Targeting glioma stem‐like cell survival and chemoresistance through inhibition of lysine‐specific histone demethylase KDM2B

Glioblastoma (GBM) ranks among the most lethal cancers, with current therapies offering only palliation. Inter‐ and intrapatient heterogeneity is a hallmark of GBM, with epigenetically distinct cancer stem‐like cells (CSCs) at the apex. Targeting GSCs remains a challenging task because of their unique biology, resemblance to normal neural stem/progenitor cells, and resistance to standard cytotoxic therapy. Here, we find that the chromatin regulator, JmjC domain histone H3K36me2/me1 demethylase KDM2B, is highly expressed in glioblastoma surgical specimens compared to normal brain. Targeting KDM2B function genetically or pharmacologically impaired the survival of patient‐derived primary glioblastoma cells through the induction of DNA damage and apoptosis, sensitizing them to chemotherapy. KDM2B loss decreased the GSC pool, which was potentiated by coadministration of chemotherapy. Collectively, our results demonstrate KDM2B is crucial for glioblastoma maintenance, with inhibition causing loss of GSC survival, genomic stability, and chemoresistance

Framtidsfrågor Restaureringskonst 2016-2017 Kungl Konsthögskolan

Restaureringskonst vid Kungl Konsthögskolan i Stockholm har läsåret 2016-2017 haft temat Framtidsfrågor. Utöver professionskunskap och teori har fronten och framtidsfrågor inom ämnet studerats. Publikationen visar en del av årets arbete i form av artiklar. Praktisk träning i dokumentation och värdering avspeglas liksom gemensamma studieresor, föreläsningar och milstolpar inom restaurering. Framtidsfrågor har inga enkla svar med för att kunskapsuppbyggnaden ska ligga i fronten är Restaureringskonst en aktiv deltagare i diskussionen

Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure: an individual participant meta-analysis

PURPOSE: It is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts. METHODS: We searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations. RESULTS: A total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI - 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages. CONCLUSION: In this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP

Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

Background!#!Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates.!##!Methods!#!We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia.!##!Results!#!With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever.!##!Conclusions!#!Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question. Trial registration The original trial whose dataset was analyzed was registered at ClinicalTrials.gov (NCT01187134) on August 23, 2010, the first patient was included on July 1, 2011