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Precision pharmacology aims to manipulate specific cellular interactions within complex tissues. In this pursuit, we introduce DART.2 (drug acutely restricted by tethering), a second-generation cell-specific pharmacology technology. The core advance is optimized cellular specificity-up to 3,000-fold in 15 min-enabling the targeted delivery of even epileptogenic drugs without off-target effects. Additionally, we introduce brain-wide dosing methods as an alternative to local cannulation and tracer reagents for brain-wide dose quantification. We describe four pharmaceuticals-two that antagonize excitatory and inhibitory postsynaptic receptors, and two that allosterically potentiate these receptors. Their versatility is showcased across multiple mouse-brain regions, including cerebellum, striatum, visual cortex and retina. Finally, in the ventral tegmental area, we find that blocking inhibitory inputs to dopamine neurons accelerates locomotion, contrasting with previous optogenetic and pharmacological findings. Beyond enabling the bidirectional perturbation of chemical synapses, these reagents offer intersectional precision-between genetically defined postsynaptic cells and neurotransmitter-defined presynaptic partners.

BackgroundThe complementary feeding period is a time of unparalleled dietary change for every human, during which the diet changes from one that is 100% milk to one that resembles the usual diet of the wider family in less than a year. Despite this major dietary shift, we know relatively little about food and nutrient intake in infants worldwide and virtually nothing about the impact of baby food “pouches” and “baby-led weaning” (BLW), which are infant feeding approaches that are becoming increasingly popular. Pouches are squeezable containers with a plastic spout that have great appeal for parents, as evidenced by their extraordinary market share worldwide. BLW is an alternative approach to introducing solids that promotes infant self-feeding of whole foods rather than being fed purées, and is popular and widely advocated on social media. The nutritional and health impacts of these novel methods of infant feeding have not yet been determined. ObjectiveThe aim of the First Foods New Zealand study is to determine the iron status, growth, food and nutrient intakes, breast milk intake, eating and feeding behaviors, dental health, oral motor skills, and choking risk of New Zealand infants in general and those who are using pouches or BLW compared with those who are not. MethodsDietary intake (two 24-hour recalls supplemented with food photographs), iron status (hemoglobin, plasma ferritin, and soluble transferrin receptor), weight status (BMI), food pouch use and extent of BLW (questionnaire), breast milk intake (deuterium oxide “dose-to-mother” technique), eating and feeding behaviors (questionnaires and video recording of an evening meal), dental health (photographs of upper and lower teeth for counting of caries and developmental defects of enamel), oral motor skills (questionnaires), and choking risk (questionnaire) will be assessed in 625 infants aged 7.0 to 9.9 months. Propensity score matching will be used to address bias caused by differences in demographics between groups so that the results more closely represent a potential causal effect. ResultsThis observational study has full ethical approval from the Health and Disability Ethics Committees New Zealand (19/STH/151) and was funded in May 2019 by the Health Research Council (HRC) of New Zealand (grant 19/172). Data collection commenced in July 2020, and the first results are expected to be submitted for publication in 2022. ConclusionsThis large study will provide much needed data on the implications for nutritional intake and health with the use of baby food pouches and BLW in infancy. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12620000459921; http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379436. International Registered Report Identifier (IRRID)DERR1-10.2196/29048

The cerebellar cortex has a key role in generating predictive sensorimotor associations. To do so, the granule cell layer is thought to establish unique sensorimotor representations for learning. However, how this is achieved and how granule cell population responses contribute to behavior have remained unclear. To address these questions, we have used in vivo calcium imaging and granule cell-specific pharmacological manipulation of synaptic inhibition in awake, behaving mice. These experiments indicate that inhibition sparsens and thresholds sensory responses, limiting overlap between sensory ensembles and preventing spiking in many granule cells that receive excitatory input. Moreover, inhibition can be recruited in a stimulus-specific manner to powerfully decorrelate multisensory ensembles. Consistent with these results, granule cell inhibition is required for accurate cerebellum-dependent sensorimotor behavior. These data thus reveal key mechanisms for granule cell layer pattern separation beyond those envisioned by classical models.

Addressed toward course coordinators and departmental leaders interested in redesigning an undergraduate mathematics course, we highlight the steps our team at the University of Maryland, College Park has taken in bringing active learning to our Precalculus course. We provide examples of ways in which we have coordinated active learning across redesigned sections, as well as preliminary results of the effects of active learning on student success. Finally, given the broad set of experiences and backgrounds of our team members, we argue for the unique insight our redesign offers in restructuring a gatekeeper mathematics course to be focused on active learning.

"When you hear hoofbeats, look for horses, not zebras." This common saying in medicine (often attributed to Theodore Woodward, MD, of the University of Maryland School of Medicine) advises doctors to stick to the expected or likely diagnosis, rather than anticipating an unusual or atypical one. As a result, uncommon medical diagnoses are often colloquially referred to as zebras. In this article, the authors would like to reverse the advice in this saying, suggesting that in mathematics education, and with pattern tasks in particular, looking for zebras can be a good exercise. The authors argue that when working with students on the first few stages of patterns (the hoofbeats), they often engage in looking only for horses and miss out on spotting the zebras. Identifying and working with patterns is a fundamental component of mathematical thinking. Creating ambiguity in task prompts can encourage students to identify unconventional pattern extensions.

Context: The patient-physician relationship plays a crucial role in patient satisfaction and clinical outcomes. Narrative Medicine seeks to improve the experience of providing and receiving healthcare by engaging with patient stories and developing narrative competence. Its potential role in establishing care with a Primary Care Provider (PCP) has not been previously studied. Objective: To assess patient reactions to and engagement with an invitation to share about themselves personally via electronic messaging through the healthcare record (MyChart) as part of establishing care with a new PCP. Study Design and Analysis: Over a 7-week period, patients who met the inclusion criteria (age > 18, English speaking, active on MyChart, scheduled for a first visit with a new PCP) were sent a MyChart message asking what they wanted their healthcare team to know about them as a person. Responses were discussed during the office visit and patients who viewed the message were given a survey about their experience with receiving the message and its impact on their clinic visit. Patient responses to the MyChart messages were analyzed for themes using NVivo. Setting: Family Medicine clinic in Cottage Grove, Wisconsin Population Studied: Adult outpatients at a family medicine clinic Intervention: MyChart message from the study provider asking 'What do you want your healthcare team to know about you as a person?' Outcome Measures: Percentage of patients reading and responding to the MyChart message; Themes of patient responses as coded by two raters; Survey responses about patient experience of being asked this question Results: Of 57 MyChart messages sent to new patients, 40 (70%) were read. Of those read, 15 (38%) responded. Major response themes included Health, Personal information, and Reactions to the message. Of 24 surveys collected, 95% of patients had a positive or neutral response to receiving the MyChart message; 86% felt it positively impacted their visit, and 93% felt it increased their comfort level with their new PCP. Conclusions: This pilot project suggests that most patients appreciate the opportunity to share something about themselves when establishing care with a new PCP, and that MyChart is one viable way to facilitate this communication. Potential future areas of study include exploring the most effective protocol for inviting patients to share personal narrative, and how these narratives impact patient and physician experience of establishing care., Presenters Samantha Gallo, Elizabeth Fleming, [...]

In this article, we explore how the solving of linear equations is represented in English­-language algebra text books from the early nineteenth century when schooling was becoming institutionalized, and then survey contemporary teachers. In the text books, we identify the increasing presence of a prescribed order of steps (a canonical method) for solving linear equations. Teachers' reactions to correct student solutions that do not follow this canonical method suggest its centrality to school algebra instruction. We reflect on these observations using the notions of didactical transposition, instructional exchange, and a metaphorical alchemy that creates school subjects from disciplinary knowledge.

Two major arms of skin ageing are changes in the skin's biophysical conditions and alterations in the skin microbiome. This work partitioned both arms to study their interaction in detail. Leveraging the resolution provided by shotgun metagenomics, we explored how skin microbial species, strains and gene content interact with the biophysical traits of the skin during ageing. With a dataset well‐controlled for confounding factors, we found that skin biophysical traits, especially the collagen diffusion coefficient, are associated with the composition and the functional potential of the skin microbiome, including the abundance of bacterial strains found in nosocomial infections and the abundance of antibiotic resistance genes. Our findings reveal important associations between skin biophysical features and ageing‐related changes in the skin microbiome and generate testable hypotheses for the mechanisms of such associations. [ABSTRACT FROM AUTHOR]