What is important for people with nontuberculous mycobacterial disease? An EMBARC-ELF patient survey

Experiencias de los pacientes; Enfermedad pulmonarExperiències dels pacients; Malaltia pulmonarPatient experiences; Lung diseasePatients' experiences of NTM pulmonary disease highlight important and unmet needs for better pharmacological treatment and education of medical staffEuropean Respiratory Society (EMBARC Clinical Research Collaboration

Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

<p>Background: Cancer-Associated Fibroblasts (CAFs) are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR), equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART) for medically inoperable stage-I/II non-small-cell lung cancers.</p> <p>Methods: CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR) at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining.</p> <p>Results: Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell) with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed.</p> <p>Conclusions: Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.</p&gt

MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer

BACKGROUND: Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC. METHODS: From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (n = 335) and correlation analyses with several well-known angiogenic markers were done. RESULTS: 128 miRs were significantly up- or down-regulated; normal versus long DSS (n = 68) and/or normal versus short DSS (n = 63) and/or long versus short DSS (n = 37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR-106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (r = 0.17, P = 0.002), though most prominent in the subgroup with nodal metastasis (r = 0.34, P<0.001). CONCLUSIONS: Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted

Prognostic Impact of MiR-155 in Non-Small Cell Lung Cancer Evaluated by in Situ Hybridization

<p>Abstract</p> <p>Background</p> <p>In recent years, microRNAs (miRNAs) have been found to play an essential role in tumor development. In lung tumorigenesis, targets and pathways of miRNAs are being revealed, and further translational research in this field is warranted. MiR-155 is one of the miRNAs most consistently involved in various neoplastic diseases. We aimed to investigate the prognostic impact of the multifunctional miR-155 in non-small cell lung cancer (NSCLC) patients.</p> <p>Methods</p> <p>Tumor tissue samples from 335 resected stage I to IIIA NSCLC patients were obtained and tissue microarrays (TMAs) were constructed with four cores from each tumor specimen. <it>In situ </it>hybridization (ISH) was used to evaluate the expression of miR-155.</p> <p>Results</p> <p>There were 191 squamous cell carcinomas (SCCs), 95 adenocarcinomas (ACs), 31 large cell carcinomas and 18 bronchioalveolar carcinomas. MiR-155 expression did not have a significant prognostic impact in the total cohort (P = 0.43). In ACs, high miR-155 expression tended to a significant negative prognostic effect on survival in univariate analysis (P = 0.086) and was an independent prognostic factor in multivariate analysis (HR 1.87, CI 95% 1.01 - 3.48, P = 0.047). In SCC patients with lymph node metastasis, however, miR-155 had a positive prognostic impact on survival in univariate (P = 0.034) as well as in multivariate (HR 0.45, CI 95% 0.21-0.96, P = 0.039) analysis.</p> <p>Conclusions</p> <p>The prognostic impact of miR-155 depends on histological subtype and nodal status in NSCLC.</p

Praksisstudienes omfang og organisering i bioingeniørutdanningen

Source at https://www.bioingenioren.no/arkiv/.Siden 2005 har omfang og innhold i bioingeniørutdanningen vært definert av en nasjonal rammeplan for å sikre likeverdig sluttkompetanse for alle kandidater. Fra 2019 ble en ny forskrift om nasjonale retningslinjer fastsatt. Både tidligere rammeplan og nye retningslinjer har regulert læringsutbyttene og omfang av praksis i utdanningen. I denne studien kartlegges omfang og organisering av praksisstudiene ved de ulike studieprogrammene, dette for å undersøke forskjeller og likheter og tilrettelegge for at studiestedene kan lære av hverandre. Det er innhentet data fra hvert studieprogram for omfang og organisering av veiledet intern praksis, ekstern praksis samt bacheloroppgaven. Dette ble kartlagt for alle studiestedene før og etter innføring av nye retningslinjer. Resultatene viser ulikheter i omfang og organisering av praksisstudiene og bacheloroppgaven mellom studieprogrammene i Norge og da særlig i organisering av intern praksis. De nye retningslinjene åpner samtidig opp for en videre fortolkning av praksisbegrepet og av krav til omfang og organisering av praksis. For å sikre likeverdig sluttkompetanse for ferdigutdannede, uavhengig av studiested, er det behov for i større grad enes om hva som gir tilstrekkelig omfang og god kvalitet i praksis i bioingeniørutdanningen. Denne deskriptive studien viser behov for videre forskningssamarbeid mellom studiestedene, for å utvikle en bioingeniørutdanning av best mulig kvalitet for fremtiden

Praksisstudienes omfang og organisering i bioingeniørutdanningen

Siden 2005 har omfang og innhold i bioingeniørutdanningen vært definert av en nasjonal rammeplan for å sikre likeverdig sluttkompetanse for alle kandidater. Fra 2019 ble en ny forskrift om nasjonale retningslinjer fastsatt. Både tidligere rammeplan og nye retningslinjer har regulert læringsutbyttene og omfang av praksis i utdanningen. I denne studien kartlegges omfang og organisering av praksisstudiene ved de ulike studieprogrammene, dette for å undersøke forskjeller og likheter og tilrettelegge for at studiestedene kan lære av hverandre. Det er innhentet data fra hvert studieprogram for omfang og organisering av veiledet intern praksis, ekstern praksis samt bacheloroppgaven. Dette ble kartlagt for alle studiestedene før og etter innføring av nye retningslinjer. Resultatene viser ulikheter i omfang og organisering av praksisstudiene og bacheloroppgaven mellom studieprogrammene i Norge og da særlig i organisering av intern praksis. De nye retningslinjene åpner samtidig opp for en videre fortolkning av praksisbegrepet og av krav til omfang og organisering av praksis. For å sikre likeverdig sluttkompetanse for ferdigutdannede, uavhengig av studiested, er det behov for i større grad enes om hva som gir tilstrekkelig omfang og god kvalitet i praksis i bioingeniørutdanningen. Denne deskriptive studien viser behov for videre forskningssamarbeid mellom studiestedene, for å utvikle en bioingeniørutdanning av best mulig kvalitet for fremtiden.publishedVersio

Praksisstudienes omfang og organisering i bioingeniørutdanningen

Since 2005, scope and content of the biomedical laboratory scientist education have been defined by national guidelines to ensure equal final competence for all candidates. From 2019, a new regulation on national guidelines was approved. Both new and old guidelines have regulated the learning outcomes and scope of practice in education. In this study, the scope and organization of the practical studies at the various study programs are characterized, in order to investigate differences and similarities and to facilitate that the study programs can learn from each other. Data has been obtained from each study program for the scope and organization of supervised internal practice, external practice and the bachelor thesis are reported for all study programs before and after the introduction of new guidelines. This study shows differences in the scope and organization of the practice and the bachelor thesis between the study programs in Norway and especially in the organization of internal practice. At the same time, the new guidelines open up for a further interpretation of the concept of practice and of requirements for the scope and organization of practice. In order to ensure equal final competence for the graduates, regardless of place of study, there is a need to agree to a greater extent on what provides sufficient scope and good quality of clinical practice in the study programs of biomedical laboratory scientists. This descriptive study shows the need for further research collaboration between the educational institutions, in order to develop a biomedical laboratory scientist education of the best possible quality for the future.publishedVersio

Praksisstudienes omfang og organisering i bioingeniørutdanningen

Siden 2005 har omfang og innhold i bioingeniørutdanningen vært definert av en nasjonal rammeplan for å sikre likeverdig sluttkompetanse for alle kandidater. Fra 2019 ble en ny forskrift om nasjonale retningslinjer fastsatt. Både tidligere rammeplan og nye retningslinjer har regulert læringsutbyttene og omfang av praksis i utdanningen. I denne studien kartlegges omfang og organisering av praksisstudiene ved de ulike studieprogrammene, dette for å undersøke forskjeller og likheter og tilrettelegge for at studiestedene kan lære av hverandre. Det er innhentet data fra hvert studieprogram for omfang og organisering av veiledet intern praksis, ekstern praksis samt bacheloroppgaven. Dette ble kartlagt for alle studiestedene før og etter innføring av nye retningslinjer. Resultatene viser ulikheter i omfang og organisering av praksisstudiene og bacheloroppgaven mellom studieprogrammene i Norge og da særlig i organisering av intern praksis. De nye retningslinjene åpner samtidig opp for en videre fortolkning av praksisbegrepet og av krav til omfang og organisering av praksis. For å sikre likeverdig sluttkompetanse for ferdigutdannede, uavhengig av studiested, er det behov for i større grad enes om hva som gir tilstrekkelig omfang og god kvalitet i praksis i bioingeniørutdanningen. Denne deskriptive studien viser behov for videre forskningssamarbeid mellom studiestedene, for å utvikle en bioingeniørutdanning av best mulig kvalitet for fremtiden.publishedVersio

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology