Target-induced death by apoptosis in human lymphokine-activated natural killer cells

Activated human natural killer (NK) cells undergo rapid apoptotic cell death after ligand binding to the Fc receptor (CD16). We examined whether human NK cells die after engagement in cytolytic functions. Peripheral blood NK cells, with and without prior activation in vitro with interleukin-2 (IL-2), were tested for the occurrence of cell death after incubation with K562, the prototype NK-sensitive target cell. A proportion (15.2%) of NK cells that were stimulated for 3 days with IL- 2 and then incubated for 4 hours with K562 cells showed rapid cell death, but NK cells not stimulated with IL-2 did not. This cell death was found to involve nuclear condensation and fragmentation and DNA cleavage, all of which are characteristic of apoptosis. These data indicate that a proportion of activated human NK cells undergo apoptosis as they engage in target cell lysis. Target-induced NK cell death may represent an important mechanism for regulation of inflammatory processes involving NK cells.     

Cost–utility analysis of an advanced pressure ulcer management protocol followed by trained wound,ostomy, and continence nurses

The high prevalence of severe pressure ulcers (PUs) is an important issue that requires to be highlighted in Japan. In a previous study, we devised an advanced PU management protocol to enable early detection of and intervention for deep tissue injury and critical colonization. This protocol was effective for preventing more severe PUs. The present study aimed to compare the cost‐effectiveness of the care provided using an advanced PU management protocol, from a medical provider's perspective, implemented by trained wound, ostomy, and continence nurses (WOCNs), with that of conventional care provided by a control group of WOCNs. A Markov model was constructed for a 1‐year time horizon to determine the incremental cost‐effectiveness ratio of advanced PU management compared with conventional care. The number of quality‐adjusted life‐years gained, and the cost in Japanese yen (¥) ($US1 = ¥120; 2015) was used as the outcome. Model inputs for clinical probabilities and related costs were based on our previous clinical trial results. Univariate sensitivity analyses were performed. Furthermore, a Bayesian multivariate probability sensitivity analysis was performed using Monte Carlo simulations with advanced PU management. Two different models were created for initial cohort distribution. For both models, the expected effectiveness for the intervention group using advanced PU management techniques was high, with a low expected cost value. The sensitivity analyses suggested that the results were robust. Intervention by WOCNs using advanced PU management techniques was more effective and cost‐effective than conventional care.     

Viscoelastic properties of bovine articular cartilage attached to subchondral bone at high frequencies

Background  

Articular cartilage is a viscoelastic material, but its exact behaviour under the full range of physiological loading frequencies is unknown. The objective of this study was to measure the viscoelastic properties of bovine articular cartilage at loading frequencies of up to 92 Hz.     

When "no" might not quite mean "no"; the importance of informed and meaningful non-consent: results from a survey of individuals refusing participation in a health-related research project

Background  

Low participation rates can lead to sampling bias, delays in completion and increased costs. Strategies to improve participation rates should address reasons for non-participation. However, most empirical research has focused on participants' motives rather than the reasons why non-participants refuse to take part. In this study we investigated the reasons why older people choose not to participate in a research project.     

Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo

The symptoms of major psychotic illness are diverse and vary widely across individuals. Furthermore, the prepsychotic phase is indistinct, providing little indication of the precise pattern of symptoms that may subsequently emerge. Likewise, although in some individuals who have affected family members the occurrence of disease may be predicted, the specific symptom profile may not. An important question, therefore, is whether predictive physiological markers of symptom expression can be identified. We conducted a placebo-controlled, within-subjects study in healthy individuals to investigate whether individual variability in baseline physiology, as assessed using functional magnetic resonance imaging, predicted psychosis elicited by the psychotomimetic drug ketamine and whether physiological change under drug reproduced those reported in patients. Here we show that brain responses to cognitive task demands under placebo predict the expression of psychotic phenomena after drug administration. Frontothalamic responses to a working memory task were associated with the tendency of subjects to experience negative symptoms under ketamine. Bilateral frontal responses to an attention task were also predictive of negative symptoms. Frontotemporal activations during language processing tasks were predictive of thought disorder and auditory illusory experiences. A subpsychotic dose of ketamine administered during a second scanning session resulted in increased basal ganglia and thalamic activation during the working memory task, paralleling previous reports in patients with schizophrenia. These results demonstrate precise and predictive brain markers for individual profiles of vulnerability to drug-induced psychosis.