Risk Assessment of Medical Study Procedures in the Documents Submitted to a Research Ethics Committee

Several frameworks assist research ethics committees (RECs) in risk assessment of medical studies. However, little is known about how researchers describe risks of the procedures in study protocols and participant information sheets. We examined 349 study protocols and participant information sheets submitted to an REC and evaluated the risk assessments performed for 1,510 study procedures. Risks had been assessed for 399 (26%) procedures in study protocols and for 425 (28%) procedures in participant information sheets. Physical risks were assessed six times more frequently than psychological risks. Risks of medical procedures are not always detailed in study protocols or participant information sheets. Risk descriptions of procedures believed to be familiar to potential participants may be omitted.Peer reviewe

Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas

Background: TGF-β induces apoptosis in Burkitt's lymphoma cells. Results: PUMA is a direct target gene of TGF-β signaling and is required for rapid apoptosis. Conclusion: TGF-β-mediated direct induction of PUMA contributes to apoptosis in human and murine c-Myc-driven lymphomas. Significance: These studies link TGF-β signaling and transcriptional activation of PUMA, two factors with critical roles in regulating B-cell survival

X-ray absorption spectroscopy study of diluted magnetic semiconductors: Zn1-xMxSe (M = Mn, Fe, Co) and Zn1-xMnxY (Y = Se, Te)

We have investigated 3d electronic states of doped transition metals in II-VI diluted magnetic semiconductors, Zn1-xMxSe (M = Mn, Fe, Co) and Zn1-xMnxY (Y = Se, Te), using the transition-metal L2,3-edge X-ray absorption spectroscopy (XAS) measurements. In order to explain the XAS spectra, we employed a tetragonal cluster model calculation, which includes not only the full ionic multiplet structure but also configuration interaction (CI). The results show that CI is essential to describe the experimental spectra adequately, indicating the strong hybridization between the transition metal 3d and the ligand p orbitals. In the study of Zn1-xMnxY (Y = Se, Te), we also found considerable spectral change in the Mn L2,3-edge XAS spectra for different ligands, confirming the importance of the hybridization effects in these materials.Comment: This paper consists of 22 pages including 4 figures. This paper is submitted to Physical Review

Yhtenäiset vaatimukset lääketieteen ja hammaslääketieteen tohtorintutkinnolle Suomessa

Oulussa järjestettiin 13.6.2018 lääketieteen ja hammaslääketieteen tohtorintutkinnon konsensuskokous, jossa käytiin läpi vallitsevia käytäntöjä ja muutostarpeita. Ohjeellinen tutkinnon laajuus on neljä vuotta kokopäiväistä työtä, ja muodollisesti tutkinnon myöntää yhtä yliopistoa lukuun ottamatta aina vastaava tiedekunta. Ohjaajia on tyypillisesti kahdesta kolmeen, ja yksi on pääohjaaja. Seurantaryhmä on käytössä tai ollaan ottamassa käyttöön kaikissa yliopistoissa. Aktiivinen seurantaryhmä tukee merkittävästi ohjausprosessia. Väitöskirjojen asiantuntijoina toimivat esitarkastajat ja vastaväittäjät ovat yleensä muualta kuin suorituspaikan yliopistosta. Osittain tästä syystä suuria eroja eri yliopistojen tohtorintutkinnon vaatimusten välillä ei todettu. Haasteena väitöskirjatyössä on kliinisen työn paine ja nuorten kollegoiden ruuhkavuosien kuormittuminen, mitkä heikentävät mahdollisuuksia tutkimustyöhön. Myönteisiä muutoksia ovat olleet tohtoriopintojen systematisoituminen sekä ohjaamisen tason ja väitöskirjantekijöiden tuen paraneminen. Kaikki osallistuneet kannattivat käytäntöjen vakiinnuttamista ja yhtenäistämistä säännöllisellä konsensuskokoustyöskentelyllä.</p

Influence of wood species on toxicity of log-wood stove combustion aerosols: A parallel animal and air-liquid interface cell exposure study on spruce and pine smoke

Background Wood combustion emissions have been studied previously either by in vitro or in vivo models using collected particles, yet most studies have neglected gaseous compounds. Furthermore, a more accurate and holistic view of the toxicity of aerosols can be gained with parallel in vitro and in vivo studies using direct exposure methods. Moreover, modern exposure techniques such as air-liquid interface (ALI) exposures enable better assessment of the toxicity of the applied aerosols than, for example, the previous state-of-the-art submerged cell exposure techniques. Methods We used three different ALI exposure systems in parallel to study the toxicological effects of spruce and pine combustion emissions in human alveolar epithelial (A549) and murine macrophage (RAW264.7) cell lines. A whole-body mouse inhalation system was also used to expose C57BL/6 J mice to aerosol emissions. Moreover, gaseous and particulate fractions were studied separately in one of the cell exposure systems. After exposure, the cells and animals were measured for various parameters of cytotoxicity, inflammation, genotoxicity, transcriptome and proteome. Results We found that diluted (1:15) exposure pine combustion emissions (PM1 mass 7.7 ± 6.5 mg m− 3, 41 mg MJ$^{Zahl}$) contained, on average, more PM and polycyclic aromatic hydrocarbons (PAHs) than spruce (PM1 mass 4.3 ± 5.1 mg m− 3, 26 mg MJ− 1) emissions, which instead showed a higher concentration of inorganic metals in the emission aerosol. Both A549 cells and mice exposed to these emissions showed low levels of inflammation but significantly increased genotoxicity. Gaseous emission compounds produced similar genotoxicity and a higher inflammatory response than the corresponding complete combustion emission in A549 cells. Systems biology approaches supported the findings, but we detected differing responses between in vivo and in vitro experiments. Conclusions Comprehensive in vitro and in vivo exposure studies with emission characterization and systems biology approaches revealed further information on the effects of combustion aerosol toxicity than could be achieved with either method alone. Interestingly, in vitro and in vivo exposures showed the opposite order of the highest DNA damage. In vitro measurements also indicated that the gaseous fraction of emission aerosols may be more important in causing adverse toxicological effects. Combustion aerosols of different wood species result in mild but aerosol specific in vitro and in vivo effects

Neither loss of Bik alone, nor combined loss of Bik and Noxa, accelerate murine lymphoma development or render lymphoma cells resistant to DNA damaging drugs

The pro-apoptotic BH3-only protein, BIK, is widely expressed and although many critical functions in developmental or stress-induced death have been ascribed to this protein, mice lacking Bik display no overt abnormalities. It has been postulated that Bik can serve as a tumour suppressor, on the basis that its deficiency and loss of apoptotic function have been reported in many human cancers, including lymphoid malignancies. Evasion of apoptosis is a major factor contributing to c-Myc-induced tumour development, but despite this, we found that Bik deficiency did not accelerate Eμ-Myc-induced lymphomagenesis. Co-operation between BIK and NOXA, another BH3-only protein, has been previously described, and was attributed to their complementary binding specificities to distinct subsets of pro-survival BCL-2 family proteins. Nevertheless, combined deficiency of Bik and Noxa did not alter the onset of Eμ-Myc transgene induced lymphoma development. Moreover, although p53-mediated induction of Bik has been reported, neither Eμ-Myc/Bik−/− nor Eμ-Myc/Bik−/−Noxa−/− lymphomas were more resistant than control Eμ-Myc lymphomas to killing by DNA damaging drugs, either in vitro or in vivo. These results suggest that Bik, even in combination with Noxa, is not a potent suppressor of c-Myc-driven tumourigenesis or critical for chemotherapeutic drug-induced killing of Myc-driven tumours

Photocatalytic Decomposition of Formic Acid on Mo2C-Containing Catalyst

Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to filtered air and wood smoke. Samples were collected before (pre), at 24 h and 44 h after exposure, to air and wood smoke. Data are given as medians with interquartile range. (DOCX 62 kb

Human Embryonic Stem Cells Express Elevated Levels of Multiple Pro-Apoptotic BCL-2 Family Members

Two of the greatest challenges in regenerative medicine today remain (1) the ability to culture human embryonic stem cells (hESCs) at a scale sufficient to satisfy clinical demand and (2) the ability to eliminate teratoma-forming cells from preparations of cells with clinically desirable phenotypes. Understanding the pathways governing apoptosis in hESCs may provide a means to address these issues. Limiting apoptosis could aid scaling efforts, whereas triggering selective apoptosis in hESCs could eliminate unwanted teratoma-forming cells. We focus here on the BCL-2 family of proteins, which regulate mitochondrial-dependent apoptosis. We used quantitative PCR to compare the steady-state expression profile of all human BCL-2 family members in hESCs with that of human primary cells from various origins and two cancer lines. Our findings indicate that hESCs express elevated levels of the pro-apoptotic BH3-only BCL-2 family members NOXA, BIK, BIM, BMF and PUMA when compared with differentiated cells and cancer cells. However, compensatory expression of pro-survival BCL-2 family members in hESCs was not observed, suggesting a possible explanation for the elevated rates of apoptosis observed in proliferating hESC cultures, as well as a mechanism that could be exploited to limit hESC-derived neoplasms

Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.

While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clones with EBV, but surprisingly not transduction with individual BL-associated latent viral genes, restored protection from apoptosis. Expression profiling and functional analysis of apoptosis-related proteins and transcripts in BL cells revealed that EBV inhibits the upregulation of the proapoptotic BH3-only proteins, BIM and PUMA. We conclude that latent EBV genes cooperatively enhance the survival of BL cells by suppression of the intrinsic apoptosis pathway signalling via inhibition of the potent apoptosis initiators, BIM and PUMA.Cell Death and Differentiation advance online publication, 29 September 2017; doi:10.1038/cdd.2017.150