It Is Tough and Tiring but It Works—Children’s Experiences of Undergoing Radiotherapy

Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children’s experiences of preparing for and undergoing radiotherapy, and furthermore to describe children’s suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children’s suggestions for improvement during radiotherapy. An overarching theme emerged: “It is tough and tiring but it works”. Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs.     

PKCβ Phosphorylates PI3Kγ to Activate It and Release It from GPCR Control

All class I phosphoinositide 3-kinases (PI3Ks) associate tightly with regulatory subunits through interactions that have been thought to be constitutive. PI3Kγ is key to the regulation of immune cell responses activated by G protein-coupled receptors (GPCRs). Remarkably we find that PKCβ phosphorylates Ser582 in the helical domain of the PI3Kγ catalytic subunit p110γ in response to clustering of the high-affinity IgE receptor (FcεRI) and/or store-operated Ca²⁺- influx in mast cells. Phosphorylation of p110γ correlates with the release of the p84 PI3Kγ adapter subunit from the p84-p110γ complex. Ser582 phospho-mimicking mutants show increased p110γ activity and a reduced binding to the p84 adapter subunit. As functional p84-p110γ is key to GPCR-mediated p110γ signaling, this suggests that PKCβ-mediated p110γ phosphorylation disconnects PI3Kγ from its canonical inputs from trimeric G proteins, and enables p110γ to operate downstream of Ca²⁺ and PKCβ. Hydrogen deuterium exchange mass spectrometry shows that the p84 adaptor subunit interacts with the p110γ helical domain, and reveals an unexpected mechanism of PI3Kγ regulation. Our data show that the interaction of p110γ with its adapter subunit is vulnerable to phosphorylation, and outline a novel level of PI3K control.     

Birds Do It. Bees Do It. So Why Not Single Women and Lesbians?

Infertile couples have come to take assisted reproductive technologies (ART) for granted. An increasing number of single women and lesbian couples also desire to have children and turn to ART, especially donor insemination, to fulfill this desire. While most married couples find that access to ART is limited primarily by the ability to pay, for single women and lesbian couples, the story may be much different. In the United States, they may find that doctors and infertility clinics view their desires as immoral and refuse to accept them as patients, although other doctors and clinics readily accept them. In most other countries, however, it is against the law for single women and lesbian couples to make use of ART, including donor insemination.
In this paper I will argue that marital status and sexual orientation should not serve as a barrier to accessing the world of reproductive medicine. I will base this conclusion on two arguments. First, that justice requires that we treat like cases alike. Just as we would not accept or reject patients for cardiac rehabilitation programs based on factors such as a history of poor eating habits, so too we should not look at nonmedical factors such as marital status when deciding whether to treat infertility. For the second justification for the conclusion of equal access to ART, I will examine the concept of the family. I will argue that it is morally acceptable for single women and lesbian couples to have children and to head families.     

It’s all in your gut and mind

Obesity has become a global problem affecting adults and children alike. Lifestyle choices both personal and industry driven can be blamed for the rise in obesity. One must distinguish between the possibly reversible overweight condition and the almost intractable actual morbid obesity where predisposing genetic factors may come into play. Both however exhibit consequences to health with a severity that cannot be underestimated. Deleterious changes to metabolism can lead to type II diabetes and atherosclerosis and other organ dysfunctions. It has long been recognized that there are two main types of fatty tissue in the body, white adipose tissue (WAT) serving a storage function and brown adipose tissue (BAT) serving a thermogenic function. The new discovery has been that WAT cells can be induced to undergo conversion (browning) to BAT to yield what is called beige adipose tissue, acquiring the thermogenic function. The clinical dream is to be able to promote browning and to induce, what may be called, burning off the fat. In this B&B article I entice the reader with a recent study that shows how two key hormones insulin and leptin operate cooperatively in the brain to monitor and regulate energy balance and the downstream effect of browning. I present other studies to add additional perspectives to the understanding of the mechanisms in peripheral tissues and other hormones that play additional key roles. Whether obesity can be conquered therapeutically by manipulating the regulatory systems is still an open question.     

Do Bumblebees Forage Optimally, and Does It Matter?

Foraging behavior of bumblebees has been in the past analyzedfrom two major perspectives. On the one hand, behavioral mechanismshave been studied to learn more about the animal. On the otherextreme, the animal has been used incidentally to examine optimalforaging theory (O.F.T.). Major problems have arisen when theorydesigned to answer evolutionary questions was used to determineproximal mechanisms. While O.F.T. could be highly useful inmaking predictions to point out useful problems, the bottleneckto our understanding at the present resides in the lack of experimentsthat test alternative hypotheses. Whether or not a bumblebee worker's foraging behavior is adaptive(enhances fitness), however, or is optimal (maximizes fitness)cannot yet be resolved by observations or experimentation onindividual bees. However, calculations can show the potentialenergy costs and payoffs of alternative potential foraging behaviors.Rapid progress could be made by examining the mechanisms offoraging behavior that act to enhance foraging returns, withoutworrying about whether or not the behavior is "optimal."     

Ubiquitin Binding in Endocytosis – How Tight Should It Be and Where Does It Happen?

Ubiquitin is an important tag in membrane transport. From studies in yeast, monoubiquitin has been considered sufficient to elicit uptake of cell surface transporters and receptors into endosomes. Two articles in the current issue of Traffic (Hawryluk et al. and Barriere et al.) indicate that stronger binding is required to retain and concentrate cargo in endocytic microdomains of the plasma membrane. High avidity interactions can be obtained by tandemly arrayed ubiquitin interaction motifs (UIM), in proteins such as the endocytic adaptors epsin and Eps15, interacting with polyubiquitin or by UIM-containing proteins binding several ubiquitins brought together through oligomerization of receptors. A controversial issue has been where such interactions take place. One view is that the association of epsin with ubiquitinated cargo is negatively regulated by its interaction with clathrin (Chen H and De Camilli P. Proc Natl Acad Sci USA 2005;102:2766-2771). This contention is now challenged by the articles of Hawryluk et al. and Barriere et al. Hawryluk et al. demonstrate that epsin and Eps15 consistently co-localize with clathrin but never with caveolin.     

Consequences of Cathodal Stimulation for Behavior: When Does It Help and When Does It Hurt Performance?

Cathodal Transcranial Direct Current Stimulation (C-tDCS) has been reported, across different studies, to facilitate or hinder performance, or simply to have no tangible effect on behavior. This discrepancy is most prominent when C-tDCS is used to alter a cognitive function, questioning the assumption that cathodal stimulation always compromises performance. In this study, we aimed to study the effect of two variables on performance in a simple cognitive task (letter Flanker), when C-tDCS was applied to the left prefrontal cortex (PFC): (1) the time of testing relative to stimulation (during or after), and (2) the nature of the cognitive activity during stimulation in case of post-tDCS testing. In three experiments, we had participants either perform the Flanker task during C-tDCS (Experiment 1), or after C-tDCS. When the Flanker task was administered after C-tDCS, we varied whether during stimulation subjects were engaged in activities that posed low (Experiment 2) or high (Experiment 3) demands on the PFC. Our findings show that the nature of the task during C-tDCS has a systematic influence on the outcome, while timing per se does not.     

Is It Human? Discriminating between Real Tracks and Track-Like Structures

Some human footprints-like hollows in the tuffaceous ground of an ancient quarry and of a recent anthropic path, created by the inhabitants no more than 30 years ago near the small village of Carangi (Caserta province, Southern Italy), allowed scientists to study some of the most misleading alteration processes of the volcanic tuff formations. The closeness of this site to the “Ciampate del Diavolo” ichnosite, bearing some of the oldest human fossil footprints, and the common stratigraphical and sedimentological background permitted accurate comparisons between actual human fossil footprints and footprint-like depressions, which can be easily mistaken for actual fossil evidence. This comparative study has permitted the reporting of some useful features and advice on distinguishing actual fossil footprints from natural and/or anthropic pseudo-tracks.     

The Efficiency of the Human CD8+ T Cell Response: How Should We Quantify It,What Determines It,and Does It Matter?

Multidisciplinary techniques, in particular the combination of theoretical and experimental immunology, can address questions about human immunity that cannot be answered by other means. From the turnover of virus-infected cells in vivo, to rates of thymic production and HLA class I epitope prediction, theoretical techniques provide a unique insight to supplement experimental approaches. Here we present our opinion, with examples, of some of the ways in which mathematics has contributed in our field of interest: the efficiency of the human CD8+ T cell response to persistent viruses.     

If You’ve Got It,Flaunt It: Humans Flaunt Attractive Partners to Enhance Their Status and Desirability

Mating decisions are influenced by conspecifics’ mate choices in many species including humans. Recent research has shown that women are more attracted to men with attractive putative partners than those with less attractive partners. We integrate these findings with traditional accounts of social signaling and test five hypotheses derived from it. In our study, 64 men and 75 women were paired with attractive and unattractive opposite-sex putative partners and asked whether they would prefer to give surveys to peers or to older adults. Consistent with predictions, both men and women wanted to show off (flaunt) attractive partners by administering surveys to peers and both men and women wanted to hide (conceal) unattractive partners from peers by administering surveys to older adults. These decisions were mediated by how participants expected others to evaluate their status and desirability when they administered the surveys, consistent with partners serving a social signaling function in humans.     

Voxel-Wise Perfusion Assessment in Cerebral White Matter with PCASL at 3T; Is It Possible and How Long Does It Take?

Purpose

To establish whether reliable voxel-wise assessment of perfusion in cerebral white matter (WM) is possible using arterial spin labeling (ASL) at 3T in a cohort of healthy subjects.

Materials and Methods

Pseudo-continuous ASL (PCASL) with background suppression (BS) optimized for WM measurements was performed at 3T in eight healthy male volunteers aged 25–41. Four different labeling schemes were evaluated by varying the labeling duration (LD) and post-labeling delay (PLD). Eight slices with voxel dimension 3.75x3.75x5 mm³ were acquired from the anterosuperior aspect of the brain, and 400 image/control pairs were collected for each run. Rigid head immobilization was applied using individually fitted thermoplastic masks. For each voxel in the resulting ASL time series, the time needed to reach a 95% significance level for the ASL signal to be higher than zero (paired t-test), was estimated.

Results

The four protocols detected between 88% and 95% (after Bonferroni correction: 75% and 88%) of WM voxels at 95% significance level. In the most efficient sequence, 80% was reached after 5 min and 95% after 53 min (after Bonferroni correction 40% and 88% respectively). For all protocols, the fraction of significant WM voxels increased in an asymptotic fashion with increasing scan time. A small subgroup of voxels was shown to not benefit at all from prolonged measurement.

Conclusion

Acquisition of a significant ASL signal from a majority of WM voxels is possible within clinically acceptable scan times, whereas full coverage needs prohibitively long scan times, as a result of the asymptotic trajectory.     

Flush early and avoid the rush? It may depend on where you stand

Optimal escape theory predicts that animals should flee at an optimal distance from the approaching predator (flight initiation distance, FID). However, FID usually increases with increasing alert distance (AD) or starting distance (SD). As an explanation for this pattern, the “flush early and avoid the rush” (FEAR) hypothesis states that prey should escape soon after detecting an approaching predator due to the cost of continuously monitoring risk. However, the positive relationship observed may also result from a mathematical artefact. Meanwhile, it is unknown whether animals would consistently follow this rule in different environmental contexts. We explored escape behaviours in light-vented bulbuls (Pycnonotus sinensis) perched at different heights. FID generally increased with increasing AD and decreasing perch height. The positive relationships between AD and FID were outside the 95% confidence levels of simulated slopes from Monte Carlo simulations, suggesting that the relationships observed reflect biological effects rather than merely a mathematical artefact. Increasing perch height was also associated with longer buffer distance (defined as FID minus AD or SD), suggesting that the birds tend to delay their flush after detecting an approaching predator when perched high. The effects of environmental contexts (and the associated predation risk) on the AD-FID relationship should be considered when performing inter-specific comparisons or meta-analyses.