Many doctors regard online reviews and ratings of their professional work as menacing or defamatory. Some even expect that their reputation and economic success could be deeply compromised. Constant ...jurisdiction in Germany however has straightened out, that there is no avoidance strategy. In this overview I consider some options for doctors, who actively want to go into the matter.
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.
The highly conserved Notch signaling pathway plays pleiotropic roles during embryonic development and is important for the regulation of selfrenewing tissues. The physiological functions of this ...signaling cascade range from stem cell maintenance and influencing cell fate decisions of barely differentiated progenitor cells, to the induction of terminal differentiation processes, all of which have been found to be recapitulated in different forms of cancers. Although Notch signaling has mostly been associated with oncogenic and growth-promoting roles, depending on the tissue type it can also function as a tumor suppressor. Here we describe recent findings on Notch signaling in cancer and tumor angiogenesis, and highlight some of the therapeutic approaches that are currently being developed to interfere with tumor growth and progression.
Optical modulators encode electrical signals to the optical domain and thus constitute a key element in high-capacity communication links. Ideally, they should feature operation at the highest speed ...with the least power consumption on the smallest footprint, and at low cost. Unfortunately, current technologies fall short of these criteria. Recently, plasmonics has emerged as a solution offering compact and fast devices. Yet, practical implementations have turned out to be rather elusive. Here, we introduce a 70 GHz all-plasmonic Mach-Zehnder modulator that fits into a silicon waveguide of 10 μm length. This dramatic reduction in size by more than two orders of magnitude compared with photonic Mach-Zehnder modulators results in a low energy consumption of 25 fJ per bit up to the highest speeds. The technology suggests a cheap co-integration with electronics.
Abstract Background Depression is a common co-morbidity of cancer that has a detrimental effect on quality of life, treatment adherence and potentially survival. We conducted an epidemiological ...multi-center study including a population-based random comparison sample and estimated the prevalence of depressive symptoms by cancer site, thereby identifying cancer patients with the highest prevalence of depression. Patients and methods We included 4020 adult cancer inpatients and outpatients from five distinct regions across Germany in a proportional stratified random sample based on the nationwide cancer incidence and a comparison group consisting of 5018 participants. Both groups reported depressive symptoms by filling in the Patient Health Questionnaire (PHQ-9). In multivariate analyses adjusted for age and sex, we calculated the odds of being depressed. Results Out of 5818 eligible patients, 69% participated (51% women, mean age = 58 years). We estimated that one in four cancer patients (24%) is depressed (PHQ-9 ≥ 10). The odds of being depressed among cancer patients were more than five times higher than in the general population (OR, 5.4; 95% CI, 4.6–6.2). Patients with pancreatic (M = 8.0, SD = 5.0), thyroid (M = 7.8, SD = 6.3) and brain tumours (M = 7.6, SD = 4.9) showed the highest prevalence, whereas patients with prostate cancer (M = 4.3, SD = 3.8) and malignant melanoma (M = 5.3, SD = 4.3) had the lowest levels of depressive symptoms. Conclusion Our results help clinicians identify cancer patients in need of psychosocial support when navigating in the growing survivor population.
Altered expression of mitochondrial DNA (mtDNA) occurs in ageing and a range of human pathologies (for example, inborn errors of metabolism, neurodegeneration and cancer). Here we describe ...first-in-class specific inhibitors of mitochondrial transcription (IMTs) that target the human mitochondrial RNA polymerase (POLRMT), which is essential for biogenesis of the oxidative phosphorylation (OXPHOS) system
. The IMTs efficiently impair mtDNA transcription in a reconstituted recombinant system and cause a dose-dependent inhibition of mtDNA expression and OXPHOS in cell lines. To verify the cellular target, we performed exome sequencing of mutagenized cells and identified a cluster of amino acid substitutions in POLRMT that cause resistance to IMTs. We obtained a cryo-electron microscopy (cryo-EM) structure of POLRMT bound to an IMT, which further defined the allosteric binding site near the active centre cleft of POLRMT. The growth of cancer cells and the persistence of therapy-resistant cancer stem cells has previously been reported to depend on OXPHOS
, and we therefore investigated whether IMTs have anti-tumour effects. Four weeks of oral treatment with an IMT is well-tolerated in mice and does not cause OXPHOS dysfunction or toxicity in normal tissues, despite inducing a strong anti-tumour response in xenografts of human cancer cells. In summary, IMTs provide a potent and specific chemical biology tool to study the role of mtDNA expression in physiology and disease.
Previous findings have suggested that class IIa histone deacetylases (HDACs) (HDAC4, -5, -7, and -9) are inactive on acetylated substrates, thus differing from class I and IIb enzymes. Here, we ...present evidence supporting this view and demonstrate that class IIa HDACs are very inefficient enzymes on standard substrates. We identified HDAC inhibitors unable to bind recombinant human HDAC4 while showing inhibition in a typical HDAC4 enzymatic assay, suggesting that the observed activity rather reflects the involvement of endogenous copurified class I HDACs. Moreover, an HDAC4 catalytic domain purified from bacteria was 1,000-fold less active than class I HDACs on standard substrates. A catalytic Tyr is conserved in all HDACs except for vertebrate class IIa enzymes where it is replaced by His. Given the high structural conservation of HDAC active sites, we predicted the class IIa His-Nε2 to be too far away to functionally substitute the class I Tyr-OH in catalysis. Consistently, a Tyr-to-His mutation in class I HDACs severely reduced their activity. More importantly, a His-976-Tyr mutation in HDAC4 produced an enzyme with a catalytic efficiency 1,000-fold higher than WT, and this "gain of function phenotype" could be extended to HDAC5 and -7. We also identified trifluoroacetyl-lysine as a class IIa-specific substrate in vitro. Hence, vertebrate class IIa HDACs may have evolved to maintain low basal activities on acetyl-lysines and to efficiently process restricted sets of specific, still undiscovered natural substrates.
Optical switches operated around <inline-formula> <tex-math notation="LaTeX">\varepsilon</tex-math></inline-formula>-near-zero (ENZ) of transparent conducting oxides (TCOs) are analyzed. A digital ...optical switching behavior is derived that is quite different from earlier predictions. The digital modulation characteristic originates from the fact that the nonlinear switching is, to a large extent, performed in the ENZ layer. The ENZ layer, however, arises from carrier accumulation in the TCO and is confined to a relatively thin layer with a characteristic dimension that does not change upon applying a higher voltage. An accurate treatment of this inhomogeneous layer is vital to reliably predict modulation characteristics. Such nonlinear accumulation processes and inhomogeneous material properties require refined simulations, which is why we apply an iterative solver based on a high-order finite-element method. More precisely, we solve the nonlinear stationary quantum hydrodynamic model to derive the carrier concentration upon applying an electrical field across the modulator. The result is then directly coupled to Maxwell's equation, which shows a strong local enhancement of the electromagnetic fields in the ENZ layer. In an exemplary implementation, we forecast the feasibility of 6 <inline-formula> <tex-math notation="LaTeX">\mu\textrm{m} </tex-math></inline-formula> long TCO absorption modulators with on-state losses of 2.8 dB and extinction ratios above 10 dB.
Plasmonic-organic hybrid technology affords the potential for exceptional bandwidth, extremely small footprint, and very low drive voltages resulting in substantially improved energy efficiency for ...devices. Optical loss is a well-recognized problem for plasmonic technologies but is currently addressed with some notable success. Thereby, the optimization of electrically poled organic electro-optic (OEO) materials is most critical since a large electro-optical coefficient allows implementation of short active device structures that result in lower insertion losses and lower voltage-length products. Most importantly, short structures also guarantee largest bandwidths and best energy efficiencies. Yet, an efficient optimization of in-device performance of OEO materials requires the development of novel computational simulation methods, especially as waveguide width dimensions reach tens of nanometers in plasmonic waveguides and as electrode surface/material interfacial effects become more and more dominant. The focus of this communication is on novel multi-scale modeling methods, including coarse-grained Monte Carlo statistical mechanical simulations combined with quantum mechanical methods to simulate and analyze the linear and nonlinear optical properties for high chromophore number density solid-state OEO materials. New chromophores are developed with the assistance of theory and may lead to an order of magnitude improvement in device performance.
MEHNERT A., LEHMANN C., GRAEFEN M., HULAND H. & KOCH U. (2010) European Journal of Cancer Care19, 736–745 Depression, anxiety, post‐traumatic stress disorder and health‐related quality of life and ...its association with social support in ambulatory prostate cancer patients
The aim of this study is to identify anxiety, depression and post‐traumatic stress disorder in prostate cancer patients and to investigate the association with social support and health‐related quality of life. A total of 511 men who had undergone prostatectomy were surveyed during ambulatory follow‐up care for an average of 27 months after surgery using standardised self‐report measures (e.g. Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist – Civilian Version, Illness‐Specific Social Support Scale, Short‐Form Health Survey). Seventy‐six per cent of patients evaluated their disease as ‘not’ or a ‘little threatening’. The cancer diagnosis and uncertainty were most frequently reported as ‘distressing’, while medical treatment and doctor–patient interaction were most frequently evaluated as ‘most helpful’. The number of patients reporting increased levels of psychological distress was 16%, with 6% demonstrating signs of having severe mental health problems'. No higher levels of anxiety and depression were observed in cancer patients compared with age‐adjusted normative comparison groups. Lack of positive support, detrimental interactions and perceived threat of cancer were found to be predictors of psychological co‐morbidity (P < 0.001). Lack of positive support, detrimental interactions, threat of cancer, disease stage and age significantly predicted mental health (P < 0.001), whereas the impact of social support on physical health was rather weak. Findings emphasise the need for routine psychosocial screening.
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