Patient-Reported Outcome Measures may optimize shared decision-making for cancer risk management in BRCA mutation carriers

Purpose: The aim of this study was to compare patient-reported outcomes (PROs) of BRCA1/2 mutation carriers, either after bilateral prophylactic mastectomy (BPM) or during breast surveillance, to improve shared decision-making in their cancer risk management. Methods: Unaffected BRCA1/2 mutation carriers at least one year after BPM followed by immediate breast reconstruction (BPM-IBR) or one year under surveillance were eligible. After informed consent, the Hospital Anxiety and Depression Scale (HADS) and BREAST-Q were administered and compared between the different strategies. PROs were also compared to available normative data. Results: Ninety-six participants were analyzed in this study and showed significant differences between strategies in age, age at genetic testing, and time since BPM or starting breast surveillance. All HADS scores were below 8 suggesting no signs of anxiety or depression in both groups. Higher mean ‘Q-physical well-being’ scores were reported by the surveillance group (81.78 [CI 76.99–86.57]) than the BPM group (76.96 [CI 73.16 – 80.75]; p = 0.011). Overall, for both questionnaires better scores were seen when compared to age-matched normative data. Conclusions: No signs of anxiety or depression were seen in the surveillance or BPM-IBR group. Slightly better mean BREAST-Q scores were seen for the surveillance group in comparison to BPM-IBR, except for ‘Q-psychological well-being’. The difference in ‘Q-physical well-being’ was significantly worse for BPM-IBR. Approaches to obtain longitudinal PROs and reference values should be explored in the future, which could add value to shared decision-making in regards to breast cancer risk management in this specific patient population

Sequential dependency for affective appraisal of food images

Abstract How we perceive the world is not solely determined by our experiences at a given moment in time, but also by what we have experienced in our immediate past. Here, we investigated whether such sequential effects influence the affective appraisal of food images. Participants from 16 different countries (N = 1278) watched a randomly presented sequence of 60 different food images and reported their affective appraisal of each image in terms of valence and arousal. For both measures, we conducted an inter-trial analysis, based on whether the rating on the preceding trial(s) was low or high. The analyses showed that valence and arousal ratings for a given food image are both assimilated towards the ratings on the previous trial (i.e., a positive serial dependence). For a given trial, the arousal rating depends on the arousal ratings up to three trials back. For valence, we observed a positive dependence for the immediately preceding trial only, while a negative (repulsive) dependence was present up to four trials back. These inter-trial effects were larger for males than for females, but independent of the participants’ BMI, age, and cultural background. The results of this exploratory study may be relevant for the design of websites of food delivery services and restaurant menus

Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations.

Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5' arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 "hits" occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis

Sulfide Bridged Covalent Quinoxaline Frameworks for Lithium Organosulfide Batteries

The chelating ability of quinoxaline cores and the redox activity of organosulfide bridges in layered covalent organic frameworks COFs offer dual active sites for reversible lithium Li storage. The designed COFs combining these properties feature disulfide and polysulfide bridged networks showcasing an intriguing Li storage mechanism, which can be considered as a lithium organosulfide Li OrS battery. The experimental computational elucidation of three quinoxaline COFs containing systematically enhanced sulfur atoms in sulfide bridging demonstrates fast kinetics during Li interactions with the quinoxaline core. Meanwhile, bilateral covalent bonding of sulfide bridges to the quinoxaline core enables a redox mediated reversible cleavage of the sulfur amp; 63743;sulfur bond and the formation of covalently anchored lithium sulfide chains or clusters during Li interactions, accompanied by a marked reduction of Li polysulfide Li PS dissolution into the electrolyte, a frequent drawback of lithium sulfur Li S batteries. The electrochemical behavior of model compounds mimicking the sulfide linkages of the COFs and operando Raman studies on the framework structure unravels the reversibility of the profound Li ion organosulfide interactions. Thus, integrating redox active organic framework materials with covalently anchored sulfides enables a stable Li OrS battery mechanism which shows benefits over a typical Li S batter