Effects of sex on placebo effects in chronic pain participants: a cross-sectional study.

ABSTRACT: Sex-related differences can influence outcomes of randomized clinical trials and may jeopardize the effectiveness of pain management and other therapeutics. Thus, it is essential to understand the mechanistic and translational aspects of sex differences in placebo outcomes. Recently, studies in healthy participants have shed light on how sex-related placebo effects might influence outcomes, yet no research has been conducted in a patient population. Herein, we used a tripartite approach to evaluate the interaction of prior therapeutic experience (eg, conditioning), expectations, and placebo effects in 280 chronic (orofacial) pain patients (215 women). In this cross-sectional study, we assessed sex differences in placebo effects, conditioning as a proxy of prior therapeutic effects, and expectations evaluated before and after the exposure to positive outcomes, taking into account participant-experimenter sex concordance and hormonal levels (estradiol and progesterone assessed in premenopausal women). We used mediation analysis to determine how conditioning strength and expectations impacted sex differences in placebo outcomes. Independent of gonadal hormone levels, women showed stronger placebo effects than men. We also found significant statistical sex differences in the conditioning strength and reinforced expectations whereby reinforced expectations mediated the sex-related placebo effects. In addition, the participant-experimenter sex concordance influenced conditioning strength, reinforced expectations, and placebo effects in women but not in men. Our findings suggest that women experience larger conditioning effects, expectations, and placebo effects emphasizing the need to consider sex as a biological variable when placebo components of any outcomes are part of drug development trials and in pain management.

Mirrored patterns of lateralized neuronal activation reflect old and new memories in the avian auditory cortex.

In monolingual humans, language-related brain activation shows a distinct lateralized pattern, in which the left hemisphere is often dominant. Studies are not as conclusive regarding the localization of the underlying neural substrate for language in sequential language learners. Lateralization of the neural substrate for first and second language depends on a number of factors including proficiency and early experience with each language. Similar to humans learning speech, songbirds learn their vocalizations from a conspecific tutor early in development. Here, we show mirrored patterns of lateralization in the avian analog of the mammalian auditory cortex (the caudomedial nidopallium [NCM]) in sequentially tutored zebra finches (Taeniopygia guttata​) in response to their first tutor song, learned early in development, and their second tutor song, learned later in development. The greater the retention of song from their first tutor, the more right-dominant the birds were when exposed to that song; the more birds learned from their second tutor, the more left-dominant they were when exposed to that song. Thus, the avian auditory cortex may preserve lateralized neuronal traces of old and new tutor song memories, which are dependent on proficiency of song learning. There is striking resemblance in humans: early-formed language representations are maintained in the brain even if exposure to that language is discontinued. The switching of hemispheric dominance related to the acquisition of early auditory memories and subsequent encoding of more recent memories may be an evolutionary adaptation in vocal learners necessary for the behavioral flexibility to acquire novel vocalizations, such as a second language.

Recruitment and retention of urban schoolchildren into a randomized double-blind vitamin D supplementation trial.

BACKGROUND: While rarely used for supplementation trials in the United States, schools present a practical alternative to a clinical setting. PURPOSE: We describe the successful recruitment and retention of urban schoolchildren into a 6-month randomized, double-blind vitamin D3 supplementation trial. METHODS: Boston-area urban schoolchildren, aged 8-15 years, were recruited in 2011-2012 through classroom and auditorium presentations. Informed consent forms in five languages were sent home to parents. Retention methods included regular telephone calls and gift cards for completed study visits. RESULTS: In total, 691 schoolchildren enrolled. Their mean (standard deviation) age was 11.7 (1.4) years; 59% were racial/ethnic minorities and 68% qualified for free or reduced-price school meals. Multi-level, culturally sensitive, creative approaches contributed to success in recruitment and retention. Of 691 participants, 81% completed the 6-month intervention period. Reasons for attrition included missed appointments and fear of a blood draw. More children from households with higher incomes were retained than those from households with lower incomes (85% vs 79%, respectively, P = 0.04). LIMITATIONS: The need for three fasting blood draws over the 6-month supplementation period was a limiting factor in the recruitment and retention of children in this study. CONCLUSION: Recruitment of urban children into a school-based randomized controlled trial represents a feasible approach for a supplementation study. Particular attention to children of lower socioeconomic status may enhance participation and retention when conducting intervention studies among diverse populations.