Summary Oestrogen receptors are overexpressed in around 70% of all breast cancers, and are a target for endocrine therapy. These receptors can be visualised on PET with use of 16α-18 ...F-fluoro-17β-oestradiol (18 F-FES) as a tracer. Compared with biopsy, which enables assessment of individual sites, whole-body18 F-FES-PET enables quantification of oestrogen-receptor expression in all metastases. In several studies, measurement of tumour protein expression in oestrogen receptors by18 F-FES-PET, concurrent with biopsy, detected oestrogen-receptor-positive tumour lesions with a sensitivity of 84% and specificity of 98%. Roughly 45% of patients with metastatic breast cancer have discordant oestrogen-receptor expression across lesions (ie,18 F-FES-positive and18 F-FES-negative metastases). Low tumour18 F-FES uptake in metastases can predict failure of hormonal therapy in patients with oestrogen-receptor-positive primary tumours. Finally,18 F-FES-PET has shown that oestrogen-receptor binding capacity changes after intervention with hormonal drugs, but findings need to be confirmed. Factors other than oestrogen-receptor expression, including menopausal status and concomitant therapies, that can affect tumour18 F-FES uptake must be taken into account.
Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal ...maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.
De novo missense mutations and in‐frame coding deletions in the X‐linked gene SMC1A (structural maintenance of chromosomes 1A), encoding part of the cohesin complex, are known to cause Cornelia de ...Lange syndrome in both males and females. For a long time, loss‐of‐function (LoF) mutations in SMC1A were considered incompatible with life, as such mutations had not been reported in neither male nor female patients. However, recently, the authors and others reported LoF mutations in females with intellectual disability (ID) and epilepsy.
Here we present the detailed phenotype of two females with de novo LoF mutations in SMC1A, including a de novo mutation of single base deletion c.2364del, p.(Asn788Lysfs*10), predicted to result in a frameshift, and a de novo deletion of exon 16, resulting in an out‐of‐frame mRNA splice product p.(Leu808Argfs*6). By combining our patients with the other recently reported females carrying SMC1A LoF mutations, we ascertained a phenotypic spectrum of (severe) ID, therapy‐resistant epilepsy, absence/delay of speech, hypotonia and small hands and feet. Our data show the existence of a novel phenotypic entity – distinct from CdLS – and caused by de novo SMC1A LoF mutations.
Abstract: Objective: Burnout constitutes a health risk, and interventions are needed to reduce it. The aim of this study was to synthesize evidence regarding the relationship between physical ...activity and burnout by conducting a systematic review of longitudinal and intervention studies. Methods: A literature search resulted in the identification of a final set of ten studies: four longitudinal and six intervention studies. In separate analyses for each category, evidence was synthesized by extracting the study characteristics and assessing the methodological quality of each study. The strength of evidence was calculated with the standardized index of convergence (SIC). Results: In longitudinal studies, we found moderately strong evidence (SIC(4)=-1) for a negative relationship between physical activity and the key component of burnout, i.e., exhaustion. We found strong evidence (SIC(6)=-0.86) for the effect of physical activity on reducing exhaustion in intervention studies. As only one study could be classified as a high quality study, these results of previous studies need to be interpreted with some caution. Conclusions: This systematic review suggests that physical activity constitutes an effective medium for the reduction of burnout. Although consistent evidence was found, there is a lack of high quality longitudinal and intervention studies considering the influence of physical activity on burnout. Therefore, future research should be conducted with the aim to produce high quality studies, to develop a full picture of physical activity as a strategy to reduce burnout.
Highlights • Neoadjuvant radiotherapy is administered only for rectal cancer. • There is a lack of robust evidence for adjuvant chemotherapy in rectal cancer. • Rectal and colon cancer harbor a ...different composition of potential drug targets. • Rectal and colon cancer differ in their metastatic patterns. • Metastatic rectal and colon cancer are commonly treated alike.
Weight gain during chemotherapy in women with breast cancer is commonly reported. However, there are important differences between studies that examined weight change during chemotherapy; e.g. type ...of chemotherapy, menopausal status, time between body weight measurements and sample size. The purpose of this meta-analysis was to quantify changes in body weight during chemotherapy for women with breast cancer, taking these differences into account.
We identified relevant studies using PubMed, Scopus and Embase databases. The search was limited to human studies published in English up to and including December 2015. Only studies among women with early stage breast cancer treated with chemotherapy, with reported body weight before and after chemotherapy and type of chemotherapy were included. Random-effect models were used, and heterogeneity between studies was explored through stratified analyses and meta-regression. Sensitivity analyses were done to explore whether a specific study markedly affected the results.
In total 25 papers were found, including data from 2620 women. Overall, body weight increased during chemotherapy: 2.7 kg (95% CI 2.0, 7.5) with a high degree of heterogeneity (I
= 94.2%). Stratified analyses showed weight gain in all strata, but did not substantially reduce heterogeneity. Univariate meta-regression showed less weight gain in prospective studies compared to chart review studies (-2.0, 95% CI: -3.1, -0.8). Studies including cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimes showed a greater weight gain compared to those that did not (2.2, 95% CI: 1.1, 3.3); and papers published until the year 2000 showed a greater weight gain compared to those published after 2000 (1.9, 95% CI:-0.8, 3.1). In the multivariate models only studies including CMF regimes and studies published until 2000 were associated with significant weight gain of respectively 1.3 and 1.4 kg.
Despite the high heterogeneity, this meta-analysis shows significant weight gain during chemotherapy for women with breast cancer. Weight gain was more pronounced in papers published until 2000 and women receiving CMF as chemotherapy regime. Although weight gain after chemotherapy has decreased over the course of time, weight gain is still substantial and deserves clinical attention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Novel observations of surface grain‐size distributions are used in combination with intra‐wave modeling to examine the processes responsible for the sorting of sediment grains on a relatively steep ...beach (slope = 1:7.5). The field observations of the mean grain size collected with a digital camera system at consecutive low and high tides for a 2 week period show significant temporal and spatial variation. This variation is reproduced by the modeling approach when the surf zone flow‐circulation is relatively weak, showing coarse grain sizes at the location of the shore break and finer sediment onshore and offshore of the shore break. The model results suggest that grain size sorting is dominated by the wave‐breaking‐related suspended sediment transport which removes finer sediment from the shore break and transports it both on‐shore and offshore. The transport capacity of wave‐breaking‐related suspended sediment is controlled by the sediment response time scale in the advection‐diffusion equation, where small (large) values promote onshore (offshore) transport. Comparisons with the observed beach profile evolution suggest a relatively short time scale for the suspended sediment response which could be explained by the vigorous breaking of the waves at the shore break.
Key Points
Grain size sorting
Beach profile stability
Formation of a shore break
RATIONALE:Nuclear receptor Nur77, also known as NR4A1, TR3, or NGFI-B, is expressed in human atherosclerotic lesions in macrophages, endothelial cells, T cells and smooth muscle cells. Macrophages ...play a critical role in atherosclerosis and the function of Nur77 in lesion macrophages has not yet been investigated.
OBJECTIVE:This study aims to delineate the function of Nur77 in macrophages and to assess the effect of bone marrow–specific deficiency of Nur77 on atherosclerosis.
METHODS AND RESULTS:We investigated Nur77 in macrophage polarization using bone marrow-derived macrophages (BMM) from wild-type and Nur77-knockout (Nur77) mice. Nur77 BMM exhibit changed expression of M2-specific markers and an inflammatory M1-phenotype with enhanced expression of interleukin-12, IFNγ, and SDF-1α and increased NO synthesis in (non)-stimulated Nur77 BMM cells. SDF-1α expression in nonstimulated Nur77 BMM is repressed by Nur77 and the chemoattractive activity of Nur77 BMM is abolished by SDF-1α inhibiting antibodies. Furthermore, Nur77 mice show enhanced thioglycollate-elicited migration of macrophages and B cells. The effect of bone marrow–specific deficiency of Nur77 on atherosclerosis was studied in low density lipoprotein receptor-deficient (Ldlr) mice. Ldlr mice with a Nur77-deficient bone marrow transplant developed 2.1-fold larger atherosclerotic lesions than wild-type bone marrow–transplanted mice. These lesions contain more macrophages, T cells, smooth muscle cells and larger necrotic cores. SDF-1α expression is higher in lesions of Nur77-transplanted mice, which may explain the observed aggravation of lesion formation.
CONCLUSIONS:In conclusion, in bone marrow–derived cells the nuclear receptor Nur77 has an anti-inflammatory function, represses SDF-1α expression and inhibits atherosclerosis.
The current coronavirus disease 2019 (COVID‐19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35‐year‐old ...renal transplant recipient who suffered from a severe COVID‐19 pneumonia. The clinical course was complicated by extreme overexposure to the mammalian target of rapamycin inhibitor everolimus, following coadministration of chloroquine and lopinavir/ritonavir therapy. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence‐based COVID‐19 therapy and concurrent pressure for exploration of experimental pharmacological treatment options. However, the risk‐benefit balance of experimental or off‐label therapy may be weighed differently in organ transplant recipients than in otherwise healthy COVID‐19 patients, owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy. With this case report, we aimed to achieve increased awareness and improved management of drug‐drug interactions associated with the various treatment options for COVID‐19 in renal transplant patients.
This article reports on a case of coronavirus disease 2019 in a renal transplant recipient and aims to enhance awareness and provide guidance for the clinical management of drug interactions between immunosuppressive therapy and experimental or investigational antiviral agents.
Is cyclooxygenase‐1 involved in neuroinflammation? Ghazanfari, Nafiseh; Waarde, Aren; Dierckx, Rudi A. J. O. ...
Journal of neuroscience research,
November 2021, 2021-11-00, 20211101, Letnik:
99, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Purpose: Reactive microglia are an important hallmark of neuroinflammation. Reactive microglia release various inflammatory mediators, such as cytokines, chemokines, and prostaglandins, which are ...produced by enzymes like cyclooxygenases (COX). The inducible COX‐2 subtype has been associated with inflammation, whereas the constitutively expressed COX‐1 subtype is generally considered as a housekeeping enzyme. However, recent evidence suggests that COX‐1 can also be upregulated and may play a prominent role in the brain during neuroinflammation. In this review, we summarize the evidence that supports this involvement of COX‐1. Methods: Five databases were used to retrieve relevant studies that addressed COX‐1 in the context of neuroinflammation. The search resulted in 32 articles, describing in vitro, in vivo, post mortem, and in vivo imaging studies that specifically investigated the COX‐1 isoform under such conditions. Results: Reviewed literature generally indicated that the overexpression of COX‐1 was induced by an inflammatory stimulus, which resulted in an increased production of prostaglandin E2. The pharmacological inhibition of COX‐1 was shown to suppress the induction of inflammatory mediators like prostaglandin E2. Positron emission tomography (PET) imaging studies in animal models confirmed the overexpression of COX‐1 during neuroinflammation. The same imaging method, however, could not detect any upregulation of COX‐1 in patients with Alzheimer's disease. Conclusion: Taken together, studies in cultured cells and living rodents suggest that COX‐1 is involved in neuroinflammation. Most postmortem studies on human brains indicate that the concentration of COX‐1‐expressing microglial cells is increased near sites of inflammation. However, evidence for the involvement of COX‐1 in neuroinflammation in the living human brain is still largely lacking.
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