit use, explaining 46% of the variability for Kit use. Time since graduation was inversely associated with Kit use, and a trend was observed for smaller practices to be associated with lower use. CONCLUSION: Given these findings, future research and practice should explore innovative strategies to gain initial agreement among physicians to employ such clinical tools. Participation of older physicians and solo-practitioners in this process should be emphasized.

Inhibition of the Kit Ligand/c-Kit Axis Attenuates Metastasis in a Mouse Model Mimicking Local Breast Cancer Relapse after Radiotherapy.

PURPOSE: Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis. EXPERIMENTAL DESIGN: 4T1 cells were injected in 20 Gy preirradiated mammary tissue to mimic postradiation relapses, or in nonirradiated mammary tissue, as control, of immunocompetent BALB/c mice. Molecular, biochemical, cellular, histologic analyses, adoptive cell transfer, genetic, and pharmacologic interventions were carried out. RESULTS: Tumors growing in preirradiated mammary tissue had reduced angiogenesis and were more hypoxic, invasive, and metastatic to lung and lymph nodes compared with control tumors. Increased metastasis involved the mobilization of CD11b(+)c-Kit(+)Ly6G(high)Ly6C(low)(Gr1(+)) myeloid cells through the HIF1-dependent expression of Kit ligand (KitL) by hypoxic tumor cells. KitL-mobilized myeloid cells homed to primary tumors and premetastatic lungs, to give rise to CD11b(+)c-Kit(-) cells. Pharmacologic inhibition of HIF1, silencing of KitL expression in tumor cells, and inhibition of c-Kit with an anti-c-Kit-blocking antibody or with a tyrosine kinase inhibitor prevented the mobilization of CD11b(+)c-Kit(+) cells and attenuated metastasis. C-Kit inhibition was also effective in reducing mobilization of CD11b(+)c-Kit(+) cells and inhibiting lung metastasis after irradiation of established tumors. CONCLUSIONS: Our work defines KitL/c-Kit as a previously unidentified axis critically involved in promoting metastasis of 4T1 tumors growing in preirradiated mammary tissue. Pharmacologic inhibition of this axis represents a potential therapeutic strategy to prevent metastasis in breast cancer patients with local relapses after radiotherapy. Clin Cancer Res; 18(16); 4365-74. ©2012 AACR.

Les maladies inflarnmatoires chroniques de l'intestin: "survival kit" pour internistes et généralistes [Inflammatory bowel disease: a "survival kit" for general practitioners]

There are approximately 12000 patients suffering from inflammatory bowel disease (IBD) in Switzerland. IBD can be debilitating not only because of the direct consequences in the gut but also because of extraintestinal manifestations. An early diagnosis is the key in defining optimal therapeutic interventions. The management is multidisciplinary and the general practitioner should work in direct collaboration with a gastroenterologist. Optimal management should aim at inducing and maintaining remission as well as reducing the risk of complications such as abcesses, fistulas or colorectal cancer.

Expression des récepteurs aux facteurs de croissance (autres que KIT et PDGFRA) dans les tumeurs stromales gastro-intestinales : étude anatomo-clinique et immunohistochimique de 80 cas

Résumé Les tumeurs stromales gastro-intestinales (GISTs) sont des tumeurs de malignité variable du tractus gastro-intestinal d'évolution difficilement prévisible. Plus de 95% d'entre elles expriment les récepteurs KIT (90%) ou PDGFRA (5%), deux récepteurs aux facteurs de croissance à activité tyrosine-kinase. Peu de données existent quant à l'expression éventuelles d'autres récepteurs aux facteurs de croissance dans les GISTs. Buts de l'étude: Les buts de cette étude étaient double: 1-évaluer l'expression de plusieurs récepteurs aux facteurs de croissance, à l'exclusion de KIT et PDGFRA, au sein d'un collectif de GISTs; 2 -voir s'il existait une corrélation entre l'expression d'un ou plusieurs de ces récepteurs, les données anatomo-pathologiques et/ou l'évolution clinique Matériel et méthodes 80 GISTs ont été examinées sur le plan clinique, anatomo-pathologique, immunohistochimique et évolutif. L'immunoexpression des récepteurs aux facteurs de croissance suivants a été examinée: IGF-1r - insulin-like growth factor-1 receptor, FGFr fibroblast growth factor receptor, C-MET - hepatocyte growth factor receptor, TGFßr (type 1) - transforming growth factor beta receptor, type 1, CD105/endogline, RET et NGFr/gp75 (nerve growth factor receptor). Résultats 52.7% des GISTs exprimaient C-MET, 50% CD105iendogline, 36.7% RET, 25% NGFr/gp75, 17.5°Io TGFßr, 7.5% FGFr, et 0% IGF-lr. La présence ou non d'une expression de CD105 et son intensité étaient significativement associées à une évolution défavorable, tant pour les patients présentant une maladie localisée au diagnostic que pour ceux qui étaient métastatiques au diagnostic. L'expression de C-MET était aussi corrélée, mais de façon moins significative; à une évolution défavorable. En analyse multivariée, l'expression de CD105 est un facteur pronostique indépendant défavorable. Conclusion Les GISTs expriment de façon variable des récepteurs aux facteurs de croissance autres que KIT et PDGFRA. Les récepteurs au TGFß, au FGF et à l'IGF sont peu exprimés. L'endogline/CD105 et le récepteur C-MET sont plus fréquemment exprimés et leur expression est associée à une évolution clinique défavorable.

Al-Bīrūnī's Kitāb Sānk and Kitāb Pātanğal:A Historical and Textual Study

The historical pole of this research distinguishes differing historical and cultural contexts in which the scholar al-Bïrûnî evolved. Between the years 973 and 1017, he lived in Khwarezm (Kät and JürjänTya), Ray, and Jürjän. He also dwelt in Kabul and Ghazna, both situated on a passage between Persia and India, and travelled to some parts of early medieval India between the years 1017 and 1030. Evidence pointing to him having made actual direct observations beyond the abode of Islam remains scanty. According to his writings, only five locales emerge as having been visited by him, all situated in today's Afghanistan and Pakistan. When al-BTrunl visited these places, he encountered the society of the Indian Shähis, who followed a form of Brahmanism. Al-Bïrûnï's knowledge of Sanskrit was the result of a long process that lasted at least 30 years (1000-1030). In order to reach the level of Sanskrit that enabled him to translate several works from Sanskrit into Arabic, he needed to work with literate people well-versed in Sanskrit, who may also have had some comprehension of Arabic, and/or Persian. The textual pole of this dissertation examines the question of the relationship between al- Bïrûnï's Arabic Kitab Sank and Kitäb Pätangal - two works related to Sämkhya-Yoga - and their possible Sanskrit sources. A philological survey based on these Arabic translations and on Sämkhya-Yoga Sanskrit literature highlights that al-Bïrûnï's translations, both, are related to the classical phase in the development of these two Indian philosophical systems. Despite the early spread of Yoga and Sämkhya ideas through Sanskrit literature, it seems that between the early 11th and 16th centuries they lost vitality amongst Indian scholars. Therefore, al-Bïrûnï's translation of works related to these specific Indian philosophies in the early 11th century CE deserves attention. The second pole of this study also demonstrates that al-BTrünl's hermeneutics played an important part in his transmission of these two Indian schools of thought, as he highly transformed his source in both form and substance. This dissertation considers the question of the relationship between al-Bïrûnï's Arabic translations and their possible Sanskrit sources from the viewpoint of Translation Studies; which makes it possible to point out potential candidates for being al-Bïrûnï's original Sanskrit sources with some confidence. Overall, the Kitäb Sank and the Kitäb Pätangal represent original works of Sämkhya and Yoga, as viewed and transmitted by a Perso-Muslim scholar, rather than pure translations of Sanskrit work.