Toll-like receptor (TLR) 2 has recently been associated with cellular responses to numerous microbial products, including LPS and bacterial lipoproteins. However, many preparations of LPS contain low ...concentrations of highly bioactive contaminants described previously as "endotoxin protein," suggesting that these contaminants could be responsible for the TLR2-mediated signaling observed upon LPS stimulation. To test this hypothesis, commercial preparations of LPS were subjected to a modified phenol re-extraction protocol to eliminate endotoxin protein. While it did not influence the ability to stimulate cells from wild-type mice, repurification eliminated the ability of LPS to activate cells from C3H/HeJ (Lpsd) mice. Additionally, only cell lines transfected with human TLR4, but not human or murine TLR2, acquired responsiveness to both re-extracted LPS and to a protein-free, synthetic preparation of lipid A. These results suggest that neither human nor murine TLR2 plays a role in LPS signaling in the absence of contaminating endotoxin protein.
We review the recent advances in our understanding of the behavior of ferrofluids that occurred during the last 5 years. Ferrofluids can be viewed as a particular interesting class of dipolar fluids, ...which have a wide range of potential application in biomedicine and technology that is responsible for the fast growing number of research papers in this area. We will concentrate on the issues of phase behavior and microstructure formation with and without an externally applied magnetic field. In addition we discuss the influence of polydispersity that is an almost unavoidable feature of any real ferrofluid. We will focus on the theoretical aspects of those issues, however, we tried also to discuss new results coming from experiments and relate them to our current theoretical understanding of ferrofluids.
Objective
Psychological distress is common in cancer patients, and awareness of its indicators is essential. We aimed to assess the prevalence of psychological distress and to identify problems ...indicative of high distress.
Methods
We used the distress thermometer (DT) and its 34‐item problem list to measure psychological distress in 3724 cancer patients (mean age 58 years; 57% women) across major tumor entities, enrolled in an epidemiological multicenter study. To identify distress‐related problems, we conducted monothetic analyses.
Results
We found high levels of psychological distress (DT ≥ 5) in 52% of patients. The most prevalent problems were fatigue (56%), sleep problems (51%), and problems getting around (47%). Sadness, fatigue, and sleep problems were most strongly associated with the presence of other problems. High distress was present in 81.4% of patients reporting all 3 of these problems (DT M = 6.4). When analyzing only the subset of physical problems, fatigue, problems getting around, and indigestion showed the strongest association with the remaining problems and 76.3% of patients with all 3 problems were highly distressed (DT M = 6.1).
Conclusions
Our results show a high prevalence of psychological distress in cancer patients, as well as a set of problems that indicate the likely presence of other problems and high distress and can help clinicians identify distressed patients even if no routine distress screening is available.
•This updated ESMO Clinical Practice Guideline provides key recommendations on the management of cancer-related fatigue.•Authorship includes a multidisciplinary group of experts from different ...institutions and countries in Europe and abroad.•Key treatment recommendations are provided including levels of evidence and grades of recommendation where applicable.
Borrelia burgdorferi lipoproteins activate inflammatory cells through Toll-like receptor 2 (TLR2), suggesting that TLR2 could play a pivotal role in the host response to B. burgdorferi. TLR2 does ...play a critical role in host defense, as infected TLR2(-/-) mice harbored up to 100-fold more spirochetes in tissues than did TLR2(+/+) littermates. Spirochetes persisted at extremely elevated levels in TLR2-deficient mice for at least 8 wk following infection. Infected TLR2(-/-) mice developed normal Borrelia-specific Ab responses, as measured by quantity of Borrelia-specific Ig isotypes, the kinetics of class switching to IgG, and the complexity of the Ags recognized. These findings indicate that the failure to control spirochete levels in tissues is not due to an impaired acquired immune response. While macrophages from TLR2(-/-) mice were not responsive to lipoproteins, they did respond to nonlipoprotein components of sonicated spirochetes. These TLR2-independent responses could play a role during the inflammatory response to B. burgdorferi, as infected TLR2(-/-) mice developed greater ankle swelling than wild-type littermates. Thus, while TLR2-dependent signaling pathways play a major role in the innate host defense to B. burgdorferi, both inflammatory responses and the development of the acquired humoral response can occur in the absence of TLR2.
The current meta-analysis examines the relationship between shared leadership and team performance. It also assesses the role of team confidence (i.e., collective efficacy and team potency) in this ...relationship. Mediation analyses supported the hypothesis that team confidence partially mediates the effects of shared leadership on team performance. We also found support for the notion that shared leadership explains unique variance in team performance, over and above that of vertical leadership. Furthermore, a variety of substantive continuous and categorical variables were investigated as moderators of the shared leadership–team performance relationship. Specifically, the relationship between shared leadership and team performance was moderated by task interdependence, team tenure, and whether performance was objectively versus subjectively measured. Finally, results suggest that the approach used when measuring shared leadership can also play a role in the observed validity. Theoretical and practical implications of these findings are discussed.
Since 1990, the integer quantum Hall effect has provided the electrical resistance standard, and there has been a firm belief that the measured quantum Hall resistances are described only by ...fundamental physical constants-the elementary charge e and the Planck constant h. The metrological application seems not to rely on detailed knowledge of the microscopic picture of the quantum Hall effect; however, technical guidelines are recommended to confirm the quality of the sample to confirm the exactness of the measured resistance value. In this paper, we give our present understanding of the microscopic picture, derived from systematic scanning force microscopy investigations on GaAs/(AlGa)As quantum Hall samples, and relate these to the technical guidelines.
The agent of Lyme disease, Borrelia burgdorferi, produces membrane lipoproteins possessing potent inflammatory properties linked to disease pathology. The recent association of toll-like receptors ...(TLR) 2 and 4 with LPS responses prompted the examination of TLR involvement in lipoprotein signaling. The ability of human cell lines to respond to lipoproteins was correlated with the expression of TLR2. Transfection of TLR2 into cell lines conferred responsiveness to lipoproteins, lipopeptides, and sonicated B. burgdorferi, as measured by nuclear translocation of NF-kappaB and cytokine production. The physiological importance of this interaction was demonstrated by the 10-fold greater sensitivity of TLR2-transfected cells to lipoproteins than LPS. Futhermore, TLR2-dependent signaling by lipoproteins was facilitated by CD14. These data indicate that TLR2 facilitates the inflammatory events associated with Lyme arthritis. In addition, the widespread expression of lipoproteins by other bacterial species suggests that this interaction may have broad implications in microbial inflammation and pathogenesis.
Type I interferon (IFN) has been identified in patients with Lyme disease, and its abundant expression in joint tissues of C3H mice precedes development of Lyme arthritis. Forward genetics using C3H ...mice with severe Lyme arthritis and C57BL/6 (B6) mice with mild Lyme arthritis identified the Borrelia burgdorferi arthritis-associated locus 1 (Bbaa1) on chromosome 4 (Chr4) as a regulator of B. burgdorferi-induced IFNβ expression and Lyme arthritis severity. B6 mice introgressed with the C3H allele for Bbaa1 (B6.C3-Bbaa1 mice) displayed increased severity of arthritis, which is initiated by myeloid lineage cells in joints. Using advanced congenic lines, the physical size of the Bbaa1 interval has been reduced to 2 Mbp, allowing for identification of potential genetic regulators. Small interfering RNA (siRNA)-mediated silencing identified Cdkn2a as the gene responsible for Bbaa1 allele-regulated induction of IFNβ and IFN-stimulated genes (ISGs) in bone marrow-derived macrophages (BMDMs). The Cdkn2a-encoded p19 alternative reading frame (p19ARF) protein regulates IFNβ induction in BMDMs as shown by siRNA silencing and overexpression of ARF. In vivo studies demonstrated that p19ARF contributes to joint-specific induction of IFNβ and arthritis severity in B. burgdorferi-infected mice. p19ARF regulates B. burgdorferi-induced IFNβ in BMDMs by stabilizing the tumor suppressor p53 and sequestering the transcriptional repressor BCL6. Our findings link p19ARF regulation of p53 and BCL6 to the severity of IFNβ-induced Lyme arthritis in vivo and indicate potential novel roles for p19ARF, p53, and BCL6 in Lyme disease and other IFN hyperproduction syndromes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Core components of peer-to-peer (PTP) support for cancer survivors include informational, emotional, and psychosocial aspects. Previous literature on peer support in cancer includes both ...professionally and peer-led support. Our objective was to summarize studies on the effects of non-professionally led PTP support in cancer.
Methods
We performed a systematic research on studies in PTP support of adult cancer survivors with an interventional design, comparing outcomes of PTP support against any control. We included all studies with a precise definition of a PTP support, published from January 2000 up to March 2023 in peer-reviewed journals in English or German.
Results
Out of
N
= 609 identified publications, we were are able to include
n
= 18 randomized-controlled trials (RCTs) fulfilling our inclusion criteria. Main settings were dyadic support via telephone, face-to-face (FTF), and web-based online support. Most common outcomes were distress, depressive symptoms, anxiety, and quality of life (QoL). Overall, we found only small effects of PTP support on depression/anxiety, coping, or sexual functioning. Beneficial effects associated with the PTP intervention were apparent in particular in BRCA, in FTF settings, and in assessments of cancer-specific QoL outcomes.
Conclusion
This review shows that there are a few RCT investigating the effect of PTP support with short-term effects. Overall, there is a need for more RCTs with high methodological standards to evaluate the effectiveness of PTP support.
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