Pharmacological interventions for people with borderline personality disorder

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of pharmacological treatment for adolescents and adults with borderline personality disorder (BPD)

Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Conclusions: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan

Psychological therapies for people with borderline personality disorder

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of psychological therapies for people with borderline personality disorder (BPD)

Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Conclusions: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan

Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023

Funding Information: We would like to thank Karina Kaae, Lanni Fugl Niebuhr Nielsen and Joan Nevermann Jensen for their laboratory expertise, and acknowledge the great effort by clinicians and laboratory technicians at hospitals across Denmark and at Landspítali, Reykjavik, in securing samples and data essential for WGS-based surveillance efforts, as well as the dedicated technical staff maintaining and developing the registries and epidemiological databases at the core of national surveillance in Denmark. Publisher Copyright: © 2023 European Centre for Disease Prevention and Control (ECDC). All rights reserved.A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus. An increase in incidence rates of invasive (iGAS) and non-invasive (nGAS) group A Streptococcus infection has been reported by several countries across Europe during the 2022/23 winter season [1-3]. Through analysis of all whole genome sequencing (WGS) data acquired for national surveillance of iGAS in Denmark since 2018, we aimed to investigate current genomic developments and the impact of emerging lineages on iGAS incidence rates in 2023. In Denmark, iGAS is not notifiable except in case of meningitis, however, test results from all 10 Departments of Clinical Microbiology (DCMs) are submitted to the Danish Microbiology Database (MiBa) [4] and can be used to monitor incidence rates. Iceland also experienced a higher iGAS incidence in early 2023, and we also present Icelandic WGS data on iGAS isolates from 2022 and 2023.Peer reviewe