Quantifying anhedonia-like symptoms in marmosets using appetitive Pavlovian conditioning.

Blunted reward responsivity is associated with anhedonia in humans and is a core feature of depression. This protocol describes how to train the common marmoset, Callithrix jacchus, on an appetitive Pavlovian conditioning paradigm to measure behavioral and cardiovascular correlates of anticipatory and consummatory phases of reward processing. We describe how to use intracerebral infusions to manipulate brain regions whose activity is relevant to impaired reward processing in depression and how the paradigm can be used to test antidepressant efficacy. For complete details on the use and execution of this protocol, please refer to Alexander et al. (2019)

Perceptual Anchoring in Preschool Children: Not Adultlike, but There

BACKGROUND: Recent studies suggest that human auditory perception follows a prolonged developmental trajectory, sometimes continuing well into adolescence. Whereas both sensory and cognitive accounts have been proposed, the development of the ability to base current perceptual decisions on prior information, an ability that strongly benefits adult perception, has not been directly explored. Here we ask whether the auditory frequency discrimination of preschool children also improves when given the opportunity to use previously presented standard stimuli as perceptual anchors, and whether the magnitude of this anchoring effect undergoes developmental changes. METHODOLOGY/PRINCIPAL FINDINGS: Frequency discrimination was tested using two adaptive same/different protocols. In one protocol (with-reference), a repeated 1-kHz standard tone was presented repeatedly across trials. In the other (no-reference), no such repetitions occurred. Verbal memory and early reading skills were also evaluated to determine if the pattern of correlations between frequency discrimination, memory and literacy is similar to that previously reported in older children and adults. Preschool children were significantly more sensitive in the with-reference than in the no-reference condition, but the magnitude of this anchoring effect was smaller than that observed in adults. The pattern of correlations among discrimination thresholds, memory and literacy replicated previous reports in older children. CONCLUSIONS/SIGNIFICANCE: The processes allowing the use of context to form perceptual anchors are already functional among preschool children, albeit to a lesser extent than in adults. Nevertheless, immature anchoring cannot fully account for the poorer frequency discrimination abilities of young children. That anchoring is present among the majority of typically developing preschool children suggests that the anchoring deficits observed among individuals with dyslexia represent a true deficit rather than a developmental delay

Separating the influences of prereading skills on early word and nonword reading

The essential first step for a beginning reader is to learn to match printed forms to phonological representations. For a new word, this is an effortful process where each grapheme must be translated individually (serial decoding). The role of phonological awareness in developing a decoding strategy is well known. We examined whether beginning readers recruit different skills depending on the nature of the words being read (familiar words vs. nonwords). Print knowledge, phoneme and rhyme awareness, rapid automatized naming (RAN), phonological short-term memory (STM), nonverbal reasoning, vocabulary, auditory skills, and visual attention were measured in 392 prereaders 4 and 5 years of age. Word and nonword reading were measured 9 months later. We used structural equation modeling to examine the skills–reading relationship and modeled correlations between our two reading outcomes and among all prereading skills. We found that a broad range of skills were associated with reading outcomes: early print knowledge, phonological STM, phoneme awareness and RAN. Whereas all of these skills were directly predictive of nonword reading, early print knowledge was the only direct predictor of word reading. Our findings suggest that beginning readers draw most heavily on their existing print knowledge to read familiar words

Predicting In Vivo Efficacy of Potential Restenosis Therapies by Cell Culture Studies: Species-Dependent Susceptibility of Vascular Smooth Muscle Cells

Although drug-eluting stents (DES) are successfully utilized for restenosis therapy, the development of local and systemic therapeutic means including nanoparticles (NP) continues. Lack of correlation between in vitro and in vivo studies is one of the major drawbacks in developing new drug delivery systems. The present study was designed to examine the applicability of the arterial explant outgrowth model, and of smooth muscle cells (SMC) cultures for prescreening of possible drugs. Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies. The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (rat≥rabbit>porcine>human). Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive. The validity of in vitro culture studies for the screening of controlled release delivery systems such as nanoparticles is limited. It is suggested that prescreening studies of possible drug candidates for restenosis therapy should include both SMC cell cultures of rat and human, appropriately designed with a suitable serum

Patient and general population values for luminal and perianal fistulising Crohn’s disease health states

Background In patients with Crohn’s disease (CD), luminal disease activity paralleled by perianal fstulas may seriously impair health-related quality of life (HRQoL). Health utility values are not available from patients with CD that refect the health loss associated with both luminal and perianal CD. Objective To generate utilities for luminal and concomitant perianal fstulising CD health states directly from patients and from members of the general public. Methods A cross-sectional survey was undertaken enrolling CD patients and a convenience sample of members of the general population. Respondents were asked to evaluate four common CD heath states [severe luminal disease (sCD), mild luminal disease (mCD), severe luminal disease with active perianal fstulas (sPFCD), and mild luminal disease with active perianal fstulas (mPFCD)] by 10-year time trade-of (TTO). In addition, patients assessed their current HRQoL by the TTO method. Results Responses of 206 patients (40.8% with perianal fstulas) and 221 members of the general population were analysed. Mean±SD utilities among patients for sPFCD, sCD, mPFCD and mCD states were 0.69±0.33, 0.73±0.31, 0.80±0.29 and 0.87±0.26. Corresponding values in the general public were: 0.59±0.31, 0.65±0.29, 0.80±0.26 and 0.88±0.25. Patients with active perianal fstulas, previous non-resection surgeries, and higher pain intensity scores valued their current health as worse (p<0.05). Conclusions TTO is a feasible method to assess HRQoL in patients with perianal fstulising disease, often not captured by health status questionnaires. Utilities from this study are intended to support the optimization of treatment-related decision making in patients with luminal disease paralleled by active perianal fstulas