Detection of tumors with fluoromarker-releasing bacteria

Combining the specificity of tumor-targeting bacteria with the sensitivity of biomarker detection would create a screening method able to detect small tumors and metastases. To create this system, we genetically modified an attenuated strain of Salmonella enterica to release a recombinant fluorescent biomarker (or fluoromarker). Salmonella expressing ZsGreen were intravenously administered to tumor-bearing mice and fluoromarker production was induced after 48 hr. The quantities and locations of bacteria and ZsGreen were measured in tumors, livers and spleens by immunofluorescence, and the plasma concentration of ZsGreen was measured using single-layer ELISA. In the plasma, the ZsGreen concentration was in the range of 0.5–1.5 ng/ml and was dependent on tumor mass (with a proportion of 0.81 ± 0.32 ng·ml⁻¹·g⁻¹). No adverse reaction to ZsGreen or bacteria was observed in any mice. ZsGreen was released at an average rate of 4.3 fg·CFU⁻¹·hr⁻¹ and cleared from the plasma with a rate constant of 0.259 hr⁻¹. ZsGreen production was highest in viable tissue (7.6 fg·CFU⁻¹·hr⁻¹) and lowest in necrotic tissue (0.47 fg·CFU⁻¹·hr⁻¹). The mass transfer rate constant from tumor to blood was 0.0125 hr⁻¹. Based on these measurements, this system has the capability to detect tumors as small as 0.12 g. These results demonstrate four essential mechanisms of this method: (i) preferential tumor colonization by bacteria, (ii) fluoromarker release in vivo, (iii) fluoromarker transport through tumor tissue and (iv) slow enough systemic clearance to enable measurement. This bacteria-based blood test would be minimally invasive and has the potential to identify previously undetectable microscopic tumors.     

Time-Lagged Moment-to-Moment Interplay Between Negative Affect and Paranoia: New Insights in the Affective Pathway to Psychosis

Evidence suggests that affect plays a role in the development of psychosis but the underlying mechanism requires further investigation. This study examines the moment-to-moment dynamics between negative affect (NA) and paranoia prospectively in daily life. A female general population sample (n = 515) participated in an experience sampling study. Time-lagged analyses between increases in momentary NA and subsequent momentary paranoia were examined. The impact of childhood adversity, stress sensitivity (impact of momentary stress on momentary NA), and depressive symptoms on these time-lagged associations, as well as associations with follow-up self-reported psychotic symptoms (Community Assessment of Psychic Experiences and the Symptom Checklist-90-Revised) were investigated. Moments of NA increase resulted in a significant increase in paranoia over 180 subsequent minutes. Both stress sensitivity and depressive symptoms impacted on the transfer of NA to paranoia. Stress sensitivity moderated the level of increase in paranoia during the initial NA increase, while depressive symptoms increased persistence of paranoid feelings from moment to moment. Momentary paranoia responses to NA increases were associated with follow-up psychotic symptoms. Examination of microlevel momentary experience may thus yield new insights into the mechanism underlying co-occurrence of altered mood states and psychosis. Knowledge of the underlying mechanism is required in order to determine source and place where remediation should occur.Key words: momentary assessment methodology, stress, childhood adversity, psychotic symptoms, depressive symptoms     

Negative affective stress reactivity: The dampening effect of snacking

The present study sets out to further elucidate the complex relationship between daily hassles, snacking, and negative affect (NA). The aim of the present study was to examine whether or not moment‐to‐moment energy intake from snacks moderates the association between momentary stress and NA. And, if so, can this moderating effect be replicated by using the amount of macronutrient intake (i.e., carbohydrates, fat, and protein) as moderator on the association between momentary stress and NA? Adults (N = 269), aged 20–50 years, participated in this study. Stress, NA, and snack intake were assessed 10 times a day for 7 consecutive days in daily life with an experience sampling smartphone application. Multilevel regression analyses were performed to assess the hypothesized associations. Our study revealed a dampening effect of snacking on negative affective stress reactivity. However, this dampening effect could not be replicated by the amount of macronutrient intake from snacks. On the contrary, the amount of carbohydrates has an enhancing effect on negative affective stress reactivity. In the end, our study suggests that the critical question is which mechanisms are decisive in the dampening role of snacking on stress reactivity. A multidisciplinary approach may provide a full perspective.     

Do physicians discuss end-of-life decisions with family members? A mortality follow-back study

Objective

Deaths from chronic illness are often preceded by a potentially life-shortening end-of-life decision (ELD). Involving family in these ELDs may have psychosocial benefits for them and the dying person. This study aims to examine how often ELDs are discussed with relatives of the dying person and which characteristics determine their involvement in those ELDs.

Physiological processes of inflammation and edema initiated by sustained mechanical loading in subcutaneous tissues: A scoping review

Deep tissue injuries are pressure ulcers which initiate in the subcutaneous tissues and extend through a bottom‐up pathway. Once deep tissue injuries are visual at skin level, serious irreversible tissue damage has already occurred. In pressure ulcer development, inflammation and edema are coupled physiological processes associated with tissue damage arising due to sustained mechanical loading. This study aimed to provide an in‐depth overview of the physiological processes of inflammation and edema initiated by sustained mechanical loading in subcutaneous tissues, in the context of pressure ulceration. A scoping review was performed according to the framework by Arksey and O'Malley. The databases MEDLINE, EMBASE, Web of Science, and Scopus, and the reference lists of included studies were searched for in vivo (animal, human), and in vitro studies matching the study objectives (from inception to 28 May 2018). No restrictions for inclusion were applied for study design, setting, participants, and year of publication. A total of 12 studies were included, varying in study design, sample characteristics, amount and duration of mechanical loads that were applied, follow‐up time, and assessment methods. Neutrophil infiltration and edema occur in the subcutaneous tissues nearly immediately after the application of load on soft tissues. The amount of neutrophils and edema increase in the first days after the mechanical insult and decrease once healing has been initiated and no supplementary mechanical load was applied. One study indicated that edema may extend up to the level of the dermo‐epidermal junction. Further research should focus on how deep tissue inflammation and edema are reflected into unique tissue changes at skin level, and how abnormal inflammatory responses manifest (e.g. when the nervous system is not functioning normally).