Mindfulness and skills-based eHealth intervention to reduce distress in cancer-affected patients in the Reduct trial: Intervention protocol of the make it training optimized.

Introduction: Cancer-affected patients experience high distress due to various burdens. One way to expand psycho-oncological support is through digital interventions. This protocol describes the development and structure of a web-based psycho-oncological intervention, the Make It Training optimized. This intervention is currently evaluated in the Reduct trial, a multicenter randomized controlled trial. Methods: The Make It Training optimized was developed in six steps: A patient need and demand assessment, development and acceptability analysis of a prototype, the formation of a patient advisory council, the revision of the training, implementation into a web app, and the development of a motivation and evaluation plan. Results: Through a process of establishing cancer-affected patients' needs, prototype testing, and patient involvement, the Make It Training optimized was developed by a multidisciplinary team and implemented in a web app. It consists of 16 interactive self-guided modules which can be completed within 16 weeks. Discussion: Intervention protocols can increase transparency and increase the likelihood of developing effective web-based interventions. This protocol describes the process and results of developing a patient-oriented intervention. Future research should focus on the further personalization of web-based psycho-oncological interventions and the potential benefits of combining multiple psychotherapeutic approaches.

Sex-specific differences in olfactory sensitivity for putative human pheromones in nonhuman primates.

In humans, the volatile C19-steroids androsta-4,16-dien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST) have been shown to modulate autonomic nervous system responses, and to cause hypothalamic activation in a gender-specific manner. Using two conditioning paradigms, the authors here show that pigtail macaques and squirrel monkeys of both sexes were able to detect AND and EST at concentrations in the micromolar and mM range, respectively. Male and female spider monkeys, in contrast, differed markedly in their sensitivity to these two odorous steroids, with males not showing any behavioral responses to the highest concentrations of AND tested and females not responding to the highest concentrations of EST. These data provide the first examples of sex-specific bimodal distributions of olfactory sensitivity in a nonhuman primate species.

Olfactory responsiveness to two odorous steroids in three species of nonhuman primates.

Social communication by means of odor signals is widespread among mammals. In pigs, for example, the C19-steroids 5-alpha-androst-16-en-3-one and 5-alpha-androst-16-en-3-ol are secreted by the boar and induce the mating stance in the sow. In humans, the same substances have been shown to be compounds of body odor and are presumed to affect human behavior. Using an instrumental conditioning paradigm, we here show that squirrel monkeys, spider monkeys and pigtail macaques are able to detect androstenone at concentrations in the micromolar range and thus at concentrations at least as low as those reported in pigs and humans. All three species of nonhuman primates were considerably less sensitive to androstenol, which was detected at concentrations in the millimolar range. Additional tests, using a habituation-dishabituation paradigm, showed that none of the 10 animals tested per species was anosmic to the two odorous steroids. These results suggest that androstenone and androstenol may be involved in olfactory communication in the primate species tested and that the specific anosmia to these odorants found in approximately 30% of human subjects may be due to their reduced number of functional olfactory receptor genes compared with nonhuman primates.

The number of functional olfactory receptor genes and the relative size of olfactory brain structures are poor predictors of olfactory discrimination performance with enantiomers.

The ability of four squirrel monkeys and three pigtail macaques to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was investigated in terms of a conditioning paradigm. All animals from both species were able to discriminate between the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveole and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaaldehyde and limonene oxide. The pigtail macaques, but not the squirrel monkeys, also discriminated between the antipodes of perillaalcohol and isopulegol. A comparison of the across-task patterns of discrimination performance shows a high degree of similarity among the two primate species and also between these nonhuman primates and human subjects tested in an earlier study on the same tasks. These findings suggest that between-species comparisons of the relative size of olfactory brain structures or of the number of functional olfactory receptor genes are poor predictors of olfactory discrimination performance with enantiomers.

Detecting danger--or just another odorant? Olfactory sensitivity for the fox odor component 2,4,5-trimethylthiazoline in four species of mammals.

2,4,5-trimethylthiazoline (TMT) is a volatile component of the anal gland secretion of the red fox and elicits behavioral and physiological fear responses in the rat. Using instrumental conditioning paradigms, we determined olfactory detection thresholds for TMT in three rats, a natural prey species of the red fox, and compared their performance to that of three squirrel monkeys, three spider monkeys and four pigtail macaques, all non-prey species of the red fox. We found that the rats were able to discriminate concentrations between 0.04 and 0.10 ppt (parts per trillion) of TMT from the odorless solvent which is by far the lowest olfactory detection threshold for an odorant reported in rats so far. In contrast, the spider monkeys needed 0.14-1.38 ppb (parts per billion), the pigtail macaques 0.41-4.07 ppb, and the squirrel monkeys 4.07-13.80 ppb to detect TMT which does not rank among the lowest olfactory thresholds reported for these three primate species. Thus, these results support the assumption that the behavioral relevance of an odorant may be an important determinant of a species' olfactory sensitivity.

Olfactory sensitivity for carboxylic acids in spider monkeys and pigtail macaques.

Using a conditioning paradigm, the olfactory sensitivity of four spider monkeys and four pigtail macaques for a homologous series of carboxylic acids (n-propionic acid to n-heptanoic acid) was investigated. With only few exceptions, the animals of both species significantly discriminated concentrations <1 p.p.m. from the odorless solvent and in several cases individual monkeys even demonstrated thresholds <1 p.p.b. The results showed (i). both primate species to have a well-developed olfactory sensitivity for carboxylic acids, which for some substances matches or even is markedly better than that of species such as the rat or the dog and (ii). a significant correlation between perceptibility in terms of olfactory detection thresholds and carbon chain length of the carboxylic acids in both species tested. These findings lend further support to the growing body of evidence suggesting that between-species comparisons of the number of functional olfactory receptor genes or of neuroanatomical features are poor predictors of olfactory performance, and that general labels such as 'microsmat' or 'macrosmat'-which usually are based on allometric comparisons of olfactory brain structures-are inadequate to describe a species' olfactory capabilities.