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Objectives: To investigate the role of specialised genitourinary multidisciplinary team meetings (MDTMs) in decision‐making and identify factors that influence the probability of receiving a treatment plan with curative intent for patients with muscle invasive bladder cancer (MIBC). Patients and methods: Data relating to patients with cT2‐4aN0/X‐1 M0 urothelial cell carcinoma, diagnosed between November 2017 and October 2019, were selected from the nationwide, population‐based Netherlands Cancer Registry ('BlaZIB study'). Curative treatment options were defined as radical cystectomy (RC) with or without neoadjuvant chemotherapy, chemoradiation or brachytherapy. Multilevel logistic regression analyses were used to examine the association between MDTM factors and curative treatment advice and how this advice was followed. Results: Of the 2321 patients, 2048 (88.2%) were discussed in a genitourinary MDTM. Advanced age (>80 years) and poorer World Health Organization performance status (score 1–2 vs 0) were associated with no discussion (P < 0.001). Being discussed was associated with undergoing treatment with curative intent (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.9–4.9), as was the involvement of a RC hospital (OR 1.70, 95% CI 1.09–2.65). Involvement of an academic centre was associated with higher rates of bladder‐sparing treatment (OR 2.05, 95% CI 1.31–3.21). Patient preference was the main reason for non‐adherence to treatment advice. Conclusions: For patients with MIBC, the probability of being discussed in a MDTM was associated with age, performance status and receiving treatment with curative intent, especially if a representative of a RC hospital was present. Future studies should focus on the impact of MDTM advice on survival data. [ABSTRACT FROM AUTHOR]

In charitable advertisements, organizations often display the image of a person in need with different facial emotional expressions. Prior research showed the positive effect of using a sad‐ (vs. happy‐ or neutral‐) faced image in evoking sympathy from viewers. Across five studies (N = 2141), we demonstrate that a sad‐faced image evokes not only sympathy but also an inference about the organization's manipulative intent. Moreover, we show that inference of manipulative intent and sympathy simultaneously mediate the effects of facial expression on donation and on attitude toward the advertising campaign, but in opposing directions. While greater sympathy leads to larger donation, greater inference of manipulative intent lowers donation, together contributing to a null effect of facial expression on donation. In contrast, using a sad‐faced image reduces attitude toward the advertising campaign because the mediating effect of inference of manipulative intent tends to be larger than the mediating effect of sympathy in absolute size. The negative effect of a sad‐faced image on attitude toward the advertising campaign is attenuated when the prominence of the image is low (vs. high). Finally, we show that these effects also emerge in the cause‐related marketing advertising context. [ABSTRACT FROM AUTHOR]

Objective: To contribute to the debate regarding the minimum volume of radical cystectomies (RCs) that a hospital should perform by evaluating the association between hospital volume (HV) and postoperative mortality. Patients and Methods: Patients who underwent RC for bladder cancer between 1 January 2008 and 31 December 2018 were retrospectively identified from the Netherlands Cancer Registry. To create a calendar‐year independent measure, the HV of RCs was calculated per patient by counting the RCs performed in the same hospital in the 12 months preceding surgery. The relationship of HV with 30‐ and 90‐day mortality was assessed by logistic regression with a non‐linear spline function for HV as a continuous variable, which was adjusted for age, tumour, node and metastasis (TNM) stage, and neoadjuvant treatment. Results: The median (interquartile range; range) HV among the 9287 RC‐treated patients was 19 (12–27; 1–75). Of all the included patients, 208 (2.2%) and 518 (5.6%) died within 30 and 90 days after RC, respectively. After adjustment for age, TNM stage and neoadjuvant therapy, postoperative mortality slightly increased between an HV of 0 and an HV of 25 RCs and steadily decreased from an HV of 30 onwards. The lowest risks of postoperative mortality were observed for the highest volumes. Conclusion: This paper, based on high‐quality data from a large nationwide population‐based cohort, suggests that increasing the RC volume criteria beyond 30 RCs annually could further decrease postoperative mortality. Based on these results, the volume criterion of 20 RCs annually, as recently recommended by the European Association of Urology Guideline Panel, might therefore be reconsidered. [ABSTRACT FROM AUTHOR]

Background: During the lead implantation of most spinal cord neurostimulators, the patient has to be comfortable and without pain. However, the patient is expected to provide feedback during electrical mapping. Titrating sedatives and analgesics for this double goal can be challenging. In comparison with our standard sedative agent propofol, the pharmacological profile of dexmedetomidine is more conducive to produce arousable sedation. The latter, however, is associated with hemodynamic side effects. We investigated whether dexmedetomidine is preferable over propofol during neurostimulator implantation.Methods: This single-center single-blinded randomized controlled trial included 72 patients with an indication for a neurostimulator, randomized to sedation with either propofol (0.5 mg/kg for 10 minutes, followed by 2.0 mg/kg/h) or dexmedetomidine (1 μg/kg for 10 minutes, followed by 0.6 μg/kg/h). The primary outcome was patient satisfaction with the sedation. The secondary outcomes were patient's and operator's comfort, number of titration adjustments, standard intraoperative hemodynamic and respiratory parameters and side effects.Results: Data of 69 patients (dexmedetomidine n = 35; propofol n = 34) were analyzed. Those receiving dexmedetomidine were more satisfied with the sedation than those receiving propofol; i.e. with sedation delivery (median 100.0 vs 83.3, P < .01), procedural recall (median 95.8 vs 83.3, P = .03), and sedation side effects (median 90.0 vs 83.3, P = .01). Fewer changes in the dexmedetomidine titration were necessary to maintain arousable sedation. Over time, mean arterial pressure and heart rate were significantly lower in the dexmedetomidine group. Hemodynamic side effects were comparable across groups.Conclusions: Dexmedetomidine sedation resulted in higher patient satisfaction and allowed for better arousable sedation than sedation with propofol. Although differences in hemodynamic parameters were found between the groups, these differences were not regarded as clinically relevant. [ABSTRACT FROM AUTHOR]

After a service failure, citizens expect a recovery strategy that restores perceived justice and places a reasonable value on their loss. Offering monetary compensation is a strategy commonly used in private settings, but less so in public settings. To date, compensation effects have not been researched in public settings. To investigate citizens' evaluations of perceived justice, negative emotions and post-recovery satisfaction we used a 2 (sector: public, private) by 2 (compensation promised: yes, no) by 2 (compensation offered: yes, no) factorial between-subjects experimental design (student sample), and replicated this in a second study ( US citizens sample). Results showed that compensation leads to similar positive effects in public and private settings, confirming earlier private setting research that applied justice theory. Explicitly promising compensation prior to a service encounter had no effect. However, promising compensation and not offering it led to decreased citizens' evaluations, which confirms expectancy disconfirmation theory. [ABSTRACT FROM AUTHOR]

Objective During implantation of a neuromodulative system, high patient satisfaction is closely associated with the equilibrium between an effective analgesia and sedation regimen, and the possibility for the patient to be awake and cooperative during procedure. This study assessed the efficacy of the sedative dexmedetomidine to achieve this balance, with patient satisfaction as the primary outcome. Methods Ten patients undergoing implantation of a dorsal column and dorsal root ganglion stimulator received dexmedetomidine (1 mcg/kg over 10 minutes, followed by 0.6 mcg/kg/hour) in combination with remifentanil at a set dose (3 mcg/kg/hour). Sedation was titrated to a Ramsay Sedation Score of 3. Recorded were as follows: patient satisfaction score, patient comfort score, operator comfort score, pain score, rescue medication and number of adjustments of dexmedetomidine intra-operatively, as well as sedation level, hemodynamic (blood pressure and heart rate), and respiratory characteristics (SpO2). Results Scores were high on patient satisfaction (median 8.5; IQR 2.0), patient comfort (3.0; IQR 1.25), and operator comfort (4.0; IQR 1.0). In all patients, intra-operative heart rate and mean arterial pressure were lower compared with baseline values. No respiratory depression or other complications related to anesthesia were reported. Moments of incident pain were effectively treated in 6 patients requiring an extra bolus of remifentanil. Conclusion In this study group, dexmedetomidine combined with remifentanil provided a high level of patient satisfaction and comfort, as well as operator comfort, without any clinically relevant adverse events. All patients were highly cooperative and instructable; incident pain needs to be closely monitored. [ABSTRACT FROM AUTHOR]

Our study assessed whether rising age, socioeconomic status (SES) and the presence of serious comorbidity affected treatment choice and survival in a population-based series of patients with muscle-invasive bladder cancer (MIBC) in The Netherlands. Therefore, a consecutive series was studied, including all patients diagnosed with MIBC between 1995 and 2009 in the Eindhoven Cancer Registry, preceding centralization of cystectomy. The independent effects of age, SES and serious comorbidity on therapy choice and their effects on overall survival were estimated by multivariate logistic regression and multivariate Cox proportional hazard analyses, respectively. Out of the 2,445 patients, 38% were aged ≥75 years at diagnosis and 63% had at least one serious comorbid condition. Higher age and serious comorbidity were independent predictors for abstaining from cystectomy, where SES was not (61-74 vs. ≤60: odds ratio [OR], 0.8; 95% confidence interval [CI], 0.6-1.0; ≥75 vs. ≤60: OR, 0.1; 95% CI,0.1-0.2; one comorbid condition vs. none: OR, 0.7; 95% CI, 0.5-0.9; two vs. none: OR, 0.6; 95% CI, 0.5-0.8). Patients undergoing cystectomy, external beam radiotherapy or interstitial radiotherapy survived longer independent of age, SES and serious comorbidity (hazard ratio [HR]: 0.4; 95% CI: 0.4-0.5; HR: 0.8; 95% CI: 0.7-0.9; HR: 0.4; 95% CI: 0.3-0.5, respectively). Consequently, preceding centralization of cystectomy, higher age and serious comorbidity were independent predictors for abstaining from cystectomy owing to an expected high rate of short-term medical problems. As cystectomy is associated with a better survival, independently of age, SES and serious comorbidity, it can be questioned whether cystectomy has been underutilised in elderly and in patients with serious comorbidity. Centralization might be a solution for this suggested underutilisation. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? The present study is one of the first to investigate urologists' and patients' compliance with recommendations based on a risk calculator that calculates the probability of indolent prostate cancer. A threshold was set for a recommendation of active surveillance vs active treatment. Active surveillance recommendations based on a prostate cancer risk calculator were followed by most patients, but 30% with active treatment recommendations chose active surveillance instead. This indicates that the threshold may be too high for urologists and patients. OBJECTIVES To assess urologists' and patients' compliance with treatment recommendations based on a prostate cancer risk calculator (RC) and the reasons for non-compliance., To assess the difference between patients who were compliant and non-compliant with recommendations based on this RC., PATIENTS AND METHODS Eight urologists from five Dutch hospitals included 240 patients with prostate cancer (PCa), aged 55-75 years, from December 2008 to February 2011., The urologists used the European Randomized Study of Screening for Prostate Cancer RC which predicts the probability of potentially indolent PCa (P[indolent]), using serum prostate-specific antigen (PSA), prostate volume and pathological findings on biopsy., Inclusion criteria were PSA <20 ng/mL, clinical stage T1 or T2a-c disease, <50% positive sextant biopsy cores, ≤20 mm cancer tissue, ≥40 mm benign tissue and Gleason ≤3 + 3. If the P(indolent) was >70%, active surveillance (AS) was recommended, and active treatment (AT) otherwise., After the treatment decision, patients completed a questionnaire about their treatment choice, related (dis)advantages, and validated measurements of other factors, e.g. anxiety., RESULTS Most patients (45/55, 82%) were compliant with an AS recommendation. Another 54 chose AS despite an AT recommendation (54/185, 29%)., The most common reason for non-compliance with AT recommendations by urologists was the patient's preference for AS ( n= 30). These patients most often reported the delay of physical side effects of AT as the main advantage ( n= 19)., Those who complied with AT recommendations had higher mean PSA levels (8 vs 7 ng/mL, P= 0.02), higher mean amount of cancer tissue (7 vs 3 mm, P < 0.001), lower mean P(indolent) (36% vs 55%, P < 0.001), and higher mean generic anxiety scores (42 vs 38, P= 0.03) than those who did not comply., CONCLUSIONS AS recommendations were followed by most patients, while 29% with AT recommendations chose AS instead., Although further research is needed to validate the RC threshold, the current version is already useful in treatment decision-making in men with localized PCa. [ABSTRACT FROM AUTHOR]

When confronted with violations of justice, people may be motivated not only to punish the violator, but also to compensate the victim. Whereas prior research has primarily concentrated on the question of when people are willing to punish, we provide a more comprehensive picture by also studying the willingness to compensate and by assessing the moderating role of empathic concern. Study 1 introduces the altruistic compensation game and shows that especially high empathic (compared to low empathic) people are willing to give up parts of their own resources to financially compensate the victims of distributive injustice. Study 2 completes the picture by directly comparing altruistic compensation with altruistic punishment. The study showed that high empathic people decided to compensate the victim, but low empathic people decided to punish the offender. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

People often mimic each other's behaviors. As a consequence, they share each other's emotional and cognitive states, which facilitates liking. Mimicry, however, does not always affect liking. In two studies, we investigate whether the mimicry-liking link is influenced by people's social value orientations. More specifically, we examine whether prosocials and proselfs are differently affected when being mimicked or not. Prosocials and proselfs indicated their liking for the interaction partner after being or not being mimicked in a face-to-face interaction. The results of two studies showed that prosocials rated the interaction partner as less likeable when they were not mimicked than when they were mimicked. Proselfs, however, were not affected by mimicry. These results show that people's social motives play a role in whether or not the effects of mimicry on liking occur: Proselfs are less sensitive to the mimicry acts of others. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We argue that offers in bargaining are guided by the emotions that proposers anticipate when contemplating their offers. In particular, we reason that positive offers may be driven by fear and guilt, where fear is more related to the perceived consequences of having one's offer rejected, and guilt is more related to concerns for the opponents' outcomes. Two studies on ultimatum bargaining corroborate this view. In Study 1, we used two well-documented manipulations to affect the consequences of having one's offer rejected and the initial entitlements of one's opponent. Both factors affected offers: Offers were higher when the consequences of having one's offer rejected were lower, and when the initial entitlements of one's opponent were higher. In agreement with our predictions, the former effect was mediated by anticipated fear and the latter by anticipated guilt. In Study 2, we directly manipulated both mediators. The findings further corroborate our reasoning by showing that both feelings also have a direct effect on ultimatum offers. These findings highlight the potential contribution of studying specific emotions in bargaining behavior. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In humans, 90% of the population is right handed. Although population hand preference has been found in some primate species, the evolution of manual lateralization in primates is not yet clear. To gain insight into manual lateralization of ancestral primates, we studied hand usage in unspecialized quadru-pedal, nocturnal lemurs, using a large sample size. We compared two closely related mouse lemur species to explore the variation of hand preference within the same genus. We tested 44 gray mouse lemurs and 19 Goodman's mouse lemurs in a forced food grasping task. The tests were videotaped. Measures of hand preference (i.e. the hand that is spontaneously chosen for a specific task) and successful hand usage (i.e. the hand that is successful in completing a specific task) were taken to explore manual lateralization. Both species showed manual lateralization at an individual, but not at a population level. Goodman's mouse lemurs showed stronger individual hand preferences than gray mouse lemurs. This suggests that strength in hand preference is variable within the same genus. No sex and age effects were found. The hand preference of offspring was negatively correlated to that of their mothers, but not correlated to that of their fathers. Thus, no clear genetic effect can be derived from these results. In the Goodman's mouse lemurs, hand preference increased with increasing task experience. However, successful hand usage was not affected by task experience, suggesting that successful hand usage is a more stable measurement for manual lateralization than hand preference. [ABSTRACT FROM AUTHOR]

Prion diseases are invariably fatal, neurodegenerative diseases transmitted by an infectious agent, PrPSc, a pathogenic, conformational isoform of the normal prion protein (PrPC). Heterocyclic compounds such as acridine derivatives like quinacrine abolish prion infectivity in a cell culture model of prion disease. Here, we report that these compounds execute their antiprion activity by redistributing cholesterol from the plasma membrane to intracellular compartments, thereby destabilizing membrane domains. Our findings are supported by the fact that structurally unrelated compounds with known cholesterol-redistributing effects – U18666A, amiodarone, and progesterone – also possessed high antiprion potency. We show that tricyclic antidepressants (e.g. desipramine), another class of heterocyclic compounds, displayed structure-dependent antiprion effects and enhanced the antiprion effects of quinacrine, allowing lower doses of both drugs to be used in combination. Treatment of ScN2a cells with quinacrine or desipramine induced different ultrastructural and morphological changes in endosomal compartments. We synthesized a novel drug from quinacrine and desipramine, termed quinpramine, that led to a fivefold increase in antiprion activity compared to quinacrine with an EC50 of 85 nm. Furthermore, simvastatin, an inhibitor of cholesterol biosynthesis, acted synergistically with both heterocyclic compounds to clear PrPSc. Our data suggest that a cocktail of drugs targeting the lipid metabolism that controls PrP conversion may be the most efficient in treating Creutzfeldt-Jakob disease. [ABSTRACT FROM AUTHOR]

Apoptin induces apoptosis specifically in tumour cells, where Apoptin is enriched in the DNA-dense heterochromatin and nucleoli. In vitro, Apoptin interacts with dsDNA, forming large nucleoprotein superstructures likely to be relevant for apoptosis induction. Its N- and C-terminal domains also have cell-killing activity, although they are less potent than the full-length protein. Here, we report that both Apoptin’s N- and C-terminal halves separately bound DNA, indicating multiple independent binding sites. The reduced cell killing activity of both truncation mutants was mirrored in vitro by a reduced affinity compared to full-length Apoptin. However, none of the truncation mutants cooperatively bound DNA or formed superstructures, which suggests that cooperative DNA binding by Apoptin is required for the formation of nucleoprotein superstructures. As Apoptin’s N- and C-terminal fragments not only share apoptotic activity, but also affinity for DNA, we propose that both properties are functionally linked. [Copyright &y& Elsevier]

Recombinant, bacterially expressed apoptin protein induces apoptosis in human tumour cell lines but not in normal cells, mimicking the behaviour of ectopically expressed apoptin. Recombinant apoptin is isolated exclusively as a highly stable multimeric complex of 30–40 monomers, with little, if any, α-helical and β-sheet structure. Despite its apparent disorder, multimeric apoptin is biologically active. Here, we present evidence that most of the apoptin moieties within the complex may well share a similar conformation. Furthermore, the multimer has extensive and uniform hydrophobic patches and conformationally stable domains. Only a small fraction of apoptin subunits can exchange between multimers under physiologically relevant conditions. These results prompt a model in which the apoptin multimer has a highly stable core of nonexchangeable subunits to which exchangeable subunits are attached through hydrophobic interactions. In combination with previous findings, our results lead us to propose that the stable core of apoptin is the biologically relevant structure. [ABSTRACT FROM AUTHOR]

Mitotic metaphase plates of fifty-seven species of Crotalaria have been studied to determine the chromosome number and compare the size and shape of the chromosomes. The predominance of 2n = 16 is confirmed, but 2n = 32 is general in Section Incanae subsection Jncanae and the first instance, in the Old World, of 2n = 32 is reported for C. massaiensis. The shorter and thinner types of chromosome seem most common in the apparently more derived groups of the genus, when a recent classification is adopted. Globulins extracted from thirty-six species (twenty-four also examined cytologically) and subjected to disc electrophoresis show four recognizable protein-band patterns. The two major types of pattern show reasonable correlation with the generic subdivisions and a comparable distribution to the major types of chromosome form. Evidence from both lines of investigation suggests that subsections of Incanae should perhaps be raised to sectional rank. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with polypharmacy and underprescribing in older adults.