Search

Objectives: Antibiotic resistance requires continuous monitoring by experts to decide whether empirical antibiotic therapies (EATs) should be replaced by alternative antibiotics. The exact moment and criteria for this change are unclear and generally based on consensus between experts. This scoping review aims to identify from the literature the resistance thresholds used for a change in EAT and the criteria on which they are based., Methods: Scoping review for which a comprehensive structured literature search was conducted. Rayyan, software for systematic reviews, was used for the screening of abstracts and titles. Data sources were Pubmed and a hand-search of reference lists and grey literature. Papers were eligible if they concerned any type of bacterial infectious disease and mentioned or defined antibiotic resistance thresholds for decision-making purposes for EAT. The inclusion and analysis of articles was done by two researchers; any conflicts were resolved through discussion or by consulting a third reviewer., Results: We identified 3146 unique papers. Following title/abstract screening, 125 papers were comprehensively read, and 16 papers were included. The included papers gave thresholds for urinary tract infections, respiratory tract infections, meningitis, skin and soft tissue infections, gonorrhoea, and bone and joint infections. Six criteria were found that were commonly used to base the thresholds on. These were: disease severity, efficacy of treatment, adverse drug events, risk of Clostridioides difficile infection, costs, and increased resistance. The number of criteria used to define each threshold varied from one to six between papers., Conclusions: The thresholds used for EATs are few, commonly based on expert opinion estimates, and can therefore have broad ranges. Used criteria underlying reported thresholds are heterogenous and require standardization. Considering the rising trend in resistance, there is a clear need for rigid tools to determine thresholds in order to support guideline development with the best and timely evidence., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The endoplasmic reticulum (ER) is the largest organelle contacting virtually every other organelle for information exchange and control of processes such as transport, fusion, and fission. Here, we studied the role of the other organelles on ER network architecture in the cell periphery. We show that the co-migration of the ER with other organelles, called ER hitchhiking facilitated by late endosomes and lysosomes is a major mechanism controlling ER network architecture. When hitchhiking occurs, emerging ER structures may fuse with the existing ER tubules to alter the local ER architecture. This couples late endosomal/lysosomal positioning and mobility to ER network architecture. Conditions restricting late endosomal movement-including cell starvation-or the depletion of tether proteins that link the ER to late endosomes reduce ER dynamics and limit the complexity of the peripheral ER network architecture. This indicates that among many factors, the ER is controlled by late endosomal movement resulting in an alteration of the ER network architecture., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. Here, we describe MOSPD1 and MOSPD3 as ER-localized tethers interacting with FFAT motif-containing proteins. Using BioID, we identify proteins interacting with VAP and MOSPD proteins and find that MOSPD1 and MOSPD3 prefer unconventional FFAT-related FFNT (two phenylalanines [FF] in a neutral tract) motifs. Moreover, VAPA/VAPB/MOSPD2 and MOSPD1/MOSPD3 assemble into two separate ER-resident complexes to interact with FFAT and FFNT motifs, respectively. Because of their ability to interact with FFNT motifs, MOSPD1 and MOSPD3 could form MCS between the ER and other organelles. Collectively, these findings expand the VAP family of proteins and highlight two separate complexes in control of interactions between intracellular compartments., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Substance abuse treatment centers require reliable and valid instruments to monitor treatment progress, to evaluate treatment effectiveness, and to initiate clinical trials. Currently the Measurements in the Addictions for Triage and Evaluation (MATE) 2.1, an instrument that serves these purposes, is considered quite lengthy and intensive, especially in the case of allocation to milder treatment intensity. Therefore, a self-reported version of the MATE-Q was designed for patients with mild to moderate substance-abuse and co-occurring problems. The aim of the present study was to assess concurrent validity with the interviewer version of the MATE (version 2.1)., Materials and Methods: Data were collected at 2 locations of a Dutch substance abuse treatment center, one location in a large city and one in a suburban area. A correlational design was employed, where each included participant completed a MATE-Q and a MATE 2.1 within 3 days or less (administered at intake, before treatment initiation). A total of 98 treatment-seeking patients were included (51.0% alcohol as a primary problem, 19.4% cannabis, 14.3% gambling and 6.1% cocaine). Measurements included the MATE-Q and the MATE 2.1. Intraclass correlation coefficients (ICCs) for single measures were calculated, deploying the 2-way mixed procedure with absolute agreement. Descriptives of scores comprise means and Cronbach's alpha for internal consistency., Results: For the majority (15 out of 24) of the scores ICCs were equal or above 0.7. For 93 patients (95%), the primary problem substance or problem behavior was reported correspondingly. Nine MATE-Q mean scores differed significantly from their MATE 2.1 counterparts., Discussion/conclusion: For the majority of scores, the MATE-Q has acceptable concurrent validity for the assessment of patients with mild to moderate substance abuse and co-occurring problems., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Upon nuclear envelope (NE) fragmentation in the prometaphase, the nuclear and cytosolic proteomes mix and must be redefined to reinstate homeostasis. Here, by using a molecular GFP ladder, we show that in early mitosis, condensed chromatin excludes cytosolic proteins. When the NE reforms tightly around condensed chromatin in late mitosis, large GFP multimers are automatically excluded from the nucleus. This can be circumvented by limiting DNA condensation with Q15, a condensin II inhibitor. Soluble small and other nuclear localization sequence (NLS)-targeted proteins then swiftly enter the expanding nuclear space. We then examined proteasomes, which are located in the cytoplasm and nucleus. A significant fraction of 20S proteasomes is imported by the importin IPO5 within 20 min of reformation of the nucleus, after which import comes to an abrupt halt. This suggests that maintaining the nuclear-cytosol distribution after mitosis requires chromatin condensation to exclude cytosolic material from the nuclear space, and specialized machineries for nuclear import of large protein complexes, such as the proteasome., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

When cell surface receptors engage their cognate ligands in the extracellular space, they become competent to transmit potent signals to the inside of the cell, thereby instigating growth, differentiation, motility and many other processes. In order to control these signals, activated receptors are endocytosed and thoroughly curated by the endosomal network of intracellular vesicles and proteolytic organelles. In this Review, we follow the epidermal growth factor (EGF) receptor (EGFR) from ligand engagement, through its voyage on endosomes and, ultimately, to its destruction in the lysosome. We focus on the spatial and temporal considerations underlying the molecular decisions that govern this complex journey and discuss how additional cellular organelles - particularly the ER - play active roles in the regulation of receptor lifespan. In summarizing the functions of relevant molecules on the endosomes and the ER, we cover the order of molecular events in receptor activation, trafficking and downregulation, and provide an overview of how signaling is controlled at the interface between these organelles., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Lung cancer is the second most prevalent cancer in both women and men with some 221,200 new cases and 158,040 deaths reported in 2015. Almost 90% of these are non-small cell lung cancer (NSCLC) and these patients have a very poor prognosis. Recently a new treatment option for NSCLC appeared that strongly improved treatment responses-immunotherapy. Here we review the various forms of immunotherapy and how immune modification of proteasomes in lung cancer may support the immune system in controlling NSCLC. These immunoproteasomes then support recognition of NSCLC and may act as a biomarker for selecting responding patients to immunotherapy.

Background: Three substance abuse treatment centres set up a benchmarking project for routine outcome management (ROM) of structured cognitive behavioral treatments for outpatients with a substance use disorder., Aim: To present the results of five years benchmarking., Method: All patients were included at intake and the follow-up assessment was performed by a call-center nine months later. Twice a year aggregated data were fed back to management and treatment teams., Results: Since 2005, clinical outcome data, including substance abuse data, have been collected for more than half of all 15.786 treated patients. At follow-up, nine months after intake, 23% was abstinent, 28% reported moderate substance use and 49% reported excessive substance use., Conclusion: The Dutch centres for the treatment of substance abuse were successful in setting up ROM projects to monitor and compare the development and the effects of outpatient addiction treatments. The clinical results are acceptable and correspond to the results of the American project called match. It is not yet clear whether the biannual feedback of aggregated outcomes to management and treatment teams has contributed to the creation of learning organisations, but it has provided transparency and has made it possible for teams to learn from the outcomes.